Showing papers by "Suzanne Oparil published in 2003"
Boston University1, Rush University Medical Center2, University of Tennessee Health Science Center3, University of Michigan4, University at Buffalo5, University of Mississippi6, University of Miami7, University of Alabama at Birmingham8, Case Western Reserve University9, National Institutes of Health10
TL;DR: The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated, and empathy builds trust and is a potent motivator.
Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure" provides a new guideline
for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of
more than 140 mm Hg is a much more important cardiovascular disease
(CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75
mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive
at 55 years of age have a 90% lifetime risk for developing hypertension; (3)
Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80
to 89 mm Hg should be considered as prehypertensive and require health-promoting
lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should
be used in drug treatment for most patients with uncomplicated hypertension,
either alone or combined with drugs from other classes. Certain high-risk
conditions are compelling indications for the initial use of other antihypertensive
drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor
blockers, β-blockers, calcium channel blockers); (5) Most patients with
hypertension will require 2 or more antihypertensive medications to achieve
goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes
or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal
BP, consideration should be given to initiating therapy with 2 agents, 1 of
which usually should be a thiazide-type diuretic; and (7) The most effective
therapy prescribed by the most careful clinician will control hypertension
only if patients are motivated. Motivation improves when patients have positive
experiences with and trust in the clinician. Empathy builds trust and is a
potent motivator. Finally, in presenting these guidelines, the committee recognizes
that the responsible physician's judgment remains paramount.
24,988 citations
TL;DR: In those older than age 50, systolic blood pressure of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP, and hypertension will be controlled only if patients are motivated to stay on their treatment plan.
Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.
14,975 citations
TL;DR: The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated, and empathy builds trust and is a potent motivator.
Abstract: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.
4,565 citations
TL;DR: The novel concept that structural and functional abnormalities in the vasculature, including endothelial dysfunction, increased oxidative stress, vascular remodeling, and decreased compliance, may antedate hypertension and contribute to its pathogenesis has gained support in recent years.
Abstract: Increased recognition of specific causes of hypertension may lead to therapies that address specific pathophysiologic mechanisms and cause fewer adverse effects. Research to identify such therapies...
611 citations
TL;DR: This large prospective study of hypertensive patients with left ventricular hypertrophy found that increasing albuminuria is associated with a graded increase in risk, and any threshold identified would be much lower than the threshold traditionally defined in diabetic populations.
Abstract: An increased urine albumin–creatinine ratio (UACR) is associated with increasing cardiovascular risk in hypertensive patients with left ventricular hypertrophy. The authors found no UACR values whe...
558 citations
TL;DR: Eplerenone was as effective in reducing SBP and DBP in the high renin patient, but more effective than losartan in the low renin patients, and was superior to placebo in white patients.
219 citations
TL;DR: The hypothesis that atrial natriuretic peptide protects against pressure overload–induced cardiac hypertrophy and remodeling by negative modulation of genes involved in extracellular matrix deposition is supported.
Abstract: This study tested the hypothesis that atrial natriuretic peptide has direct antihypertrophic actions on the heart by modulating expression of genes involved in cardiac hypertrophy and extracellular matrix production. Hearts of male, atrial natriuretic peptide–null and control wild-type mice that had been subjected to pressure overload after transverse aortic constriction and control unoperated hearts were weighed and subjected to microarray, Northern blot, and immunohistochemical analyses. Microarray and Northern blot analyses were used to identify genes that are regulated differentially in response to stress in the presence and absence of atrial natriuretic peptide. Immunohistochemical analysis was used to identify and localize expression of the protein products of these genes. Atrial natriuretic peptide–null mice demonstrated cardiac hypertrophy at baseline and an exaggerated hypertrophic response to transverse aortic constriction associated with increased expression of the extracellular matrix molecule...
169 citations
TL;DR: Although C-reactive protein is clearly linked to increased cardiovascular disease risk in women, the hormone-induced rise in this biomarker is not associated with increased risk and may be related to a first-pass effect of C- reactive protein production in the liver after oral estrogen absorption.
