Showing papers in "Journal of The American Society of Hypertension in 2008"
TL;DR: It is recommended that HBPM should become a routine component of BP measurement in the majority of patients with known or suspected hypertension and patients should be advised to purchase oscillometric monitors that measure BP on the upper arm with an appropriate cuff size and that have been shown to be accurate according to standard international protocols.
Abstract: Home blood pressure monitoring (HBPM) overcomes many of the limitations of traditional office blood pressure (BP) measurement and is both cheaper and easier to perform than ambulatory BP monitoring. Monitors that use the oscillometric method are currently available that are accurate, reliable, easy to use, and relatively inexpensive. An increasing number of patients are using them regularly to check their BP at home, but although this has been endorsed by national and international guidelines, detailed recommendations for their use have been lacking. There is a rapidly growing literature showing that measurements taken by patients at home are often lower than readings taken in the office and closer to the average BP recorded by 24-hour ambulatory monitors, which is the BP that best predicts cardiovascular risk. Because of the larger numbers of readings that can be taken by HBPM than in the office and the elimination of the white-coat effect (the increase of BP during an office visit), home readings are more reproducible than office readings and show better correlations with measures of target organ damage. In addition, prospective studies that have used multiple home readings to express the true BP have found that home BP predicts risk better than office BP (class IIa; level of evidence A). This call-to-action article makes the following recommendations: 1) It is recommended that HBPM should become a routine component of BP measurement in the majority of patients with known or suspected hypertension; 2) Patients should be advised to purchase oscillometric monitors that measure BP on the upper arm with an appropriate cuff size and that have been shown to be accurate according to standard international protocols. They should be shown how to use them by their healthcare providers; 3) Two to three readings should be taken while the subject is resting in the seated position, both in the morning and at night, over a period of 1 week. A total of ≥12 readings are recommended for making clinical decisions; 4) HBPM is indicated in patients with newly diagnosed or suspected hypertension, in whom it may distinguish between white-coat and sustained hypertension. If the results are equivocal, ambulatory BP monitoring may help to establish the diagnosis; 5) In patients with prehypertension, HBPM may be useful for detecting masked hypertension; 6) HBPM is recommended for evaluating the response to any type of antihypertensive treatment and may improve adherence; 7) The target HBPM goal for treatment is
185 citations
TL;DR: Neither ABPM nor self-BP monitoring are mandatory for the routine diagnosis of hypertension, but these modalities can enhance the ability for identification of white-coat and masked hypertension and evaluate the extent of BP control in patients on drug therapy.
Abstract: This American Society of Hypertension position paper focuses on the importance of out-of-office blood pressure (BP) measurement for the clinical management of patients with hypertension and its complications. Studies have supported direct and independent associations of cardiovascular risk with ambulatory BP and inverse associations with the degree of BP reduction from day to night. Self-monitoring of the BP (or home BP monitoring) also has advantages in evaluating patients with hypertension, especially those already on drug treatment, but less is known about its relation to future cardiovascular events. Data derived from ambulatory BP monitoring (ABPM) allow the identification of high-risk patients, independent from the BP obtained in the clinic or office setting. While neither ABPM nor self-BP monitoring are mandatory for the routine diagnosis of hypertension, these modalities can enhance the ability for identification of white-coat and masked hypertension and evaluate the extent of BP control in patients on drug therapy.
163 citations
TL;DR: Testing a hypothesis that urinary AGT levels are enhanced in chronic kidney disease (CKD) patients and correlated with some clinical parameters confirmed the earlier report and showed that a new ELISA assay is a valid approach for measuring urinaryAGT.
Abstract: We previously reported that urinary excretion rates of angiotensinogen (AGT) provide a specific index of the activity of the intrarenal renin-angiotensin system in angiotensin II-dependent hypertensive rats. Meanwhile, we have recently developed direct enzyme-linked immunosorbent assays (ELISAs) to measure plasma and urinary AGT in humans. This study was performed to test a hypothesis that urinary AGT levels are enhanced in chronic kidney disease (CKD) patients and correlated with some clinical parameters. Eighty patients with CKD (37 women and 43 men, from 18 to 94 years old) and seven healthy volunteers (two women and five men, from 27 to 43 years old) were included. Plasma AGT levels showed a normal distribution; however, urinary AGT-creatinine ratios (UAGT/UCre) deviated from the normal distribution. When a logarithmic transformation was executed, Log(UAGT/UCre) levels showed a normal distribution. Therefore, Log(UAGT/UCre) levels were used for further analyses. Log(UAGT/UCre) levels were not correlated with age, gender, height, body weight, body mass index, systolic blood pressure, diastolic blood pressure, serum sodium levels, serum potassium levels, urinary sodium-creatinine ratios, plasma renin activity, or plasma AGT levels. However, Log(UAGT/UCre) levels were significantly correlated positively with urinary albumin-creatinine ratios, fractional excretion of sodium, urinary protein-creatinine ratios, and serum creatinine, and correlated negatively with estimated glomerular filtration rate. Log(UAGT/UCre) levels were significantly increased in CKD patients compared with control subjects (1.8801 +/- 0.0885 vs. 0.9417 +/- 0.1048; P = .0024). These data confirmed our earlier report and showed that a new ELISA assay is a valid approach for measuring urinary AGT.
139 citations
TL;DR: In conclusion, eplerenone demonstrated substantial efficacy in treatment-resistant hypertension and was well-tolerated with modest changes in plasma potassium and serum aldosterone.
