Marc A. Pfeffer

Bio: Marc A. Pfeffer is an academic researcher from Brigham and Women's Hospital. The author has contributed to research in topics: Heart failure & Myocardial infarction. The author has an hindex of 166, co-authored 765 publications receiving 133043 citations. Previous affiliations of Marc A. Pfeffer include Partners HealthCare & University of Miami.

An Ongoing Study of Anemia Correction in Chronic Kidney Disease

Abstract: To the Editor: Evidence-based medicine assimilates available data to direct decisions regarding the care of patients. Extrapolations from epidemiologic observations and laboratory or clinical markers of disease severity have supported new treatments that were subsequently found to be without value in randomized, controlled clinical trials.1 In addition, therapies considered to be beneficial and safe owing to their effect on surrogate markers have been found to be ineffective or harmful in such trials.1,2 Even the results of randomized, controlled trials can be misleading, especially when the trials are not adequately powered.3 The use of erythropoietic agents to treat anemia in . . .

Mechanisms and predictors of mitral regurgitation after high-risk myocardial infarction.

Abstract: Background Mitral regurgitation (MR) has been associated with adverse outcomes after myocardial infarction (MI). Without structural valve disease, functional MR has been related to left ventricular (LV) remodeling and geometric deformation of the mitral apparatus. The aims of this study were to elucidate the mechanistic components of MR after high-risk MI and to identify predictors of MR progression during follow-up. Methods The Valsartan in Acute Myocardial Infarction Echo substudy prospectively enrolled 610 patients with LV dysfunction, heart failure, or both after MI. MR at baseline, 1 month, and 20 months was quantified by mapping jet expansion in the left atrium in 341 patients with good-quality echocardiograms. Indices of LV remodeling, left atrial size, and diastolic function and parameters of mitral valve deformation, including tenting area, coaptation depth, anterior leaflet concavity, annular diameters, and contractility, were assessed and related to baseline MR. The progression of MR was further analyzed, and predictors of worsening among the baseline characteristics were identified. Results Tenting area, coaptation depth, annular dilatation, and left atrial size were all associated with the degree of baseline MR. Tenting area was the only significant and independent predictor of worsening MR; a tenting area of 4 cm 2 was a useful cutoff to identify worsening of MR after MI and moderate to severe MR after 20 months. Conclusions Increased mitral tenting and larger mitral annular area are determinants of MR degree at baseline, and tenting area is an independent predictor of progression of MR after MI. Although LV remodeling itself contributes to ischemic MR, this influence is directly dependent on alterations in mitral geometry.

Serum Calcification Propensity and Fetuin-A: Biomarkers of Cardiovascular Disease in Kidney Transplant Recipients.

Abstract: Background "T50," shortened transformation time from primary to secondary calciprotein particles may reflect deranged mineral metabolism predisposing to vascular calcification and cardiovascular disease (CVD). The glycoprotein fetuin-A is a major T50 determinant. Methods The Folic Acid For Vascular Outcome Prevention In Transplantation (FAVORIT) cohort is a completed, large, multiethnic controlled clinical trial cohort of chronic, stable kidney transplant recipients (KTRs). We conducted a longitudinal case-cohort analysis using a randomly selected subcohort of patients, and all individual cases who developed CVD. Serum T50 and fetuin-A were determined in this total of n = 685 FAVORIT trial participants at randomization. Results During a median surveillance of 2.18-years, 311 incident or recurrent CVD events occurred. Shorter T50 (minutes) or reduced fetuin-A concentrations (g/L) were associated with CVD after adjustment for treatment assignment, systolic blood pressure, age, sex, race, preexisting CVD and diabetes, smoking, body mass index, total cholesterol/HDL cholesterol, kidney allograft vintage and type, calcineurin inhibitor, or lipid-lowering drug use, estimated glomerular filtration rate, and urinary albumin/creatinine: tertile 1 (lowest) to tertile 3 (highest) comparisons, T50, (hazard ratio [HR] 1.86; 95% CI 1.20-2.89); fetuin-A, (HR 2.25; 95% CI 1.38-3.69). Elevated high sensitivity c-reactive protein (hsCRP) was an effect modifier of both these associations. Conclusions Shortened T50, as well as reduced fetuin-A levels, ostensible promoters of vascular calcification, remained associated with greater risk for CVD outcomes, after adjustment for major CVD risk factors, measures of kidney function and damage, and KTR clinical characteristics and demographics, in a large, multiethnic cohort of long-term KTRs. Increased hsCRP was an effect modifier of these CVD risk associations.

