Cardiovascular Disease And Hypertension

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	Is Hyperuricemia the Missing Piece in the Metabolic Syndrome Puzzle? Content Type Journal ArticleCategory Clinical Trial ReportPages 1-3DOI 10.1007/s11906-012-0249-8Authors Zohreh Soltani, Section of Nephrology and Hypertension, Louisiana State University Health Science Center, 1542 Tulane Ave, New Orleans, LA 70113, USAEfrain Reisin, Section of Nephrology and Hypertension, Louisiana State University Health Science Center, 1542 Tulane Ave, New Orleans, LA 70113, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) The Effect of Weight Loss in Obesity and Chronic Kidney Disease Abstract  Several epidemiologic investigations have confirmed that obesity is a significant risk factor for the appearance of proteinuria and end-stage kidney disease in a normal population. Weight loss induced by low-calorie diets, physical exercise, or bariatric surgery is accompanied by an important antiproteinuric effect. Reduction in proteinuria is already observed after a few weeks from the onset of weight loss and it is evident even in patients with modest weight losses. Reduction in proteinuria by weight loss has been described in chronic proteinuric nephropathies of different etiologies. The mechanisms through which weight loss may reverse proteinuria are likely to be plural: better control of blood pressure, improvement of serum lipid profile, improvement of insul... Screening for Pheochromocytomas and Paragangliomas Abstract  Pheochromocytomas and paragangliomas are highly heterogeneous neuroendocrine tumors that must be considered not only in patients with hypertension and other manifestations of catecholamine excess but also in patients with incidentalomas or mutations in one of the ten tumor susceptibility genes identified to date. To first think of the tumor remains the critical step for screening in patients with signs and symptoms. In these patients, biochemical testing is straightforward and should include measurements of plasma or urinary metanephrines, comprising separately measured normetanephrine and metanephrine. Tumors due to an underlying germline mutation are often found in the absence of hypertension or other signs or symptoms of the tumor. Screening for disease in thes... Mendelian Randomization: Application to Cardiovascular Disease Abstract  In the absence of an ethical, practical, and economical randomized trial, the epidemiologist is left to explore other methods in efforts to assert causality. An approach based on genotypic variation has the potential to mitigate against some of the problems found within conventional observational studies. Genetic variations associated with risk factors of interest at the population level can be used as proxy measures for these risk factors and to generate estimates of causal effect. The potential and the possible limitations of this approach within the cardiovascular field are presented in this review. Content Type Journal ArticleCategory Pathogenesis of Hypertension: Genetic and Environmental Factors (DT O?Connor, Section Editor)Pages 1-9DOI 10.1007/s11906-0... Between Candidate Genes and Whole Genomes: Time for Alternative Approaches in Blood Pressure Genetics Abstract  Blood pressure has a significant genetic component, but less than 3% of the observed variance has been attributed to genetic variants identified to date. Candidate gene studies of rare, monogenic hypertensive syndromes have conclusively implicated several genes altering renal sodium balance, and studies of essential hypertension have inconsistently implicated over 50 genes in pathways affecting renal sodium balance and other functions. Genome-wide linkage scans have replicated numerous quantitative trait loci throughout the genome, and over 50 single nucleotide polymorphisms (SNPs) have been replicated in multiple genome-wide association studies. These studies provide considerable evidence that epistasis and other interactions play a role in the genetic architectu... M-Atrial Natriuretic Peptide: A Novel Antihypertensive Protein Therapy Abstract  The natriuretic peptides, specifically atrial natriuretic peptide (ANP), are increasingly recognized to play a fundamental role in blood pressure (BP) regulation. This role in BP regulation reflects the pluripotent cardiorenal actions of ANP, which include diuresis, enhancement of renal blood flow and glomerular filtration rate, systemic vasodilatation, suppression of aldosterone, and inhibition of the sympathetic nervous system. These actions of ANP, in addition to recent human studies demonstrating an association of higher plasma ANP with lower risk of hypertension, support the development of an ANP-based therapy for hypertension. M-ANP is a novel ANP-based peptide that is resistant to proteolytic degradation and possesses greater BP-lowering, renal function?en... Epinephrine and the Metabolic Syndrome Abstract  Epinephrine is the prototypical stress hormone. Its stimulation of all ? and ? adrenergic receptors elicits short-term systolic hypertension, hyperglycemia, and other aspects of the metabolic syndrome. Acute epinephrine infusion increases cardiac output and induces insulin resistance, but removal of the adrenal medulla has no consistent effect on blood pressure. Epinephrine is the most effective endogenous agonist at the ?2 receptor. Transgenic mice that cannot make epinephrine and mice that lack the ?2 receptor become hypertensive during exercise, presumably owing to the absence of ?2-mediated vasodilatation. Epinephrine-deficient mice also have cardiac remodeling and poor cardiac responses to stress, but do not develop resting hypertension. Mice that cannot... Noninvasive Studies of Central Aortic Pressure This article reviews noninvasive techniques of measuring central arterial pressure that have been validated against intra-arterial pressure. This paper explains methods to derive central (aortic and carotid) pressure from radial and brachial sites. It focuses on specific issues of brachial calibration applied to carotid pressure waveforms, which were regarded as a surrogate of aortic pressures used in three major studies (Framingham, Asklepios, and Australian National Blood Pressure 2 studies). We explain why radial-based methods are superior to carotid-based methods for estimating central pressure. Physiological principles of pressure measurement need be satisfied to ensure accurate recording. Content Type Journal ArticleCategory Pathogenesis of Hypertension (DT O?Connor, Sect... An Emerging Role of Degrading Proteinases in Hypertension and the Metabolic Syndrome: Autodigestion and Receptor Cleavage Abstract  One of the major challenges for hypertension research is to identify the mechanisms that cause the comorbidities encountered in many hypertensive patients, as seen in the metabolic syndrome. An emerging body of evidence suggests that human and experimental hypertensives may exhibit uncontrolled activity of proteinases, including the family of matrix metalloproteinases, recognized for their ability to restructure the extracellular matrix proteins and to play a role in hypertrophy. We propose a new hypothesis that provides a molecular framework for the comorbidities of hypertension, diabetes, capillary rarefaction, immune suppression, and other cell and organ dysfunctions due to early and uncontrolled extracellular receptor cleavage by active proteinases. The protei... The Nox Family of NADPH Oxidases: Friend or Foe of the Vascular System? Abstract  NADPH (nicotinamide adenine dinucleotide phosphate) oxidases are important sources of reactive oxygen species (ROS). In the vascular system, ROS can have both beneficial and detrimental effects. Under physiologic conditions, ROS are involved in signaling pathways that regulate vascular tone as well as cellular processes like proliferation, migration and differentiation. However, high doses of ROS, which are produced after induction or activation of NADPH oxidases in response to cardiovascular risk factors and inflammation, contribute to the development of endothelial dysfunction and vascular disease. In vascular cells, the NADPH oxidase isoforms Nox1, Nox2, Nox4, and Nox5 are expressed, which differ in their activity, response to stimuli, and the type of ROS relea... Target Organ Damage in African American Hypertension: Role of APOL1 Abstract  Apolipoprotein L1 (APOL1) gene association studies and results of the African American Study of Kidney Disease and Hypertension are disproving the longstanding concept that mild to moderate essential hypertension contributes substantially to end-stage renal disease susceptibility in African Americans. APOL1 coding variants underlie a spectrum of kidney diseases, including that attributed to hypertension (labeled arteriolar or hypertensive nephrosclerosis), focal segmental glomerulosclerosis, and HIV-associated nephropathy. APOL1 nephropathy risk variants persist because of protection afforded from the parasite that causes African sleeping sickness. This breakthrough will lead to novel treatments for hypertensive African Americans with low-level proteinuria, for whom... Disorders of Blood Pressure Regulation?Role of Catecholamine Biosynthesis, Release, and Metabolism This article reviews recent advances within this rapidly changing field, particularly focusing on the role of genetic polymorphisms within key catecholamine biosynthetic enzymes, cofactors, and storage molecules. In addition, mechanisms linking the sympathetic nervous system and other adverse cardiovascular states (obesity, insulin resistance, dyslipidaemia) are discussed, along with speculation as to how recent scientific advances may lead to the emergence of novel antihypertensive treatments. Content Type Journal ArticleCategory Pathogenesis of Hypertension: Genetic and Environmental Factors (DT O?Connor, Section Editor)Pages 1-8DOI 10.1007/s11906-011-0239-2Authors Gemma Currie, Department of Endocrinology, Western Infirmary, Glasgow, G11 6NT UKE. Marie Freel, Institute of C... MicroRNAs in Hypertension: Mechanisms and Therapeutic Targets This article reviews the potential role of microRNAs in the mechanisms associated with the development and consequences of hypertension and discusses advances in microRNA-based approaches that may be important in treating hypertension. Content Type Journal ArticleCategory Vascular Mechanisms (F Ruschitzka, Section Editor)Pages 1-9DOI 10.1007/s11906-011-0235-6Authors Sándor Bátkai, Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Str. 1, 0625 Hannover, GermanyThomas Thum, Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Str. 1, 0625 Hannover, Germany Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hyperten... Implications of Changes in Plasma Asymmetric Dimethylarginine During Treatment of Hypertension Content Type Journal ArticleCategory Clinical Trial ReportPages 406-408DOI 10.1007/s11906-011-0233-8Authors Bertrand N. Mukete, James J. Peters VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USASteven A. Atlas, James J. Peters VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 Journal Volume Volume 13 Journal Issue Volume 13, Number 6 (Source: Current Hypertension Reports) Effects of Relaxin on Arterial Dilation, Remodeling, and Mechanical Properties Abstract  Administering relaxin to conscious rats and humans elicits systemic and renal vasodilation. The molecular mechanisms vary according to the duration of relaxin exposure?so-called ?rapid? (within minutes) or ?sustained? (hours to days) vasodilatory responses?both being endothelium-dependent. Rapid responses are mediated by G?i/o protein coupling to phosphoinositol-3 kinase/Akt (protein kinase B)?dependent phosphorylation and activation of nitric oxide synthase. Sustained responses are mediated by vascular endothelial and placental growth factors, as well as increases in arterial gelatinase activity. Thus, after hours or days of relaxin treatment, respectively, arterial MMP-9 or MMP-2 hydrolyze ?big? endothelin (ET) at a gly-leu bond to form ET1-32,... Improvement of Sodium Status to Optimize the Efficacy of Renin-Angiotensin System Blockade Abstract  Blockade of the renin-angiotensin-aldosterone system (RAAS) offers superior renoprotection in the treatment of patients with hypertension, but the efficacy of RAAS inhibition strongly depends on sodium status, presumably in relation to extracellular volume status. Because assessing volume status by physical examination is challenging, 24-hour urine collection and NT-proBNP levels are useful tools for guiding volume management and achieving sodium status targets. Content Type Journal ArticleCategory Invited CommentaryPages 1-3DOI 10.1007/s11906-011-0234-7Authors Gozewijn D. Laverman, Department of Internal Medicine, Division of Nephrology, ZGT Hospital Almelo, Almelo, The NetherlandsGerjan Navis, Department of Internal Medicine, Division of Nephrology, Universi... Beyond Genome-Wide Association Studies: New Strategies for Identifying Genetic Determinants of Hypertension Abstract  Genetic linkage and association methods have long been the most important tools for gene identification in humans. These approaches can either be hypothesis-based (i.e., candidate-gene studies) or hypothesis-free (i.e., genome-wide studies). The first part of this review offers an overview of the latest successes in gene finding for blood pressure (BP) and essential hypertension using these DNA sequence?based discovery techniques. We further emphasize the importance of post?genome-wide association study (post-GWAS) analysis, which aims to prioritize genetic variants for functional follow-up. Whole-genome next-generation sequencing will eventually be necessary to provide a more comprehensive picture of all DNA variants affecting BP and hypertension. The second ... Is Bitter Better? The Benefits of Chocolate for the Cardiovascular System Content Type Journal ArticleCategory Clinical Trial ReportPages 1-3DOI 10.1007/s11906-011-0232-9Authors H. Evren Kaynak, Department of Internal Medicine, Division of Cardiology, University of Texas Medical School at Houston, 6431 Fannin, MSB 1.246, Houston, TX 77030, USAHeinrich Taegtmeyer, Department of Internal Medicine, Division of Cardiology, University of Texas Medical School at Houston, 6431 Fannin, MSB 1.246, Houston, TX 77030, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Sunitinib, Hypertension, and Heart Failure: A Model for Kinase Inhibitor-Mediated Cardiotoxicity Abstract  Kinase inhibitors have emerged as an important new class of agents for the treatment of diverse tumors. Sunitinib malate is a small-molecule, oral, multi-kinase inhibitor approved for use in treating renal cell carcinoma and gastrointestinal stromal tumor. It has also demonstrated efficacy in treating pancreatic neuroendocrine tumors and is being evaluated for the treatment of other cancers. Initially developed for its inhibition of the vascular endothelial growth factor (VEGF) signaling pathway, sunitinib has been associated with hypertension and heart failure. This review examines the incidence and severity of these adverse events, relevant findings from other agents that inhibit VEGF signaling, the mechanisms underlying these effects, and suggestions for their ... Resistant Hypertension: Concepts and Approach to Management Abstract  Resistant hypertension (RH), defined simply, is blood pressure (BP) requiring the use of four or more antihypertensive agents, whether controlled or uncontrolled. RH is an increasingly common problem in elderly patients and may affect as many as 20% of the hypertensive population. Unfortunately, at least 30% of patients evaluated for RH are actually adequately controlled when more carefully assessed by home BP monitoring or ambulatory BP monitoring, thus representing a white coat effect. It is also essential to exclude pseudoresistance resulting from improper BP recording techniques or failure of the patient to adhere to the prescribed treatment