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.

Evaluating Discrimination of Risk Prediction Models: The C Statistic

Abstract: Risk prediction models help clinicians develop personalized treatments for patients. The models generally use variables measured at one time point to estimate the probability of an outcome occurring within a given time in the future. It is essential to assess the performance of a risk prediction model in the setting in which it will be used. This is done by evaluating the model’s discrimination and calibration. Discrimination refers to the ability of the model to separate individuals who develop events from those who do not. In time-toevent settings, discrimination is the ability of the model to predict who will develop an event earlier and who will develop an event later or not at all. Calibration measures how accurately the model’s predictions match overall observed event rates. In this issueof JAMA,Melgaardet al used theCstatistic, a global measure of model discrimination, to assess the ability of the CHA2DS2-VASc model to predict ischemic stroke, thromboembolism, or death in patients with heart failure and to do so separately for patients who had or did not have atrial fibrillation (AF).1

Relations of thyroid function to body weight: cross-sectional and longitudinal observations in a community-based sample.

Abstract: Background Overt hypothyroidism and hyperthyroidism may be associated with weight gain and loss. We assessed whether variations in thyroid function within the reference (physiologic) range are associated with body weight. Methods Framingham Offspring Study participants (n = 2407) who attended 2 consecutive routine examinations, were not receiving thyroid hormone therapy, and had baseline serum thyrotropin (TSH) concentrations of 0.5 to 5.0 mIU/L and follow-up concentrations of 0.5 to 10.0 mIU/L were included in this study. Baseline TSH concentrations were related to body weight and body weight change during 3.5 years of follow-up. Results At baseline, adjusted mean weight increased progressively from 64.5 to 70.2 kg in the lowest to highest TSH concentration quartiles in women (P Conclusions Thyroid function (as assessed by serum TSH concentration) within the reference range is associated with body weight in both sexes. Our findings raise the possibility that modest increases in serum TSH concentrations within the reference range may be associated with weight gain.

Associations of adiponectin, resistin, and tumor necrosis factor-alpha with insulin resistance.

Abstract: Context: Adipose tissue-derived adipokines may contribute to insulin resistance. Objective: We tested the hypothesis that adipokines are associated with insulin resistance in a community-based cohort and that associations are maintained in people with and without the metabolic syndrome (high vs. low risk of diabetes). Design, Setting, and Participants: We studied a cross-sectional sample of 2356 individuals attending the seventh examination (1998–2001) of the Framingham Offspring Study. We measured levels of glucose, insulin, adiponectin, resistin, and TNFα in fasting blood samples and defined metabolic syndrome by updated National Cholesterol Education Program criteria. We used ANOVA to test associations of adipokines with insulin resistance and multivariable logistic regression models to assess joint associations of adipokines and metabolic syndrome with insulin resistance. Main Outcome Measure: Homeostasis model (HOMA-IR), with insulin resistance defined by HOMA-IR greater than the 75th percentile, was measured. Results: Age- and sex-adjusted HOMA-IR levels were inversely related to adiponectin (r = −0.40, P < 0.0001) and positively related to resistin (r = 0.13, P < 0.0001) and TNFα (r = 0.12, P < 0.0001). The prevalence of insulin resistance increased with decreasing tertiles of adiponectin (from 10.9% in the third to 42.5% in the first tertile; P < 0.0001) and increasing tertiles of resistin (from 19.3 to 30.9%; P < 0.0001) and TNFα (from 18.8 to 32.0%; P < 0.0001). Results were similar after adjustment for body mass index. These associations were present in individuals with or without the metabolic syndrome. In multivariable regression models, metabolic syndrome and adipokines individually and jointly were significantly associated with insulin resistance. Conclusion: Adverse levels of adipokines are associated with insulin resistance in individuals at low or high diabetes risk.

Serum Insulin-like Growth Factor I and Risk for Heart Failure in Elderly Individuals without a Previous Myocardial Infarction: The Framingham Heart Study

Abstract: In this prospective, community-based study, serum insulin-like growth factor I level was inversely related to the risk for congestive heart failure in elderly people without a previous myocardial i...

Increased Platelet Aggregability Associated With Platelet GPIIIa PlA2 Polymorphism : The Framingham Offspring Study

Abstract: The platelet glycoprotein IIb/IIIa (GP IIb/IIIa) plays a pivotal role in platelet aggregation Recent data suggest that the Pl A2 polymorphism of GPIIIa may be associated with an increased risk for cardiovascular disease However, it is unknown if there is any association between this polymorphism and platelet reactivity We determined GPIIIa genotype and platelet reactivity phenotype data in 1422 subjects from the Framingham Offspring Study Genotyping was performed using PCR based restriction fragment length polymorphism analysis Platelet aggregability was evaluated by the Born method The threshold concentrations of epinephrine and adenosine diphosphate (ADP) were determined Allele frequencies of Pl A1 and Pl A2 were 084 and 016, respectively The presence of one or two Pl A2 alleles was associated with increased platelet aggregability as indicated by incremen- tally lower threshold concentrations for epinephrine and ADP For epinephrine, the mean concentrations were 09 µmol/L (09–10) for homozygous Pl A1 , 07 µmol/L (07–09) for the heterozygous Pl A1 / Pl A2 and 06 µmol/L (04–10) for homozygous Pl A2 individuals, p = 0009 The increase in aggregability induced by epinephrine remained highly significant (p = 0007) after adjustment for covariates For ADP-induced aggregation, the respective mean concentrations were 31 µmol/L (30–32), 30 µmol/L (29–32), and 28 µmol/L (24–33), p = 019 after adjustment for covariates Our findings indicate that molecular variants of the gene encoding GPIIIa play a role in platelet reactivity in vitro Our observations are compatible with and provide an explanation for the reported association of the Pl A2 allotype with increased risk for cardiovascular disease

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.