Showing papers by "Suzanne Oparil published in 2005"

Reduction in Albuminuria Translates to Reduction in Cardiovascular Events in Hypertensive Patients. Losartan Intervention for Endpoint Reduction in Hypertension Study

Abstract: Few data are available to clarify whether changes in albuminuria over time translate to changes in cardiovascular risk. The aim of the present study was to examine whether changes in albuminuria during 4.8 years of antihypertensive treatment were related to changes in risk in 8206 patients with hypertension and left ventricular hypertrophy in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Urinary albumin/creatinine ratio (UACR) was measured at baseline and annually. Time-varying albuminuria was closely related to risk for the primary composite end point (ie, when UACR decreased during treatment, risk was reduced accordingly). When the population was divided according to median baseline value (1.21 mg/mmol) and median year 1 UACR (0.67 mg/mmol), risk increased stepwise and significantly for the primary composite end point from those with low baseline/low year 1 (5.5%), to low baseline/high year 1 (8.6%), to high baseline/low year 1 (9.4%), and to high baseline/high year 1 (13.5%) values. Similar significant, stepwise increases in risk were seen for the components of the primary composite end point (cardiovascular mortality, stroke, and myocardial infarction). The observation that changes in UACR during antihypertensive treatment over time translated to changes in risk for cardiovascular morbidity and mortality was not explained by in-treatment level of blood pressure. We propose that monitoring of albuminuria should be an integrated part of the management of hypertension. If albuminuria is not decreased by the patient's current antihypertensive and other treatment, further intervention directed toward blood pressure control and other modifiable risks should be considered.

Stroke Reduction in Hypertensive Adults With Cardiac Hypertrophy Randomized to Losartan Versus Atenolol The Losartan Intervention For Endpoint Reduction in Hypertension Study

Abstract: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study showed that treatment with the angiotensin II type-1 receptor antagonist losartan reduces overall stroke risk compared with conventional therapy with the beta-blocker atenolol. We conducted secondary analyses in LIFE to determine the extent to which the cerebrovascular benefits of losartan apply to different clinical subgroups and stroke subtypes and to assess the dependence of these benefits on baseline and time-varying covariates. Among 9193 hypertensive patients with electrocardiographic evidence of left ventricular hypertrophy, random allocation to losartan-based treatment lowered the risk of fatal (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.43 to 0.96; P=0.032) and atherothrombotic stroke (HR, 0.72; 95% CI, 0.59 to 0.88; P=0.001) compared with atenolol-based therapy. Although comparable risk reductions occurred for hemorrhagic and embolic stroke, these were not statistically significant. The number of neurological deficits per stroke was similar, but there were fewer strokes in the losartan group for nearly every level of stroke severity. Effects were consistent in all clinical subgroups except for those defined by age and ethnicity. The benefits of losartan on all strokes were independent of baseline and time-varying risk factors, including blood pressure. The number needed to treat for 5 years to prevent 1 stroke was 54 for the average participant, declining to 25, 24, and 9 for patients with cerebrovascular disease, isolated systolic hypertension, and atrial fibrillation, respectively. In conclusion, substantial cerebrovascular benefit could be realized with the institution of losartan-based therapy over conventional therapy among hypertensive patients with left ventricular hypertrophy across the spectrum of cardiovascular risk.

Gender and blood pressure.

Abstract: The prevalence, impact, and control of hypertension differ between the sexes in the US population. In addition, pregnancy, oral contraceptive use, and menopausal hormone therapy May influence blood pressure regulation in ways that have therapeutic implications for some women. Whether gender should be a significant consideration in the choice of individual antihypertensive drugs continues to be a topic of intense interest and debate. This brief review will discuss recent findings that bear on considerations of gender in the management of hypertension, particularly among older women.

Endothelin-A Receptor Blockade Prevents and Partially Reverses Neonatal Hypoxic Pulmonary Vascular Remodeling

Abstract: Hypoxia-induced pulmonary vascular remodeling (HPVR) may lead to persistent pulmonary hypertension of the newborn or cor pulmonale. Endothelin-1 (ET-1), via endothelin-A (ETA) receptor activation, mediates hypoxic pulmonary vasoconstriction. Our objectives were to develop a newborn mouse model of HPVR and to test the hypothesis that ETA blockade would prevent and reverse HPVR in this model. C57BL/6 mice (n = 64) were exposed to 12% oxygen (HYP group) or room air (RA group) from birth to 2 wk of age. The mice were injected intraperitoneally daily with either BQ-610 (ETA blocker) or vehicle (cottonseed oil) from birth (prevention study) or from 6 d of age (reversal study). HPVR was assessed histologically by pulmonary vascular morphometry by an examiner masked to study group, and by measurement of the right ventricle to left ventricle (RV/LV) thickness ratio. Hypoxia increased medial wall thickness (%WT) in pulmonary arteries <100 μm in diameter and RV/LV thickness ratio. BQ-610 prevented the hypoxia-induced increase in %WT and RV/LV thickness ratio when given from birth, and later therapy partially reversed the hypoxia-induced increase in %WT but not RV/LV thickness ratio. These data show that in the newborn mouse model, chronic hypoxia leads to HPVR that can be completely prevented and partially reversed by ETA blockade. These results indicate that ET-1, acting via ETA receptors, is a mechanism of pathophysiologic significance underlying neonatal HPVR. Development of this newborn mouse model of HPVR facilitates investigation of mechanisms underlying this important and severe disease entity in human infants.