regimen. Concurrent use of drugs that may interfere with prescribed antihypertensive agents, including many over the cou... Blood Pressure Targets for Patients with Diabetes or Kidney Disease Abstract  The most recent scientific guideline statements from foundations and societies dealing with diabetes and kidney disease argue for blood pressure (BP) goals lower than 130/80 mm Hg, but whether the evidence from properly done clinical trials supports this BP level remains questionable. A review of all the evidence suggests that almost all of the data come from retrospective data analyses of randomized cardiovascular and chronic kidney disease (CKD) trials. Meta-analyses of all clinical trials to date demonstrate that reducing BP reduces risk for stroke and coronary heart disease, but none have achieved a mean BP goal of less than 130/80 mm Hg. In fact, only two prospective trials achieved a BP lower than 130/80 mm Hg in people with type... The Roles of Integrins in Mediating the Effects of Mechanical Force and Growth Factors on Blood Vessels in Hypertension Abstract  Hypertension is characterized by a sustained increase in vasoconstriction and attenuated vasodilation in the face of elevated mechanical stress in the blood vessel wall. To adapt to the increased stress, the vascular smooth muscle cell and its surrounding environment undergo structural and functional changes known as vascular remodeling. Multiple mechanisms underlie the remodeling process, including increased expression of humoral factors and their receptors as well as adhesion molecules and their receptors, all of which appear to collaborate and interact in the response to pressure elevation. In this review, we focus on the interactions between integrin signaling pathways and the activation of growth factor receptors in the response to the increased mechanical st... Immune Mechanisms in Hypertension Abstract  Inflammation plays an important role in the pathogenesis of hypertension. Innate and adaptive immune response may contribute to this process. The mechanisms implicating immune response in hypertension are still elusive. To date, the evidence originates in three major areas of data: cytokine production, central nervous system (CNS) stimulation, and kidney damage. The cytokine microenvironment can become proinflammatory and propagate low-grade inflammation, which may contribute to vascular injury and end-organ damage in hypertension. In addition, stimulation of the CNS by some stimuli (e.g., angiotensin II) causes mild hypertension that may modulate peripheral immune responses leading to aggravation of blood pressure elevation. The immune response can induce kidney ... Heart Failure Associated with Sunitinib: Lessons Learned from Animal Models Abstract  Sunitinib is a highly potent, multitargeted anticancer agent. However, there is growing clinical evidence that sunitinib induces cardiac dysfunction. Disruption of multiple signaling pathways, which are important in the maintenance of adult cardiac function, is likely to result in cardiovascular toxicity. Basic and translational evidence implicates a potential role for specific growth factor signaling pathways. This review discusses the relevant translational data from animal models of heart failure, focusing on three key pathways that are inhibited by sunitinib: AMP-activated protein kinase (AMPK), platelet-derived growth factor receptors (PDGFRs), and the vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3. We hypothesize that disruption of these p... Does Sustained Weight Loss Reverse the Metabolic Syndrome? Abstract  The prevalence of the metabolic syndrome (MetS) has increased rapidly in North America in recent years. Presently, the MetS is found in 34.3% of the population, and the prevalence is likely to continue to increase in parallel with the obesity epidemic. Losing weight and long-term maintenance of the weight loss are primary targets to beneficially reverse all of the components of the MetS. This paper reviews the clinical and experimental evidence for the reversal of the metabolic complications related to the MetS that follows a sustained weight loss. Content Type Journal ArticlePages 1-9DOI 10.1007/s11906-011-0221-zAuthors Annie Ferland, Division of Endocrinology, Metabolism and Diabetes, MS 8106, University of Colorado Anschutz Medical Campus, Anschutz Medical... Systolic Blood Pressure and Mortality in Patients on Hemodialysis Abstract  Hypertension is extremely common in patients with end-stage renal disease who are receiving hemodialysis, and cardiovascular disease remains the leading cause of death in these patients. However, optimal blood pressure management strategies in this high-risk population are still controversial. This review first discusses the complex association of systolic blood pressure with clinical outcomes in patients on hemodialysis, with a focus on several recent studies. Next, it updates the reader on issues related to optimal timing and methods of blood pressure measurement, appropriate blood pressure targets, and pharmacologic and nonpharmacologic hypertension treatment strategies for patients on hemodialysis. Content Type Journal ArticlePages 1-8DOI 10.1007/s11906-01... Hydrochlorothiazide Versus Calcium Channel Blockers: What is the Best Add-on to a Renin-Angiotensin System Blocker for Treating Hypertension in Patients with Renal Disease? Abstract  Hypertension remains an important problem that increases the risk of cardiovascular disease and is a leading cause of mortality worldwide. Achieving long-term control of arterial hypertension, which has an estimated prevalence of 28% in the US adult population, would translate into a significant reduction in cardiovascular events. Specific causes can be identified and treated for certain forms of secondary hypertension, but often it is multifactorial. Therefore, it makes sense to attain blood pressure control by addressing more than one pressor mechanism. Several clinical studies have demonstrated that combination antihypertensive therapy is more effective than monotherapy, and a review of currently published data suggests that approximately 75% of hypertensive in... Salivary Cortisol Predicts Cardiovascular Mortality Content Type Journal ArticlePages 1-2DOI 10.1007/s11906-011-0220-0Authors Reshma Pahuja, Division of Endocrinology/Metabolism, Department of Medicine, Medical College of Wisconsin, 9200 West Wisconsin Ave., Milwaukee, WI 53226, USATheodore A. Kotchen, Division of Endocrinology/Metabolism, Department of Medicine, Medical College of Wisconsin, 9200 West Wisconsin Ave., Milwaukee, WI 53226, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Blood Oxygen Level?Dependent (BOLD) MRI in Renovascular Hypertension Abstract  Establishing whether large vessel occlusive disease threatens tissue oxygenation and viability in the post-stenotic kidney is difficult for clinicians. Development of blood oxygen level?dependent (BOLD) MRI methods can allow functional evaluation of regional differences in deoxyhemoglobin levels within the kidney without requiring contrast. The complex renal circulation normally provides a gradient of oxygenation from a highly vascular cortex to much reduced levels in the deep sections of medulla, dependent upon adjustments in renal afferent arterioles, oxygen consumption related to solute transport, and arteriovenous shunting related to the juxtaposition of descending and ascending vasa recta. Studies with BOLD imaging have identified adaptation to substantial ... Something New to Offer: Renal Denervation Content Type Journal ArticlePages 1-1DOI 10.1007/s11906-011-0219-6Authors Norman K. Hollenberg, Departments of Medicine and Radiology, Harvard Medical School, Brigham and Women?s Hospital, Mailstop PBB1-Rad Building, 15 Francis Street, Boston, MA 02115, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Is Nocturnal Blood Pressure Reduction the Secret to Reducing the Rate of Progression of Hypertensive Chronic Kidney Disease? Abstract  Hypertension is a significant risk factor for cardiovascular and renal disease. Lowering blood pressure (BP) has been shown to reduce the incidence of cardiovascular disease, but randomized trials have not demonstrated a benefit of lowering BP for the progression of renal disease except in secondary analyses in patients with significant proteinuria. Recently, there has been increasing interest in measuring BP outside of the clinic, using both home and ambulatory blood pressure monitoring (ABPM). ABPM has the advantage of measuring BP throughout both the day and night. Elevated nighttime BP and a lack of decline in BP from day to night (nondipping) are more potent risk factors for cardiovascular and renal outcomes than elevated daytime or clinic BP. Studies have sh... Population-Wide Dietary Sodium Restriction: A Cautious View Abstract  ?What I tell you three times is true??Lewis Carroll. How many times have we been told that reducing dietary sodium intake will improve the health of whole populations? But is there adequate evidence to support this idea? Some recent studies have indicated that caution is needed. Targeting those most likely to benefit should prevent inadvertent harm and free the rest of the population from yet another nagging plea to alter their lifestyle. Content Type Journal ArticlePages 1-3DOI 10.1007/s11906-011-0216-9Authors M. Gary Nicholls, Department of Medicine, Christchurch Hospital, University of Otago-Christchurch, Riccarton Avenue, Christchurch, New Zealand Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hy... Update on Pathophysiology and Treatment of Hypertension in the Elderly Abstract  Hypertension is common in the elderly, and its prevalence increases with aging. The vascular system is a prototypical aging tissue, and arterial stiffness plays a major role in hypertension as the individual ages. Some unique aging changes in the nitric oxide and angiotensin II pathways are particularly important for vascular aging. Studies focusing on direct measures of vascular stiffness have increased understanding of the pathophysiology behind increased arterial stiffness. Goal blood pressure in the elderly is debated, but based on current outcome data, a goal blood pressure of 150/80?90 mm Hg is reasonable in at least the very elderly. This review discusses in detail the various landmark hypertension studies in the elderly. We recommend use of thi... Mechanisms and Management of Hypertension in Pregnant Women Abstract  Hypertension is the most common medical disorder encountered during pregnancy. A recent report highlighted hypertensive disorders as one of the major causes of pregnancy-related maternal deaths in the United States. Significant advances in our understanding of preeclampsia, a form of hypertension unique to pregnancy, have occurred in recent years. The optimal timing and choice of therapy for hypertensive pregnancy disorders involves carefully weighing the risk-versus-benefit ratio for each individual patient, with an overall goal of improving maternal and fetal outcomes. In this review, we summarize the mechanisms thought to be involved, review the current management guidelines for hypertensive pregnancy disorders as recommended by international guideline groups, ... Improving Genetic Testing for Gitelman?s Syndrome Abstract  Gitelman?s syndrome (GS) is a rare, autosomal recessive, salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl cotransporter (NCC). Because 18 to 40% of suspected GS patients carry only one SLC12A3 mutant allele, large genomic rearrangements may account for unidentified mutations. Here, we directly sequenced genomic DNA from a large cohort of 448 unrelated patients suspected of having GS. We found 172 distinct mutations, of which 100 were unreported previously. In 315 patients (70%), we identified two mutations; in 81 patients (18%), we identified one; and in 52 patients (12%), we did not detect a mutation. In 88 patients, we performed a search for large rearrangements by multiplex ligation-dependent probe ampl... Potential Dopamine-1 Receptor Stimulation in Hypertension Management Abstract  The role of dopamine receptors in blood pressure regulation is well established. Genetic ablation of both dopamine D1-like receptor subtypes (D1, D5) and D2-like receptor subtypes (D2, D3, D4) results in a hypertensive phenotype in mice. This review focuses on the dopamine D1-like receptor subtypes D1 and D5 (especially D1 receptors), as they play a major role in regulating sodium homeostasis and blood pressure. Studies mostly describing the role of renal dopamine D1-like receptors are included, as the kidneys play a pivotal role in the maintenance of sodium homeostasis and the long-term regulation of blood pressure. We also attempt to describe the interaction between D1-like receptors and other proteins, especially angiotensin II type 1 and type 2 receptors, whic... Do Genetic Variants of the Renin-Angiotensin System Predict Blood Pressure Response to Renin-Angiotensin System?Blocking Drugs? A Systematic Review of Pharmacogenomics in the Renin-Angiotensin System Abstract  The concept of ?pharmacogenomics? or ?pharmacogenetics? promises to offer the ultimate in personalized medicine, and the renin-angiotensin system (RAS) is one of the most plausible candidates for the application of this approach in the area of hypertension. For the past two decades, genetic variants of the RAS have been tested for association with blood pressure response, but the results have been inconsistent. The problems have been attributed to many issues, but the most fundamental concern is thought to be the statistical power of the studies. Therefore, we have tried to put together a new systematic review using a database search including only recent reports with adequate numbers of subjects, and 11 reports were identified. From the results, we were a... Progression of Pre-hypertension Content Type Journal ArticlePages 1-3DOI 10.1007/s11906-011-0208-9Authors Thomas D. Giles, 109 Holly Drive, Metairie, LA 70005, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Body Mass and Risk Content Type Journal ArticlePages 1-1DOI 10.1007/s11906-011-0210-2Authors Norman K. Hollenberg, Departments of Medicine and Radiology, Brigham and Women?s Hospital, Harvard Medical School, Mailstop PBB1-Rad Building, 15 Francis Street, Boston, MA 02115, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Prevention of Microalbuminuria in Diabetes Mellitus: Results of the ROADMAP Trial Content Type Journal ArticlePages 1-3DOI 10.1007/s11906-011-0209-8Authors Guido Grassi, Clinica Medica, Ospedale San Gerardo, Via Pergolesi 33, 20052 Monza (Milano), ItalyGiuseppe Mancia, Clinica Medica, Ospedale San Gerardo dei Tintori (Monza), Università Milano-Bicocca, Milano, Italy Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Effects of Antihypertensive Treatment on Endothelial Function Abstract  Essential hypertension is characterized by endothelial dysfunction due to reduced availability of nitric oxide (NO) secondary to increased generation of oxygen-free radicals. Some antihypertensive drugs may improve or restore endothelial function independently of their blood pressure lowering effect. The newer generation of ?