Abstract: Resistant hypertension is defined as uncontrolled hypertension despite intensive treatment with at least three antihypertensive agents, one of which ideally should be a diuretic. To determine the efficacy and safety of the selective aldosterone antagonist eplerenone in this population, we studied patients with resistant hypertension (clinic blood pressure [BP] >140 mm Hg systolic or >90 mm Hg diastolic on maximal doses of more than three antihypertensive agents, including a loop or thiazide diuretic). At baseline and after 12 weeks of eplerenone therapy (50 to 100 mg daily titrated to effect), patients underwent clinic and 24-hour BP measurements, serum potassium, plasma renin activity, and serum aldosterone measurements. Patients (n = 52) completing the trial averaged 62 +/- 10 years of age, were overweight (mean body mass index, 32.1 +/- 5.5 kg/m(2)), and had variable renal function (glomerular filtration rate, 106 +/- 38 mL/minute); 70% were men and 74% were non-Black. The mean number of antihypertensive agents at baseline was 3.7 +/- 0.8 (range, three to seven drugs) to achieve a clinic BP of 150.5/84.1 mm Hg. The mean serum aldosterone was 12.9 +/- 7.6 ng/mL and plasma renin activity was 2.3 +/- 2.7 ng/mL/hour. After eplerenone, the change from baseline in the clinic BP was -17.6/-7.9 mm Hg (P 5.5 mEq/L, but 0.3 for both SBP and DBP, P < .0001), weakly related to baseline serum aldosterone (r = -0.30; P = .05), and unrelated to plasma renin activity, age, gender, or race. In conclusion, eplerenone demonstrated substantial efficacy in treatment-resistant hypertension and was well-tolerated with modest changes in plasma potassium. Serum aldosterone and plasma renin activity did not predict BP responses to eplerenone in this population.
112 citations
TL;DR: In this article, a review of the literature about the relationship between heavy drinking and hypertension is presented. But the authors do not consider the role of gender, ethnicity, other lifestyle traits, drinking pattern, and choice of beverage.
Abstract: In recent decades alcohol use has joined other correlates of hypertension (HTN), such as obesity and salt intake, as a major research focus about HTN risk factors. In cross-sectional and prospective epidemiologic studies, higher blood pressure (BP) has consistently been found among persons reporting usual daily intake of three standard-sized drinks or more. Although definitive mechanisms have not been established, several aspects of the data, including short and intermediate term experiments, suggest a causal relationship. Heavier drinking may, in fact, be the commonest cause of reversible HTN, and reduction of heavy alcohol intake plays an important public health role in HTN management. Additional to the mechanism, unresolved issues about the alcohol-BP relationship include whether there is a threshold dosage of alcohol for association with HTN, the sequelae of alcohol-associated HTN and the roles of interactions with gender, ethnicity, other lifestyle traits, drinking pattern, and choice of beverage. This article reviews these areas and includes new data about the beverage choice aspect.
69 citations
TL;DR: The impairment of endothelium-dependent vasodilatory response to acetylcholine in two different mouse strains with Mas deficiency indicates a key role of Mas in endothelial function by its effects on the generation and metabolism of NO and ROS.
Abstract: The Mas gene codes for an angiotensin (1-7) receptor. There is accumulating evidence that Mas is involved in vascular homeostasis. We have recently backcrossed Mas-knockout mice to two different genetic backgrounds, C57Bl/6 and FVB/N. FVB/NMas-deficient mice exhibited elevation in blood pressure (BP) and impaired endothelial function. In the present study, we aimed to address the question whether this phenotype is strain-specific. Therefore, we evaluated endothelial function in C57Bl/6Mas-deficient mice. Similar to FVB/NMas-knockout animals, Mas-deficiency in C57Bl/6 mice leads to endothelial dysfunction evaluated by the acute BP effect of acetylcholine administration. Measurements of nitric oxide (NO) and reactive oxygen species (ROS) and the systems involved in their metabolism revealed an imbalance between these vasoactive factors in C57Bl/6Mas-knockout mice, which may explain the impairment of endothelial function in these animals. However, endothelial dysfunction was less prominent in Mas-deficient mice on a C57Bl/6 background compared to FVB/N. Moreover, C57Bl/6Mas-deficient mice remained normotensive while FVB/N-based animals exhibited elevated BP. The impairment of endothelium-dependent vasodilatory response to acetylcholine in two different mouse strains with Mas deficiency indicates a key role of Mas in endothelial function by its effects on the generation and metabolism of NO and ROS.
69 citations
TL;DR: With recent advances in ambulatory BP monitoring and BP self-measurement and the inclusion of antihypertensive agents that target the underlying pathophysiological mechanisms related to the morning BP surge, control of morning hypertension is clinically feasible and should be an important therapeutic target.
Abstract: The early morning surge in blood pressure (BP) in patients with hypertension is associated with an increased risk of cardiovascular events, such as myocardial infarction and stroke, especially in the presence of comorbidities of diabetes, cardiac and renal disease. A variety of nonhemodynamic factors contribute to the early morning prothrombotic state, including increased atherothrombotic plaque vulnerability and endovascular shear stress, increased coagulability, platelet aggregation, and blood viscosity, and reduced fibrinolysis. In addition, there is a strong association between morning hypertension and vascular damage throughout the circulation, which may involve the myocardium, large arteries, and other target organs. Because morning hypertension is often unrecognized, the resultant target-organ damage may progress relentlessly. With recent advances in ambulatory BP monitoring and BP self-measurement and the inclusion of antihypertensive agents that target the underlying pathophysiological mechanisms related to the morning BP surge (ie, the sympathetic nervous system and the renin-angiotensin-aldosterone system), control of morning hypertension is clinically feasible and should be an important therapeutic target.
