; for the Fracture Intervention Trial Research Group Context.-Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures. Objective.-To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density (BMD) but no vertebral fractures. Design.-Randomized, blinded, placebo-controlled trial. Setting.-Eleven community-based clinical research centers. Subjects.-Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm 2 or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later). Intervention.-All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial. Main Outcome Measures.-Clinical fractures confirmed by x-ray reports, new vertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry. Results.-Alendronate increased BMD at all sites studied (PϽ.001) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group, but not significantly so (14% reduction; relative hazard [RH], 0.86; 95% confidence interval [CI], 0.73-1.01). Alendronate reduced clinical fractures by 36% in women with baseline osteoporosis at the femoral neck (Ͼ2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects. Conclusions.-In women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD.

The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study is a national, population-based, longitudinal study of 30,000 African-American and white adults aged ≧45 years. The objective is to determine the causes for the excess stroke mortality in the Southeastern US and among African-Americans. Participants are randomly sampled with recruitment by mail then telephone, where data on stroke risk factors, sociodemographic, lifestyle, and psychosocial characteristics are collected. Written informed consent, physical and physiological measures, and fasting samples are collected during a subsequent in-home visit. Participants are followed via telephone at 6-month intervals for identification of stroke events. The novel aspects of the REGARDS study allow for the creation of a national cohort to address geographic and ethnic differences in stroke.

Insulin resistance may be an important cause of a constellation of cardiovascular risk factors in adults, and onset of this syndrome may occur in childhood. However, children normally experience transient insulin resistance at puberty. There were 357 normal children (159 girls, 198 boys) age 10-14 years who underwent euglycemic clamp studies to assess the effects of Tanner stage (T), sex, ethnicity, and BMI on insulin resistance. Insulin resistance increased immediately at the onset of puberty (T2), but returned to near prepubertal levels by the end of puberty (T5). Its peak occurred at T3 in both sexes, and girls were more insulin resistant than boys at all T stages. White boys appeared to be more insulin resistant than black boys; no difference was seen between white and black girls. Insulin resistance was strongly related to BMI, triceps skinfold thickness, and waist circumference, and this relationship was independent of Tanner stage or sex. Differences in BMI and adiposity did not, however, entirely explain the insulin resistance of puberty. These results demonstrate that 1) significant differences in insulin resistance are present between boys and girls; 2) insulin resistance increases significantly at T2, T3, and T4, but decreases to near prepubertal levels at T5; and 3) while insulin resistance is related to BMI and anthropometric measures of fatness, these factors do not completely explain the insulin resistance that occurs during the Tanner stages of puberty.

The Coronary Drug Project was conducted between 1966 and 1975 to assess the long-term efficacy and safety of five lipid-influencing drugs in 8,341 men aged 30 to 64 years with electrocardiogram-documented previous myocardial infarction. The two estrogen regimens and dextrothyroxine were discontinued early because of adverse effects. No evidence of efficacy was found for the clofibrate treatment. Niacin treatment showed modest benefit in decreasing definite nonfatal recurrent myocardial infarction but did not decrease total mortality. With a mean follow-up of 15 years, nearly 9 years after termination of the trial, mortality from all causes in each of the drug groups, except for niacin, was similar to that in the placebo group. Mortality in the niacin group was 11% lower than in the placebo group (52.0 versus 58.2%; p = 0.0004). This late benefit of niacin, occurring after discontinuation of the drug, may be a result of a translation into a mortality benefit over subsequent years of the early favorable effect of niacin in decreasing nonfatal reinfarction or a result of the cholesterol-lowering effect of niacin, or both.

The waist-hip ratio offers additional prognostic information beyond BMI and waist circumference.

Objectives To define the incidence and cumulative risk of atrial fibrillation (AF) in a population-based cohort of whites and African-Americans. Background African-Americans reportedly have a lower risk of AF than whites despite their higher exposure to AF risk factors. However, precise estimates of AF incidence in African-Americans have not been previously published. Methods We studied the incidence of AF in the Atherosclerosis Risk in Communities Study, which has followed up 15,792 men and women aged 45-65 at baseline from four communities in the United States since 1987. AF cases were identified from ECGs conducted at baseline and three follow-up visits, and from hospitalizations and death certificates through the end of 2004. During follow-up, 1,085 new cases of AF were identified (196 in African-Americans, 889 in whites). Results Crude incidence rates of AF were 6.7, 4.0, 3.9 and 3.0 per 1,000 persons per year in white men, white women, African-American men and African-American women, respectively. Increasing age was exponentially associated with an elevated risk of AF. Compared to whites, African-Americans had a 41% (95% confidence interval: 8%-62%) lower age- and sex-adjusted risk of being diagnosed with AF. The cumulative risk of AF at age 80 was 21% in white men, 17% in white women, and 11% in African-American men and women. Conclusion In this population-based cohort, African-Americans presented a lower risk of AF than whites. Still, the burden of AF among the former is substantial, with 1 in 9 receiving a diagnosis of AF before the age of 80.

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BackgroundThe SMART study was a trial of intermittent use of antiretroviral therapy (ART) (drug conservation [DC]) versus continuous use of ART (viral suppression [VS]) as a strategy to reduce toxicities, including cardiovascular disease (CVD) risk. We studied the predictive value of high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and D-dimer with CVD morbidity and mortality in HIV-infected patients who were enrolled in SMART beyond other measured CVD risk factors.MethodsA blood sample was available in 5098 participants who were enrolled in the SMART study for the measurement of IL-6, hsCRP and D-dimer. Hazard ratios (HR) with 95% CI for CVD events were estimated for each quartile (Q) for each biomarker vs the 1st quartile and for 1 SD higher levels. For both treatment groups combined, unadjusted and adjusted HRs were determined using Cox regression models.ResultsThere were 252 participants who had a CVD event over a median follow-up of 29 months. Adjusted HRs (95% CI) for CVD for Q4 vs Q1 were 4.65 (2.61, 8.29), 2.10 (1.40, 3.16), and 2.14 (1.38, 3.33) for IL-6, hsCRP and D-dimer, respectively. Associations were similar for the DC and VS treatment groups (interaction p-values were >0.30). The addition of the three biomarkers to a model that included baseline covariates significantly improved model fit (p<0.001). Area under the curve (AUC) estimates improved with inclusion of the three biomarkers in a model that included baseline covariates corresponding to other CVD risk factors and HIV factors (0.741 to 0.771; p<0.001 for difference).ConclusionsIn HIV-infected individuals, IL-6, hsCRP and D-dimer are associated with an increased risk of CVD independent of other CVD risk factors. Further research is needed to determine whether these biomarkers can be used to improve CVD risk prediction among HIV positive individuals.