Abstract: Inflammation plays a central role in the pathogenesis of many forms of vascular disease, including atherosclerosis. Atherogenesis begins with endothelial damage, and the damaged endothelium expresses adhesion molecules, chemokines, and proinflammatory cytokines that direct atherosclerotic plaque formation and spill into the circulation as biomarkers of atherosclerotic disease risk. Menopausal hormone therapy, including a variety of estrogen preparations with or without a progestin, has negative modulatory effects on most of these soluble inflammatory markers, including E-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and tumor necrosis factor-α, inconsistent effects on interleukin-6, and stimulatory effects on transforming growth factor-β, a vasoprotective cytokine. In contrast, C-reactive protein, a circulating proinflammatory cytokine produced in both liver and atherosclerotic arteries, increases in response to oral conjugated estrogens but not to transdermal estrogen. Although C-reactive protein is clearly linked to increased cardiovascular disease risk in women, the hormone-induced rise in this biomarker is not associated with increased risk and may be related to a first-pass effect of C-reactive protein production in the liver after oral estrogen absorption. Many important questions about the effects of ovarian hormones on vascular inflammation and the pathogenesis of vascular disease cannot be answered in human subjects. Insights from fundamental mechanistic studies in animal models are needed to delineate the cellular/molecular events that determine whether these hormones protect or injure blood vessels.
76 citations
TL;DR: A subgroup analysis in the LIFE study was performed to determine whether angiotensin II AT1-receptor antagonism with losartan reduces cardiovascular morbidity and mortality, compared with active therapy with established -blockerbased therapy, in hypertensive participants with electrocardiogram-defined LVH.
Abstract: In hypertensive patients without clinically evident vascular disease, losartan and atenolol were equally effective in reducing blood pressure, but losartan was more effective in preventing cardiova...
74 citations
TL;DR: Eplerenone therapy was effective in the treatment of mild to moderate hypertension over a 14-month period, either as monotherapy or in combination with another antihypertensive agent.
70 citations
TL;DR: Homozygous deletion of the pro‐atrial natriuretic peptide (Nppa) gene (ANP–/–) has been associated with both cardiac hypertrophy and salt‐sensitive hypertension in mice, suggesting that cardiachypertrophy in ANP-/– mice may be related, at least in part, to increased afterload.
Abstract: 1. Homozygous deletion of the pro-atrial natriuretic peptide (Nppa) gene (ANP-/-) has been associated with both cardiac hypertrophy and salt-sensitive hypertension in mice, suggesting that cardiac hypertrophy in ANP-/- mice may be related, at least in part, to increased afterload. 2. To test the hypothesis that cardiac hypertrophy in ANP-/- mice is independent of blood pressure, male ANP-/- and wild-type ANP+/+ mice were fed a low (0.05%) or basal (0.55%) NaCl diet. Five weeks later, mean arterial pressure (MAP) was measured in conscious mice; the whole heart, atria, left and right ventricles (LV and RV, respectively), brain, lung, kidney, liver and spleen were weighed and fixed for histological analysis. Separate groups of mice were subjected to echocardiographic examination under tribromoethanol anaesthesia. 3. Mean arterial pressure and atrial, LV and RV mass were greater in ANP-/- mice than in ANP+/+ mice fed the basal salt diet. Salt depletion equalized MAP in the two genotypes, but did not alter the relative cardiac hypertrophy in ANP-/- mice. The ANP-/- mice had significant LV cardiomyocyte hypertrophy when fed either basal or low-salt diets. 4. Left ventricle chamber dimensions did not differ between genotypes, but were significantly reduced in mice fed the low-salt diet; LV posterior wall and septal thickness were greater in ANP-/- than ANP+/+ mice and were not altered by diet, indicating a concentric pattern of LV hypertrophy in ANP-/- mice. Left ventricle function (cardiac output, stroke volume, ejection fraction, circumferential wall stress and velocity of circumferential wall shortening) did not differ between strains on either diet; circumferential wall stress was reduced in the low-salt groups; other functional parameters were not altered by diet. 5. These findings indicate that ANP deletion results in cardiomyocyte hypertrophy and biventricular hypertrophy independent of blood pressure, supporting the concept that ANP has direct antihypertrophic effects in the heart.
TL;DR: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), sponsored by the National Heart, Lung, and Blood Institute, is the largest outcome trial of antihypertensive treatment ever carried out and the only large blood pressure (BP) trial to be carried out in a US population in the past decade.