Cardiac Troponin I and Risk of Cardiac Events in Patients With Heart Failure and Preserved Ejection Fraction.

Abstract: Background: Levels of cTn (cardiac troponin) are frequently elevated in patients with heart failure (HF) and reduced ejection fraction (EF) and correlate with the risk for mortality. However, facto...

Klotho, fibroblast growth factor-23, and the renin-angiotensin system - an analysis from the PEACE trial.

Abstract: AIMS Klotho, an essential co-receptor for fibroblast growth factor (FGF)-23, has potentially beneficial inhibitory effects on the renin-angiotensin system. Limited data exist on the prognostic value of Klotho and FGF-23 levels in combination or their ability to predict benefit from angiotensin-converting enzyme (ACE) inhibition. METHODS AND RESULTS A total of 3555 patients with stable ischaemic heart disease and left ventricular ejection fraction > 40% enrolled in the PEACE trial of trandolapril vs. placebo had Klotho levels drawn at randomization. Patients were characterized by quartiles of Klotho and FGF-23 concentrations. Six-year Kaplan-Meier rates and adjusted risk were calculated in the placebo arm for the composite of cardiovascular (CV) death or hospitalization for heart failure and its components. Low [quartile (Q) 1-3] Klotho concentration was associated with an increased rate of CV death or hospitalization for heart failure as compared with Q4 (8.2% vs. 4.2%; P = 0.03). After multivariable adjustment for clinical variables and renal and CV biomarkers (estimated glomerular filtration rate, cystatin-C, urine albumin-to-creatinine ratio, FGF-23, high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein), low Klotho concentration remained strongly associated with increased risk of CV death or hospitalization for heart failure [adjusted hazard ratio (HR) 2.62; 95% confidence interval (CI) 1.35-5.08; P < 0.01]. The combination of low Klotho and high (Q4) FGF-23 concentration identified patients at particularly elevated risk (adjusted HR 3.99; 95% CI 1.67-9.56; P < 0.01). This high-risk combination additionally predicted benefit from trandolapril (HR 0.39; 95% CI 0.23-0.68; Pinteraction < 0.01). CONCLUSIONS Low Klotho concentration is associated with an increased risk of CV death or heart failure hospitalization in patients with stable ischaemic heart disease. The combination of low Klotho and high FGF-23 further identifies patients at distinctly elevated risk who derive clinical benefit from the ACE-inhibitor trandolapril.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

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.

Cochrane Handbook for Systematic Reviews of Interventions

Abstract: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

A New Equation to Estimate Glomerular Filtration Rate

Abstract: The Modification of Diet in Renal Disease (MDRD) Study equation underestimates glomerular filtration rate (GFR) in patients with mild kidney disease. Levey and associates therefore developed and va...

Lifetime Prevalence and Age-of-Onset Distributions of DSM-IV Disorders in the National Comorbidity Survey Replication

Abstract: Context Little is known about lifetime prevalence or age of onset of DSM-IV disorders. Objective To estimate lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the recently completed National Comorbidity Survey Replication. Design and Setting Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using the fully structured World Health Organization World Mental Health Survey version of the Composite International Diagnostic Interview. Participants Nine thousand two hundred eighty-two English-speaking respondents aged 18 years and older. Main Outcome Measures Lifetime DSM-IV anxiety, mood, impulse-control, and substance use disorders. Results Lifetime prevalence estimates are as follows: anxiety disorders, 28.8%; mood disorders, 20.8%; impulse-control disorders, 24.8%; substance use disorders, 14.6%; any disorder, 46.4%. Median age of onset is much earlier for anxiety (11 years) and impulse-control (11 years) disorders than for substance use (20 years) and mood (30 years) disorders. Half of all lifetime cases start by age 14 years and three fourths by age 24 years. Later onsets are mostly of comorbid conditions, with estimated lifetime risk of any disorder at age 75 years (50.8%) only slightly higher than observed lifetime prevalence (46.4%). Lifetime prevalence estimates are higher in recent cohorts than in earlier cohorts and have fairly stable intercohort differences across the life course that vary in substantively plausible ways among sociodemographic subgroups. Conclusions About half of Americans will meet the criteria for a DSM-IV disorder sometime in their life, with first onset usually in childhood or adolescence. Interventions aimed at prevention or early treatment need to focus on youth.