Showing papers by "Marc A. Pfeffer published in 1999"
TL;DR: Among survivors of myocardial infarction on standard therapy plus placebo, CRP levels tended to increase over 5 years of follow-up, and these data further support the potential for nonlipid effects of this agent.
Abstract: Background—Elevated plasma concentrations of C-reactive protein (CRP) are associated with increased cardiovascular risk. We evaluated whether long-term therapy with pravastatin, an agent that reduces cardiovascular risk, might alter levels of this inflammatory parameter. Methods and Results—CRP levels were measured at baseline and at 5 years in 472 randomly selected participants in the Cholesterol and Recurrent Events (CARE) trial who remained free of recurrent coronary events during follow-up. Overall, CRP levels at baseline and at 5 years were highly correlated (r50.60, P,0.001). However, among those allocated to placebo, median CRP levels and the mean change in CRP tended to increase over time (median change, 14.2%; P50.2 and mean change, 10.07 mg/dL; P50.04). By contrast, median CRP levels and the mean change in CRP decreased over time among those allocated to pravastatin (median change, 217.4%; P50.004 and mean change, 20.07 mg/dL; P50.002). Thus, statistically significant differences were observed at 5 years between the pravastatin and placebo groups in terms of median CRP levels (difference, 221.6%; P50.007), mean CRP levels (difference, 237.8%; P50.002), and absolute mean change in CRP (difference, 20.137 mg/dL; P50.003). These effects persisted in analyses stratified by age, body mass index, smoking status, blood pressure, and baseline lipid levels. Attempts to relate the magnitude of change in CRP to the magnitude of change in lipids in both the pravastatin and placebo groups did not reveal any obvious relationships. Conclusions—Among survivors of myocardial infarction on standard therapy plus placebo, CRP levels tended to increase over 5 years of follow-up. In contrast, randomization to pravastatin resulted in significant reductions in this inflammatory marker that were not related to the magnitude of lipid alterations observed. Thus, these data further support the potential for nonlipid effects of this agent. (Circulation. 1999;100:230-235.)
1,480 citations
TL;DR: Pulse pressure, an easily measurable correlate of pulsatile hemodynamic load, is an independent predictor of risk of CHF in this elderly cohort of men and women.
Abstract: ContextArterial stiffness increases with age. Thus, pulse
pressure, an index of arterial stiffening, may predict congestive heart
failure (CHF) in the elderly.ObjectiveTo study prospectively the association between pulse
pressure and risk of CHF.DesignProspective cohort study.SettingThe community-based East Boston Senior Health Project,
East Boston, Mass.PatientsA total of 1621 men and women (mean [SD] age, 77.9
[5.0] years) free of CHF who had blood pressure measurements taken in
1988-1989 and were followed up for 3.8 years.Main Outcome MeasureIncidence of CHF as ascertained by hospital
discharge diagnosis (n=208) and death certificates
(n=13).ResultsAfter controlling for age, sex, mean arterial pressure,
history of coronary heart disease, diabetes mellitus, atrial
fibrillation, valvular heart disease, and antihypertensive medication
use, pulse pressure was an independent predictor of CHF. For each 10-mm
Hg elevation in pulse pressure, there was a 14% increase in risk of
CHF (95% confidence interval, 1.05-1.24;
P=.003). Those in the highest tertile of pulse
pressure (>67 mm Hg) had a 55% increased risk of CHF
(P=.02) compared with those in the lowest
(<54 mm Hg). Pulse pressure was more predictive than systolic blood
pressure alone and was independent of diastolic blood pressure.ConclusionPulse pressure, an easily measurable correlate of
pulsatile hemodynamic load, is an independent predictor of risk of CHF
in this elderly cohort.
550 citations
TL;DR: In this article, the authors used prospectively defined criteria to assess the incidence of stroke, a prespecified secondary end point, and transient ischemic attack (TIA) over a median 5-year follow-up period.
Abstract: Background—The role of lipid modification in stroke prevention is controversial, although increasing evidence suggests that HMG-CoA reductase inhibition may reduce cerebrovascular events in patients with prevalent coronary artery disease. Methods and Results—To test the hypothesis that cholesterol reduction with pravastatin may reduce stroke incidence after myocardial infarction, we followed 4159 subjects with average total and LDL serum cholesterol levels (mean, 209 and 139 mg/dL, respectively) who had sustained an infarction an average of 10 months before study entry and who were randomized to pravastatin 40 mg/d or placebo in the Cholesterol and Recurrent Events (CARE) trial. Using prospectively defined criteria, we assessed the incidence of stroke, a prespecified secondary end point, and transient ischemic attack (TIA) over a median 5-year follow-up period. Patients were well matched for stroke risk factors and the use of antiplatelet agents (85% of subjects in each group). Compared with placebo, prav...
412 citations
TL;DR: Data provide strong evidence of an association of increased conduit vessel stiffness, as indicated by increased pulse pressure, with stroke and total mortality, independent of the effects of mean arterial pressure, in elderly patients with isolated systolic hypertension.
