Author
Ralph B. D'Agostino
Other affiliations: VA Boston Healthcare System, University of Illinois at Urbana–Champaign, Northwestern University ...read more
Bio: Ralph B. D'Agostino is an academic researcher from Wake Forest University. The author has contributed to research in topics: Framingham Heart Study & Framingham Risk Score. The author has an hindex of 226, co-authored 1287 publications receiving 229636 citations. Previous affiliations of Ralph B. D'Agostino include VA Boston Healthcare System & University of Illinois at Urbana–Champaign.
Papers published on a yearly basis
Papers
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TL;DR: An increased plasma homocysteine level independently predicts risk of the development of CHF in adults without prior myocardial infarction.
Abstract: ContextElevated plasma homocysteine levels are associated with increased risk
of vascular disease. It is unclear whether elevated homocysteine levels are
a risk factor for congestive heart failure (CHF).ObjectiveTo study prospectively the association between nonfasting plasma homocysteine
and incidence of CHF.Design, Setting, and ParticipantsCommunity-based prospective cohort study of 2491 adults (mean age 72
years, 1547 women) who participated in the Framingham Heart Study during the
1979-1982 and 1986-1990 examinations and were free of CHF or prior myocardial
infarction (recognized or unrecognized) at baseline.Main Outcome MeasureIncidence of a first episode of CHF during an 8-year follow-up period.ResultsDuring follow-up, 156 subjects (88 women) developed CHF. In multivariable
analyses controlling for established risk factors for CHF including the occurrence
of myocardial infarction (recognized or unrecognized) during follow-up, plasma
homocysteine levels higher than the sex-specific median value were associated
with an adjusted hazards ratio for heart failure of 1.93 in women (95% confidence
interval, 1.19-3.14) and 1.84 in men (95% confidence interval, 1.06-3.17).
The relation of plasma homocysteine levels to CHF risk was more continuous
in women than in men. In analyses restricted to participants without any manifestation
of coronary heart disease at baseline, the association of plasma homocysteine
levels with risk of CHF was maintained in men and women.ConclusionsAn increased plasma homocysteine level independently predicts risk of
the development of CHF in adults without prior myocardial infarction. Additional
investigations are warranted to confirm these findings.
196 citations
University of Washington1, Erasmus University Rotterdam2, University of North Carolina at Chapel Hill3, University of Michigan4, University of Greifswald5, Johns Hopkins University6, National Institutes of Health7, Boston University8, St George's, University of London9, Medical University of Graz10, University of Edinburgh11, University of Mainz12, Group Health Cooperative13, University of Turku14, National Research Council15, University of Maryland, Baltimore16, Harvard University17, Houston Methodist Hospital18, Baylor College of Medicine19, University of California, Berkeley20, Tel Aviv University21, University of Helsinki22, Wellcome Trust23, University of Iceland24, Broad Institute25, University of Pennsylvania26, Cedars-Sinai Medical Center27, University of Tampere28, Hannover Medical School29, Veterans Health Administration30, Ludwig Maximilian University of Munich31, Tufts University32, Leipzig University33, University of Düsseldorf34, University of Texas Health Science Center at Houston35, University of Ulm36, University of Pittsburgh37
TL;DR: A meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium identified three genomic regions associated with common carotid intima media thickness and two different areas associated with the presence of carotids plaque.
Abstract: Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10(-8)). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.
195 citations
TL;DR: The association between increased body mass index and waist-to-hip ratio and prothrombotic factors and impaired fibrinolysis suggests that obesity is a risk factor whose effect is mediated in part by a prothromabotic state.
Abstract: Although obesity is associated with increased cardiovascular risk, the mechanism has not been fully explained. Since thrombosis is a critical component of cardiovascular disease, we examined the relationship between obesity and hemostatic factors. We studied 3230 subjects (55% females, mean age 54 years) without a history of cardiovascular disease in cycle 5 of the Framingham Offspring Study. Obesity was assessed by body mass index and waist-to-hip ratio. Fasting blood samples were obtained for fibrinogen, plasminogen activator inhibitor (PAI-1) antigen, tissue plasminogen activator (tPA) antigen, factor VII antigen, von Willebrand factor (VWF), and plasma viscosity. Body mass index was directly associated with fibrinogen, factor VII, PAI-1 and tPA antigen in both men and women (p
193 citations
TL;DR: Social networks were found to be inversely associated with interleukin-6 levels in men, and the possibility that inflammatory markers may be potential mediators between social integration and coronary heart disease merits further investigation.
