Objectives To assess the prognostic utility of lipoprotein (a) [Lp(a)] in individuals with coronary artery disease (CAD). Background Data regarding an association between Lp(a) and cardiovascular (CV) risk in secondary prevention populations are sparse. Methods Plasma Lp(a) was measured in 6762 subjects with CAD from three studies; data were then combined with eight previously published studies for a total of 18,979 subjects. Results Across the three studies, increasing levels of Lp(a) were not associated with the risk of CV events when modeled as a continuous variable (OR 1.03 per log-transformed SD, 95% CI 0.96-1.11) or by quintile (OR Q5:Q1 1.05, 95% CI, 0.83-1.34). When data were combined with previously published studies of Lp(a) in secondary prevention, subjects with Lp(a) levels in the highest quantile were at increased risk of CV events (OR 1.40, 95% CI 1.15-1.71), but with significant between-study heterogeneity (P=0.001). When stratified on the basis of LDL cholesterol, the association between Lp(a) and CV events was significant in studies in which average LDL cholesterol was ≥130 mg/dl (OR 1.46, 95% CI 1.23-1.73, P<0.001), whereas this relationship was not significant for studies with an average LDL cholesterol <130 mg/dl (OR 1.20, 95 CI 0.90-1.60, P=0.21). Conclusions Lp(a) is significantly associated with the risk of CV events in patients with established CAD; however, there exists marked heterogeneity across trials. In particular, the prognostic value of Lp(a) in patients with low cholesterol levels remains unclear.

Objectives This study sought to test 2 hypotheses: 1) fibroblast growth factor (FGF)-23 identifies patients with stable ischemic heart disease (SIHD) at high risk of cardiovascular events independent of clinical factors, renal function, and established cardiovascular biomarkers; and 2) FGF-23 identifies patients who derive greater clinical benefit from angiotensin-converting enzyme inhibitor therapy. Background FGF-23 is an endocrine regulator of mineral metabolism and markedly elevated levels are associated with cardiovascular events in patients with chronic kidney disease. Data in patients with SIHD are more sparse. Methods FGF-23 levels were measured in 3,627 patients with SIHD randomly assigned to trandolapril or placebo within the PEACE (Prevention of Events With Angiotensin-Converting Enzyme) trial and followed up for a median of 5.1 years. Results After adjustment for clinical risk predictors, left ventricular ejection fraction, markers of renal function, and established cardiovascular biomarkers, FGF-23 concentration was independently associated with an increased risk of cardiovascular death or heart failure among patients allocated to placebo (quartile 4 hazard ratio: 1.73; 95% confidence interval, 1.09 to 2.74; p = 0.02) and significantly improved metrics of discrimination. Furthermore, among patients in the top quartile of FGF-23 levels, trandolapril significantly reduced cardiovascular death or incident heart failure (hazard ratio: 0.45; 95% confidence interval: 0.28 to 0.72), whereas there was no clinical benefit in the remaining patients (hazard ratio: 1.07; 95% confidence interval: 0.75 to 1.52; p interaction = 0.0039). This interaction was independent of and additive to stratification based on renal function. Conclusions Elevated levels of FGF-23 are associated with cardiovascular death and incident heart failure in patients with SIHD and identify patients who derive significant clinical benefit from angiotensin-converting enzyme inhibitor therapy regardless of renal function.

Background-Aggressive blood pressure (BP) control has been advocated in patients with acute coronary syndrome, but few data exist in this population relative to cardiovascular outcomes. Methods and Results-We evaluated 4162 patients enrolled in the PRavastatin Or atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction (PROVE IT-TIMI) 22 trial (acute coronary syndrome patients randomized to pravastatin 40 mg versus atorvastatin 80 mg). The average follow-up BP (systolic and diastolic) was categorized into 10-mm Hg increments. The primary outcome was a composite of death due to any cause, myocardial infarction, unstable angina requiring rehospitalization, revascularization after 30 days, and stroke. The secondary outcome was a composite of death due to coronary heart disease, nonfatal myocardial infarction, or revascularization.The relationship between BP (systolic or diastolic) followed a J-or U-shaped curve association with primary, secondary, and individual outcomes, with increased events rates at both low and high BP values, both unadjusted and after adjustment for baseline variables, baseline C-reactive protein, and on-treatment average levels of low-density