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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
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Journal ArticleDOI
TL;DR: The association of sex with clinical characteristics and outcomes in patients following myocardial infarction in the Valsartan in Acute Myocardial Infarction Trial (VALIANT) is examined.
Abstract: Purpose: As many as 70% of heart failure (HF) patients suffer from at least one other chronic condition Comorbidity in HF is associated with frequent hospitalizations Self-care can mitigate poor outcomes Yet, lack of confidence is known to interfere with self-care when more than one chronic condition exists The mechanism by which comorbidity, self-care confidence and self-care behaviors interact to predict hospitalization in HF patients is unclear The aim of this study was test an explanatory model of predictors of hospitalization by: 1) identifying the contribution of comorbidity to HF self-care behaviors and hospitalization, and 2) testing comorbidity as a moderator of the relationship between self-care confidence and HF self-care behaviors Methods: We conducted a secondary analysis of data from a cross sectional study of 628 HF patients enrolled across Italy All participants: 1) had a confirmed diagnosis of HF; 2) were stable in the preceding month; 3) were age > 18 years; and 4) had symptoms in the last month so that we could analyze their symptom management behaviors Both comorbidity, as measured by the 12 item Charlson Comorbidity Index total score, and hospitalization were evaluated from medical record review Self-care was measured with the Self-Care of HF Index v62 All three scales (maintenance, management, confidence) yield standardized scores ranging 0-100 with higher scores indicating higher HF self-care Structural equation modeling and post-hoc simple slope analysis were used to analyze the dataResults: Participants were primarily male (58%), older (73 years old, SD=11) and NYHA class II or III (75%) In model testing, higher numbers of hospitalization were associated with lower self-caremaintenance (ie treatment adherence and symptom monitoring) and higher comorbidity Higher self-care maintenance was associated with higher self-care confidence Higher self-care management (ie symptom management behaviors) was associated with lower comorbidity and higher self-care confidence Slope analysis showed that comorbidity moderated the relationship between self-care confidence and self-caremaintenance As the level of comorbidity increased, the effect of self-care confidence on self-care maintenance decreased The final model fit the data well (fit indices: CFI=099, RMSEA=003) Conclusion: Self-care confidence plays a key role in the relationship between comorbidity and self-care in influencing hospitalization When patients have comorbid conditions, interventions designed to improve self-care confidence may help to decrease hospitalizations