-blockers, such as nebivolol and carvedilol, which provide antioxidant activity, can improve endothelial function in patients with hypertension. Dihydropyridine and non-dihydropyridine calcium antagonists reverse impaired endothelium-dependent vasodilatation in different vascular districts, through a mechanism related to an antioxidant effect. However, conflicting results are found in the brachial artery. Angiotensin-converting enzyme (ACE) i... To ACCELERATE Hypertension Control Content Type Journal ArticlePages 1-3DOI 10.1007/s11906-011-0203-1Authors Helmy M. Siragy, Professor of Medicine and Endocrinology, Department of Medicine, University of Virginia Health Center, P.O. Box 801409, Charlottesville, VA 22908, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Antihypertensive Therapy in Diabetes: The Legacy Effect and RAAS Blockade Abstract  Two recently published post-monitoring follow-up studies of the United Kingdom Prospective Diabetes Study (UKPDS) have shown that although early and intensive treatment of hyperglycemia provides benefits for cardiovascular mortality that extend over time, the effects of a tight antihypertensive strategy in patients with diabetes did not seem to last during the following years. The authors concluded that blood pressure control is of crucial importance in patients with diabetes but is not protective against cardiovascular events when it is not sustained. Several lines of evidence suggest, however, that early and intensive antihypertensive treatment with some classes of drugs exerts benefits that may persist during the following years. Particularly, blockade of the r... Mechanisms of Antiangiogenic-Induced Arterial Hypertension Abstract  Antiangiogenic therapy has emerged as an important concept in the treatment of solid tumors. Vascular endothelial growth factor (VEGF) represents an important therapeutic target, as it is the primary mediator of angiogenesis and is induced by multiple tumor-relevant stimuli. Arterial hypertension has been commonly reported in all clinical trials testing inhibitors of angiogenesis (especially inhibitors of VEGF/VEGFR-2 signalling), with incidence ranging from 11% to 43% in all studies. The mechanism of elevated blood pressure in patients treated with antiangiogenic agents is not fully understood, but it is probably multifactorial, involving endothelial dysfunction and capillary rarefaction. Recently, several studies have suggested that early blood pressure rise was... Does Blood Pressure Variability Modulate Cardiovascular Risk? This article reviews evidence that variability in BP also predicts risk of stroke and other vascular events independently of mean BP and evidence that drug-class effects on variability in BP explain differences in the effectiveness of BP-lowering drugs in preventing stroke. Content Type Journal ArticlePages 1-10DOI 10.1007/s11906-011-0201-3Authors Peter M. Rothwell, University Department of Clinical Neurology, John Radcliffe Hospital, Level 6, West Wing, Headington, Oxford, OX3 9DU UK Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Mechanisms and Potential Therapies for Preeclampsia Abstract  Preeclampsia is a pregnancy-induced hypertensive disorder found most commonly in nulliparous women. Recent research performed in animal models of the disease has revealed some of the underlying mechanisms of preeclampsia. Specifically, placental insufficiency and the resulting hypoxia/ischemia have been shown to be crucial to disease progression. In response to placental hypoxia/ischemia, several pathways are activated, which contribute to the clinical manifestations of the disease: increased circulating levels of the anti-angiogenic protein sFlt-1, activation of the maternal inflammatory response, suppressed nitric oxide production, enhanced endothelin-1 production, and induction of reactive oxygen formation. Despite advances in the understanding of the disorder,... Mineralocorticoid Receptor Blockade in Chronic Kidney Disease Abstract  Aldosterone antagonists have been highly successful in treating congestive heart failure and resistant hypertension. Until recently, therapies targeting the mineralocorticoid receptor in chronic kidney disease (CKD) have received little attention, largely because of the risk of hyperkalemia and the incorrect assumption that traditional therapy with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or both consistently reduces activity of the renin-angiotensin system in all patients. Control of extracellular volume and low-dose mineralocorticoid receptor blocker therapy may offer additional antihypertensive and anti-inflammatory benefits in select CKD populations. Content Type Journal ArticlePages 1-7DOI 10.1007/s11906-011-0202-2Authors ... Sympathetic Mechanisms, Organ Damage, and Antihypertensive Treatment Abstract  Sympathetic activation characterizes essential hypertension, contributing to the development and progression of the high blood pressure state. Throughout the years, evidence has been accumulated to show that adrenergic overdrive also participates in the pathogenesis of the end-organ damage associated with hypertension, including cardiac hypertrophy, left ventricular diastolic dysfunction, and heart failure, as well as the vascular structural and functional alterations that frequently can be detected in large, medium-size, and small arteries. Adrenergic overdrive also participates in the renal insufficiency and failure that may accompany the clinical course of the hypertensive state. This paper reviews evidence collected over the past few years documenting the impo... Coupling Between Respiratory and Sympathetic Activities as a Novel Mechanism Underpinning Neurogenic Hypertension Abstract  Enhanced sympathetic outflow to the heart and resistance vessels greatly contributes to the onset and maintenance of neurogenic hypertension. There is a consensus that the development of hypertension (clinical and experimental) is associated with an impairment of sympathetic reflex control by arterial baroreceptors. More recently, chronic peripheral chemoreflex activation, as observed in obstructive sleep apnea, has been proposed as another important risk factor for hypertension. In this review, we present and discuss recent experimental evidence showing that changes in the respiratory pattern, elicited by chronic intermittent hypoxia, play a key role in increasing sympathetic activity and arterial pressure in rats. This concept parallels results observed in other... Diabetic Retinopathy and Blockade of the Renin-Angiotensin System: So What is New? Content Type Journal ArticlePages 1-1DOI 10.1007/s11906-011-0199-6Authors Norman K. Hollenberg, Departments of Medicine and Radiology, Brigham and Women?s Hospital, Harvard Medical School, Mailstop PBB1-Rad Building, 15 Francis Street, Boston, MA 02115, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) The Importance of Potassium in Managing Hypertension Abstract  Dietary potassium intake has been demonstrated to significantly lower blood pressure (BP) in a dose-responsive manner in both hypertensive and nonhypertensive patients in observational studies, clinical trials, and several meta-analyses. In hypertensive patients, the linear dose?response relationship is a 1.0 mm Hg reduction in systolic BP and a 0.52 mm Hg reduction in diastolic BP per 0.6 g per day increase in dietary potassium intake that is independent of baseline potassium deficiency. The average reduction in BP with 4.7 g (120 mmol) of dietary potassium per day is 8.0/4.1 mm Hg, depending race and on the relative intakes of other minerals such as sodium, magnesium, and calcium. If the dietary sodium chloride intake is high, ther... Hypertension in multicultural and minority populations: Linkin communication to compliance Abstract  Cardiovascular disease disproportionately affects minority populations, in part because of multiple sociocultural factors that directly affect compliance with antihypertensive medication regimens. Compliance is a complex health behavior determined by a variety of socioeconomic individual, familial, and cultural factors. In general, provider-patient communication has been shown to be linked to patient satisfaction, compliance, and health outcomes. In multicultural and minority populations, the issue of communication may play an even larger role because of linguistic and contextual barriers that preclude effective provider-patient communication. These factors may further limit compliance. The ESFT Model for Communication and Compliance is an individual, patient-base... New Approaches to Quantifying Sympathetic Nerve Activity Abstract  The importance of the sympathetic nervous system in the pathophysiology of human and experimental models of hypertension is well established. Underpinning recent advances has been direct recording from sympathetic nerves via implanted electrodes in animals or microneurography in human subjects. However, the limited life of a recording electrode and the prolonged nature of the development of hypertension bring with it the difficulty of comparing sympathetic nerve activity between groups. New developments in high-frequency radiotelemetry in animals have heralded a new age in long-term sympathetic recordings ideal for hypertension research. Standard multifiber recordings in human and animal studies have provided information about the frequency and amplitude of sympat... Vascular Mechanisms in the Pathogenesis of Stroke This article reviews recent data on vascular mechanisms that participate in the pathogenesis of stroke. Content Type Journal ArticlePages 1-8DOI 10.1007/s11906-011-0195-xAuthors Cristina Sierra, Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital and Lady Davis Institute for Medical Research, McGill University, 3755 Côte-Ste-Catherine Road, Montreal, QC H3T 1E2, CanadaAntonio Coca, Hypertension Unit, Department of Internal Medicine, Institute of Medicine and Dermatology, Hospital Clinic (IDIBAPS), University of Barcelona, 170 Villarroel, 08036 Barcelona, SpainErnesto L. Schiffrin, Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital and Lady Davis Institute for Medical Research, McGill University, 3755 Côte-Ste-Catherine Road, Montreal, QC H3T 1E... Alcohol Consumption, Blood Pressure, and the Risk of Stroke Abstract  A synergistic effect of alcohol and hypertension has been suggested to increase the risk for stroke. However, the contribution of alcohol-induced hypertension to stroke morbidity and mortality may be greater than observed, because the effects of different drinking patterns have not been separately investigated. Alcohol-induced transient peaks in systolic blood pressure may predispose to stroke. Recent studies have measured time trends of blood pressure elevations in relation to alcohol consumption. They found a significant morning surge in blood pressure, which was related to alcohol intake in a dose-dependent manner and was independent of smoking. Men with a severe form of hypertension showed a 12-fold increased risk for cardiovascular disease mortality associate... Home Blood Pressure Monitoring: How Good a Predictor of Long-Term Risk? Abstract  Most management decisions for the diagnosis and treatment of hypertension are made using blood pressure (BP) measurements made in the clinic. However, home BP recordings may be of superior prognostic value. In this review, we show that home BP recordings are generally superior to clinic BP measurements in predicting long-term prognosis. Home BP has been shown to significantly predict important end points including all-cause mortality, progression of chronic kidney disease, and functional decline in the elderly. In addition, home BP recordings significantly and strongly predict cardiovascular events. These findings are robust, as they concur despite having been studied in disparate populations, using heterogeneous methods of clinic and home BP measurement, and with... Renal Nerve Ablation for Resistant Hypertension Content Type Journal ArticlePages 1-3DOI 10.1007/s11906-011-0189-8Authors Alan H. Gradman, Temple University School of Medicine (Clinical Campus), 1239 Shady Avenue, Pittsburgh, PA 15232, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Metabolic Syndrome and Heart Failure?The Risk, Paradox, and Treatment Abstract  The constellation of obesity, hypertension, dyslipidemia, and insulin resistance?together referred to as metabolic syndrome (MetS)?is increasing in prevalence in the American population and also worldwide. The individual components of MetS and MetS as a whole increase the risk of heart failure, cardiovascular mortality, and all-cause mortality. Despite this adverse association, numerous studies have documented an obesity paradox, in which overweight and obese people with established cardiovascular disease, including hypertension, coronary heart disease, heart failure, and peripheral arterial disease, have a better prognosis than patients who are not overweight or obese. Current treatment strategies for these patients include weight loss, control of blood press... Mineralocorticoid Actions in the Brain and Hypertension Abstract  Mineralocorticoid receptors (MR) and epithelial sodium channels (ENaC) in the brain mediate central aldosterone-induced sympathetic hyperactivity and hypertension. Enzymes for biosynthesis of aldosterone are present in the brain, and aldosterone can be produced locally in the brain. Hypothalamic aldosterone levels increase in Dahl salt-sensitive rats on high-salt diet, and in Wistar rats with chronic central infusion of sodium-rich artificial cerebrospinal fluid (CSF) or with subcutaneous infusion of angiotensin II. Functional studies using antagonists of MR, ENaC, and ouabain-like compounds (?ouabain?), as well as specific aldosterone synthase inhibitors, suggest that an increase in local synthesis of aldosterone via MR and ENaC in the brain increases ?ouaba... Vitamin D Therapy and Cardiovascular Health Abstract  Vitamin D belongs to the family of nuclear steroid hormones, which has pleiotropic effects on several organ systems. Different vitamin D compounds have been studied as potential cardioprotective agents over the past 20 years. The results of these clinical studies vary based on the form and dosage of vitamin D administered during the trial. In the past 5 years, many have described an association of vitamin D compounds and cardiovascular health through reduction in blood pressure, reduction in inflammatory biomarkers, improved insulin sensitivity, and reduction in cardiovascular disease complications and death. Because there are several vitamin D compounds, it is important to consider the full breadth of the literature when examining vitamin D and cardiovas... Aldosterone Synthase Inhibition: A Promising Beginning Content Type Journal ArticlePages 1-4DOI 10.1007/s11906-011-0185-zAuthors Norman K. Hollenberg, Departments of Medicine and Radiology, Brigham and Women?s Hospital, Harvard Medical School, Mailstop PBB1-Rad Building, 15 Francis Street, Boston, MA 02115, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Nycthemeral Relationship between Renal Function and Sodium Homeostasis Abstract  Nycthemeral changes in renal function have been known for a long time, but our knowledge about the underlying mechanisms is still far from complete. From a theoretical point of view, many physiological systems could be involved in turning the kidney from a sodium-excretory organ during daytime into a sodium-conserving organ during nighttime. Although blood pressure itself may regulate sodium output directly through pressure natriuresis, this mechanism can be unmasked only when other influences on the kidney can be eliminated. Hence, there is not enough evidence that pressure natriuresis governs cyclic variations in sodium output in the intact human being. Although the glomerular filtration rate follows a nocturnal variation pattern that is more or less in phase wi... Neural Mechanisms of Angiotensin II?Salt Hypertension: Implications for Therapies Targeting Neural Control of the Splanchnic Circulation Abstract  Chronically elevated plasma angiotensin II (AngII) causes a salt-sensitive form of hypertension that is associated with a differential pattern of peripheral sympathetic outflow. This ?AngII-salt sympathetic signature? is characterized by a transient reduction in sympathetic nervous system activity (SNA) to the kidneys, no change in SNA to skeletal muscle, and a delayed activation of SNA to the splanchnic circulation. Studies suggest that the augmented sympathetic influence on the splanchnic vascular bed increases vascular resistance and decreases vascular capacitance, leading to hypertension via translocation of blood volume from the venous to the arterial circulation. This unique sympathetic