69 citations
TL;DR: Findings support the rationale for combining agents with complementary mechanisms of action, such as amlodipine and valsartan, in the management of stage 2 hypertension.
Abstract: Achieving blood pressure (BP) targets in stage 2 hypertension usually requires two or more drugs, which should be selected from different classes. This study compared the efficacy and tolerability of amlodipine/valsartan with amlodipine in patients with stage 2 hypertension. In this multicenter, randomized, double-blind, 8-week study, 646 patients with stage 2 hypertension (mean sitting systolic blood pressure [MSSBP] >/=160 mm Hg) received amlodipine/valsartan 5/160 mg or amlodipine 5 mg for 2 weeks, prior to being force-titrated to amlodipine/valsartan 10/160 mg or amlodipine 10 mg, respectively, for a further 6 weeks. Hydrochlorothiazide could be added at Week 4 if MSSBP was >/=130 mm Hg. At endpoint Week 4, reductions in MSSBP were significantly greater in patients receiving amlodipine/valsartan than in those receiving amlodipine (30.1 mm Hg vs. 23.5 mm Hg; P /=180 mm Hg were also greater for amlodipine/valsartan at Week 4 (40.1 mm Hg vs. 31.7 mm Hg for amlodipine; P = .0018). Differences favoring amlodipine/valsartan were also seen for BP control. Amlodipine/valsartan was generally well tolerated. These findings support the rationale for combining agents with complementary mechanisms of action, such as amlodipine and valsartan, in the management of stage 2 hypertension.
68 citations
TL;DR: Blockade of AT(1) receptors showed a superior corrective effect on the altered structure of resistance arteries in essential hypertension that was independent of the magnitude of BP reduction, and resulted in values similar to those in normotensive controls.
Abstract: Angiotensin II (Ang II) has been linked to vascular dysfunction and target-organ damage. Blockade of the angiotensin II type 1 receptor (AT1) with an angiotensin receptor blocker may reverse vascular pathology independent of blood pressure (BP) lowering. Stage I hypertensive, nondiabetic patients (61% male; age 38 to 67 years) were randomized after a 4-week washout period to olmesartan medoxomil 20 to 40 mg or atenolol 50 to 100 mg plus additional agents (hydrochlorothiazide, amlodipine, or hydralazine) as needed for a goal BP 140/90 mm Hg. At baseline and after 1 year of treatment, subcutaneous gluteal resistance arteries were examined on a pressurized myograph to evaluate remodeling. Biopsies were available from 22 atenolol recipients, 27 olmesartan medoxomil recipients, and 11 normal volunteer controls. BP was reduced to a comparable degree by olmesartan medoxomil (from 149 11/92 8m m Hg to 120 9/77 6m m Hg;P .05 [mean standard deviation]) and atenolol (from 147 10/90 6m m Hg to 125 12/78 7m m Hg;P .05 [mean standard deviation]) from baseline for each arm (P .08 for the 40-week treatment mean between arms). After one year’s treatment, the wall-to-lumen ratio in arteries from patients treated with olmesartan medoxomil was significantly reduced (from 14.9% to 11.1%; P .01), whereas no significant change was observed in arteries from atenolol-treated patients (from 16.0% to 15.5%; P NS); the wall-to-lumen ratio in controls was 11.0%. Blockade of AT1 receptors showed a superior corrective effect on the altered structure of resistance arteries in essential hypertension that was independent of the magnitude of BP reduction, and resulted in values similar to those in normotensive controls. © 2008 American Society of Hypertension. All rights reserved.
58 citations
TL;DR: NPs are considered as circulating markers of congestive heart failure, however, their therapeutic potential for the treatment of cardiovascular diseases such as hypertension, renal insufficiency, cardiac hypertrophy, congestiveheart failure, and stroke has just begun to unfold.
Abstract: Thus far, three related natriuretic peptides (NPs) and three distinct receptors have been identified, which have advanced our knowledge towards understanding the control of high blood pressure, hypertension, and cardiovascular disorders to a great extent. Biochemical and molecular studies have been advanced to examine receptor function and signaling mechanisms and the role of second messenger cyclic guanosine monophosphate in pathophysiology of hypertension, renal hemodynamics, and cardiovascular functions. The development of gene-knockout and gene-duplication mouse models along with transgenic mice have provided a framework for understanding the importance of the antagonistic actions of NP receptors in cardiovascular events at the molecular level. Now, NPs are considered as circulating markers of congestive heart failure, however, their therapeutic potential for the treatment of cardiovascular diseases such as hypertension, renal insufficiency, cardiac hypertrophy, congestive heart failure, and stroke has just begun to unfold. Indeed, alternative avenues of investigations in this important area need to be undertaken, as we are at the initial stage of the molecular therapeutic and pharmacogenomic implications.
58 citations
TL;DR: It is suggested that a long-term HS diet induces renal injury and hypertension, which is associated with decreased renal VEGF expression in normotensive rodent animals.