50 citations

Journal ArticleDOI
TL;DR: The effect of three different neurohumoral modulators in large trials which provide data on clinical outcomes in patients with HF, across the full range of LVEF is explored, incorporating the three commonly described HF phenotypes.
Abstract: Recently, the Prospective Comparison of ARNI (angiotensin receptor–neprilysin inhibitor) with ARB (angiotensin receptor blocker) Global Outcomes in Heart Failure with Preserved Ejection Fraction (PARAGON-HF) trial suggested that women might obtain more benefit than men from sacubitril/valsartan, compared with valsartan, in heart failure with preserved ejection fraction (HFpEF).1–3 However, the picture is more complicated as there was also an interaction between left ventricular ejection fraction (LVEF) and the effect of sacubitril/valsartan.2 Patients with a LVEF at or below the median (57%) seemed to gain more benefit from sacubitril/valsartan than those with a LVEF above the median.2 To make matters more complex still, it is well known that the distribution of LVEF is different in women and men, with women, on average, having a higher LVEF than men, be it in the general population or in individuals with heart failure (HF).4–6 Despite a higher LVEF, women with HFpEF had worse systolic function, as assessed by tissue Doppler echocardiography, compared to men with HFpEF.7 To further investigate the relationship between sex, LVEF and treatment in HF, we explored the effect of three different neurohumoral modulators in large trials which provide data on clinical outcomes in patients with HF, across the full range of LVEF, incorporating the three commonly described HF phenotypes – HF with reduced ejection fraction (HFrEF, LVEF <40%), HFpEF (LVEF >50%) and HF with mid-range ejection fraction (HFmrEF, LVEF 40–50%).8 We pooled individual patient-level data from: (i) three trials using an angiotensin receptor blocker – the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) – the CHARM-Alternative and CHARM-Added trials in HFrEF and the CHARM-Preserved trial in HFmrEF/HFpEF;9 (ii) three trials using a mineralocorticoid receptor antagonist (MRA) – two HFrEF trials, the Randomized Aldactone Evaluation Study (RALES) and the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF), and one HFmrEF/HFpEF trial – the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT).10–12 Only TOPCAT patients from the Americas were included; (iii) two trials using sacubitril/valsartan – the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in HF trial (PARADIGM-HF) in HFrEF and PARAGON-HF in HFmrEF/HFpEF.1,13 Cox proportional hazards modelling was used to analyse (i) the primary composite outcome (first occurrence of HF hospitalization or cardiovascular death); (ii) first HF hospitalization; and (iii) cardiovascular death. Likelihood ratio tests were used to report (i) two-way interaction between treatment and sex; and (ii) three-way interaction between treatment, sex and LVEF. LVEF, modelled as a fractional polynomial, and its interaction with treatment using the best fit model for each drug category (based on the primary composite outcome) was examined with the mfpi command in Stata. Models were stratified by trial for MRAs and sacubitril/valsartan. All analyses were conducted using Stata version 16 (Stata Corp., College Station, TX, USA). This present analysis included 2400, 1938 and 4311 women and 5199, 4229 and 8884 men in the candesartan, MRA and sacubitril/valsartan trials, respectively (Table 1). Overall mean LVEF (%) was 38.9±14.9%, 35.3±16.0% and 39.7± 15.1%, respectively. Women had a higher mean LVEF, with the difference compared to men 6.3%, 9.4% and 10.3%, respectively. Women had a lower incidence of the primary composite outcome (and its components) in each of the treatment and control groups. In keeping with prior reports from the CHARM Programme and TOPCAT, as well as a recent analysis of PARADIGM-HF and PARAGON-HF, we found that treatment with an ARB, MRA or ARNI may be of benefit beyond the upper limit of LVEF eligibility used in contemporary HFrEF clinical trials (40%) and may extend to what has been termed HFmrEF (LVEF 40–49%) and even to the lower part of the LVEF range currently categorized as HFpEF.2,6,14,15 Importantly, the benefit of each treatment seemed to extend to a higher LVEF in women, compared to men (Figure 1). There was no difference in efficacy of therapy between men and women with HFrEF. Because these are post hoc analyses, they are only hypothesis generating. However, the fact that all three neurohumoral modulating therapies demonstrated the same sex-related pattern of response raises the possibility that the differential response between women and men identified in PARAGON-HF may be real rather than due to the play of chance, although interpretation of PARAGON-HF is more complex as it had an active comparator compared with a placebo control in the other trials. Despite this consistent observation in the trials examined, the biological basis for such a finding is uncertain. As detailed elsewhere, the possibilities include sex-related differences in cardiac remodelling in response to blood pressure, age and other stimuli, and differences in age-related arterial stiffening, which is more pronounced in women than men.3 Women may also have other evidence of contractile dysfunction, compared with men, for a given ejection fraction.3 Natriuretic peptide levels are lower in women with HFpEF than in men, and women may have reduced cyclic guanosine monophosphateprotein kinase G signalling compared with men, especially after the menopause.3 The possibility that women with HF might benefit from treatment to a higher level of LVEF than previously considered could be of great clinical importance. Women with HF have fewer treatment options than men with HF because HFmrEF and HFpEF are the predominant HF phenotypes in women and no therapy has been approved by regulatory authorities for either of these phenotypes.6 More research on this matter is clearly required. Conflict of interest: P.D. and A.J. report no conflicts. C.S.P.L., M.A.P., F.Z., B.P., S.D.S. and J.J.V.McM. or their institutions were paid for their participation in one or more of these trials. J.J.V.McM reports receiving fees (all fees listed paid