signature is hypothesized to be generated by a balance of central ex... Sympathetic Neural Mechanisms in Human Blood Pressure Regulation Abstract  Sympathetic neural function is essential to human blood pressure regulation, and overactivity of sympathetic nerves may have an important role in the development of hypertension and related cardiovascular disorders. Importantly, there is extensive interindividual variability in sympathetic vasoconstrictor nerve activity, even among healthy, young, normotensive people. Therefore, the relevance of each person?s level of sympathetic nerve activity for his or her blood pressure must be evaluated in the context of other factors contributing to the overall level of blood pressure, including cardiac output and vascular adrenergic responsiveness. We include evidence showing that the balance of factors contributing to normal blood pressure in young people is influenced b... Hypertension Due to Loss of Clock: Novel Insight From the Molecular Analysis of Cry1/Cry2?Deleted Mice Abstract  In our consumer-oriented society, in which productivity requires around-the-clock activity and demanding shift work, the biologic system that regulates our internal rhythms is being compromised. Poor sleep patterns and hectic lifestyle are detrimental to harmonious physiological and metabolic body systems, with severe impact on public health. Over a trillion peripheral cellular clocks throughout the body, supervised by the master clock located in the hypothalamic suprachiasmatic nucleus, govern most aspects of physiology and behavior. To exemplify the importance of the biologic clock for health, we have recently demonstrated that mice that are arrhythmic because of the deletion of Cry1 and Cry2 clock genes suffer from salt-sensitive hypertension. In these mice, a n... The Role of Aldosterone in the Metabolic Syndrome Abstract  The metabolic syndrome associates metabolic abnormalities such as insulin resistance and dyslipidemia with increased waist circumference and hypertension. It is a major public health concern, as its prevalence could soon reach 30% to 50% in developed countries. Aldosterone, a mineralocorticoid hormone classically involved in sodium balance regulation, is increased in patients with metabolic syndrome. Besides its classic actions, aldosterone and mineralocorticoid receptor (MR) activation affect glucose metabolism, inducing insulin resistance through various mechanisms that involve oxidative stress, inflammation, and downregulation of proteins involved in insulin signaling pathways. Aldosterone and MR signaling exert deleterious effects on the cardiovascular system ... Cell Signaling of Angiotensin II on Vascular Tone: Novel Mechanisms Abstract  Angiotensin II (Ang II) is a pleiotropic hormone that influences the function of many cell types and regulates many organ systems. In the cardiovascular system, it is a potent vasoconstrictor that increases peripheral vascular resistance and elevates arterial pressure. It also promotes inflammation, hypertrophy, and fibrosis, which are important in vascular remodeling in cardiovascular diseases. The diverse actions of Ang II are mediated via AT1 and AT2 receptors, which couple to many signaling molecules, including small G proteins, phospholipases, mitogen-activated protein (MAP) kinases, phosphatases, tyrosine kinases, NADPH oxidase, and transcription factors. In general, acute Ang II stimulation induces vasoconstriction through changes in the intracellular free c... Metabolic Syndrome, Androgens, and Hypertension Abstract  Obesity is one of the constellation of factors that make up the definition of the metabolic syndrome. Metabolic syndrome is also associated with insulin resistance, dyslipidemia, hypertriglyceridemia, and type 2 diabetes mellitus. The presence of obesity and metabolic syndrome in men and women is also associated with increased risk of cardiovascular disease and hypertension. In men, obesity and metabolic syndrome are associated with reductions in testosterone levels. In women, obesity and metabolic syndrome are associated with increases in androgen levels. In men, reductions in androgen levels are associated with inflammation, and androgen supplements reduce inflammation. In women, increases in androgens are associated with increases in inflammatory cytokines, and... Stress and Its Role in Sympathetic Nervous System Activation in Hypertension and the Metabolic Syndrome Abstract  Stress in several guises is evident in individuals with hypertension and in those with the metabolic syndrome and may account, at least in part, for the extent and pattern of sympathetic nervous activation. Importantly, elevated activity of the sympathetic nervous system is related to the development of obesity-related illnesses including hypertension, insulin resistance, and renal, cardiac, and vascular impairment. Notably, evidence of subclinical organ damage is evident even in young, normotensive, overweight persons, thereby reinforcing the need to develop and implement effective early intervention. Content Type Journal ArticlePages 1-5DOI 10.1007/s11906-011-0186-yAuthors Elisabeth A. Lambert, Human Neurotransmitters Laboratory, Baker IDI Heart & Diabetes ... Knocking Out Angiotensin II in the Heart Abstract  Despite ongoing medical advances, cardiovascular disease continues to be a leading health concern. The renin-angiotensin system (RAS) plays an important role in regulating cardiovascular function, and is, therefore, the subject of extensive study. Several drugs currently used to treat hypertension and heart failure are designed to target angiotensin II synthesis and function, but thus far, none have been able to completely block the effects of RAS signaling. This review discusses current and emerging approaches towards inhibiting cardiac RAS function in order to further improve cardiovascular disease outcomes. Content Type Journal ArticlePages 1-7DOI 10.1007/s11906-011-0180-4Authors Daniela Zablocki, Department of Cell Biology and Molecular Medicine, Cardiova... How Much Blood Pressure Control is Beneficial in Patients with Chronic Kidney Disease? Content Type Journal ArticlePages 1-3DOI 10.1007/s11906-010-0177-4Authors Robert M. Carey, University of Virginia Health System, P.O. Box 801414, Charlottesville, VA 22908-1414, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Weight Loss: A Tool to Reduce Proteinuria Content Type Journal ArticlePages 1-3DOI 10.1007/s11906-010-0178-3Authors Zohreh Soltani, Section of Nephrology and Hypertension, Louisiana State University Health Science Center, 1542 Tulane Ave, New Orleans, LA 70113, USAEfrain Reisin, Section of Nephrology and Hypertension, Louisiana State University Health Science Center, 1542 Tulane Ave, New Orleans, LA 70113, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) The Kidneys and Aldosterone/Mineralocorticoid Receptor System in Salt-Sensitive Hypertension Abstract  Strong evidence supports the ability of the aldosterone/mineralocorticoid receptor (MR) system to dominate long-term blood pressure control. It is also increasingly recognized as an important mediator of cardiovascular and renal diseases, particularly in the presence of excessive salt intake. In a subgroup of individuals with metabolic syndrome, adipocyte-derived aldosterone-releasing factors cause inappropriate secretion of aldosterone in the adrenal glands during salt loading, resulting in the development of salt-induced hypertension and cardiac and renal damage. On the other hand, emerging data reveal that aldosterone is not a sole regulator of MR activity. We have identified the signaling crosstalk between MR and small GTPase Rac1 as a novel pathway to facilit... Estimation of Glomerular Filtration Rate: What Are the Pitfalls? Abstract  Because of the high prevalence of chronic kidney disease, estimation of the glomerular filtration rate (GFR) is necessary to diagnose, stage, and follow the progression of renal impairment, and to adjust the dosage of medications with predominantly renal excretion. The main pitfall of using 24-h urinary creatinine clearance is the inaccuracy of urine collection. Multiple formulas based on serum creatinine have been proposed for the estimation of renal function in daily clinical practice and in large-scale studies. The two most widely used formulas are Cockcroft-Gault (CG) for the estimation of creatinine clearance and MDRD (Modification of Diet in Renal Disease) for the estimation of GFR. However, the performance of these formulas is satisfactory only in individua... Genetics of Hypertension and Cardiovascular Disease and Their Interconnected Pathways: Lessons from Large Studies This article describes recent genome-wide association studies (GWAS) that have reported causative variants for BP/HT and CVD/heart traits and analyzes the overlapping associated gene polymorphisms. It also examines potential replication of findings from the HyperGEN data on African Americans and whites. Several genes involved in BP/HT regulation also appear to be involved in CVD. A better picture is emerging, with overlapping hot-spot regions and with interconnected pathways between BP/HT and CVD. A systemic approach to full understanding of BP/HT and CVD development and their progression to disease may lead to the identification of gene targets and pathways for the development of novel therapeutic interventions. Content Type Journal ArticleDOI 10.1007/s11906-010-0174-7Authors ... Renin and Prorenin Receptor in Hypertension: What?s New? Abstract  The (pro)renin receptor, PRR, was initially characterized as a component of the renin-angiotensin system (RAS). PRR-bound renin and prorenin display increased enzymatic activity, and binding activates intracellular signaling, upregulating the expression of profibrotic proteins. As a consequence, most studies set out to demonstrate a role of PRR in hypertension, cardiovascular and renal diseases, and organ damage, and to identify PRR as a therapeutic target to optimize RAS blockade. The results of animal studies were disappointing and did not convincingly establish PRR as major player in hypertension or in organ damage, although human studies suggested a link between a polymorphism in the PRR gene and blood pressure. New data now suggest that PRR is functionally lin... Epigenetics and Hypertension This article reviews evidence for epigenetic contributions to hypertension. For example, DNA methylation at CpG islands and histone acetylation pathways are known to limit nephron development, thereby unmasking hypertension associated with exposure to a high-salt diet. Maternal water deprivation and protein deficiency are shown to increase expression of renin-angiotensin system genes in the offspring. The methylation pattern of a serine protease inhibitor gene in human placentas is shown to be a marker for preeclampsia-associated hypertension. Mental stress induces phenylethanolamine n-methyltransferase, which may act as a DNA methylase and mimic the gene-silencing effects of methyl CpG binding protein-2 on the norepinephrine transporter gene, which, in turn, may exaggerate autonomic... Endothelial Damage and Regeneration: The Role of the Renin-Angiotensin-Aldosterone System Abstract  The renin-angiotensin-aldosterone system (RAAS) is part of the blood pressure regulating system. Its main effector peptide is angiotensin II (Ang II). Although it may induce hypertension, the proinflammatory, profibrotic, and prothrombotic effects are mainly mediated by effects of Ang II on the cellular and molecular level that are independent of blood pressure. Therefore, pharmacotherapeutic intervention within the RAAS is an important treatment modality for patients suffering from cardiovascular diseases, even those who are not hypertensive. In addition to the blood pressure lowering and vasculoprotective (pleiotropic) effects of angiotensin II type 1 (AT1) receptor blockers (ARBs), and angiotensin-converting enzyme (ACE) inhibitors, regenerative progenitor cell ... Catecholamine Storage Vesicles: Role of Core Protein Genetic Polymorphisms in Hypertension This article reviews human genetic variation at loci encoding the major granins and probes the effects of such polymorphisms on blood pressure, using twin pairs to probe heritability and individuals with the most extreme blood pressure values in the population to study hypertension. Content Type Journal ArticleDOI 10.1007/s11906-010-0170-yAuthors Kuixing Zhang, Department of Medicine and Institute for Genomic Medicine (IGM), University of California at San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0838, USAYuqing Chen, Department of Medicine and Institute for Genomic Medicine (IGM), University of California at San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0838, USAGen Wen, Department of Medicine and Institute for Genomic Medicine (IGM), ... Ethnicity and Second-Line Antihypertensive Medication Response in the ASCOT Trial Content Type Journal ArticleDOI 10.1007/s11906-010-0169-4Authors Jason T. Davis, Department of Medicine, VA San Diego Healthcare System and University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0838, USAMaple M. Fung, Department of Medicine, VA San Diego Healthcare System and University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0838, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Genetics of Salt-Sensitive Hypertension Abstract  The assessment of salt sensitivity of blood pressure is difficult because of the lack of universal consensus on definition. Regardless of the variability in the definition of salt sensitivity, increased salt intake, independent of the actual level of blood pressure, is also a risk factor for cardiovascular morbidity and mortality and kidney disease. A modest reduction in salt intake results in an immediate decrease in blood pressure, with long-term beneficial consequences. However, some have suggested that dietary sodium restriction may not be beneficial to everyone. Thus, there is a need to distinguish salt-sensitive from salt-resistant individuals, but it has been difficult to do so with phenotypic studies. Therefore, there is a need to determine the genes that ... The DASH Diet and Insulin Sensitivity Abstract  Lifestyle modifications, including adoption of the Dietary Approaches to Stop Hypertension (DASH) dietary pattern, weight loss in individuals who are overweight or obese, and physical activity, are effective in the prevention and treatment of hypertension. A healthy lifestyle may also have beneficial effects on metabolic abnormalities, such as insulin resistance, that are associated with high blood pressure. This review examines the independent and combined effects of the DASH diet and weight loss plus exercise on blood pressure and insulin sensitivity, with a focus on recently published results from the ENCORE study. Our data suggest that the DASH eating plan alone lowers blood pressure in overweight individuals with higher than optimal blood pressure, but signif... Is There a Link Between Angiotensin Receptor Blockers and Cancer? Content Type Journal ArticleDOI 10.1007/s11906-010-0162-yAuthors Frank Enseleit, Cardiovascular Center Cardiology, University Hospital, Rämistrasse 100, 8091 Zürich, SwitzerlandFrank Ruschitzka, Cardiovascular Center Cardiology, University Hospital, Rämistrasse 100, 8091 Zürich, Switzerland Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Dual-Acting Angiotensin Receptor?Neprilysin Inhibition Abstract  Lowering blood pressure by pharmacologic intervention reduces the incidence of cardiovascular events. Nevertheless, despite the widespread availability of effective antihypertensive medications, the vast majority of hypertensive patients worldwide continue to have inadequate blood pressure control. The development of new antihypertensive drugs could contribute to improving the hypertension control rate, and the blockade of new pathophysiologic pathways involved in blood pressure regulation would offer additional benefits. The dual