Fixed-dose combinations in the management of hypertension: defining the place of angiotensin receptor antagonists and hydrochlorothiazide.

Abstract: We discuss combination therapy with angiotensin receptor antagonists (angiotensin receptor blockers; ARBs) and thiazide diuretics in light of the independent actions of both types of agents, and the adverse effects of both agents independently and in the context of the physiologic synergy achieved in using these agents together. ARBs counteract many of the adverse events associated with the use of thiazide diuretics and have been shown to reduce the occurrence of new-onset diabetes mellitus. We also review outcome trials in patients with hypertension (such as LIFE [Losartan Intervention For Endpoint reduction in hypertension], VALUE [Valsartan Antihypertensive Long-term Use Evaluation], and SCOPE [Study on COgnition and Prognosis in the Elderly]), in which losartan, valsartan, and candesartan cilexetil were used in combination with hydrochlorothiazide. Fixed combination ARB/hydrochlorothiazide agents make sense as initial therapy for patients in whom BP is >20/ 10mm Hg above goal.

Body Build and Risk of Cardiovascular Events in Hypertension and Left Ventricular Hypertrophy The LIFE (Losartan Intervention For Endpoint reduction in hypertension) Study

Abstract: Body build and risk of cardiovascular events in hypertension and left ventricular hypertrophy : the LIFE (Losartan Intervention For Endpoint reduction in hypertension) study.

The Effects of Losartan Compared to Atenolol on Stroke in Patients With Isolated Systolic Hypertension and Left Ventricular Hypertrophy. The LIFE Study

Abstract: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study reported that a losartan-based antihypertensive regimen reduced cardiovascular morbidity and mortality (composite of cardiovascular death, stroke, and myocardial infarction) more than therapy based on atenolol in patients with left ventricular hypertrophy and isolated systolic hypertension (ISH). Patients aged 55-80 years with blood pressures 160-200/<90 mm Hg were followed for a mean of 4.7 years. Blood pressure was similarly reduced in the losartan (n=660) and atenolol (n=666) ISH groups. There were 88 (6.6%) patients who experienced a stroke, 18 of which were fatal. Of patients experiencing strokes, 72.7% had an ischemic stroke. ISH patients in LIFE compared to the non-ISH group had a higher incidence of any stroke and embolic stroke, and similar incidences of fatal, atherosclerotic, and hemorrhagic/other strokes. The incidence of any stroke (40% risk reduction [RR], p=0.02), fatal stroke (70% RR, p=0.035), and atherothrombotic stroke (45% RR, p=0.022) was significantly lower in losartan-treated compared to the atenolol-treated patients. The 36% RR for embolic strokes in the losartan group was not statistically significantly (p=0.33) different from the atenolol group. These data suggest that losartan-based treatment is more effective than an atenolol-based treatment for patients with ISH and a high risk for stroke.

Pulse pressure and effects of losartan or atenolol in patients with hypertension and left ventricular hypertrophy.

Abstract: In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, the primary composite end point of cardiovascular death, stroke, and myocardial infarction was reduced by losartan versus atenolol in patients with hypertension and left ventricular hypertrophy. The objective of this post hoc analysis was to determine the influence of pulse pressure on outcome. Patients were divided into quartiles of baseline pulse pressure. Cox regression, including baseline Framingham risk score as a covariate, was used to compare risk in the quartiles. In the atenolol group, there were significantly higher risks in the highest versus lowest quartile for the composite end point 28% (confidence interval [CI], 2% to 62%; P=0.035), stroke 84% (CI, 32% to 157%; P 0.2), stroke -5% (CI, -34% to 37%; P>0.2), myocardial infarction 30% (CI, -13% to 94%; P>0.2), and total mortality 32% (CI, -1% to 76%; P=0.062). In patients with hypertension and left ventricular hypertrophy in the LIFE study, there were significantly higher risks, adjusted for the Framingham risk score, for the primary composite end point, stroke, and total mortality in the highest versus lowest quartile of pulse pressure with atenolol-based treatment. The risks in the losartan group also increased with increasing pulse pressure quartile, but were lower than those in the atenolol group, and were not significant.

Estrogen Treatment Abrogates Neointima Formation in Human C-Reactive Protein Transgenic Mice

Abstract: Objective— Previously we established that the vascular injury response was attenuated in ovariectomized wild-type rodents treated with 17β-estradiol (E2). We also showed that the response to acute vascular injury in transgenic mice expressing human C-reactive protein (CRPtg) is exaggerated compared with their nontransgenic (NTG) counterparts. Herein we tested the hypothesis that E2 modulates vascular injury in the CRPtg mouse. Methods and Results— Intact (INT) or ovariectomized (OVX) CRPtg and NTG, treated with E2 or vehicle, had their right common carotid artery ligated. Resultant neointima formation was exaggerated in CRPtg compared with NTG, whether INT or OVX, but was prevented in both genotypes by E2. Expression of human CRP protein (immunohistochemical analysis) and mRNA (laser microdissection followed by real-time quantitative RT-PCR) was detected in the neointima of OVX CRPtg and was greatly diminished by E2 treatment. CRP was not detected in uninjured arteries or in the media of injured arteries,...