50 citations

Journal ArticleDOI
TL;DR: It is demonstrated that dysglycemia is associated with a higher risk of adverse clinical outcomes, even before the diagnosis of diabetes and institution of glucose lowering therapy in patients with HFpEF as well as HFrEF.
Abstract: The prevalence and consequences of prediabetic dysglycemia and undiagnosed diabetes is unknown in patients with heart failure (HF) and preserved ejection fraction (HFpEF) and has not been compared to heart failure and reduced ejection fraction (HFrEF). We examined the prevalence and outcomes associated with normoglycemia, prediabetic dysglycemia and diabetes (diagnosed and undiagnosed) among individuals with a baseline glycated hemoglobin (hemoglobin A1c, HbA1c) measurement stratified by HFrEF or HFpEF in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity programme (CHARM). We studied the primary outcome of HF hospitalization or cardiovascular (CV) death, and all-cause death, and estimated hazard ratios (HR) by use of multivariable Cox regression models. HbA1c was measured at baseline in CHARM patients enrolled in the USA and Canada and was available in 1072/3023 (35%) of patients with HFpEF and 1578/4576 (34%) patients with HFrEF. 18 and 16% had normoglycemia (HbA1c 6.4), and 40% had known diabetes (any HbA1c), with corresponding prevalence among HFrEF patients being 26 and 35%. The rates of both clinical outcomes of interest were higher in patients with undiagnosed diabetes and prediabetes, compared to normoglycemic patients, irrespective of HF subtype, and in general higher among HFrEF patients. For the primary composite outcome among HFpEF patients, the HRs were 1.02 (95% CI 0.63–1.65) for prediabetes, HR 1.18 (0.75–1.86) for undiagnosed diabetes and 2.75 (1.83–4.11) for known diabetes, respectively, p value for trend across groups < 0.001. Dysglycemia was also associated with worse outcomes in HFrEF. These findings confirm the remarkably high prevalence of dysglycemia in heart failure irrespective of ejection fraction phenotype, and demonstrate that dysglycemia is associated with a higher risk of adverse clinical outcomes, even before the diagnosis of diabetes and institution of glucose lowering therapy in patients with HFpEF as well as HFrEF.

50 citations

Journal ArticleDOI
TL;DR: Diabetes is a potent risk factor for death and heart failure hospitalization following myocardial infarction and whether diabetes modifies the relationship between left ventricular ejection fraction and outcomes in the post‐MI population is unknown.
Abstract: Aims Diabetes is a potent risk factor for death and heart failure (HF) hospitalization following myocardial infarction (MI). Whether diabetes modifies the relationship between left ventricular ejection fraction (LVEF) and outcomes in the post-MI population is unknown. Methods and results The Valsartan in Acute Myocardial Infarction trial (VALIANT) enrolled 14 703 patients with acute MI complicated by HF, systolic dysfunction, or both. We compared the risk of death, HF hospitalization, and/or recurrent MI among patients with and without diabetes using Cox proportional hazards models. To assess the relationship between diabetes, LVEF and outcomes, we assessed the relative influence of baseline LVEF on outcomes in diabetic and non-diabetic patients. Totally, 11 325 subjects (3095 diabetics) with site-reported LVEF and known diabetes status were included. At any given LVEF, diabetes was associated with a higher risk of all-cause mortality [adjusted hazard ratio (HR) 1.37, 95% CI 1.25–1.51], death or HF hospitalization (adjusted HR 1.42, 95% CI 1.31–1.51), and death or recurrent MI (adjusted HR 1.36, 95% CI 1.24–1.48). Diabetes modified the relationship between LVEF and death or HF hospitalization (P for interaction = 0.0109), such that the association between diabetes and increased risk was greater in magnitude at higher LVEF. No interaction was noted between diabetes and LVEF on risk of all-cause mortality or death or recurrent MI. Conclusion Diabetes is associated with a higher risk of death or HF hospitalization across the spectrum of LVEF in high-risk post-MI patients. The magnitude of reduction in risk of death or HF hospitalization associated with increasing LVEF is significantly attenuated among patients with diabetes when compared to patients without diabetes.

49 citations

Journal ArticleDOI
TL;DR: The VALIANT (Valsartan in Acute Myocardial Infarction) trial is testing the hypothesis that interruption of the renin-angiotensin pathway by using the ARB valsartans alone or in combination with an ACE inhibitor will be more effective in saving lives than an ACE inhibitors alone in treating patients at high risk.

49 citations


Cited by
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Journal ArticleDOI
21 May 2003-JAMA
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

Book
23 Sep 2019
TL;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

Journal ArticleDOI
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

Journal ArticleDOI
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