inhibition of the angiotensin II receptor and neprilysin could provide clinical benefits in a range of cardiovascular diseases, including hypertension and heart failure. Content Type Journal ArticleDOI 10.1007/s11906-010-0166-7Author... Aldosterone to Renin Ratio as a Predictor of Diuretic Response Content Type Journal ArticleDOI 10.1007/s11906-010-0156-9Authors Steven A. Atlas, James J. Peters VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Are There Benefits of Antihypertensive Therapy Beyond Blood Pressure Lowering? Abstract  Meta-analyses strongly suggest that the primary preventive benefit of antihypertensive therapy in uncomplicated individuals is the direct result of the lower blood pressure (BP) rather than the choice of agents. In contrast, when comorbidities are present, therapeutic benefit is governed primarily by the appropriateness of the drug class for the comorbidity profile. As progressively lower BP levels are studied, conflicting results and uncertainties continue to emerge. Given the geometric nature of the BP-risk relationship, it is to be expected that benefits will be less dramatic at lower levels of BP. Conflicting results may emerge from intrinsic problems with clinical trials, including uncertainties related to confounded composite end points, interactions of comor... Endogenous Ouabain: A Link Between Sodium Intake and Hypertension Abstract  The sodium pump, an ancestral enzyme with conserved ability to bind ouabain, plays a key role in salt conservation and is regulated by aldosterone and endogenous ouabain (EO). Plasma EO is elevated in about 45% of patients with essential hypertension and correlates with blood pressure. The relationship of EO with Na+ balance is complex. Na+ depletion raises circulating EO, whereas acute saline loads have no effect on EO in essential hypertension, and ambient levels of EO are unrelated to the saline sensitivity of blood pressure. Short-term periods of high dietary salt elevate EO and the relationship with salt balance in normal individuals is V-shaped, whereas the long-term relationship is likely to be L-shaped. Normal individuals suppress the high EO transient trig... Mitochondrial Biogenesis and Fragmentation as Regulators of Muscle Protein Degradation This article reviews the rapid progress made in the past few years regarding the role of mitochondria in the control of proteolytic systems and in the loss of muscle mass and function. Content Type Journal ArticleDOI 10.1007/s11906-010-0157-8Authors Vanina Romanello, Dulbecco Telethon Institute at Venetian Institute of Molecular Medicine, via Orus 2, 35129 Padova, ItalyMarco Sandri, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Discord from ACCORD? Content Type Journal ArticleDOI 10.1007/s11906-010-0159-6Authors Alan B. Weder, Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, 24 Frank Lloyd Wright Drive, Ann Arbor, MI 48106, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Insulin Sensitizers and Heart Failure: An Engine Flooded with Fuel Content Type Journal ArticleDOI 10.1007/s11906-010-0158-7Authors Khaled I. Khalaf, Department of Internal Medicine, University of Texas Medical School at Houston, 6431 Fannin, MSB 1.246, Houston, TX 77030, USAHeinrich Taegtmeyer, Department of Internal Medicine, University of Texas Medical School at Houston, 6431 Fannin, MSB 1.246, Houston, TX 77030, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Obesity and the Kidney Content Type Journal ArticleDOI 10.1007/s11906-010-0165-8Authors Norman K. Hollenberg, Departments of Medicine and Radiology, Brigham and Women?s Hospital, Harvard Medical School, Mailstop PBB1-Rad Building, 15 Francis Street, Boston, MA 02115, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Metabolic Syndrome: From the Genetics to the Pathophysiology Abstract  The metabolic syndrome (MS) constitutes a combination of underlying risk factors for an adverse outcome, cardiovascular disease. Thus, the clinical behavior of the MS can be regarded as a whole. Nevertheless, from a pathogenic point of view, understanding of the underlying mechanisms of each MS intermediate phenotype is far beyond their understanding as an integrative process. Systems biology introduces a new concept for revealing the pathogenesis of human disorders and suggests the presence of common physiologic processes and molecular networks influencing the risk of a disease. This paper shows a model of this concept to explain the genetic determinants of MS-associated phenotypes. Based on the hypothesis that common physiologic processes and molecular networks ... Dietary Fructose and Hypertension Abstract  The association between fructose and increased blood pressure is still incompletely defined, because experimental studies have produced dissimilar conclusions. Amplified vasopressor responses to minimal stimuli and differing responses to fructose in peripheral versus central sites may explain the controversy. Fructose induces systemic hypertension through several mechanisms mainly associated with deleterious effects on target organs (kidney, endothelium, heart) exerted by the byproducts of its metabolism, such as uric acid. The kidney is particularly sensitive to the effects of fructose because high loads of this sugar reach renal tissue. In addition, fructose increases reabsorption of salt and water in the small intestine and kidney; thus the combination of salt ... Genetic Testing for Pheochromocytoma Abstract  Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare, catecholamine-producing tumors that are usually sporadic. However, about 30% of these tumors have been identified as being of inherited origin. To date, nine genes have been confirmed as participating in PHEO or PGL tumorigenesis. Germline mutations were found in 100% of syndromic cases and in about 90% of patients with positive familial history. In nonsyndromic patients with apparently sporadic tumors, genetic mutations have been found in up to 27%, and genetic testing is now recommended for all patients with PHEOs and PGLs. Patients with syndromic lesions, a positive family history, or both should be tested for the appertaining gene. Recent discoveries have shown that the order of tested genes in nons... Cytostatic Drugs, Neuregulin Activation of ErbB Receptors, and Angiogenesis Abstract  Cytostatic drugs were developed to target specific molecular pathways shown to drive tumor growth. Although this approach has been very successful in treating cancers, its use is often hindered by off-target toxic effects. An example of this is trastuzumab, which targets the erbB2 kinase receptor. This drug successfully decreases tumor growth but adversely affects cardiac function. This observation led to important studies elucidating the importance of the erbB pathway in cardioprotection and angiogenesis. This review addresses the problem of off-target effects of cytostatic drugs (specifically trastuzumab) and their effect on cardiac function, summarizes the neuregulin-1 (NRG)/erbB signaling pathway, and discusses its importance in cardiac myocytes. It also highl... Diagnosis and Treatment of Hypertension in Children Abstract  Hypertension is a global problem, affecting both developed and developing nations. In children and adolescents, hypertension has gained ground in cardiovascular medicine, thanks to the progress made in several areas of pathophysiologic and clinical research. Childhood hypertension is often asymptomatic and is easily missed, even by health professionals. Target organ damage is detectable in children and adolescents. Management of hypertension includes lifestyle changes and pharmacologic treatment. In the case of secondary hypertension, pharmacologic treatment usually is required. In essential hypertension, assessment of early organ damage provides a useful tool for treatment decisions. Content Type Journal ArticleDOI 10.1007/s11906-010-0155-xAuthors Empar Lur... Mitochondrial Dysfunction and Oxidative Damage to Sarcomeric Proteins Abstract  Hypertension is an important risk factor for the development of heart failure. Increased production of reactive oxygen species (ROS) contributes to cardiac dysfunction by activating numerous pro-hypertrophic signaling cascades and damaging the mitochondria, thus setting off a vicious cycle of ROS generation. The way in which oxidative stress leads to exacerbation of systolic and diastolic dysfunction is still unclear, however. In skeletal muscle and ischemic myocardium, increased ROS production causes preferential oxidation of myofibrillar proteins and provides a mechanistic link between oxidative damage and impaired contractility through disruption of actin-myosin interactions, enzymatic functions, calcium sensitivity, and efficiency of cross-bridge cycling. In t... Mitochondrial Fission and Autophagy in the Normal and Diseased Heart Abstract  Sustained hypertension promotes structural, functional and metabolic remodeling of cardiomyocyte mitochondria. As long-lived, postmitotic cells, cardiomyocytes turn over mitochondria continuously to compensate for changes in energy demands and to remove damaged organelles. This process involves fusion and fission of existing mitochondria to generate new organelles and separate old ones for degradation via autophagy. Autophagy is a lysosome-dependent proteolytic pathway capable of processing cellular components, including organelles and protein aggregates. Autophagy can be either nonselective or selective and contributes to remodeling of the myocardium under stress. Fission of mitochondria, loss of membrane potential, and ubiquitination are emerging as critical ste... Nighttime Blood Pressure: A Target for Therapy? Abstract  Ambulatory blood pressure (BP) monitoring is increasingly used in the evaluation of hypertensive patients. The ability to monitor BP throughout the day and night allows the detection of abnormal nocturnal BP patterns, the most common being a ?nondipping? pattern, which is associated with increased cardiovascular risk; its correction appears to have a positive impact on cardiovascular outcome. Antihypertensive treatment should be individually adjusted to control BP during both daytime and nighttime. However, drug-induced lowering of nocturnal BP, if excessive, could amplify the morning BP surge in patients with daytime BP elevation, increasing the risk of developing a cardiovascular event. Ambulatory BP monitoring therefore represents a unique tool to establish ... Hemoconcentration, Heart Failure, and Survival Content Type Journal ArticleDOI 10.1007/s11906-010-0154-yAuthors Norman K. Hollenberg, Harvard Medical School, Departments of Medicine and Radiology, Brigham and Women?s Hospital, Mailstop PBB1-Rad Building, 15 Francis Street, Boston, MA 02115, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Vascular Endothelial Function and Hypertension: Insights and Directions Abstract  Hypertension contributes significantly to worldwide cardiovascular morbidity and mortality. Hypertension appears to have a complex association with endothelial dysfunction, a phenotypical alteration of the vascular endothelium that precedes the development of adverse cardiovascular events and portends future cardiovascular risk. This review concentrates on recent findings with respect to the mechanisms of hypertension-associated endothelial dysfunction, the interrelationship between these two entities, and the relationship of the efficacy of antihypertensive therapies to improvements in vascular homeostasis beyond blood pressure reduction. Current evidence suggests that hypertension and endothelial dysfunction are integrally related with respect to pathophysiologi... Establishing Targets for Hypertension Control in Patients with Comorbidities Abstract  Most current guidelines recommend tighter blood pressure (BP) control in hypertensive patients with comorbidities. These recommendations are based on epidemiologic data indicating that cardiovascular risk increases at lower BP levels in hypertensive patients with comorbidities than in those without comorbidities. Hypertension guidelines usually reflect outcomes from previous studies, but current recommendations for patients with comorbidities have preceded the evidence. We review recent studies investigating whether these new targets can be achieved, whether they are well tolerated, and whether they positively affect the outcomes. The results of the few current studies about outcomes in lower BP target groups are either negative or somewhat?but not decidedly?po... Mechanisms of Anthracycline Cardiotoxicity and Strategies to Decrease Cardiac Damage Abstract  Anthracyclines are common chemotherapeutic agents used to treat many different types of cancer. Unfortunately, the use of anthracyclines is limited by their cardiotoxic effects, which may become manifest as late as 20 years from initial exposure. Studies in cells and animals suggest that the mechanism of anthracycline-induced cardiotoxicity (AIC) is multifactorial. Anthracyclines induce multiple forms of cellular injury by free radical production. In addition, anthracyclines alter nucleic acid biology by intercalation into DNA and modulate intracellular signaling, leading to cell death and the disruption of homeostatic processes such as sarcomere maintenance. In an effort to decrease AIC, many strategies have been tested, but no specific therapies are univers... Assessment of Cardiovascular Risk Abstract  Atherosclerotic cardiovascular disease (CVD) is the most common cause of death worldwide. Usually atherosclerosis is caused by the combined effects of multiple risk factors. For this reason, most guidelines on the prevention of CVD stress the assessment of total CVD risk. The most intensive risk factor modification can then be directed towards the individuals who will derive the greatest benefit. To assist the clinician in calculating the effects of these multiple interacting risk factors, a number of risk estimation systems have been developed. This review address several issues regarding total CVD risk assessment: ?  Why should total CVD risk be assessed? ?  What risk estimation systems are available? ?  