Abstract: We seek to determine: 1) whether a long-term high salt diet induces hypertension and renal injury in Sprague-Dawley (SD) rats and 2) whether the high salt diet-induced hypertension and renal injury are associated with decreased renal VEGF expression. Twelve 10-wk-old male SD rats received a high salt diet (HS, 8%) and twelve SD rats received a normal salt diet (NS, 0.5 %) for 8 weeks. Using a tail cuff, weekly monitoring showed that blood pressure increased significantly after 6, 7, & 8 wks in HS group, compared to NS group (P<0.01). At 4 wks and 8 wks of diet, mean arterial pressure (MAP) was determined in conscious rats by continuous monitoring through a catheter placed in the carotid artery. MAP was not significantly different between HS and NS group in 4 wks, but was significantly higher in HS than NS group (140+/-5.3 vs.112+/-2.2 mmHg; P<0.01) in 8 wks. Increased proteinuria and albuminuria were associated with marked renal histological abnormalities in HS group, compared to those in NS group. Northern blot and ELISA demonstrated that 8 wks of HS diet significantly decreased renal expression of VEGF mRNA and protein, compared to NS group (P<0.01). In 8 wks, total urinary excretion of sFlt-1 was significantly higher in HS than NS group (9.28+/-1.05 vs. 2.05+/-0.55 ng/day; P<0.01) whereas the plasma levels of sFlt-1 remained stable. These results suggest that a long-term HS diet induces renal injury and hypertension, which are associated with decreased renal VEGF expression in normotensive rodent animals.
TL;DR: The present review aims to provide an understanding of the pathophysiology of arterial stiffness and wave reflection, to review the various techniques for their measurement, and to explore their usefulness in predicting CV risk and therapeutic benefit in comparison with traditional brachial artery cuff blood pressure (BP) by sphygmomanometry.
Abstract: Arterial stiffness of the large, elastic conduit arteries is considered a risk marker of vascular aging, as well as a new biomarker of cardiovascular (CV) disease. Arterial stiffness also plays an important role in the development of isolated systolic hypertension (ISH) in the middle-aged and elderly population. ISH is characterized by an increase in pulse pressure (PP) in association with a rise in systolic blood pressure (SBP) and a fall in diastolic blood pressure (DBP). Increased PP, however, is not always a good surrogate for arterial stiffening because of the frequent discrepancy between peripheral brachial and central aortic PP values due to varying pressure amplification. Therefore, noninvasive, easily performed methods for more direct measurement of arterial stiffness and wave reflection, such as aortic pulse wave velocity (PWV) and pulse wave analysis, have been developed for clinical use. The present review aims to provide an understanding of the pathophysiology of arterial stiffness and wave reflection, to review the various techniques for their measurement, and to explore their usefulness in predicting CV risk and therapeutic benefit in comparison with traditional brachial artery cuff blood pressure (BP) by sphygmomanometry.
TL;DR: In pathological conditions, OT plays an anti-inflammatory and cardioprotective role, improving vascular and metabolic functions; it has potential for therapeutic use.
Abstract: Oxytocin (OT), traditionally associated with reproductive functions, was revisited recently, which revealed several new functions of the hormone in cardiovascular regulation. To support this contention, we have demonstrated the presence and synthesis of OT receptors in all heart compartments and the vasculature. The functionality of these receptors has been established by the ability of OT to induce atrial natriuretic peptide and nitric oxide (NO) release from the perfused heart and atrial slices. OT's cardiovascular actions include natriuresis, blood pressure reduction, negative inotropic and chronotropic effects, parasympathetic neuromodulation, as well as vasodilatation triggered by the NO pathway that is also involved in endothelial cell growth and anti-inflammatory activity. In addition, we have reported the abundance of the OT system in the early developing heart and OT's capacity to generate cardiomyocytes from mouse embryonic stem cells. The most potent inducer of cardiac differentiation, OT-Gly-Lys-Arg, is an extended form of OT that is abundantly expressed in the fetal heart. Therefore, in pathological conditions, OT plays an anti-inflammatory and cardioprotective role, improving vascular and metabolic functions; it has potential for therapeutic use.
TL;DR: This American Society of Hypertension position paper summarizes the clinical spectrum of hypertension in pregnancy, focusing on preeclampsia, and the use of antihypertensive drugs in pregnancy and the prevention and treatment of the convulsive phase of preeclamping, with intravenous MgSO(4).
Abstract: Hypertension complicates 5% to 7% of all pregnancies. A subset of preeclampsia, characterized by new-onset hypertension, proteinuria, and multisystem involvement, is responsible for substantial maternal and fetal morbidity and is a marker for future cardiac and metabolic disease. This American Society of Hypertension (ASH) position paper summarizes the clinical spectrum of hypertension in pregnancy, focusing on preeclampsia. Recent research breakthroughs relating to etiology are briefly reviewed. Topics include classification of the different forms of hypertension during pregnancy, and status of the tests available to predict preeclampsia, and strategies to prevent preeclampsia and to manage this serious disease. The use of antihypertensive drugs in pregnancy, and the prevention and treatment of the convulsive phase of preeclampsia, eclampsia, with intravenous MgSO(4) is also highlighted. Of special note, this guideline article, specifically requested, reviewed, and accepted by ASH, includes solicited review advice from the American College of Obstetricians and Gynecologists.
TL;DR: Prorenin also contributes to the development of nephropathy in type II diabetes, probably through a (pro)renin receptor-dependent mechanism.
Abstract: Previous studies have demonstrated that prorenin plays a significant role in the development and progression of nephropathy in streptozotocin-induced diabetic animals, a model for type 1 diabetes, through a (pro)renin receptor–dependent mechanism. However, whether this novel mechanism also contributes to the mechanism of diabetic nephropathy in type 2 diabetes has remained undetermined. In 16-week-old db/db mice, a model for type 2 diabetes, we found a significant degree of glomerulosclerosis, enhanced immunostaining for the active site of renin (representing non-proteolytically activated prorenin), and an increased immunoreactivity to activated extracellular-signal–related protein kinase 1/2 in the kidneys. These changes were blocked by the chronic subcutaneous administration (1 mg/kg/day) of a decoy peptide with the “handle region” structure, which competitively inhibits prorenin binding to a “handle region”–specific binding protein, such as the (pro)renin receptor. The kidneys of db/db mice also contained increased angiotensin (Ang) I and II levels, eliciting significant microalbuminuria. Treatment with the “handle region” peptide significantly decreased the renal content of Ang I and II and inhibited the development of microalbuminuria. Thus prorenin also contributes to the development of nephropathy in type II diabetes, probably through a (pro)renin receptor–dependent mechanism.
