The effect of losartan versus atenolol on cardiovascular morbidity and mortality in patients with hypertension taking aspirin: the Losartan Intervention for Endpoint Reduction in hypertension (LIFE) study.

Objectives: We conducted a subgroup analysis in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study to determine whether aspirin interacted with the properties of losartan, an angiotensin-II receptor antagonist.

Background: Negative interactions between angiotensin-converting enzyme inhibitors and aspirin have been reported. There are no data reported from clinical trials about possible interactions between angiotensin-II receptor antagonists and aspirin.

Ethnicity and blood pressure.

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.

Estrogen treatment abrogates neointima formation in human C-reactive protein transgenic mice.

Objective: Previously we established that the vascular injury response was attenuated in ovariectomized wild-type rodents treated with 17beta-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.

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

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.

Gender and blood pressure.

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.

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

Background: Obesity may independently increase the risk of adverse events in hypertension with target-organ damage. We investigated whether body build was independently associated with higher cardiovascular risk and whether treatment with losartan relative to atenolol influenced the impact of body build on the primary composite end point of cardiovascular death, stroke, and myocardial infarction and on cardiovascular death in patients with hypertension and left ventricular hypertrophy in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study.

Methods And Results: The population of 9079 patients was divided as follows: thin (body mass index [BMI] <20 kg/m2, 2%), normal weight (BMI 20 to 24.

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

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.

The effects of losartan compared to atenolol on stroke in patients with isolated systolic hypertension and left ventricular hypertrophy. The LIFE study.

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.

Endothelin-A receptor blockade prevents and partially reverses neonatal hypoxic pulmonary vascular remodeling.

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 (ET(A)) receptor activation, mediates hypoxic pulmonary vasoconstriction. Our objectives were to develop a newborn mouse model of HPVR and to test the hypothesis that ET(A) blockade would prevent and reverse HPVR in this model.

Losartan benefits over atenolol in non-smoking hypertensive patients with left ventricular hypertrophy: the LIFE study.

We studied the impact of smoking in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, which showed superiority of losartan over atenolol for reduction of composite risk of cardiovascular death, stroke and myocardial infarction in hypertensives with left ventricular hypertrophy. We compared hazard ratios in 4656 never-smokers, and 3033 previous and 1499 current smokers, adjusting for gender, age, alcohol intake, exercise and race. Composite endpoint rate was higher in previous (28/1000 years), as well as current (39/1000 years) smokers than in never-smokers (21/1000 years).

Role of angiotensin receptor blockers as monotherapy in reaching blood pressure goals.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure emphasizes the urgent need to lower blood pressure (BP) to a goal of <140/90 mm Hg in patients with uncomplicated hypertension and to <130/80 mm Hg in high-risk patients, such as those with diabetes mellitus or chronic kidney disease, to prevent cardiovascular disease morbidity and mortality. Consequently, a meaningful measure of the efficacy of an antihypertensive therapy is its ability to achieve BP reduction to below the recommended BP goals. Angiotensin II receptor blockers (ARB) are highly effective antihypertensive agents with excellent tolerability profiles similar to those of placebo.

New-onset diabetes in treated hypertensive patients--is it clinically significant? Roundtable discussion.

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.

Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: losartan intervention for endpoint reduction in hypertension study.

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.

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

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.

Advanced glycation end-product cross-link breakers. A novel approach to cardiovascular pathologies related to the aging process.

Advanced glycation end product (AGE) formation that occurs with aging and diabetes leads to the cross-linking of proteins and subsequent changes in the physicochemical properties of tissues. Cellular responses to AGE that lead to either pathological conditions or removal of AGE are mediated by a number of receptors that have been identified on various cell types such as macrophages, endothelial cells, and smooth-muscle cells. Mechanisms by which AGE affect the cardiovascular system include AGE cross-linking of long-lived proteins such as collagen and elastin and altered cellular responses.

Roundtable discussion: blood pressure goal attainment: meeting the challenge of the JNC 7's blood pressure goals and the role of renin-angiotensin-aldosterone system blockade.

This roundtable discussion, held in December 2003, was convened to discuss the impact of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure's (JNC 7) challenging blood pressure goal objectives for the clinical management of hypertensive patients. The discussion was moderated by Michael Weber, MD, of the State University of New York Downstate College of Medicine in New York City. Participants included leading experts in the field Joseph Izzo, Jr.

Stroke reduction in hypertensive adults with cardiac hypertrophy randomized to losartan versus atenolol: the Losartan Intervention For Endpoint reduction in hypertension study.

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.

Atrial natriuretic peptide dose-dependently inhibits pressure overload-induced cardiac remodeling.

We hypothesized that a single copy of the proatrial natriuretic peptide gene (Nppa+/-) would not be adequate to protect heterozygous mice against exaggerated cardiac hypertrophy and remodeling after pressure-overload stress. Nppa+/+, Nppa+/-, and Nppa-/- mice were subjected to sham surgery or transverse aortic constriction and fed a basal salt diet. Heart weight varied inversely with Nppa gene load by 1 week after either surgery.

Interview with Suzanne Oparil, MD. Interview by Marvin Moser, MD.

In this month's issue of The Journal of Clinical Hypertension, we highlight another hypertension icon. Dr. Suzanne Oparil is a clinical cardiologist who has been involved in the investigation of some of the fundamental mechanisms of vascular disease.

Estrogen modulates inflammatory mediator expression and neutrophil chemotaxis in injured arteries.

Background: We have previously shown that estrogen (17beta-estradiol; E2) inhibits neointima formation and migration of leukocytes, particularly neutrophils, into rat carotid arteries after acute endoluminal injury. This study tested the hypothesis that E2 inhibits expression of adhesion molecules, chemokines, and proinflammatory cytokines in rat carotid arteries in the early hours after balloon injury, thus attenuating the stimulus for leukocyte entry and negatively modulating the injury response.

Methods And Results: Ovariectomized (OVX) rats were randomly assigned to treatment with E2 or vehicle (V) and subjected to balloon injury of the right carotid artery.

Does albuminuria predict cardiovascular outcome on treatment with losartan versus atenolol in hypertension with left ventricular hypertrophy? A LIFE substudy.

Objectives: To examine a possible relationship between baseline albuminuria and effect of losartan versus atenolol on cardiovascular (CV) events in hypertensive patients with left ventricular hypertrophy, the effect of losartan versus atenolol on albuminuria, and whether the benefits of losartan versus atenolol could be explained by influence of losartan on albuminuria.

Design: Double-blind, randomized, controlled trial of 4.8 years.