H... Should All Hypertensive Dialysis Patients Receive a Blocker of the Renin-Angiotensin System? Abstract  Cardiovascular mortality and hypertension remain common in the dialysis population, and two recent meta-analyses have suggested that antihypertensive pharmacotherapy reduces cardiovascular events in dialysis patients. Based on their benefits in other populations, blockers of the renin-angiotensin-aldosterone system (RAAS) are an attractive treatment option. The evidence that RAAS blockers improve surrogate end points is mixed. However, a recent meta-analysis found significant improvement in left ventricular mass with RAAS-blocking drugs in hemodialysis patients. Only a few trials have examined RAAS-blocking drugs and cardiovascular events in dialysis patients, and a recent meta-analysis found no significant benefit in hemodialysis patients. The single trial of per... The Diagnosis and Management of Syncope This article summarizes the recommendations of these guidelines, outlining the initial evaluation of transient loss of consciousness, risk stratification, diagnostic testing, and the recommended treatment for patients with syncope of various etiologies. Special points regarding the evaluation of syncope in children and the elderly are outlined, and the role of syncope management units in hospitals is discussed. Content Type Journal ArticleDOI 10.1007/s11906-010-0144-0Authors Richard Sutton, Imperial College, St Mary?s Hospital, Praed Street, London, W2 1NY UKMichele Brignole, Ospedale Tilgullio, Lavagna (GE), ItalyDavid Benditt, Cardiac Arrhythmia Center, University of Minnesota, Minneapolis, MN USAAngel Moya, Hopital Val D? Hebron, Barcelona, Spain Journal Current Hy... Optimal Blood Pressure for a Patient with Type 2 Diabetes Mellitus: Insight from the ACCORD Study Content Type Journal ArticleDOI 10.1007/s11906-010-0145-zAuthors Matthew R. Weir, Division of Nephrology, University of Maryland School of Medicine Medical Center, 22 South Greene Street, Room N3W143, Baltimore, MD 21201, USAGeorge L. Bakris, Division of Nephrology, University of Maryland School of Medicine Medical Center, 22 South Greene Street, Room N3W143, Baltimore, MD 21201, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Hypertension in the Elderly: What Is the Goal Blood Pressure Target and How Can This Be Attained? Abstract  For the aging populations of Europe, many emerging health problems in addition to myocardial infarction and stroke are associated with hypertension. Recently, the role of hypertension in the risk of vascular cognitive impairment and dementia has been highlighted, and there are studies to show that control of hypertension may slow this process. Furthermore, as many elderly individuals will also develop type 2 diabetes or impaired renal function, the risk of hypertension in these patients is more pronounced. New guidelines have tried to provide evidence-based treatment algorithms in which control of hypertension is just one aspect of general risk factor control, with the aim of decreasing the total risk. Content Type Journal ArticleDOI 10.1007/s11906-010-0138-yA... Does Blockade of the Renin-Angiotensin-Aldosterone System Slow Progression of All Forms of Kidney Disease? Abstract  The velocity of chronic kidney disease (CKD) progression is only partly dependent on the nature and activity of the underlying disease process. Activation of the renin-angiotensin-aldosterone system (RAAS) is a crucial, and often universal, event responsible for the pathophysiologic mechanisms that accelerate CKD progression. Thus, it would appear that interruption of the RAAS through the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, or direct renin inhibitors can play a principal role in slowing CKD progression, regardless of the cause. Unfortunately, applying this generalized approach to all forms of CKD has been delayed by the lack of strong, evidence-based data. The aim of this review is... Prorenin: Where Does It Stand? Content Type Journal ArticleDOI 10.1007/s11906-010-0139-xAuthors Norman K. Hollenberg, Departments of Medicine and Radiology, Brigham and Women?s Hospital, Harvard Medical School, Mailstop PBB1-Rad Building, 15 Francis Street, Boston, MA 02115, USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Masked Hypertension: Evidence of the Need to Treat Abstract  The diagnosis of masked hypertension has been made easier with the widespread availability of home blood pressure monitoring devices with levels of accuracy comparable to ambulatory blood pressure monitoring. The negative impact of masked hypertension on cardiovascular morbidity and mortality is evidenced by numerous well-designed clinic-based and population-based studies. The relationship of masked hypertension and target organ damage is also well documented. These two factors, combined with the robust evidence of reduced cardiovascular morbidity and mortality achieved with blood pressure treatment, makes the argument for actively identifying patients with masked hypertension and prescribing treatment similar to that for patients with sustained hypertension. In t... Chronic Kidney Disease and Albuminuria in Arterial Hypertension Abstract  Chronic kidney disease is a major public health problem worldwide: it is estimated that in the general population, 1 person in 10 has some degree of renal damage. Adequate blood pressure control represents the mainstay of treatment, to delay deterioration of renal function and prevent cardiovascular complications. Current evidence supports a target blood pressure value of 130/80 mm?Hg or less (ie, <125/75 mm?Hg) when proteinuria exceeds 1 g/L. Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers represent the treatment of choice, especially in the presence of proteinuria. More complete blockade of the renin-angiotensin-aldosterone system (RAAS) has been advocated, using a combination of multiple RAAS blocker drugs or su... Is the Presence of Microalbuminuria a Relevant Marker of Kidney Disease? This article reviews the current evidence concerning MA as a marker of kidney disease or kidney damage. Content Type Journal ArticleDOI 10.1007/s11906-010-0133-3Authors Richard J. Glassock, David Geffen School of Medicine at UCLA, Los Angeles, CA USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) The Impact of Obstructive Sleep Apnea on Chronic Kidney Disease Abstract  Obstructive sleep apnea (OSA) is an important clinical problem in the chronic kidney disease (CKD) population. OSA is associated with hypoxemia and sleep fragmentation, which activates the sympathetic nervous system, the renin-angiotensin-aldosterone system, alters cardiovascular hemodynamics, and results in free radical generation. In turn, a variety of deleterious processes such as endothelial dysfunction, inflammation, platelet aggregation, atherosclerosis, and fibrosis are triggered, predisposing individuals to adverse cardiovascular events and likely renal damage. Independent of obesity, OSA is associated with glomerular hyperfiltration and may be an independent predictor of proteinuria, a risk factor for CKD progression. OSA is also associated with hypertens... Prevalence and Diagnosis of Primary Aldosteronism Abstract  Primary aldosteronism (PA) is a common cause of arterial hypertension: in the PA Prevalence in Hypertensives (PAPY) Study, the prevalence of PA was 11.2% in consecutive referred hypertensive patients. When adrenal vein sampling (AVS) is available, two thirds of the cases can be attributed to a tumor and one third of cases are idiopathic; the opposite is seen when AVS is unavailable. Thus, AVS influences the relative prevalence rate of the main subtypes of PA. When adrenalectomy is undertaken based on AVS, almost 100% of patients are cured of hyperaldosteronism, one third are cured of hypertension, and 52% are markedly improved in terms of blood pressure control. Persistent hypertension can be predicted by a long history of hypertension and by the presence of exces... Detection and Treatment of Resistant Hypertension Abstract  The evaluation of patients with resistant hypertension should be directed toward confirming true treatment resistance, identifying the causes contributing to treatment resistance (including secondary causes of hypertension), and documenting target-organ damage. Treatment of resistant hypertension is aimed at reversing lifestyle factors contributing to treatment resistance, accurately diagnosing and appropriately treating secondary causes of hypertension, and effectively using multidrug regimens. Lifestyle changes, pharmacologic therapies, and nonpharmacologic therapies have all shown benefits in patients with resistant hypertension, but much additional knowledge is needed to better identify and treat these patients. Content Type Journal ArticleDOI 10.1007/s119... Systolic Pressure, Diastolic Pressure, or Pulse Pressure as a Cardiovascular Risk Factor in Renal Disease Abstract  Chronic kidney disease is a leading global health problem with an increasing prevalence. Hypertension is present in most patients with chronic kidney disease, and hypertension-related nephrosclerosis is a top cause of progressive renal damage and end-stage renal disease. Systolic blood pressure (BP) and pulse pressure, together with nocturnal BP, are the most important factors favoring the progression of renal failure. Consequently, strict control of BP and other cardiovascular risk factors is required, including an adequate degree of suppression of the renin-angiotensin system in every patient. Content Type Journal ArticleDOI 10.1007/s11906-010-0129-zAuthors José A. García-Donaire, Hypertension Unit, Hospital 12 de Octubre Av. Cordoba, s/n. 28041 Madrid Sp... Aldosterone in the Pathogenesis of Chronic Kidney Disease and Proteinuria Abstract  There has been much recent interest in the role of aldosterone as an independent contributor to the progression of chronic kidney disease. Despite treatment with agents such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, many studies have shown that there is incomplete blockade of the renin-angiotensin cascade evidenced by persistent or rising plasma aldosterone levels despite therapeutic renin-angiotensin blockade. This phenomenon is commonly referred to as ?aldosterone escape? and is thought to be one of the main contributors to chronic kidney disease progression despite conventional therapeutics. Animal models of the effects of exposure to exogenous aldosterone demonstrate the development of inflammation and fibrosis in both ... Hypertension Management and Microvascular Insulin Resistance in Diabetes Abstract  Type 2 diabetes is in essence a vascular disease and is frequently associated with hypertension, macrovascular events, and microvascular complications. Microvascular dysfunction, including impaired recruitment and capillary rarefaction, has been implicated in the pathogenesis of diabetic complications. Microvascular insulin resistance and renin-angiotensin system upregulation are present in diabetes, and each contributes to the development of hypertension and microvascular dysfunction. In the insulin-sensitive state, insulin increases microvascular perfusion by increasing endothelial nitric oxide production, but this effect is abolished by insulin resistance. Angiotensin II, acting via the type 1 receptors, induces inflammation and oxidative stress, leading to imp... Mineralocorticoid Receptor Antagonists and the Metabolic Syndrome Abstract  Key components of the metabolic syndrome (MetS), ie, obesity and insulin resistance, are associated with increased aldosterone production and mineralocorticoid receptor (MR) activation. Both MetS and hyperaldosteronism are proinflammatory and pro-oxidative states associated with cardiovascular disease. This review discusses emerging data that MR activation may contribute to abnormalities seen in MetS. In view of these data, MR antagonists may be beneficial in MetS, not only by controlling hypertension but also by reversing inflammation, oxidative stress, and defective insulin signaling at the cellular-molecular level. Clinical trials have demonstrated benefits of MR antagonists in heart failure, hypertension, and diabetic nephropathy, but additional trials are nee... The Metabolic Syndrome: How Do We Get There? Content Type Journal ArticleCategory Literature AlertDOI 10.1007/s11906-010-0128-0Authors Norman K. Hollenberg, Brigham and Women?s Hospital Departments of Medicine and Radiology, Harvard Medical School Mailstop PBB1-Rad Building, 15 Francis Street Boston MA 02115 USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Targeting the Vasoprotective Axis of the Renin-Angiotensin System: A Novel Strategic Approach to Pulmonary Hypertensive Therapy Abstract  A decade has passed since the discovery of angiotensin-converting enzyme 2 (ACE2), a component of the ACE2?angiotensin (Ang)-(1-7)?Mas counterregulatory axis of the renin angiotensin system (RAS). ACE2 is considered an endogenous regulator of the vasoconstrictive, proliferative, fibrotic, and proinflammatory effects of the ACE?Ang II?angiotensin II type 1 receptor (AT1R) axis. Both animal and clinical studies have emerged to define a role for ACE2 in pulmonary arterial hypertension (PAH). There is scientific evidence supporting the concept that ACE2 maintains the RAS balance and plays a protective role in PAH. The activation of pulmonary ACE2 could influence the pathogenesis of PAH and serve as a novel therapeutic target in PAH. Current therapeutic strategi... Polypill: Lights and Shadows Abstract  The idea of packaging and formulating several drugs commonly used in cardiovascular disease prevention into a single polypill is appealing. It is believed that the polypill would have several advantages over the separate use of several medications, enhancing acceptability and long-term adherence, with lower cost and easier accessibility. However, there are few data available on the efficacy and safety of polypill preparations for preventive purposes. The Indian Polycap Study (TIPS) was the first to systematically test the clinical application of the polypill; it included ramipril, hydrochlorothiazide, atenolol, aspirin, and simvastatin. Blood pressure and LDL levels were effectively lowered and antiplatelet function was demonstrated, but the effect of simvastatin ... Endothelium-derived Vasoactive Factors and Hypertension: Possible Roles in Pathogenesis and as Treatment Targets Abstract  Endothelial cells regulate vascular tone by releasing various contracting and relaxing factors including nitric oxide (NO), arachidonic acid metabolites (derived from cyclooxygenases, lipoxygenases, and cytochrome P450 monooxygenases), reactive oxygen species, and vasoactive peptides. Additionally, another pathway associated with the hyperpolarization of the underlying smooth muscle cells plays a predominant role in resistance arteries. Endothelial dysfunction is a multifaceted disorder, which has been associated with hypertension of diverse etiologies, involving not only alterations of the L-arginine NO-synthase?soluble guanylyl cyclase pathway but also reduced endothelium-dependent hyperpolarizations and enhanced production of contracting factors, particularly... Drug Mechanisms to Help in Managing Resistant Hypertension in Obesity Abstract  Obesity is a major risk factor for the development of hypertension. Because the prevalence of obesity is increasing worldwide, the prevalence of obesity hypertension is also increasing. Importantly, hypertension in obesity is commonly complicated by dyslipidemia and type 2 diabetes mellitus and hence imposes a high cardiovascular disease risk. Furthermore, obesity is strongly associated with resistant hypertension. Activation of the sympathetic nervous system and the renin-angiotensin system, leading to renal sodium and water retention, links obesity with hypertension. There is also evidence for the release of factors by visceral adipose tissue promoting excessive aldosterone production, and a more central role of aldosterone in obesity hypertension is emerging. R... The ?J Curve? Problem Revisited: Old and New Findings Abstract  This paper critically addresses the issue of the ?J-curve? paradox?the finding described in studies performed about 30 years ago indicating that treatment-induced systolic blood pressure values below 120 or 125 mm Hg and diastolic blood pressure values below 75 mm Hg are characterized by an increase, rather than a reduction, in the incidence of coronary events. This paper focuses on four major subjects: 1) the benefits of a lower blood pressure target during treatment; 2) the historical background of the ?J-curve? phenomenon; 3) the evidence collected in recent clinical trials regarding the existence of a ?J-curve? in treated hypertensive patients; and 4) the recent recommendations by the Task Force Committee of the European S... ESCAPE: From Hypertension to Renal Failure Content Type Journal ArticleCategory CLINICAL TRIAL REPORTDOI 10.1007/s11906-010-0124-4Authors Helmy M. Siragy, University of Virginia Health Center Department of Medicine P.O. Box 801409 Charlottesville VA 22908 USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Do the Blood Pressure Effects of Nonsteroidal Antiinflammatory Drugs Influence Cardiovascular Morbidity and Mortality? Abstract  There are many theories about why selective inhibitors of the second isoform of cyclooxygenase (COX-2) increase cardiovascular risk. Although torcetrapib raises blood pressure and cardiovascular risk, it has been difficult to prove such a link for COX-2 inhibitors in randomized clinical trials. This review shows a significant correlation in placebo-controlled trials between the five agents? elevations in blood pressures and their rate ratios for cardiovascular events. A larger body of evidence arises from randomized clinical trial comparisons