Ethnicity and blood pressure.

Abstract: The prevalence, impact, and control of hypertension differ across racial and ethnic subgroups in the United States population. Whether race/ethnicity should be a significant consideration in the choice of individual antihypertensive drugs continues to be a topic of intense interest and debate. This brief review will discuss recent findings that bear on the management of hypertension in these special patient groups.

Targeting the renin-angiotensin system for the reduction of cardiovascular outcomes in hypertension: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

Abstract: Targeting the renin-angiotensin system for the reduction of cardiovascular outcomes in hypertension : angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

New‐Onset Diabetes in Treated Hypertensive Patients‐Is It Clinically Significant?

Abstract: Following a symposium on hypertension in Chicago on September 22, 2004, a roundtable discussion was held to discuss one of the emerging controversies in hypertension management, specifically the occurrence of new-onset diabetes in treated nondiabetic hypertensive patients. How frequent is it? Is it just part of the metabolic syndrome that is common in hypertension, or do certain medications predispose patients to hyperglycemia? The question of the effect of other specific medications on insulin sensitivity and the possible reduction in the occurrence of diabetes in the hypertensive population with these agents was also discussed. Dr. Marvin Moser of the Yale University School of Medicine, New Haven, CT, moderated the discussion with Dr. James Sowers of the Missouri College of Medicine, Columbia, MO, Dr. Suzanne Oparil of the University of Alabama at Birmingham, Birmingham, AL, and Dr. Henry Black of the Rush College of Medicine, Chicago, IL.

Conflicting and confusing data from the hypertension treatment trials: whom and what should you believe?

Abstract: Following a hypertension symposium in Atlanta, GA on March 30, 2005, a roundtable was convened to discuss a confusing topic: "Conflicting Information from the Hypertension Treatment Trials: Whom and What Should You Believe?" Dr. Marvin Moser, Clinical Professor of Medicine at the Yale University School of Medicine, New Haven, CT, moderated the panel discussion. Participants included Dr. Thomas Giles, Professor of Medicine at Louisiana State University Health Sciences Center, New Orleans, LA and President of the American Society of Hypertension, and Dr. Suzanne Oparil, Professor of Medicine at the University of Alabama at Birmingham, Birmingham, AL.

366 ATRIAL NATRIURETIC PEPTIDE AND CYCLIC GUANOSINE MONOPHOSPHATE BLOCK THE STIMULATORY EFFECTS OF TRANSFORMING GROWTH FACTOR β1 ON EXTRACELLULAR MATRIX MESSENGER RIBONUCLEIC ACID EXPRESSION IN CULTURED PULMONARY ARTERY SMOOTH MUSCLE CELLS

Abstract: Our previous studies demonstrated that atrial natriuretic peptide (ANP) has a modulatory role in the development of hypoxia-induced pulmonary vascular remodeling in rats and mice. We have also shown that the expression of periostin (PN), a novel extracellular matrix (ECM)/adhesion molecule, and osteopontin (OPN) were stimulated by growth factors such as fibroblast growth factor 1 and angiotensin II in cultured rat pulmonary artery smooth muscle cells (PASMCs). Transforming growth factor (TGF)-β1 is a potent profibrogenic factor that stimulates the expression of ECM in the pulmonary vasculature under stress conditions. The current study tested the hypothesis that TGF-β1 also increases PN and OPN expression in isolated PASMCs, and ANP or cyclic guanosine monophosphate (cGMP) act as antifibrogenic factors that block the stimulatory effects of TGF-β1 on ECM molecules expression. Rat PASMCs were incubated to subconfluence in complete DMEM medium, serum deprived for 24 hours, then treated with TGF-β1 at concentrations of 0.1, 1, or 5 ng/mL for 24 hours. To study the interaction between ANP, cGMP and TGF-β1 on ECM expression, PASMCs were pretreated with ANP (1 μM), cGMP (1 mM) or vehicle for 1 hour, and then exposed to TGF-β1 (1 ng/mL) for 24 hours. Steady state mRNA levels for ECM molecules PN, OPN, collagen I and III and 18S RNA were assessed by Northern blot analysis. TGF-β1 enhanced expression of PN and OPN, but not collangen I or III, in a dose-dependent fashion. ANP or cGMP decreased the baseline levels and significantly attenuated the TGF-β1-induced expression of PN and OPN in PASMCs. These results suggest that ANP and its second messenger cGMP have antifibrogenic effect by blocking TGF-β1-induced ECM expression in PASMCs, which may play an important role in the pulmonary vascular remodeling. (Fig. 1, Fig. 2)