TL;DR: The radial tonometry method helped characterize aging change, identified spurious systolic hypertension of youth, and greater hemodynamic benefit of "new" over "old" antihypertensive drugs.
Abstract: Recent studies have shown value of arterial tonometry to generate central aortic pressure so as to explain drug effects, and predict outcome. This article describes experience with such modern pressure pulse waveform analysis in a clinical practice dealing predominantly with patients suffering from ischemic heart disease, hypertension, and cardiac failure. We describe the use of radial artery tonometry on consecutive 9,710 occasions (1,505 patients) attending a cardiovascular outpatient clinic. Ascending aortic pressure was calculated with two methods, either using a generalized transfer function with SphygmoCor((R)) (AtCor Medical, Sydney, NSW, Australia) or from direct analysis of the radial waveform. With the SphygmoCor((R)) method, aortic systolic pressure was 13 (SD 6) mm Hg less than brachial. Results were similar with the second method (average difference 14 SD; 5 mm Hg), but this method was inapplicable in 9% of cases. Differences with age in aortic systolic and pulse pressure were similar to those described in a normal cohort. Differences between aortic and peripheral pressure values were predictable on the basis of waveform patterns at either site. The radial tonometry method helped characterize aging change, identified spurious systolic hypertension of youth, and greater hemodynamic benefit of "new" over "old" antihypertensive drugs. Analysis of the pressure waveform has the potential to improve office management of patients with hypertension, cardiac failure, and angina.
TL;DR: The TROPHY results were recalculated based on the current definition of hypertension and resulted in a lower incidence of hypertension, but the outcomes were remarkably similar with both definitions and confirmed the original findings.
Abstract: Trial of Preventing Hypertension (TROPHY) investigated whether pharmacological treatment of prehypertension prevents or postpones stage 1 hypertension. Hypertension was originally defined when a participant had blood pressure (BP) >/=140 and/or >/=90 mm Hg at any three clinic visits over 4 years. Contemporary guidelines define hypertension if the BP is >/=140 and/or >/=90 at two consecutive visits. TROPHY results were recalculated based on the current definition. Participants with repeated BP of 130 - 139 and/or 85 - 89 mm Hg were randomly assigned to 2 years of candesartan or placebo, followed by 2 years of placebo for all. All participants received lifestyle counseling at every visit. When participants reached hypertension, antihypertensive treatment was initiated. The 4-year incidence of hypertension was significantly (P < .001) lower than previously reported in the placebo (-11.3%) and candesartan (-11.0%) groups. During the first 2 years, hypertension developed in 162 placebo and 53 candesartan participants (relative risk reduction [RRR], 68%; P < .001; original report 66%; P < .001). After 4 years, hypertension occurred in 197 placebo and 165 candesartan participants (RRR, 18%; P < .009; original report 16%; P < .007). The new definition resulted in a lower incidence of hypertension, but the outcomes were remarkably similar with both definitions and confirmed our original findings.
TL;DR: Augmented O- GlcNAcylation increases vascular reactivity to constrictor stimuli, possibly due to its effects on eNOS expression and activity, reinforcing the concept that O-GlcNA Cylation modulates vascular reactsivity and may play a role in pathological conditions associated with abnormal vascular function.
Abstract: O-linked N-acetylglucosaminylation (O-GlcNAcylation) plays a role in many aspects of protein function. Whereas elevated O-GlcNAc levels contribute to diabetes-related end-organ damage, O-GlcNAcylation is also physiologically important. Because proteins that play a role in vascular tone regulation can be O-GlcNAcylated, we hypothesized that O-GlcNAcylation increases vascular reactivity to constrictor stimuli. Aortas from male Sprague-Dawley rats and C57BL/6 mice were incubated for 24 hours with vehicle or PugNAc (O-GlcNAcase inhibitor, 100 μM). PugNAc incubation significantly increased O-GlcNAc proteins, as determined by Western blot. PugNAc also increased vascular contractions to phenylephrine and serotonin, an effect not observed in the presence of N ω -nitro- L -arginine methyl ester or in endothelium-denuded vessels. Acetylcholine-induced relaxation, but not that to sodium nitroprusside, was decreased by PugNAc treatment, an effect accompanied by decreased levels of phosphorylated endothelial nitric oxide synthase (eNOS) Ser-1177 and Akt Ser-473 . Augmented O-GlcNAcylation increases vascular reactivity to constrictor stimuli, possibly due to its effects on eNOS expression and activity, reinforcing the concept that O-GlcNAcylation modulates vascular reactivity and may play a role in pathological conditions associated with abnormal vascular function.
TL;DR: Observations suggest that Ang-(1-7) specifically modulates the expression of RAS components and ECM proteins in LV, which was associated with an increase in ACE2 and a decrease in Mas expression.