of selective versus nonselective inhibitors of COX-2, but these results are heterogeneous for naproxen versus other traditional agents. The best current trial evidence comes from the centrally adjudicated placebo-controlled... Inflammation and Therapy for Hypertension Abstract  It is currently accepted that hypertension, atherosclerosis, and diabetes are disorders with subtle or overt activation of inflammatory mediators. Therefore, it has become increasingly important to ascertain whether current antihypertensive drug families have proinflammatory or anti-inflammatory actions that modify the outcomes of their hemodynamic effects on blood pressure. We review the current state of knowledge about the effects of the major classes of available antihypertensive agents on inflammation and speculate on the possible contribution of these effects to observations in clinical trials. We suggest that a strategy of drug development specifically addressing inflammation in hypertension may provide increased benefit in terms of target organ damage, and ... Antihypertensive Effects of Aspirin: What is the Evidence? Abstract  Nonsteroidal anti-inflammatory drugs are known to increase blood pressure and blunt the effect of antihypertensive drugs. Surprisingly, it has been suggested recently that aspirin lowers blood pressure and could be used for preventing hypertension. This review summarizes published data on the effects of aspirin on blood pressure. Trials suggesting that aspirin administered at bedtime lowers blood pressure are uncontrolled, unmasked, and potentially biased. They also conflict with cohort studies showing an 18% increase in the risk of hypertension among aspirin users. Fortunately, short-term use of aspirin does not seem to interfere with antihypertensive drugs. Regardless of its effect on blood pressure, low-dose aspirin effectively prevents cardiovascular events in... Vascular Effects of Antihypertensive Drug Therapy Abstract  Hypertension is associated with structural and functional alterations in the vasculature that lead to hemodynamic disturbances and target organ damage. The benefit of reducing blood pressure on risk reduction is well established. Antihypertensive drugs partially correct hypertensive vascular changes by a number of mechanisms, but their influence may vary in different vascular beds. Recently, combinations of drugs with complementary or synergistic effects have shown favorable effects on the vasculature; these combinations may contribute to risk reduction and improve outcomes in the future. Clinical trial evidence has shown an improvement in morbidity and mortality indicators that could be related to vascular effects of antihypertensive drugs, but this effect needs ... New Therapeutic Approaches to Resistant Hypertension Abstract  Resistant hypertension is a common and growing clinical problem characterized by failure to achieve target blood pressure levels despite adequate use of at least three antihypertensive agents. Although numerous safe and effective pharmacologic therapies are available to treat elevated blood pressure, novel therapeutic approaches are warranted to improve the management and prognosis of patients with resistant hypertension. In this context, several lines of research have generated promising results based on both novel pharmacologic and device-based approaches that may more effectively treat resistant hypertension and its adverse consequences in the future. Content Type Journal ArticleDOI 10.1007/s11906-010-0119-1Authors Markus P. Schlaich, Baker IDI Heart & Di... Renin System Blockade, the Eye, and the Kidney in Type 1 Diabetes Mellitus Content Type Journal ArticleCategory Literature AlertDOI 10.1007/s11906-010-0113-7Authors Norman K. Hollenberg, Harvard Medical School, Brigham and Women?s Hospital Departments of Medicine and Radiology Mailstop PBB1-Rad Building, 15 Francis Street Boston MA 02115 USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) The Prognostic Significance of Heart Rate for Cardiovascular Disease and Hypertension Abstract  Five decades ago, hypertension was a debated risk factor for the development of cardiovascular disease. After further studies and the introduction of antihypertensive medications, few, if any, have doubted the important role hypertension plays as a cardiovascular risk factor. Today, a growing body of evidence emphasizes the relationship between heart rate and hypertension, and heart rate and cardiovascular disease, which makes the measurement of heart rate an important component of the cardiovascular risk assessment. Current European guidelines for managing arterial hypertension recommend the measurement of heart rate for risk stratification, but there still are no recommendations for treatment. This review discusses the evidence for a relationship between heart r... Sleep Apnea and Cardiovascular Disease Abstract  Cardiovascular disease is still the leading cause of death in North America. To improve outcomes, it will likely be necessary to identify new potentially treatable conditions. Sleep apnea affects approximately 50% of patients with cardiovascular disease and is associated with increased cardiovascular risk. Continuous positive airway pressure is currently the treatment of choice and has many short-term favorable effects. The long-term benefits, however, remain elusive. Further, it may not be the ideal treatment for central sleep apnea, and the benefits of alternatives such adaptive servo-ventilation are currently being tested. Randomized controlled trials are now needed to determine whether treating sleep apnea will improve survival and reduce cardiovascular diseas... Renal Nerves in the Maintenance of Hypertension: A Potential Therapeutic Target Abstract  Renal sympathetic efferent and afferent nerves, which lie within and immediately adjacent to the wall of the renal arteries, contribute to the maintenance of hypertension. Because the causative factors of hypertension change over time, denervation of both efferent and afferent renal nerves should result in long-term attenuation of hypertension. The importance of the renal nerves in hypertensive patients can now be defined with the novel development of percutaneous, minimally invasive renal denervation from within the renal artery using radiofrequency energy as a therapeutic strategy. Studies thus far show that catheter-based renal denervation in patients with resistant essential hypertension lowers systolic blood pressure 27 mm Hg by 12 months, with... The Evolution of Renin-Angiotensin Blockade: Angiotensin-Converting Enzyme Inhibitors as the Starting Point Abstract  The renin-angiotensin system has been a target in the treatment of hypertension for close to three decades. Several medication classes that block specific aspects of this system have emerged as useful therapies, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and, most recently, direct renin inhibitors. There has been a natural history to the development of each of these three drug classes, starting with their use as antihypertensive agents; thereafter, in each case they have been employed as end-organ protective agents. To date, there has been scant evidence to favor angiotensin receptor blockers or direct renin inhibitors over angiotensin-converting enzyme inhibitors in treating hypertension or in affording end-organ protection... Synergistic Physician and Patient Behavioral Interventions as Management Strategy for Effective Population-Based Hypertension Control Content Type Journal ArticleCategory CLINICAL TRIAL REPORTDOI 10.1007/s11906-010-0111-9Authors Pei-an Betty Shih, University of California, San Diego, Center for Human Genetics and Genomics Department of Medicine Pharmaceutical Sciences Building (PSB), Room 4261, 9500 Gilman Drive La Jolla CA 92093 USADaniel T. O?Connor, University of California, San Diego, Center for Human Genetics and Genomics Department of Medicine Pharmaceutical Sciences Building (PSB), Room 4261, 9500 Gilman Drive La Jolla CA 92093 USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) The Obesity Paradox and Cardiovascular Disease This article reviews some recent publications that have studied this phenomenon as it relates to heart failure, coronary artery disease, peripheral arterial disease, kidney disease, and a cohort of patients undergoing nonbariatric surgery. Content Type Journal ArticleDOI 10.1007/s11906-010-0099-1Authors Stephen A. Morse, Louisiana State University Health Sciences Center Section of Nephrology 1542 Tulane Avenue New Orleans LA 70112 USARajat Gulati, Louisiana State University Health Sciences Center Section of Nephrology 1542 Tulane Avenue New Orleans LA 70112 USAEfrain Reisin, Louisiana State University Health Sciences Center Section of Nephrology 1542 Tulane Avenue New Orleans LA 70112 USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source:... Oxidative Stress and Vascular Function: Implications for Pharmacologic Treatments Abstract  Production of considerable amounts of reactive oxygen species (ROS) eventually leads to oxidative stress. A key role of oxidative stress is evident in the pathologic mechanisms of endothelial dysfunction and associated cardiovascular diseases. Vascular enzymes such as NADPH oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase are involved in the production of ROS. The question remains whether pharmacologic approaches can effectively combat the excessive ROS production in the vasculature. Interestingly, existing registered cardiovascular drugs can directly or indirectly act as antioxidants, thereby preventing the damaging effects of ROS. Moreover, new compounds targeting NADPH oxidases have been developed. Finally, food-derived compounds appe... Cytokine Abnormalities in the Etiology of the Cardiometabolic Syndrome Abstract  The cardiometabolic syndrome comprises a cluster of risk factors, including abdominal obesity, dyslipidemia, hypertension, insulin resistance/glucose intolerance, and proteinuria. This syndrome is due, in part, to the accumulation of visceral fat, which promotes synthesis of proinflammatory adipokines resulting in a visceral adipose tissue-specific increase in reactive oxygen species derived from NADPH oxidase. Adipose tissue oxidative stress results in the development of systemic oxidative stress and inflammation, which further lead to development of metabolic dyslipidemia, impaired glucose metabolism, renal disease, and hypertension. Importantly, visceral?not subcutaneous?fat is the significant source of the circulating adipokines that promote these systemic... A STITCH Saves Time and Lowers Blood Pressure Content Type Journal ArticleCategory CLINICAL TRIAL REPORTDOI 10.1007/s11906-010-0110-xAuthors Suzanne Oparil, University of Alabama at Birmingham School of Medicine 1530 3rd Avenue South, ZRB 1034 Birmingham AL 35294 USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Angiotensin-Converting Enzyme 2: Central Regulator for Cardiovascular Function Abstract  Angiotensin-converting enzyme 2 (ACE2) is a new component of the renin-angiotensin system (RAS). Accumulating evidence shows that ACE2 provides protective effects in peripheral tissues and has great potential for the treatment of RAS-related diseases. The role of ACE2 in the central nervous system is not well established. However, in recent years, much more progress has been made on the studies of this carboxypeptidase in the central regulation of blood pressure and cardiovascular function in general. It has been shown that brain ACE2 interacts with the other components of the RAS (ACE, angiotensin II, and angiotensin II type 1 receptor), protects baroreflex and autonomic function, stimulates nitric oxide release, reduces oxidative stress, and prevents the develop... Obstructive Sleep Apnea and Hypertension Abstract  Obstructive sleep apnea (OSA) and hypertension commonly coexist. Observational studies indicate that untreated OSA is associated with an increased risk of prevalent hypertension, whereas prospective studies of normotensive cohorts suggest that OSA may increase the risk of incident hypertension. Randomized evaluations of continuous positive airway pressure (CPAP) indicate an overall modest effect on blood pressure. However, these studies do indicate a wide variation in the blood pressure effects of CPAP, with some patients, on an individual basis, manifesting a large antihypertensive benefit. OSA is particularly common in patients with resistant hypertension. The reason for this high prevalence of OSA is not fully explained, but data from our laboratory suggest tha... Erratum to: Literature Alert Content Type Journal ArticleCategory ErratumDOI 10.1007/s11906-010-0090-xAuthors Bernice M. Wissler, 400 Market St., Suite 700 Philadelphia PA 19106 USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Baroreflex Stimulation in Antihypertensive Treatment Abstract  Hypertension is a leading cause of morbidity and mortality worldwide. Despite the development of new medications, an alarmingly high proportion of patients are not reaching their target blood pressure goals, so nonpharmacologic therapies have been attracting more interest. Chronic baroreceptor stimulation of the carotid sinus has been shown to reduce blood pressure by inhibiting the sympathetic nervous system, particularly the renal sympathetic tone. This finding has led to the development of implantable carotid sinus stimulators, which have now been studied in both animals and humans, as a means for treating chronic hypertension. The enthusiasm for this modality has led to ongoing studies, which will provide more information on its safety and efficacy in patients... INVESTing in Hypertension Content Type Journal ArticleCategory Clinical Trial ReportDOI 10.1007/s11906-010-0101-yAuthors Robert M. Carey, University of Virginia Health System P.O. Box 801414 Charlottesville VA 22908-1414 USA Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) The Role of High-Fructose Corn Syrup in Metabolic Syndrome and Hypertension Abstract  Obesity and related diseases are an important and growing health concern in the United States and around the world. Soft drinks and other sugar-sweetened beverages are now the primary sources of added sugars in Americans? diets. The metabolic syndrome is a cluster of common pathologies, including abdominal obesity linked to an excess of visceral fat, fatty liver, insulin resistance, hyperinsulinemia, dyslipidemia, and hypertension. Trends in all of these alterations are related to the consumption of dietary fructose and the introduction of high-fructose corn syrup (HFCS) as a sweetener in soft drinks and other foods. Experimental and clinical evidence suggests a progressive association between HFCS consumption, obesity, and the other injury processes. However, e... ASTRALogy: Unrealistic Expectations? Content Type Journal ArticleCategory CLINICAL TRIAL REPORTDOI 10.1007/s11906-010-0109-3Authors Peter W. de Leeuw, University Hospital Maastricht Department of Medicine PO Box 5800 6202 AZ Maastricht The Netherlands Journal Current Hypertension ReportsOnline ISSN 1534-3111Print ISSN 1522-6417 (Source: Current Hypertension Reports) Midkine Regulation of the Renin-Angiotensin System Abstract  Hypertension and chronic kidney disease are often associated. The pathogenesis of these diseases involves the renin-angiotensin system. We have recently reported that the growth factor midkine is a novel regulator of the renin-angiotensin system. Midkine is a heparin-binding growth factor so far implicated in neuronal differentiation, neuroprotection, cardioprotection, inflammation, and cancer development. In a mouse model of chronic kidney disease induced by 5/6 nephrectomy, midkine is produced in the lung and in turn upregulates angiotensin-converting enzyme expression. Hypertension associated with 5/6 nephrectomy is not observed in midkine-deficient mice. Conversely, supplemental administration of midkine to the deficient mice induces hypertension. This review ...