Abstract: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), sponsored by the National Heart, Lung, and Blood Institute (NHLBI), is the largest outcome trial of antihypertensive treatment ever carried out and the only large blood pressure (BP) trial to be carried out in a US population in the past decade.1 The rationale for ALLHAT, which was designed in the early 1990s, was the urgent need to determine which of the several classes of antihypertensive drugs that had been developed and released for clinical use was most effective in preventing coronary heart disease (CHD), defined as fatal CHD and nonfatal myocardial infarction.2
The only randomized trials that had previously compared representatives of the antihypertensive drug classes, the Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents3 and the Treatment of Mild Hypertension Study (TOMHS),4 showed BP reductions with all classes but were not powered to evaluate CHD outcomes. Further, prior outcome trials had shown that the reduction in CHD event rates with antihypertensive treatment was less than expected based on epidemiologic data.5 Adverse effects of study drugs, particularly diuretics, including hypokalemia, hypomagnesemia, hyperuricemia, hyperlipidemia, insulin resistance, and ventricular ectopic activity, had been adduced to account for the disappointing outcomes of earlier trials by offsetting the beneficial effects of BP reduction.6,7 To further complicate the picture, benefits beyond BP reduction had been attributed to some antihypertensive drug classes, ie, improved survival and reduced morbidity in persons with heart failure or left ventricular dysfunction treated with angiotensin-converting enzyme (ACE) inhibitors8–10 and improved insulin sensitivity and lipid profiles with α-blocker treatment.11 In contrast, another antihypertensive drug class, the dihydropyridine calcium channel blockers (CCBs), had been associated with unfavorable outcomes in patients with acute myocardial infarction or unstable angina.12 There were no data …
TL;DR: The results provide novel finding that ET-AR in PASMCs in vitro is unresponsive to hypoxia per se but is robustly simulated by tyrosine kinase receptor-associated growth factors (FGF-1, FGF-2, PDGF-BB) that themselves are stimulated by Hypoxia in lung.
Abstract: We have previously demonstrated that endothelin (ET)-1 and its subtype A receptor (ET-AR) expression are increased in lung under hypoxic conditions and that activation of ET-AR by ET-1 is a major mediator of hypoxia-induced pulmonary hypertension in the rat. The present study tested the hypothesis that the hypoxia-responsive tyrosine kinase receptor-activating growth factors fibroblast growth factor (FGF)-1, FGF-2, and platelet-derived growth factor (PDGF)-BB stimulate expression of the ET-AR in pulmonary arterial smooth muscle cells (PASMCs). Quiescent rat PASMCs were incubated under hypoxia (1% O2), or with FGF-1, FGF-2, PDGF-BB, vascular endothelial growth factor, ET-1, angiotensin II, or atrial natriuretic peptide under normoxic conditions for 24 h. FGF-1 and -2 and PDGF-BB, but not hypoxia, vascular endothelial growth factor, ET-1, angiotensin II, or atrial natriuretic peptide, significantly increased ET-AR mRNA levels. FGF-1-induced ET-AR expression was inhibited by FGF-receptor inhibitor PD-166866, MEK inhibitor U-0126, transcription inhibitor actinomycin D, and translation inhibitor cycloheximide. In contrast, the stimulatory effect of FGF-1 on ET-AR mRNA expression was not altered by PI3 kinase, PKA, PKC, or adenylate cyclase inhibitors. PASMC ET-AR gene transcription, assessed by nuclear-runoff analysis, was increased by FGF-1. These results provide novel finding that ET-AR in PASMCs in vitro is unresponsive to hypoxia per se but is robustly simulated by tyrosine kinase receptor-associated growth factors (FGF-1, FGF-2, PDGF-BB) that themselves are stimulated by hypoxia in lung. This observation suggests a novel signaling mechanism that may be responsible for overexpression of ET-AR in lung, and may contribute to the hypoxia-induced pulmonary vasoconstriction, hypertension, and vascular remodeling in hypoxia-adapted animal.
TL;DR: It is demonstrated that in the anterior hypothalamic nucleus of the mouse (and probably in the rat) &agr;2A-adrenergic receptors mediate both sympathoinhibitory responses to &agR;2-ADrenergic receptor agonists and the action of atrial natriuretic peptide.
