Showing papers by "Marc A. Pfeffer published in 2001"
TL;DR: Since the original publication (in 1995) of the AHA consensus statement on secondary prevention, important evidence from clinical trials has emerged that further supports the merits of aggressive risk reduction therapies for patients with atherosclerotic cardiovascular disease.
Abstract: Since the original publication (in 1995) of the American Heart Association (AHA) consensus statement on secondary prevention, which was endorsed by the American College of Cardiology (ACC), important evidence from clinical trials has emerged that further supports the merits of aggressive risk reduction therapies for patients with atherosclerotic cardiovascular disease. As noted in that statement, aggressive risk factor management clearly improves patient survival, reduces recurrent events and the need for interventional procedures, and improves the quality of life for these patients.
The compelling evidence from recent clinical trials was the impetus …
741 citations
TL;DR: Since the original publication (in 1995) of the AHA consensus statement on secondary prevention, important evidence from clinical trials has emerged that further supports the merits of aggressive risk reduction therapies for patients with atherosclerotic cardiovascular disease.
Abstract: Since the original publication (in 1995) of the American Heart Association (AHA) consensus statement on secondary prevention, which was endorsed by the American College of Cardiology (ACC), important evidence from clinical trials has emerged that further supports the merits of aggressive risk reduction therapies for patients with atherosclerotic cardiovascular disease. As noted in that statement, aggressive risk factor management clearly improves patient survival, reduces recurrent events and the need for interventional procedures, and improves the quality of life for these patients.
The compelling evidence from recent clinical trials was the impetus …
649 citations
TL;DR: CHF subjects have elevated central pulsatile load (Zc), which is not apparent in global measures such as augmentation index or TAC, possibly because of contrasting changes in central and peripheral conduit vessels.
Abstract: Pulse pressure, an indirect measure of vascular stiffness and pulsatile load, predicts clinical events in congestive heart failure (CHF), suggesting that abnormal pulsatile load may contribute to CHF. This study was designed to assess more direct measures of central pulsatile load in CHF. Noninvasive hemodynamic evaluations were performed in 28 subjects with CHF and 40 controls using calibrated tonometry of the brachial, radial, femoral, and carotid arteries along with echocardiographic assessment of left ventricular outflow tract (LVOT) diameter and Doppler flow. Characteristic impedance (Z(c)) was calculated as the ratio of DeltaP (carotid) and DeltaQ (LVOT flow) in early systole. Carotid-radial (CR-PWV) and carotid-femoral (CF-PWV) pulse wave velocities were calculated from tonometry. Augmentation index was assessed from the carotid waveform. Total arterial compliance (TAC) was calculated using the area method. Brachial pulse pressure was elevated (62+/-16 versus 53+/-15 mm Hg, P=0.015) in CHF because of lower diastolic pressure (66+/-10 versus 73+/-9 mm Hg, P=0.003). CHF had higher Z(c) (225+/-76 versus 184+/-66 dyne. sec. cm(-5), P=0.020). CF-PWV did not differ (9.7+/-2.7 versus 9.2+/-2.0, P=0.337), whereas CR-PWV was lower in CHF (8.6+/-1.4 versus 9.4+/-1.5, P=0.038). There was no difference in TAC (1.4+/-0.5 versus 1.4+/-0.6 mL/mmHg, P=0.685), and augmentation index was lower in CHF (8+/-17 versus 21+/-13%, P=0.001). CHF subjects have elevated central pulsatile load (Z(c)), which is not apparent in global measures such as augmentation index or TAC, possibly because of contrasting changes in central and peripheral conduit vessels. This increased pulsatile load represents an important therapeutic target in CHF.
211 citations
TL;DR: Clinical and echocardiographic predictors of recovery of ventricular function in the 88% of patients in HEART who underwent reperfusion therapy were assessed, highlighting the importance of identifying factors that influence the progression and regression of left ventricular dysfunction.
