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High levels of fibroblast growth factor 23 are associated with accelerated progression of CKD. Whether high fibroblast growth factor 23 levels also predict incident CKD is uncertain.A prospective case-cohort study was conducted within the Action to Control Cardiovascular Risk in Diabetes Trial. The analytic sample consisted of a random subcohort of 590 patients with type 2 diabetes without prevalent CKD at baseline, 124 of whom developed incident CKD during follow-up, and 520 additional patients with incident CKD outside the random subcohort. The association between serum intact fibroblast growth factor 23 and incident CKD, defined as the new onset of eGFR60 ml/min per 1.73 m(2) that represented a ≥25% decrease from baseline in an individual with eGFR≥60 ml/min per 1.73 m(2) and no microalbuminuria (30 mg/g creatinine) at baseline, was tested.The mean baseline eGFR in the random subcohort was 90.9±22.7 ml/min per 1.73 m(2). During a median follow-up of 4.7 years, there was a total of 644 patients with incident CKD. The median baseline fibroblast growth factor 23 level was modestly higher among patients with incident CKD versus controls (43.5, interquartile range=34.7-55.1 versus 39.8, interquartile range=31.9-49.5 pg/ml; P0.001). Higher baseline fibroblast growth factor 23 levels were associated with higher risk of incident CKD in unadjusted and demographics-adjusted models, but the effect was attenuated after additional adjustment for clinical risk factors and baseline eGFR (hazard ratio per SD of natural log fibroblast growth factor 23, 1.09; 95% confidence interval, 0.94 to 1.27), which was the strongest predictor of incident CKD. Consistent with the results of primary analyses, baseline fibroblast growth factor 23 was not associated with eGFR slope.Higher fibroblast growth factor 23 levels are not independently associated with higher risk of incident CKD in patients with type 2 diabetes. more...

Background —Stroke is a leading cause of death and disability. Although clinical trials of the early lipid-lowering therapies did not demonstrate a reduction in the rates of stroke, data from recently completed statin trials strongly suggest benefit. Methods and Results —The effect of pravastatin 40 mg/d on stroke events was investigated in a prospectively defined pooled analysis of 3 large, placebo-controlled, randomized trials that included 19 768 patients with 102 559 person-years of follow-up. In all, 598 participants had a stroke during ≈5 years of follow-up. The 2 secondary prevention trials (CARE [Cholesterol And Recurrent Events] and LIPID [Long-term Intervention with Pravastatin in Ischemic Disease]) individually demonstrated reductions in nonfatal and total stroke rates. When the 13 173 patients from CARE and LIPID were combined, there was a 22% reduction in total strokes (95% CI 7% to 35%, P =0.01) and a 25% reduction in nonfatal stroke (95% CI 10% to 38%). The beneficial effect of pravastatin on total stroke was observed across a wide range of patient characteristics. WOSCOPS (West of Scotland Coronary Prevention Study, a primary prevention trial in hypercholesterolemic men) exhibited a similar, although smaller, trend for a reduction in total stroke. Among the CARE/LIPID participants, pravastatin was associated with a 23% reduction in nonhemorrhagic strokes (95% CI 6% to 37%), but there was no statistical treatment group difference in hemorrhagic or unknown type. Conclusions —Pravastatin reduced the risk of stroke over a wide range of lipid values among patients with documented coronary disease. This effect was due to a reduction in nonfatal nonhemorrhagic strokes. more...

Background —The results of angiographic studies have suggested that calcium channel–blocking agents may prevent new coronary lesion formation, the progression of minimal lesions, or both. Methods and Results —The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) was a multicenter, randomized, placebo-controlled, double-masked clinical trial designed to test whether amlodipine would slow the progression of early coronary atherosclerosis in 825 patients with angiographically documented coronary artery disease. The primary outcome was the average 36-month angiographic change in mean minimal diameters of segments with a baseline diameter stenosis of 30%. A secondary hypothesis was whether amlodipine would reduce the rate of atherosclerosis in the carotid arteries as assessed with B-mode ultrasonography, which measured intimal-medial thicknesses (IMT). The rates of clinical events were also monitored. The placebo and amlodipine groups had nearly identical average 36-month reductions in the minimal diameter: 0.084 versus 0.095 mm, respectively ( P =0.38). In contrast, amlodipine had a significant effect in slowing the 36-month progression of carotid artery atherosclerosis: the placebo group experienced a 0.033-mm increase in IMT, whereas there was a 0.0126-mm decrease in the amlodipine group ( P =0.007). There was no treatment difference in the rates of all-cause mortality or major cardiovascular events, although amlodipine use was associated with fewer cases of unstable angina and coronary revascularization. Conclusions —Amlodipine has no demonstrable effect on angiographic progression of coronary atherosclerosis or the risk of major cardiovascular events but is associated with fewer hospitalizations for unstable angina and revascularization. more...

Background —Few clinical trials have documented the efficacy of preventive treatment in asymptomatic women. Methods and Results —Lovastatin and minidose warfarin were evaluated in a factorially designed, placebo-controlled, randomized trial. The primary outcome was 3-year change in the mean maximum intimal-medial thickness of the carotid arteries as measured by B-mode ultrasonography. Participants (n=919) were randomized to 1 of 4 treatment groups: lovastatin alone, warfarin alone, lovastatin+warfarin combination, or a double-placebo group. Eligible participants were asymptomatic for cardiovascular disease, with evidence of early carotid atherosclerosis and moderately elevated LDL cholesterol level. Almost half (n=445) of the participants were women. To avoid confounding, 117 women taking estrogen were excluded from analysis. Both sexes experienced reductions in disease progression with lovastatin; there was no evidence of an overall sex×treatment interaction ( P =0.72). When estimates of the sex-specific results were examined post hoc, women experienced disease regression to the greatest extent with the lovastatin+warfarin combination ( P =0.02), although the women on lovastatin alone also had a reduction in progression ( P =0.09). Men experienced the greatest reduction with lovastatin alone ( P =0.02), although there is a suggestion that warfarin may also reduce progression to some extent. Conclusions —Lovastatin is beneficial in reducing disease progression in women and men. Warfarin has no effect in women, although it may reduce progression in men. In men, warfarin does not add to the benefit of lovastatin and has no advantage over lovastatin alone. more...