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.

Cardiac Abnormalities in Patients With Hutchinson-Gilford Progeria Syndrome.

Abstract: Importance Hutchinson-Gilford progeria syndrome (HGPS) is an ultrarare disorder associated with premature death due to cardiovascular events during the second decade of life. However, because of its rarity (107 identified living patients), the natural history of cardiac disease remains uncharacterized. Therefore, meaningful cardiac end points for clinical trials have been difficult to establish. Objective To examine the course of appearance of cardiac abnormalities in patients with HGPS to identify meaningful cardiac end points for use in future clinical trials. Design, Setting, and Participants In this prospective, cross-sectional, observational study, 27 consecutive patients with clinically and genetically confirmed classic HGPS were evaluated at a single center for 1 visit from July 1, 2014, through February 29, 2016, before initiation of treatment. Exposure Classic HGPS. Main Outcomes and Measures Echocardiography was used to assess ventricular and valve function using standard techniques. Diastolic left ventricular (LV) function was assessed using tissue Doppler imaging. Previously published normative data were used to adjust findings to age and body size. Results This study included 27 patients (median age, 5.6 years; age range, 2-17 years; 15 [56%] male). Among echocardiographic indicators, LV diastolic dysfunction, defined as a tissue Doppler septal or lateral early velocity z score less than −2, was the most prevalent abnormality, seen in 16 patients (59%). Diastolic dysfunction was seen in all age groups, and its prevalence increased with age, mirroring findings seen during normal aging. Indicators of LV diastolic function were more abnormal in older patients. The z scores for lateral and septal early velocities were lower ( r = −0.77, P r = −0.66, P r = 0.80, P r = 0.72, P Conclusions and Relevance In this largest-to-date cohort of patients with HGPS, LV diastolic dysfunction was the most prevalent echocardiographic abnormality and its prevalence increased with aging. Echocardiographic indicators of LV diastolic function may be useful end points in future clinical trials in this patient population.

Applicability of Cholesterol-Lowering Primary Prevention Trials to a General Population: The Framingham Heart Study

Abstract: Background Four large trials have shown cholesterol-reduction therapy to be effective for primary prevention of coronary heart disease (CHD). Methods To determine the generalizability of these trials to a community-based sample, we compared the total cholesterol and high-density lipoprotein cholesterol (HDL-C) distributions of patients in the 4 trials with those of Framingham Heart Study subjects. Lipid profiles that have not been studied were identified. Twelve-year rates of incident CHD were compared between subjects who met eligibility criteria and those who did not. Results The Framingham sample included 2498 men and 2870 women aged 30 to 74 years. Among Framingham men, 23.4% to 42.0% met eligibility criteria for each of the 4 trials based on their lipid levels; 60.2% met eligibility criteria for at least 1 trial. For the 1 trial that included women, 20.2% of Framingham women met eligibility criteria. In general, subjects with desirable total cholesterol levels and lower HDL-C levels and subjects with average total cholesterol levels and average to higher HDL-C levels have not been included in these trials. Among subjects who developed incident CHD during follow-up, 25.1% of men and 66.2% of women would not have been eligible for any trial. Most ineligible subjects who developed CHD had isolated hypertriglyceridemia (>2.25 mmol/L [>200 mg/dL]). Conclusions In our sample, 40% of men and 80% of women had lipid profiles that have not been studied in large trials to date. We observed a large number of CHD events in "ineligible" subjects in whom hypertriglyceridemia was common. Further studies are needed to define the role of lipid-lowering therapy vs other strategies for primary prevention in the general population.

Automated assessments of circumferential strain from cine CMR correlate with LVEF declines in cancer patients early after receipt of cardio-toxic chemotherapy

Abstract: In patients with cancer receiving potentially cardio-toxic chemotherapy, measurements of left ventricular (LV) circumferential or longitudinal strain are often used clinically to identify myocardial dysfunction. Using a new software algorithm, we sought to determine in individuals receiving treatment for cancer the association between automated assessments of LV mean mid-wall circumferential strain and conventional measures of LV ejection fraction (EF) both obtained from cardiovascular magnetic resonance (CMR) cine balanced steady-state free-precession (bSSFP) white-blood acquisitions. Before and 3 months after initiating treatment with potentially cardio-toxic chemotherapy, 72 individuals (aged 54 ± 14 years with breast cancer [39%], lymphoma [49%], or sarcoma [12%]) underwent serial CMR cine bSSFP assessments of LV volumes and EF, and mean mid-wall circumferential strain determined from these same cine images as well as from additional tagged CMR images. On the cine images, assessments of strain were obtained using the newly developed deformation-based segmentation algorithm. Assessments of LV volumes/EF from the cine images and strain from tagged CMR were accomplished using commercially available software. All measures were analyzed in a blinded fashion independent of one another. Acceptable measures for the automated assessments of mean mid-wall circumferential strain from the cine images were obtained in 142 of 144 visits (98.6%) with an overall analysis time averaging 6:47 ± 1:06 min. The results from these automated measures averaged −18.8 ± 2.9 at baseline and −17.6 ± 3.1 at 3 months (p = 0.001). Left ventricular EF declined slightly from 65 ± 7% at baseline to 62 ± 7% at 3 months (p = 0.0002). The correlation between strain from cine imaging and LVEF was r = −0.61 (p < 0.0001). In addition, the 3-month changes in LV strain and LVEF were correlated (r = −0.49; p < 0.0001). The correlation between cine and tagged derived assessments of strain was r = 0.23; p = 0.01. Automated measures of LV mean mid-wall circumferential strain can be obtained in 6¾ minutes from cine bSSFP LV short-axis images (used concurrently to assess LV volumes and EF) in 98.6% of patients receiving treatment for cancer with potentially cardio-toxic chemotherapy. These cine derived measures of circumferential strain correlate with early subclinical declines in LVEF.

Nutritional correlates of dietary glycaemic index: new aspects from a population perspective.

Abstract: The role of dietary glycaemic index (GI) and glycaemic load (GL) in disease aetiology is of increasing interest. However, nutritional factors related to dietary GI and GL are not well understood from a population perspective. We aimed to investigate the relation ship between GI and GL and dietary intake at the food and nutrient level. Study subjects were 1071 non-diabetic adults from the Insulin Resistance Atherosclerosis Study, Exam I, 1992-4. Usual dietary intake was assessed with a 114-item modified Block food frequency questionnaire. Published GI values were assigned to food line items. Correlation and regression analyses were conducted. Intake of white bread, beer, meats and fries/fried potatoes was positively associated with average GI, as was fat, starch and alcohol intake (before and after energy adjustment). Intake of fruits and low-fat milk was inversely associated with GI, as were intakes of mono- and disaccharides, and fibre. GL was positively correlated with carbohydrate foods and inversely with non-carbohydrate foods. Gender-specific regression models identified eight food groups explaining 63 % (men) and 55 % (women) total GI variation after adjusting for demographics; 70 % of variation in GL was explained by eleven (men) and nine (women) food groups, respectively. Although the GI of a food is an indicator of the ability of carbohydrates to raise blood glucose, dietary GI, unlike GL, appears to reflect more dimensions of diet than just carbohydrates, such as the combination of foods consumed. This may have implications for the interpretation of dietary GI in epidemiologic studies.

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.