Ralph B. D'Agostino

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.

Burden and prognostic importance of subclinical cardiovascular disease in overweight and obese individuals.

Abstract: Background— The burden and prognostic importance of subclinical cardiovascular disease (CVD) in obesity has not been investigated systematically. Methods and Results— We examined prevalence of subclinical disease in 1938 Framingham Study participants (mean age, 57 years; 59% women) by use of 5 tests (electrocardiography, echocardiography, carotid ultrasound, ankle-brachial pressure, and urinary albumin excretion) and stratified by body mass index (BMI) (normal, <25; overweight, 25 to <30.0; obese, ≥30 kg/m2) and waist circumference (WC) (increased, ≥88 cm for women or ≥102 cm for men). We investigated risk of overt CVD associated with adiposity according to presence versus absence of subclinical disease on any of the 5 tests. Prevalence of subclinical disease was higher in overweight (40.0%; adjusted odds ratio, 1.68) and obese individuals (49.7%; odds ratio, 2.82) compared with individuals with normal BMI (29.3%) and in individuals with increased WC (44.9%; odds ratio, 1.67) compared with normal WC (31.9...

The Stroke Prevention Policy Model : Linking evidence and clinical decisions

Abstract: Simulation models that support decision and cost-effectiveness analysis can further the goals of evidence-based medicine by facilitating the synthesis of information from several sources into a single comprehensive structure. The Stroke Prevention Policy Model (SPPM) performs this function for the clinical and policy questions that surround stroke prevention. This paper first describes the basic structure and functions of the SPPM, concentrating on the role of large databases (broadly defined as any database that contains many patients, regardless of study design) in providing the SPPM inputs. Next, recognizing that the use of modeling continues to be a source of some controversy in the medical community, it discusses the philosophical underpinnings of the SPPM. Finally, it discusses conclusions in the context of both stroke prevention and other complex medical decisions. We conclude that despite the difficulties in developing comprehensive models (for example, the length and complexity of model development and validation processes, the proprietary nature of data sources, and the necessity for developing new software), the benefits of such models exceed the costs of continuing to rely on more conventional methods. Although they should not replace the clinician in decision making, comprehensive models based on the best available evidence from large databases can support decision making in medicine.

Heritability of the Ankle-Brachial Index The Framingham Offspring Study

Abstract: The ankle-brachial blood pressure index (ABI) is a widely utilized measure for detecting peripheral arterial disease. Genetic contributions to variation in ABI are largely unknown. The authors sought to estimate ABI heritability in a community-based sample. From 1995 to 1998, ABI was measured in 1,097 men and 1,189 women (mean age = 57 years; range, 29-85 years) from 999 families in the Framingham Offspring cohort. Correlation coefficients for sibling pairs were calculated using the family correlations (FCOR) procedure in S.A.G.E. (Case Western Reserve University, Cleveland, Ohio). The heritability of ABI was estimated using variance-components methods in SOLAR (Southwest Foundation for Biomedical Research, San Antonio, Texas). Analyses were performed on normalized crude ABI and on normalized residuals from multiple linear regression analyses in SAS (SAS Institute, Inc., Cary, North Carolina) that adjusted for age, sex, smoking, diabetes, hypertension, ratio of total cholesterol to high density lipoprotein cholesterol, log triglyceride level, and body mass index. The mean ABI was 1.1 (range, 0.4-1.4). The age- and sex-adjusted and multivariable-adjusted sibling-pair correlation coefficients for normalized ABI were 0.15 and 0.11, respectively, resulting in heritability estimates of 0.30 and 0.22. Crude, age- and sex-adjusted, and multivariable-adjusted heritabilities for normalized ABI estimated using variance-components analysis were 0.27 (standard error, 0.06), 0.30 (standard error, 0.06), and 0.21 (standard error, 0.06), respectively (all p values < 0.0001). A modest proportion of the variability in ABI is explained by genetic factors.

Doxorubicin Exposure Causes Subacute Cardiac Atrophy Dependent on the Striated Muscle-Specific Ubiquitin Ligase MuRF1.

Abstract: Background Anthracycline chemotherapeutics, such as doxorubicin, are used widely in the treatment of numerous malignancies. The primary dose-limiting adverse effect of anthracyclines is cardiotoxicity that often presents as heart failure due to dilated cardiomyopathy years after anthracycline exposure. Recent data from animal studies indicate that anthracyclines cause cardiac atrophy. The timing of onset and underlying mechanisms are not well defined, and the relevance of these findings to human disease is unclear. Methods and Results Wild-type mice were sacrificed 1 week after intraperitoneal administration of doxorubicin (1-25 mg/kg), revealing a dose-dependent decrease in cardiac mass ( R2=0.64; P<0.0001) and a significant decrease in cardiomyocyte cross-sectional area (336±29 versus 188±14 µm2; P<0.0001). Myocardial tissue analysis identified a dose-dependent upregulation of the ubiquitin ligase, MuRF1 (muscle ring finger-1; R2=0.91; P=0.003) and a molecular profile of muscle atrophy. To investigate the determinants of doxorubicin-induced cardiac atrophy, we administered doxorubicin 20 mg/kg to mice lacking MuRF1 (MuRF1-/-) and wild-type littermates. MuRF1-/- mice were protected from cardiac atrophy and exhibited no reduction in contractile function. To explore the clinical relevance of these findings, we analyzed cardiac magnetic resonance imaging data from 70 patients in the DETECT-1 cohort and found that anthracycline exposure was associated with decreased cardiac mass evident within 1 month and persisting to 6 months after initiation. Conclusions Doxorubicin causes a subacute decrease in cardiac mass in both mice and humans. In mice, doxorubicin-induced cardiac atrophy is dependent on MuRF1. These findings suggest that therapies directed at preventing or reversing cardiac atrophy might preserve the cardiac function of cancer patients receiving anthracyclines.

Development and validation of an ankle brachial index risk model for the prediction of cardiovascular events

Abstract: Background: The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS. Design: An analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events. Methods: Subjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS+ABI, were fitted for the primary outcome of major coronary events. © 2013 The European Society of Cardiology.

G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences

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.

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.

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。

Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

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.