Abstract: We investigated the expression of specific extracellular matrix (ECM) proteins in cardiac hypertrophy induced by isoproterenol in TGR(A1-7)3292 rats. Additionally, changes in circulating and tissue renin-angiotensin system (RAS) were analyzed. Left ventricles (LV) were used for quantification of collagen type I, III, and fibronectin using immunofluorescence-labeling techniques. Angiotensin (Ang) II levels were measured by radioimmunoassay. Expression of RAS components was assessed by semi-quantitative polymerase chain reaction (PCR) or real-time PCR. Isoproterenol treatment induced an increase in the expression of collagen I, III, and fibronectin in normal rats. Collagen I and fibronectin expression were decreased in TGR(A1-7)3292 at basal conditions and both proteins increased by isoproterenol treatment; however, the levels achieved were still significantly lower than those observed in treated normal rats. The increase in collagen III observed in normal rats was completely blunted in TGR(A1-7)3292. Moreover, TGR(A1-7)3292 presented lower Ang II levels and angiotensinogen expression and a higher angiotensin-converting enzyme 2 (ACE2) expression in LV. Isoproterenol treatment increased cardiac Ang II concentration only in normal rats, which was associated with an increase in ACE2 and a decrease in Mas expression. These observations suggest that Ang-(1-7) specifically modulates the expression of RAS components and ECM proteins in LV.
TL;DR: Evaluated 30-year survival and cardiovascular outcomes of the Hypertension Detection and Follow-up Program (HDFP-GA) identified the importance of long-term follow-up of individuals in hypertension studies and trials that include CVD outcomes.
Abstract: The Evans County Heart Study (ECHS), initiated in 1960, was one of the first major studies to document cardiovascular disease (CVD) risks for African Americans and Caucasians with elevated blood pressures. In the early 1970s, the Hypertension Detection and Follow-up Program (HDFP), with a site in Georgia (HDFP-GA), was one of the first major studies to demonstrate that treating hypertension with stepped care (SC), vs. referred care (RC), has better short-term outcomes. With this background, study objectives were to evaluate 30-year survival and cardiovascular outcomes of the HDFP-GA and to compare outcomes of these patients with 1,619 hypertensive individuals (30 to 69 years of age) from the ECHS. The HDFP-GA patients included 688 individuals (Black [n = 267]; White [n = 421]) randomized to RC (n = 341) and SC (n = 347). The ECHS was comprised of 733 Black and 886 White hypertensives. All-cause mortality and CVD mortality were assessed in the HDFP-GA and compared with those in the ECHS hypertensives. After 30 years of follow-up, 65.7% of the HDFP-GA cohort had died compared with a similar 65.8% of the ECHS hypertensives. However, CVD mortality rates, while similar for the SC and RC arms, were lower than in the HDFP-GA total study group than the hypertensive participants of ECHS (32.6% vs. 40.3%; P
TL;DR: The effect of low-dose thiazide on the activity of the ACE2/Ang-(1-7)/mas-receptor axis is documented for the first time, suggesting that the opposing arm of the system does not substantially contribute to the antihypertensive effect ofLow-doseThiazides in SHR.
Abstract: Fifty years since their introduction, thiazide diuretics are established as first-line therapy in the treatment of hypertension. Because the dosing profile for thiazide agents lessened, the mechanism responsible for the blood pressure lowering effect may lie outside their diuretic properties. We evaluated the mechanism driving blood pressure reductions in spontaneously hypertensive rats (SHR) and normotensive WKY by examining the effects of low-dose hydrochlorothiazide (HCTZ) administration on renin-angiotensin system (RAS) components. The 7-day, 1.5 mg/kg/day HCTZ did not change systolic pressure in WKY, but decreased SBP by 41 +/- 2 mm Hg (p < 0.0001) in SHR. This reduction was independent of increases in water intake, urine output, or alterations in electrolyte excretion. HCTZ significantly increased the plasma concentrations of angiotensin I (Ang I) and angiotensin II (Ang II) in both WKY and SHR while reducing angiotensin converting enzyme (ACE) activity and the Ang II/Ang I ratio (17.1 +/- 2.9 before versus 10.3 +/- 2.9 after, p < 0.05) only in SHR. HCTZ increased cardiac ACE2 mRNA and activity, and neprilysin mRNA in WKY, but not SHR. Conversely in SHR, ACE2 activity was decreased and aside from a 75% increase in AT(1) mRNA in the HCTZ-treated SHR, the expression of the other variables remained unaltered. Measures of cardiac mas receptor mRNA showed no changes in response to treatment in both strains, although cardiac mas mRNA was significantly lower in untreated SHR. These data, which document for the first time the effect of low-dose thiazide on the activity of the ACE2/Ang-(1-7)/mas-receptor axis, suggest that the opposing arm of the system does not substantially contribute to the antihypertensive effect of low-dose thiazides in SHR.
TL;DR: Various classes of antihypertensive drugs are reviewed, especially their roles in delaying or preventing damage to the vulnerable pancreatic islet, and thus delaying the development of type 2 diabetes mellitus.
Abstract: Hypertension, a multifactorial-polygenic disease, interacts with multiple environmental stressors and results in functional and structural changes in numerous end organs, including the cardiovascular system. This can result in coronary heart disease, stroke, peripheral vascular disease, congestive heart failure, end-stage renal disease, insulin resistance, and damage to the pancreatic islet. Hypertension is the most important modifiable risk factor for major health problems encountered in clinical practice. Whereas hypertension was once thought to be a medical condition based on discrete blood pressure readings, a new concept has emerged defining hypertension as part of a complex and progressive metabolic and cardiovascular disease, an important part of a cardiometabolic syndrome. The central role of insulin resistance, oxidative stress, endothelial dysfunction, metabolic signaling defects within tissues, and the role of enhanced tissue renin-angiotensin-aldosterone system activity as it relates to hypertension and type 2 diabetes mellitus are emphasized. Additionally, this review focuses on the effect of hypertension on functional and structural changes associated with the vulnerable pancreatic islet. Various classes of antihypertensive drugs are reviewed, especially their roles in delaying or preventing damage to the vulnerable pancreatic islet, and thus delaying the development of type 2 diabetes mellitus.