Abstract: In the rat, activation of α 2 -adrenergic receptors in the anterior hypothalamic nucleus inhibits sympathetic nervous system activity Furthermore, local release of atrial natriuretic peptide inhibits norepinephrine release in this nucleus, blocking local activation of α 2 -adrenergic receptors, and thereby contributes to NaCl-sensitive hypertension in spontaneously hypertensive rats To further test the specificity of this mechanism, either α 2 -adrenergic receptor agonists or atrial natriuretic peptide was microinjected into anterior hypothalamic nucleus of conscious C57BL/6 mice in which the α 2 -adrenergic receptor was functionally deleted by a single point mutation (n=10 per group) In control mice, microinjection of either clonidine or guanabenz (10 −3 to 10 −7 mol/L) caused a rapid fall in mean arterial pressure that lasted for several minutes In the knockout mice there was no response to the injection of either dose of either agonist Microinjection of atrial natriuretic peptide (10 −6 to 10 −7 mol/L) caused a rapid increase in mean arterial pressure (82±13 and 655±12 mm Hg, respectively) in the control mice that was similar to the responses previously observed in Wistar-Kyoto rats In contrast, the microinjections did not significantly alter mean arterial pressure in the knockout mice These experiments demonstrate that in the anterior hypothalamic nucleus of the mouse (and probably in the rat) α 2A -adrenergic receptors mediate both sympathoinhibitory responses to α 2 -adrenergic receptor agonists and the action of atrial natriuretic peptide
TL;DR: Restenosis after revascularization procedures is accelerated in persons with type 2 diabetes, and the risk of heart attack and stroke is increased.
Abstract: BACKGROUND Restenosis after revascularization procedures is accelerated in persons with type 2 diabetes. AIM The current study tested the hypothesis that the neointimal response to endovascular injury is enhanced in female obese Zucker (OZ) rats, a model of type 2 diabetes. METHODS Animals were randomized to receive either a standard diet (SD) or a diabetogenic diet (DD) for 6 weeks. Four weeks later, balloon injury of the right common carotid artery was induced. All rats were euthanized 2 weeks after injury. Lean Zucker (LZ) rats served as controls. RESULTS At the time of death, plasma glucose was elevated in OZ rats fed a SD (208 +/- 13 mg/dl) and a DD (288 +/- 21 mg/dl) compared to corresponding LZ rats (SD: 153 +/- 8; DD: 132 +/- 7 mg/dl). The ratio of high-density lipoprotein cholesterol (HDLc) to total cholesterol (Totc), an index of atherogenicity, was reduced in OZ rats on both diets (SD: 0.77 +/- 0.06; DD: 0.80 +/- 0.09) compared to LZ controls (SD: 1.11 +/- 0.02; DD: 1.20 +/- 0.05). Histomorphometric analysis of injured arteries showed that the intima to media (I : M) ratio was significantly increased in OZ (1.37 +/- 0.07) compared to LZ (0.79 +/- 0.08) rats. Elevations in plasma glucose and triglycerides (Tg) correlated positively and decreases in HDLc negatively with an increased I : M ratio. Administration of the DD did not further enhance the I : M ratio in LZ (0.87 +/- 0.06) or OZ (1.29 +/- 0.09) rats. CONCLUSIONS These results suggest that neointima formation following endoluminal injury of the carotid artery is enhanced at an early stage in the development of diabetes mellitus.
TL;DR: Data is analyzed from the HERS study to identify risk factors for myocardial infarction and CHD death and describe use of secondary prevention strategies by the participants and to identify Elevated lipoprotein(a) levels emerged as a novel risk factor only in the placebo group.
Abstract: In this issue, Vittinghoff and colleagues analyze data from the Heart and Estrogen/progestin Replacement Study to identify risk factors for myocardial infarction and death from coronary heart disea...
TL;DR: The gender initiative, a provocative series addressing gender differences in the surgical treatment of cardiac, vascular, and thoracic disease, continues with editorials addressing long-term outcomes of coronary artery bypass grafting in women, with an encouraging trend toward improved CABG outcomes in women.
01 Jan 2003
TL;DR: The LIFE study suggests that the mechanism of stroke prevention with losartan extends beyond its blood-pressure-lowering effects, and a reduction in stroke was an important contributor to the benefit in the composite outcome observed in patients with diabetes or isolated systolic hypertension.