Abstract: Background Patients with reduced left ventricular function and ventricular enlargement after myocardial infarction are at significantly greater risk for congestive heart failure and death. Nevertheless, recovery of ventricular function occurs in a significant proportion of patients after myocardial infarction, and modern reperfusion strategies have been associated with increased recovery of function. Objective To determine the extent and predictors of recovery of ventricular function after anterior Q-wave myocardial infarction in the reperfusion era. Design Subgroup analysis of the Healing and Early Afterload Reducing Therapy study. Setting 35 medical centers in the United States and Canada. Patients 352 patients with Q-wave anterior myocardial infarction. Intervention Placebo for 14 days, followed by full-dose (10 mg) ramipril until day 90; low-dose (0.625 mg) ramipril for 90 days; or full-dose ramipril for 90 days. All patients underwent reperfusion therapy. Measurements Echocardiography was performed on day 1 (before randomization), day 14, and day 90 after myocardial infarction. Left ventricular volume and ejection fraction were measured and wall-motion analyses were performed at all three time points in 249 patients and at baseline in an additional 12 patients who died during follow-up. Echocardiographic and nonechocardiographic predictors of ventricular recovery were examined. Results By day 90, 55 of 252 (22%) patients who had abnormal ejection fraction and wall-motion abnormalities on day 1 demonstrated complete recovery of function (ejection fraction in the normal range and infarct segment length of 0%), and an additional 36% (91 of 252 patients) demonstrated partial recovery of function. At 90 days, 53% (132 of 249) of patients had greater than 5% improvement in ejection fraction, whereas only 16% (39 of 249) had a decrease in ejection fraction of more than 5%. The majority of functional improvement occurred by day 14 after infarction. Of various clinical and echocardiographic measures obtained on day 1, peak creatine kinase level was the strongest independent predictor of subsequent recovery of ventricular function in multivariate analysis. Each 100-unit increase in peak creatine kinase was associated with a 4.3% decreased odds of recovery (P Conclusion Significant myocardial stunning with subsequent improvement of ventricular function occurred in the majority of patients after Q-wave anterior myocardial infarction. A lower peak level of creatine kinase, an estimate of the extent of necrosis, is independently predictive of recovery of function. Early functional assessment (day 1 after acute myocardial infarction) had limited ability to predict recovery of ventricular function.
208 citations
TL;DR: Elevated pulse pressure provides independent prognostic information beyond that provided by known risk factors that were evaluated in this study, including the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure hypertension classification.
Abstract: Increased stiffness of the conduit arteries has been associated with increased risk of death and cardiovascular death in a number of populations. None of these populations, however, are fully representative of the US population. The cohort examined in the First National Health and Nutrition Examination Survey (NHANES I) that was free of overt cardiovascular disease was selected to be representative of the US population. We assessed and quantified the increased risk of death associated with elevated pulse pressure in this population. A cohort of 5771 subjects from NHANES I was used to determine the value of adding pulse pressure to standard cardiovascular disease risk factors for assessment of the risk of death during a mean follow-up period of 16.5 years. Analyses were performed by use of the SUDAAN statistical package for performing Cox proportional regression, logistic regression, and other standard methods in complex, weighted samples. Pulse pressure increased with increasing age, body mass index, cholesterol level, and mean arterial pressure. With increasing pulse pressure, the percentage of cigarette smokers decreased and the percentage of diabetics increased. Despite these associations with known risk factors, pulse pressure was independently predictive of an increased risk of death from cardiovascular disease, coronary heart disease, and all-cause mortality. It provides independent prognostic information beyond that provided by known risk factors that were evaluated in this study, including the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure hypertension classification. A 10 mm Hg increase in pulse pressure in persons 25 to 45 of age was associated with a 26% increase in risk of cardiovascular death (95% confidence interval [CI], 5 to 50) and with an 10% increase (95% CI, 2 to 19) in persons 46 to 77 years of age. In a cohort designed to be representative of the US population, elevated pulse pressure has been shown to provide independent prognostic information. This variable may be a marker for the extent of vascular disease and may contribute to the occurrence of clinical events.
177 citations
TL;DR: Apical regional wall stress is an independent predictor of subsequent LV remodeling after MI and appears to be attenuated by full-dose angiotensin-converting enzyme inhibition.
64 citations
TL;DR: Hemodynamic stress of the adult rat heart in vivo results in rapid activation of several parallel MAPK kinase cascades, particularly stress-activated MAPK and p38-MAPK and their target transcription factors c-Jun and ATF-2.
Abstract: The role of mitogen-activated protein kinase (MAPK) pathways as signal transduction intermediates of hemodynamic stress leading to cardiac hypertrophy in the adult heart is not fully established. In a rat model of pressure-overload hypertrophy, we examined whether activation of MAPK pathways, namely, the extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and the p38-MAPK pathways, occurs during rapid changes in hemodynamic load in vivo. A slight activation of ERK2 and marked increases in JNK1 and p38-MAPK activities were observed 30 minutes after aortic banding. The increase in p38-MAPK activity was accompanied by an increase in the phosphorylation of the p38 substrate MAPK-activated protein kinases 2 and 3. Activation of these kinases was coincident with an increase in phosphorylation of c-Jun and activating transcription factor-2 (ATF-2) and enhanced DNA binding of activator protein-1 factors. Thus, hemodynamic stress of the adult rat heart in vivo results in rapid activation of several parallel MAPK kinase cascades, particularly stress-activated MAPK and p38-MAPK and their target transcription factors c-Jun and ATF-2.
59 citations
TL;DR: The Pl A1,A2 genotype was associated with an excess of recurrent coronary events in patients after MI who did not receive pravastatin, and the ACE D allele added to this risk.