Abstract: Lack of social integration predicts coronary heart disease mortality in prospective studies; however, the biological pathways that may be responsible are poorly understood The specific aims of this study were to examine whether social networks are associated with serum concentrations of the inflammatory markers interleukin-6 (IL-6), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1) Participants in the Framingham Study attending examinations from 1998 to 2001 (n=3267) were eligible for inclusion in the study Social networks were assessed using the Berkman-Syme Social Network Index (SNI) Concentrations of IL-6, CRP, sICAM-1 and MCP-1 were measured in fasting serum samples Multivariable linear regression analyses were used to assess the association of social networks with inflammatory markers adjusting for potential confounders including age, smoking, blood pressure, total:HDL cholesterol ratio, body mass index, lipid-lowering and antihypertensive medication, diabetes, cardiovascular disease, depression and socioeconomic status Results found that the SNI was significantly inversely associated with IL-6 in men (p=003) after adjusting for potential confounders In age-adjusted analyses, social networks also were significantly inversely associated with IL-6 for women (p=003) and were marginally to modestly associated with CRP and sICAM-1 for men (p=008 and 002, respectively), but these associations were not significant in the multivariate analyses In conclusion, social networks were found to be inversely associated with interleukin-6 levels in men The possibility that inflammatory markers may be potential mediators between social integration and coronary heart disease merits further investigation
192 citations
TL;DR: It is shown that if the added predictor is not statistically significantly associated with the outcome, the null distribution is non-normal, contrary to the assumption of DeLong test, and recommended that for nested models, only the test of association be performed for the new predictors, and if the result is significant, change in AUC be estimated with an appropriate confidence interval, which can be based on the DeLong approach.
Abstract: The area under the receiver operating characteristics curve (AUC of ROC) is a widely used measure of discrimination in risk prediction models. Routinely, the Mann-Whitney statistics is used as an estimator of AUC, while the change in AUC is tested by the DeLong test. However, very often, in settings where the model is developed and tested on the same dataset, the added predictor is statistically significantly associated with the outcome but fails to produce a significant improvement in the AUC. No conclusive resolution exists to explain this finding. In this paper, we will show that the reason lies in the inappropriate application of the DeLong test in the setting of nested models. Using numerical simulations and a theoretical argument based on generalized U-statistics, we show that if the added predictor is not statistically significantly associated with the outcome, the null distribution is non-normal, contrary to the assumption of DeLong test. Our simulations of different scenarios show that the loss of power because of such a misuse of the DeLong test leads to a conservative test for small and moderate effect sizes. This problem does not exist in cases of predictors that are associated with the outcome and for non-nested models. We suggest that for nested models, only the test of association be performed for the new predictors, and if the result is significant, change in AUC be estimated with an appropriate confidence interval, which can be based on the DeLong approach.
192 citations
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TL;DR: G*Power 3 provides improved effect size calculators and graphic options, supports both distribution-based and design-based input modes, and offers all types of power analyses in which users might be interested.
Abstract: G*Power (Erdfelder, Faul, & Buchner, 1996) was designed as a general stand-alone power analysis program for statistical tests commonly used in social and behavioral research. G*Power 3 is a major extension of, and improvement over, the previous versions. It runs on widely used computer platforms (i.e., Windows XP, Windows Vista, and Mac OS X 10.4) and covers many different statistical tests of thet, F, and χ2 test families. In addition, it includes power analyses forz tests and some exact tests. G*Power 3 provides improved effect size calculators and graphic options, supports both distribution-based and design-based input modes, and offers all types of power analyses in which users might be interested. Like its predecessors, G*Power 3 is free.
40,195 citations
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
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
TL;DR: Because of the increased complexity of analysis and interpretation of clinical genetic testing described in this report, the ACMG strongly recommends thatclinical molecular genetic testing should be performed in a Clinical Laboratory Improvement Amendments–approved laboratory, with results interpreted by a board-certified clinical molecular geneticist or molecular genetic pathologist or the equivalent.
17,834 citations
TL;DR: In those older than age 50, systolic blood pressure of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP, and hypertension will be controlled only if patients are motivated to stay on their treatment plan.
Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.
14,975 citations