TL;DR: Children and adolescents with hypertension and especially obesity-associated hypertension can be identified and should be evaluated for additional metabolic risk factors and therapeutic interventions, including lifestyle changes and medications, when indicated.
Abstract: Hypertension and obesity are both common health problems in children and adolescents. More than 17% of children are obese and even more children are overweight. Hypertension, although defined differently in children than in adults, can be detected in 3% to 4% of children, and approximately 30% of obese adolescents have high blood pressure (BP) associated with obesity. Children with high BP and obesity frequently have other risk factors that are components of the metabolic syndrome. Evidence of target organ damage, including left ventricular hypertrophy, is detectable in many children with hypertension and is more commonly found in children with high BP and obesity. Both obesity and hypertension are considered inflammatory conditions. There are some emerging data in the young that show an association of insulin resistance, obesity, and high BP with inflammatory markers. Children and adolescents with hypertension and especially obesity-associated hypertension can be identified and should be evaluated for additional metabolic risk factors. Considering the heightened risk for premature cardiovascular (CV) disease, therapeutic interventions, including lifestyle changes and medications, when indicated, are important for all children and adolescents with obesity-associated hypertension.
TL;DR: The results suggest the presence of a pathophysiological association between arterial stiffening and BP postural changes, even in subjects without pronounced vascular aging or orthostatic hypotension, is implied.
Abstract: Carotid-femoral pulse wave velocity (PWV), an integrated marker of segmental aortic stiffness, was recently proposed as one of the underlying mechanisms inducing orthostatic hypotension in the elderly with marked arterial rigidity. We examined the relationship between PWV (Complior; Colson, Paris, France) and orthostatic blood pressure (BP) changes, measured repeatedly, over a wide range of age and arterial stiffness. Sixty-nine hypertensive subjects (age, 37 to 76 years; 39 untreated and 30 treated) were studied. BP, in both sitting and erect position, was measured at two occasions a few weeks apart, and in between PWV was assessed by means of pulse wave analysis. In untreated hypertensive subjects, the orthostatic alterations in systolic, but not in diastolic blood pressure (DBP), were inversely related to PWV, independently from age, gender, mean BP, and diabetes mellitus. The greater the aortic stiffness the larger was the systolic blood pressure (SBP) decrease during upraises. On the contrary, no such association was found between PWV and orthostatic changes of BP in treated hypertensive subjects. These results suggest the presence of a pathophysiological association between arterial stiffening and BP postural changes. Antihypertensive drug treatment, as well as other factors that have not been evaluated in the present study, might have modulated this association. However, it might be argued that a causal association between arterial stiffness – disturbed baroreflex sensitivity – postural BP changes, even in subjects without pronounced vascular aging or orthostatic hypotension, is implied.
TL;DR: Some of the evidence suggests that activation of PPARalpha and PPARgamma in hypertension may exert beneficial cardiovascular protective effects, however, a recent meta-analysis suggests an excess of myocardial infarction and borderline excess of cardiovascular death in type 2 diabetic patients treated with rosiglitazone.
Abstract: Peroxisome proliferator-activated receptors (PPARs) alpha and gamma are ligand-activated transcription factors belonging to the nuclear receptor superfamily. PPARα has effects on fatty acid metabolism and its activation by fibrates results in reduction of triglyceride concentrations in blood. PPARγ induces differentiation of adipocytes, and its activation by thiazolidinediones (TZDs) has insulin sensitizing effects, for which reason these agents are used for treating type 2 diabetes. PPARα and PPARγ are present in the vasculature, where they have been shown to exert antioxidant and anti-inflammatory effects and to blunt the development of fibrosis and remodeling in experimental models and in several cardiovascular clinical conditions. This review will discuss some of the evidence, both experimental and clinical, that suggests that activation of PPARα and PPARγ in hypertension may exert beneficial cardiovascular protective effects. However, a recent meta-analysis suggests an excess of myocardial infarction and borderline excess of cardiovascular death in type 2 diabetic patients treated with rosiglitazone. Thus the safety of use of PPARγ activators for cardiovascular prevention and whether they are protective or actually may be harmful remains to be established.
TL;DR: The prognostic value of the diurnal BP changes is comparable when using different clock-dependent or independent definitions of day and night, and the area under the ROC curve did not differ among the different definitions ofday and night.
Abstract: Although the prognostic value of the day-night blood pressure (BP) changes is established, the most appropriate method for defining day and night is undefined. We assessed the prognostic value of the day-night BP changes by using three definitions of day and night in 2,934 initially untreated hypertensive subjects who underwent 24-hour ambulatory BP monitoring. Over a median follow-up period of 7 years, there were 356 cardiovascular events and 176 deaths. Total cardiovascular events and all-cause mortality were similarly higher in non-dippers (night/day ratio of systolic BP >10% or >0%) than in dippers regardless of the definition of day and night. In a receiver-operated characteristic (ROC) curve analysis of the night/day ratio of systolic BP on the occurrence of events, the area under the ROC curve did not differ among the different definitions of day and night (large fixed-clock intervals, narrow fixed-clock intervals, diary) for both total cardiovascular events (0.61 [95% confidence interval (CI): 0.58 to 0.64], 0.61 [95% CI: 0.57 to 0.63], 0.62 [95% CI: 0.58 to 0.65], respectively; P = 0.20) and all-cause mortality (0.65 [95% CI: 0.61 to 0.70], 0.64 [95% CI: 0.60 to 0.69], 0.65 [95% CI: 0.61 to 0.70], respectively; P = 0.78). The prognostic value of the diurnal BP changes is comparable when using different clock-dependent or independent definitions of day and night.