Abstract: Increased arterial stiffness results in increased characteristic impedance of the aorta and increased pulse wave velocity, which increases systolic and pulse pressures. An association between increased pulse pressure and adverse cardiovascular events has been found in normotensive and hypertensive patient populations. Increased pulse pressure has also been associated with thickening of the carotid intima and media. However, the relationship between pulse pressure and stroke has not previously been evaluated. In this study, we examined the hypothesis that pulse pressure is an independent predictor of stroke in elderly patients with systolic hypertension entered in the Systolic Hypertension in the Elderly Program. Differences in baseline characteristics were examined by tertiles of pulse pressure. The independent prognostic value of pulse pressure and mean arterial pressure for predicting either stroke or total mortality was assessed with Cox proportional hazards models that included pulse pressure, mean arterial pressure, and other variables that were significant on univariate analysis. This analysis demonstrated an 11% increase in stroke risk and a 16% increase in risk of all-cause mortality for each 10-mm Hg increase in pulse pressure. Each 10-mm Hg increase in mean arterial pressure was independently associated with a 20% increase in the risk of stroke and a 14% increase in the risk of all-cause mortality. These data provide strong evidence of an association of increased conduit vessel stiffness, as indicated by increased pulse pressure, with stroke and total mortality, independent of the effects of mean arterial pressure, in elderly patients with isolated systolic hypertension.
408 citations
TL;DR: The CHARM program is a program designed to investigate the clinical usefulness of the long-acting angiotensin II type 1 receptor blocker, candesartan cilexetil, in a broad spectrum of patients with symptomatic heart failure, and to evaluate the effects on the combined endpoint of cardiovascular mortality or CHF hospitalization.
296 citations
TL;DR: This analysis suggests that a reduction in SCD risk with ACE inhibitors is an important component of this survival benefit, consistent with prior reports showing that ACE inhibitors decrease the risk of death following a recent MI by reducing cardiovascular mortality.
266 citations
TL;DR: One noninvasive blood pressure measurement provides two independent prognostic factors for survival, as assessed by pulse pressure, may contribute to increased mortality in patients with left ventricular dysfunction, independent of mean arterial pressure.
252 citations
TL;DR: Pravastatin reduced clinical events in revascularized postinfarction patients with average cholesterol levels and its use should be considered in most patients following coronary revascularization.
104 citations
TL;DR: The SPICE Registry provides a contemporary description of the demographics and management of patients with documented left ventricular systolic dysfunction and the contemporary use of ACE inhibitors appears to be higher than previously reported and the main reason for non-use is perceived intolerance.
Abstract: Aims The reported prevalence of angiotensin-converting enzyme (ACE) inhibitor use in patients with heart failure varies considerably. Recent reports suggest that many patients who could benefit from such therapy are not receiving ACE inhibitors. The Study of Patients Intolerant of Converting Enzyme Inhibitors (SPICE) Registry was established to understand better the demographics, characteristics, and contemporary use of ACE inhibitors in an international registry.
Methods and Results Between August 1996 and April 1997, each of 105 study centres from eight countries in North America and Europe was invited to review retrospectively the medical records of 100 consecutive patients with left ventricular ejection fractions ≤35%. The median age of the 9580 Registry patients was 66 years, 26% were women, the median ejection fraction was 27%, and the primary aetiology of left ventricular dysfunction was ischaemic (63%). Eighty percent of patients were receiving ACE inhibitors. The most common reason for non-use of ACE inhibitors was intolerance (9%).
Conclusion The SPICE Registry provides a contemporary description of the demographics and management of patients with documented left ventricular systolic dysfunction. The contemporary use of ACE inhibitors (80%) appears to be higher than previously reported and the main reason for non-use is perceived intolerance (9%).
103 citations
TL;DR: Within the LDL cholesterol levels in CARE (115 to 174 mg/dl), baseline values influenced both the risk of events in the placebo group as well as the clinical effectiveness of pravastatin therapy.
87 citations
TL;DR: The adverse effect of left ventricular hypertrophy, as measured by the weight of the heart on the pathologist's scale, was recognized in the early part of this century, even before routine measurem...
Abstract: The adverse effect of left ventricular hypertrophy, as measured by the weight of the heart on the pathologist's scale, was recognized in the early part of this century, even before routine measurem...
TL;DR: In this article, the authors tested the hypothesis that regional end-systolic left ventricular (ESLV) wall stress is associated with extracellular matrix remodeling activity after myocardial infarction.
TL;DR: The rate of left ventricular dilatation after MI in rats is proportional to initialLeft ventricular function remains relatively constant as the ventricle progressively enlarges, although left Ventricle function remained relatively constant in animals with large infarcted regions.
TL;DR: A better understanding of abnormalities in pulsatile load in hypertension will facilitate risk stratification in and treatment of patients with hypertension.
Abstract: The hemodynamics of hypertension and antihypertensive therapy have generally been approached in terms of the steady-flow load on the heart. Recent evidence, however, suggests that the pulsatile component of hemodynamic load may play a fundamental role in both the development and progression of hypertensive cardiovascular disease and its clinical sequelae. Pulse pressure, a correlate of conduit vessel stiffness, has been shown to be an important independent predictor of clinical events in hypertensive patients and in the general population. Unrecognized effects on pulsatile hemodynamics may account for the differential effects of various agents on left ventricular mass and events. A better understanding of abnormalities in pulsatile load in hypertension will facilitate risk stratification in and treatment of patients with hypertension.
TL;DR: In this paper, the authors compared the abilities of two methods to measure ejection fraction (EF) and contrast left ventriculography (CFA) to predict cardiovascular events.
TL;DR: In this article, the expression of TNF and iNOS in the heart is increased in an experimental model of dilated cardiomyopathy that minimizes the confounding effects of surgery, supporting a role for activation of innate immunity signaling pathways in the pathogenesis of heart failure.
TL;DR: In the United States, hypertension affects about 25% of the adult population in the USA and about 50 million people in the UK as mentioned in this paper, and great strides have been made in improving awareness, treatment and control of high blood pressure.