Author
Marc A. Pfeffer
Other affiliations: Partners HealthCare, University of Miami, Mount Sinai Hospital ...read more
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.
Papers published on a yearly basis
Papers
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TL;DR: In both age groups, cardiovascular disease risk assessment was improved by considering both SBP andDBP, not just SBP, DBP, or pulse pressure separately, according to JNC-VI classification system.
Abstract: ContextThe sixth Joint National Committee (JNC-VI) classification system of
blood pressure emphasizes both systolic blood pressure (SBP) and diastolic
blood pressure (DBP) for cardiovascular disease risk assessment. Pulse pressure
may also be a valuable risk assessment tool.ObjectiveTo compare relationships of SBP, DBP, and pulse pressure, separately
and jointly, with cardiovascular disease-related mortality in men.Design and SettingData from the Multiple Risk Factor Intervention Trial (MRFIT), which
screened men aged 35 to 57 years from 1973 through 1975 at 22 US centers,
was used to assess cardiovascular disease-related mortality through 1996.ParticipantsA total of 342 815 men without diabetes or a history of myocardial
infarction were divided into 2 groups based on their age at MRFIT screening
(35- to 44-year-olds and 45- to 57-year olds). Participant blood pressure
levels were classified into a JNC-VI blood pressure category based on SBP
and DBP (optimal, normal but not optimal, high normal, stage 1 hypertension,
stage 2-3 hypertension), and pulse pressure was calculated.Main Outcome MeasureCardiovascular disease-related mortality.ResultsThere were 25 721 cardiovascular disease-related deaths. Levels
of SBP and DBP were more strongly related to cardiovascular disease than pulse
pressure. Relationships of SBP, DBP, and pulse pressure to cardiovascular
disease-related mortality varied within JNC-VI category. Concordant elevations
of SBP and DBP were associated with a greater risk of cardiovascular disease-related
mortality for both age groups of men. Among men aged 45 to 57 years, higher
SBP and lower DBP (discordant elevations) also yielded a greater risk of cardiovascular
disease-related mortality.ConclusionIn both age groups, cardiovascular disease risk assessment was improved
by considering both SBP and DBP, not just SBP, DBP, or pulse pressure separately.
302 citations
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VU University Medical Center1, Cardiff University2, University of Navarra3, Brigham and Women's Hospital4, University of Oslo5, University of Milan6, University Health System7, Charité8, University of Brescia9, University of Michigan10, University of Göttingen11, University of Perugia12, University of Warwick13, Monash University14, Athens State University15, Northwestern University16, Boston University17, Campbell University18, Medical University of Graz19
TL;DR: To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials.
Abstract: The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes, suboptimal study designs, or inadequate statistical power. Many novel agents are in various stages of research and development for potential use in patients with HF-PEF. To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials. This paper represents a synthesis of a workshop held in Bergamo, Italy, and it examines new and emerging therapies in the context of specific, targeted HF-PEF phenotypes where positive clinical benefit may be detected in clinical trials. Specific considerations related to patient and endpoint selection for future clinical trials design are also discussed.
302 citations
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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
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Emory University1, University of California, Los Angeles2, Medical University of South Carolina3, University Health System4, Bayer Corporation5, University of Pittsburgh6, Northwestern University7, University of Alabama at Birmingham8, Castle Hill Hospital9, Janssen Pharmaceutica10, Vanderbilt University11, Center for Drug Evaluation and Research12, Athens State University13, Novartis14, British Heart Foundation15, University of Brescia16, Duke University17, Harvard University18, Medical University of Graz19, University of Michigan20, Henry Ford Hospital21, University of California, San Francisco22
TL;DR: To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the Food and Drug Administration and included representatives from academia, industry, and regulatory agencies.
Abstract: The burden of heart failure with preserved ejection fraction (HFpEF) is considerable and is projected to worsen. To date, there are no approved therapies available for reducing mortality or hospitalizations for these patients. The pathophysiology of HFpEF is complex and includes alterations in cardiac structure and function, systemic and pulmonary vascular abnormalities, end-organ involvement, and comorbidities. There remain major gaps in our understanding of HFpEF pathophysiology. To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the Food and Drug Administration and included representatives from academia, industry, and regulatory agencies. This document summarizes the proceedings from this meeting.
295 citations
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TL;DR: Whether dual RAAS blockade with the direct renin inhibitor aliskiren in combination with an ACEi or ARB will reduce major morbidity and mortality in a broad range of high-risk patients with type 2 diabetes is determined.
Abstract: Background. Patients with type 2 diabetes are at increased risk of macro- and microvascular disease, and the presence of albuminuria and/or reduced kidney function further enhances macrovascular risk. Angiotensin-convertingenzyme inhibitors reduce both macro- and microvascular events, yet the residual renal and cardiovascular risk still remains high. Aliskiren a novel oral direct renin inhibitor that unlike ACEi and ARBs, lowers plasma renin activity, angiotensin Iand angiotensin IIlevels, may thereby provide greater benefit compared to ACEi or ARB alone. Methods. The primary objective of the ALTITUDE trial is to determine whether aliskiren 300 mg once daily, reduces cardiovascular and renal morbidity and mortality compared withplacebowhenaddedtoconventionaltreatment(including ACEi or ARB). ALTITUDE is an international, randomized, double-blind, placebo-controlled, parallel-group study, which will include three categories of high-risk patients with type 2 diabetes (aged ≥35 years): those with either urinary albumin/creatinine ratio (UACR) ≥200 mg/g; microalbuminuria(UACR) ≥20 <200mg/gandeGFR ≥30 <60 mL/min/1.73 m 2 ; and thirdly, those with a history of cardiovascular disease and eGFR ≥30 <60 mL/min/1.73 m 2 with or without microalbuminuria. ALTITUDE is an event driven trial that aims to randomize 8600 patients with a planned follow-up time of 48 months. The primary outcome measure is time to first event for the composite endpoint of cardiovascular death, resuscitated death, myocardial infarction, stroke, unplanned hospitalization for heart failure,onsetofend-stagerenaldiseaseordoublingofbaseline serum creatinine concentration. Secondary endpoints include a composite CV endpoint and a composite renal endpoint.
295 citations
Cited by
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Boston University1, Rush University Medical Center2, University of Tennessee Health Science Center3, University of Michigan4, University at Buffalo5, University of Mississippi6, University of Miami7, University of Alabama at Birmingham8, Case Western Reserve University9, National Institutes of Health10
TL;DR: The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated, and empathy builds trust and is a potent motivator.
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.
24,988 citations
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23 Sep 2019TL;DR: 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.
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.
21,235 citations
28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组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�ly.
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。
18,940 citations
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TL;DR: The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use.
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...
18,691 citations
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TL;DR: 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.
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.
17,213 citations