Cardiovascular Disease And Hypertension guide

Understanding Cardiovascular Disease And Hypertension
The Link Between Cardiovascular Disease And Hypertension You must be aware that hypertension is often called the silent killer" and not in vain. There is a definite link between cardiovascular disease and hypertension. High blood pressure is very dangerous if left untreated and very often due to mild symptoms it is not diagnosed until it is too late. When you hear that your 45 years old friend died of sudden massive cardiac arrest, chances are that he or she were suffering from hypertension and did not know about it, left it untreated and boom! The heart just gave out. What Are The Statistics Saying About Cardiovascular Disease And Hypertension? The statistics show that three in every five people who die of heart attack did previously suffer from hypertension. It is true that cardiovascular disease and hypertension are closely inter-related as anyone who suffers from moderate and severe hypertension fall into high risk group for cardiovascular disease. This happens because the hypertension puts too much pressure on the heart, which after some time unless

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Hypertension and atrial fibrillation: diagnostic approach, prevention and treatment. Position paper of the Working Group 'Hypertension Arrhythmias and Thrombosis' of the European Society of Hypertension.

Author: Manolis, Athanasios J. a; Rosei, Enrico Agabiti b; Coca, Antonio c; Cifkova, Renata d; Erdine, Serap E. e; Kjeldsen, Sverre f; Lip, Gregory Y.H. g; Narkiewicz, Krzysztof h; Parati, Gianfranco i; Redon, Josep j; Schmieder, Roland k; Tsioufis, Costas l; Mancia, Giuseppe m

Page: 239-252

Ambulatory blood pressure monitoring in Australia: 2011 consensus position statement.

Author: Head, Geoffrey A. a; McGrath, Barry P. b; Mihailidou, Anastasia S. c; Nelson, Mark R. d; Schlaich, Markus P. a; Stowasser, Michael e; Mangoni, Arduino A. f; Cowley, Diane e; Brown, Mark A. g; Ruta, Lee-Anne h; Wilson, Alison h

Page: 253-266

Reflections on determinants of augmentation index.

Author: Avolio, Alberto; Butlin, Mark; Xu, Ke

Page: 267-268

The threat of ethnicity for cardiovascular disease risk.

Author: Carrington, Melinda J. a; Grassi, Guido b

Page: 269-270

Effect of treatment on cardiac small resistance arteries in hypertension and diabetes: trick or treat.

Author: Schiffrin, Ernesto L. a,b

Page: 271-272

Systolic and diastolic pulse wave velocity: a confusing parameter or a new frontier?.

Author: Salvi, Paolo

Page: 273-274

Physical activity and sedentary behaviour at different life stages and adult blood pressure in the 1958 British cohort.

Author: Pouliou, Theodora; Ki, Myung; Law, Catherine; Li, Leah; Power, Chris

Page: 275-283

Serum 25-hydroxyvitamin D levels and all-cause and cardiovascular disease mortality among US adults with hypertension: the NHANES linked mortality study.

Author: Zhao, Guixiang a; Ford, Earl S. a; Li, Chaoyang b; Croft, Janet B. a

Page: 284-289

Blood pressure and other metabolic syndrome factors and risk of brain tumour in the large population-based Me-Can cohort study.

Author: Edlinger, Michael a; Strohmaier, Susanne a; Jonsson, Hakan b; Bjorge, Tone c,d; Manjer, Jonas e; Borena, Wegene T. a; Haggstrom, Christel f; Engeland, Anders c,d; Tretli, Steinar g; Concin, Hans h; Nagel, Gabriele i; Selmer, Randi d; Johansen, Dorthe e; Stocks, Tanja f; Hallmans, Goran j; Stattin, Par f,k; Ulmer, Hanno a

Page: 290-296

Supine and upright haemodynamic effects of sublingual nitroglycerin and inhaled salbutamol: a double-blind, placebo-controlled, randomized study.

Author: Tahvanainen, Anna M. a; Tikkakoski, Antti J. a; Leskinen, Miia H. a; Nordhausen, Klaus b; Kahonen, Mika a,c; Koobi, Tiit c; Mustonen, Jukka T. a,d; Porsti, Ilkka H. a,d

Page: 297-306

Aortic augmentation index and pulse wave velocity in response to head-up tilting: effect of autonomic failure.

Author: Huijben, Auke M.T. a; Mattace-Raso, Francesco U.S. b; Deinum, Jaap c; Lenders, Jacques c,d; van den Meiracker, Anton H. a

Page: 307-314

Peroxisome proliferator-activated receptor-[gamma] activation reduces cyclooxygenase-2 expression in vascular smooth muscle cells from hypertensive rats by interfering with oxidative stress.

Author: Martin, Angela a,*; Perez-Giron, Jose V. a,*; Hernanz, Raquel a; Palacios, Roberto a; Briones, Ana M. b; Fortuno, Ana c; Zalba, Guillermo c; Salaices, Mercedes b; Alonso, Maria J. a

Page: 315-326

Insulin resistance, prehypertension, hypertension and blood pressure values in paediatric age.

Author: Genovesi, Simonetta a; Brambilla, Paolo b; Giussani, Marco b; Galbiati, Sara a; Mastriani, Silvana a; Pieruzzi, Federico a; Stella, Andrea a; Valsecchi, Maria Grazia c; Antolini, Laura c

Page: 327-335

Influence of parental history of hypertension on screen time and physical activity in young offspring.

Author: Gopinath, Bamini a; Hardy, Louise L. b; Baur, Louise A. b,c; Teber, Erdahl a; Mitchell, Paul a

Page: 336-341

Changes in blood pressure during healthy pregnancy: a longitudinal cohort study.

Author: Grindheim, Guro a; Estensen, Mette-Elise b,c; Langesaeter, Eldrid a; Rosseland, Leiv Arne a,d; Toska, Karin e

Page: 342-350

Markers of cardiovascular disease risk after hypertension in pregnancy.

Author: Mangos, George J.; Spaan, Julia J.; Pirabhahar, Saiyini; Brown, Mark A.

Page: 351-358

The relationship between hypertension and obesity across different ethnicities.

Author: Foulds, Heather J.A. a,b,c; Bredin, Shannon S.D. c,d; Warburton, Darren E.R. a,b,c

Page: 359-367

Longitudinal changes in blood pressure during weight loss and regain of weight in obese boys and girls.

Author: Holm, Jens-Christian a,b,c,d; Gamborg, Michael b; Neland, Mette e; Ward, Leigh f; Gammeltoft, Steen c; Heitmann, Berit L. b; Sorensen, Thorkild I.A. b; Ibsen, Karsten K. d

Page: 368-374

Circulating ACE2 activity is increased in patients with type 1 diabetes and vascular complications.

Author: Soro-Paavonen, Aino a; Gordin, Daniel a; Forsblom, Carol a; Rosengard-Barlund, Milla a; Waden, Johan a; Thorn, Lena a; Sandholm, Niina a; Thomas, Merlin C. b; Groop, Per-Henrik a,b; on behalf of the FinnDiane Study Group

Page: 375-383

Effects of diabetes and hypertension on structure and distensibilty of human small coronary arteries.

Author: Lynch, Fiona M. a; Izzard, Ashley S. a; Austin, Clare a; Prendergast, Brian b; Keenan, Daniel b; Malik, Rayaz A. a; Heagerty, Anthony M. a

Page: 384-389

Mild hyperparathyroidism: a novel surgically correctable feature of primary aldosteronism.

Author: Maniero, Carmela a; Fassina, Ambrogio b; Seccia, Teresa M. a; Toniato, Antonio d; Iacobone, Maurizio e; Plebani, Mario c; De Caro, Raffaele f; Calo, Lorenzo A. a; Pessina, Achille C. a; Rossi, Gian P. a

Page: 390-395

The change in arterial stiffness over the cardiac cycle rather than diastolic stiffness is independently associated with left ventricular mass index in healthy middle-aged individuals.

Author: Hermeling, Evelien a; Vermeersch, Sebastian J. b,c; Rietzschel, Ernst R. d; de Buyzere, Marc L. d; Gillebert, Thierry C. d; van de Laar, Roel J. e; Ferreira, Isabel f; Hoeks, Arnold P. a; van Bortel, Luc M. b; Reneman, Robert S. g; Segers, Patrick b; Reesink, Koen D. a

Page: 396-402

Tissue Doppler indexes of left ventricular systolic function in relation to the pulsatile and steady components of blood pressure in a general population.

Author: Sakiewicz, Wojciech a; Kuznetsova, Tatiana b; Kloch-Badelek, Malgorzata c; D'hooge, Jan d; Ryabikov, Andrew e; Kunicka, Katarzyna a; Swierblewska, Ewa a; Thijs, Lutgarde b; Jin, Yu b; Loster, Magdalena c; Malyutina, Sofia e; Stolarz-Skrzypek, Katarzyna c; Kawecka-Jaszcz, Kalina c; Narkiewicz, Krzysztof a; Staessen, Jan A. b,f; on behalf of the European Project On Genes in Hypertension (EPOGH) Investigators

Page: 403-410

Left ventricular hypertrophy and renal dysfunction during antihypertensive treatment adversely affect cardiovascular prognosis in hypertensive patients.

Author: Salvetti, Massimo; Muiesan, Maria L.; Paini, Anna; Monteduro, Cristina; Agabiti-Rosei, Claudia; Aggiusti, Carlo; Bertacchini, Fabio; Stassaldi, Deborah; Castellano, Maurizio; Agabiti-Rosei, Enrico

Page: 411-420

Inappropriately high left-ventricular mass in asymptomatic mild-moderate aortic stenosis.

Author: Cioffi, Giovanni a; de Simone, Giovanni b; Cramariuc, Dana c,d; Mureddu, Gian F. e; Gerdts, Eva c,d

Page: 421-428

Pulse wave encephalopathy.

Author: O'Rourke, Michael F. a; Safar, Michel E. b

Page: 429

Validation of carotid blood pressure assessment by tonometry.

Author: Takenaka, Tsuneo; Kikuta, Tomohiro; Watanabe, Yusuke; Inoue, Tsutomu; Takane, Hiroshi; Ohno, Yoichi; Suzuki, Hiromichi

Page: 429-432

Response to 'Validation of carotid blood pressure assessment by tonometry'.

Author: Segers, Patrick a; Vermeersch, Sebastian a,b; Kips, Jan a,b; Van Bortel, Luc b

Page: 432

The history of primary hyperaldosteronism with simultaneous hypercortisolism.

Author: Ferri, Claudio; Grassi, Davide

Page: 432-433

Adrenal venous sampling crucial in primary aldosteronism?.

Author: Dekkers, Tanja; Deinum, Jaap

Page: 433-435

Supracentrimetric nodule on computed tomography does not exclude adrenal venous sampling before surgery for primary aldosteronism.

Author: Sarlon-Bartoli, Gabrielle; Silhol, Francois; Vaisse, Bernard

Page: 435-436

Meta-analysis supports ACCORD blood pressure but effect of excessive DBP lowering uncertain.

Author: Allen, Michael J.M. a; Kelly, Kim D. b; Fleming, Isobel a

Page: 436-438

Blood pressure lowering in diabetic patients.

Author: Reboldi, Gianpaolo a; Gentile, Giorgio a; Angeli, Fabio b; Ambrosio, Giuseppe c; Mancia, Giuseppe d; Verdecchia, Paolo e

Page: 438-439

European Society of Hypertension scientific newsletter: hypertension and aortic diseases.

Author: Baguet, Jean-Philippe a,b; Chavanon, Olivier c; Sessa, Carmine d; Thony, Frederic e; Lantelme, Pierre f; Barone-Rochette, Gilles a,b; Mallion, Jean-Michel a

Page: 440-443

the blood pressure is brought under control it simply collapses under the stress. There are plenty of warning signals when you suffer from hypertension, however it is to easy to ignore these signs due to various reasons, i.e. lack of time, unable to realize their importance, inability to slow down due to high demand of professional life, etc. How Can You Control Cardiovascular Disease And Hypertension? Though there is medication to control hypertension this needs to be taken regularly and seriously which very few people do. Besides, you need to change your life style without which there is little chance that you would get rid of high blood pressure. You need to eat healthy, exercise daily, cut down stress levels, avoid alcohol and stop smoking. This is a very long list the alternative of which would be a life like a vegetable followed by a stroke (caused by thickening and narrowing of the arteries) or plain death followed by cardiac failure. If you want to live and lead a qualitative life, you need to take full control of your life or face the terrible consequences. There are many research studies which are looking into the possibility of making a drug that can reverse cardiovascular disease and these show promising results. However, until such a drug is discovered and well within your reach you need to keep a close watch on all the factors that strengthen the cardiovascular disease and hypertension link through all the means available to you.

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