Abstract: Chromosome 17q21-23 harbors genes for platelet glycoprotein IIIa and angiotensin-converting enzyme (ACE), which are polymorphic for alleles PlA2 and ACE “D.” These alleles have been independently and often associated with ischemic coronary artery disease (CAD). We sought to determine if the PlA2 and ACE D polymorphisms were risk factors for recurrent coronary events. In the Cholesterol And Recurrent Events (CARE) trial, 4,159 men and women with documented myocardial infarction (MI) were randomized to receive either placebo or pravastatin, and were followed prospectively for 5 years. PlA and ACE genotypes were determined in 767 patients: 385 cases who had experienced a recurrent primary event (death due to coronary disease or nonfatal MI), and 382 age- and gender-matched controls. In patients receiving placebo, the PlA1,A2 genotype conferred a relative risk (RR) of 1.38 (confidence intervals [CI] 1.04 to 1.83; p = 0.028; adjusted RR = 1.32, CI = 0.99 to 1.76; p = 0.058]) for the primary end point. Compared with the placebo group, pravastatin reduced the excess RR of coronary disease death and recurrent MI in the PlA1,A2 patient population by 31% (p = 0.06). The ACE D allele appeared to have modestly additive effects on the PlA1,A2 risk. Among the PlA1,A2 patients, pravastatin had little effect on the risk of recurrent events with the ACE II genotype, but reduced the adjusted RR from 1.42 (placebo) to 0.58 for ACE ID patients, and from 1.56 (placebo) to 0.83 for ACE DD. The PlA1,A2 genotype was associated with an excess of recurrent coronary events in patients after MI who did not receive pravastatin, and the ACE D allele added to this risk. These data suggest that it would be important to perform a larger study to address the potential role of these genotypes in therapeutic decision making.
58 citations
TL;DR: In this article, the changes in vasoconstrictive neurohormones, N-terminal proatrial natriuretic peptide (Nt-proANP), and BNP and their relationship with left ventricular (LV) remodeling after anterior myocardial infarction (MI) were studied.
41 citations
TL;DR: D detection of isomer 1a only in the resulting 13C CP-MAS NMR spectrum demonstrated that there has been epimerization of 1b to 1a during crystallization, thus confirming the configurational lability at the metal center.
Abstract: Bulk solid samples of various ratios of the cyclometalated arene ruthenium diastereomers (S)Ru- and (R)Ru-[(η6-C6H6)Ru(C6H4-2-(R)-CH(Me)NMe2)PMe2Ph]+PF6- (3a/3b), of which the configurational stabi...
33 citations
TL;DR: Renal function and effectiveness of angiotensin-converting enzyme inhibitor therapy in patients with chronic stable coronary disease in the Prevention of Events with ACE inhibition (PEACE) trial is studied.
TL;DR: EPHESUS, a trial of a novel aldosterone antagonist, eplerenone, in patients with myocardial infarction, left ventricular dysfunction and pulmonary congestion will determine whether this approach produces additive clinical benefits in modernly managed patients.
Abstract: Impressive clinical benefits have been derived by inhibiting the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors. There is growing evidence that aldosterone plays a contributing role in the pathogenesis of heart failure beyond its sodium retention properties. EPHESUS, a trial of a novel aldosterone antagonist, eplerenone, in patients with myocardial infarction, left ventricular dysfunction and pulmonary congestion will determine whether this approach produces additive clinical benefits in modernly managed patients.
TL;DR: A framework to consider the completed and ongoing clinical outcomes RCTs with ARBs is provided, which collectively will evaluate and quantitate the role of ARBs in clinical practice.
Abstract: JRAAS 2001;2:215-18 Based on multiple, well-conducted, randomised clinical outcome trials (RCT), inhibition of the renin-angiotensin system (RAS) with an angiotensin-converting enzyme inhibitor (ACE-I) has become a firmly established therapeutic approach for reducing morbidity and the risk of death across a broad spectrum of cardiovascular diseases (Figure 1). More recently, another pharmacologic class of agents that inhibits the RAS has become clinically available.Angiotensin II (Ang II) type 1 (AT1)-receptor blockers (ARBs) offer a more complete and specific way of inhibiting the actions of Ang II at the AT1-receptor. Unlike ACEI, ARBs do not directly interfere with the breakdown of bradykinin. When introduced, ARBs promised more complete inhibition of the RAS with greater efficacy and better tolerance than ACE-I. Although the better tolerance comparison appears to have been substantiated, the more important issue of clinical effectiveness of ARBs remains unsettled. We are fortunately in the midst of an impressive series of RCTs, which collectively will evaluate and quantitate the role of ARBs in clinical practice. Based on the ACE-I experience,we provide a framework to consider the completed and ongoing clinical outcomes RCTs with ARBs (Figure 2).
TL;DR: Despite a totality of evidence indicating clear benefits of statin therapy in secondary and primary prevention of cardiovascular disease, a large number of additional trials are currently planned or in progress to help understand, treat, and prevent CVD.
Abstract: Despite a totality of evidence indicating clear benefits of statin therapy in secondary and primary prevention of cardiovascular disease (CVD), a large number of additional trials are currently planned or in progress to help us better understand, treat, and prevent CVD. Both monotherapy and combination statin regimens are being studied to optimize treatment of the total patient and to assess mechanisms and benefits of various components of the total lipid profile.