TL;DR: In addition to smoking and triglycerides, biomarkers for endothelial dysfunction were associated with impaired LAE and SAE in young adults.
Abstract: Reduced arterial elasticity and endothelial dysfunction both may indicate early cardiovascular (CV) disease in young adults. Pulse waveform analysis estimates large (LAE) and small (SAE) artery elasticity noninvasively. We assessed the associations between LAE and SAE and markers of endothelial dysfunction and CV risk factors. The Coronary Artery Risk Development in Young Adults (CARDIA) assessed arterial elasticity and other characteristics cross-sectionally in 389 men and 381 women age 27 to 42 years in 1995 (CARDIA year 10) and circulating levels of P-selectin and soluble intercellular adhesion molecule 1 (sICAM1) in 2000. We adjusted for variables included in the estimation of arterial elasticity (year 10 height, body mass index, age, heart rate, and blood pressure) and other year 10 characteristics. Mean adjusted SAE was 8.5 vs. 7.6 mL/mm Hg × 100 in those with urine albumin/creatinine ratio ≤4 vs. microalbuminuria (ratio >25; P trend = .008). Mean LAE was 25.6 vs. 24.2 mL/mm Hg × 10 in the lowest vs. highest quintile of P-selectin ( P trend = .004). sICAM1 was unrelated to either LAE or SAE. Plasma triglycerides were inversely related to LAE ( P trend = .029). Cigarette smokers had lower SAE than nonsmokers ( P trend = .009). In addition to smoking and triglycerides, biomarkers for endothelial dysfunction were associated with impaired LAE and SAE in young adults.
TL;DR: I increases the amplitude and the duration of the reflected aortic pressure wave, increases wasted LV pressure energy, workload, and oxygen demand, and indices of left ventricular workload including wasted LV energy subendocardial viability and tension time index increased upon HOWI.
Abstract: Swimming/hydrotherapy produces hemodynamic and physiological changes related to water immersion (WI). To evaluate the effects of head out (HO) WI on central hemodynamics, we prospectively studied 21 healthy subjects (62% male, age 37 ± 13 years). Central aortic blood pressures (CA-BPs) and reflected wave properties were evaluated using applanation tonometry at baseline and upon 2 minutes of waist (W) and mid-chest (C) HOWI. Heart rate (HR) decreased from 83 ± 15 to 73 ±10 beats/min ( P P = .20), CA-PP increased stepwise (27 ± 7 to 32 ± 8 to 33 ± 6 mm Hg; P s − P i ), and HR-corrected augmentation index (AI a @75) increased stepwise from baseline-W-C level HOWI [(P s − P i ): 2 ± 3 to 7 ± 4 mm Hg, P a @75: 8 ± 11 to 19 ± 10%; P c ) and reflected wave systolic duration (Δt r ) increased progressively (ED c : 389 ± 23 to 408 ± 25 to 435 ± 13 milliseconds; P r : 106 ± 32 to 165 ± 21 ms; P
TL;DR: The Canadian hypertension community has successfully initiated certain aspects of the national strategic plan, and these programs could be adopted by countries with an organized and committed hypertension community.
Abstract: Canada has a similar prevalence of hypertension to the U.S., which is lower than the prevalence in many European countries. In contrast, Canada had similar treatment and control rates of hypertension to Europe, which are substantially lower than those of the U.S. To address this disparity, a national strategic plan was developed. While the strategy never received government resources for implementation, the Canadian hypertension community has successfully initiated certain aspects of the strategy. To date, programs include: a health professional education program, a national surveillance program, a public awareness program, and a program to reduce dietary sodium. The initiatives rely heavily on volunteers and on collaboration between many organizations and various government departments. Initially largely supported by corporate donations, the programs have received increased government resources over the last 2 years. The development of a funded leadership position beginning in 2006 (Canadian Institutes of Health Research Canada Chair in Hypertension Prevention and Control) has accelerated the initiatives. In the first 4 years of the health professional education program, there were large increases in the diagnosis and treatment of hypertension with corresponding reductions in cardiovascular disease. The Canadian programs could be adopted by countries with an organized and committed hypertension community.
TL;DR: The results indicate that heart rate plays differential roles in the development of arterial stiffness and subclinical atherosclerosis during young adulthood.
Abstract: Heart rate, a hemodynamic parameter, is an important determinant of arterial wall stiffness. However, information on the relationship of heart rate to arterial wall thickness is inconsistent. This study examined the influence of heart rate on arterial stiffness and thickness in Black and White young adults. The study cohort consisted of 255 Black and 659 White adults age 25 to 43 years enrolled in the Bogalusa Heart Study. Carotid artery intima-media thickness (IMT) was measured by B-mode ultrasound and aorta-femoral pulse wave velocity (af-PWV) by echo-Doppler. There was no difference in heart rate between Blacks and Whites. Males vs. females displayed lower heart rate and higher segmental and composite carotid IMT; Blacks vs. Whites had higher composite carotid IMT (0.83 mm vs. 0.80 mm, P P P = .01 for Blacks; β = .06, P = .07 for Whites; β = .09, P = .003 for total sample), but not with carotid IMT. These results indicate that heart rate plays differential roles in the development of arterial stiffness and subclinical atherosclerosis during young adulthood.