Summary Background The JUPITER trial showed that some patients with LDL-cholesterol concentrations less than 3·37 mmol/L (<130 mg/dL) and high-sensitivity C-reactive protein (hsCRP) concentrations of ...2 mg/L or more benefit from treatment with rosuvastatin, although absolute rates of cardiovascular events were low. In a population eligible for JUPITER, we established whether coronary artery calcium (CAC) might further stratify risk; additionally we compared hsCRP with CAC for risk prediction across the range of low and high hsCRP values. Methods 950 participants from the Multi-Ethnic Study of Atheroslcerosis (MESA) met all criteria for JUPITER entry. We compared coronary heart disease and cardiovascular disease event rates and multivariable-adjusted hazard ratios after stratifying by burden of CAC (scores of 0, 1–100, or >100). We calculated 5-year number needed to treat (NNT) by applying the benefit recorded in JUPITER to the event rates within each CAC strata. Findings Median follow-up was 5·8 years (IQR 5·7–5·9). 444 (47%) patients in the MESA JUPITER population had CAC scores of 0 and, in this group, rates of coronary heart disease events were 0·8 per 1000 person-years. 74% of all coronary events were in the 239 (25%) of participants with CAC scores of more than 100 (20·2 per 1000 person-years). For coronary heart disease, the predicted 5-year NNT was 549 for CAC score 0, 94 for scores 1–100, and 24 for scores greater than 100. For cardiovascular disease, the NNT was 124, 54, and 19. In the total study population, presence of CAC was associated with a hazard ratio of 4·29 (95% CI 1·99–9·25) for coronary heart disease, and of 2·57 (1·48–4·48) for cardiovascular disease. hsCRP was not associated with either disease after multivariable adjustment. Interpretation CAC seems to further stratify risk in patients eligible for JUPITER, and could be used to target subgroups of patients who are expected to derive the most, and the least, absolute benefit from statin treatment. Focusing of treatment on the subset of individuals with measurable atherosclerosis could allow for more appropriate allocation of resources. Funding National Institutes of Health–National Heart, Lung, and Blood Institute.
Aims
We aimed to investigate the association between endothelial dysfunction, assessed by brachial flow‐mediated dilation (FMD), and the incidence of heart failure (HF) in the community‐based ...Multi‐Ethnic Study of Atherosclerosis.
Methods and results
Brachial artery FMD was measured in a nested case‐cohort sample including 3496 of 6814 Multi‐Ethnic Study of Atherosclerosis participants without prevalent cardiovascular disease (mean age 61 years, 50% women). Multivariable probability‐weighted Cox proportional hazards analysis was used to examine the association between FMD and incident HF. We also investigated the association between FMD and HF with reduced vs. preserved ejection fraction HFrEF (left ventricular ejection fraction <45%) vs. HFpEF (left ventricular ejection fraction ≥45%). During follow‐up (median 12 years), 149 participants developed incident HF (incidence rate 3.7 events per 1000 person years). There were 56 HFrEF and 69 HFpEF events (incidence rates 1.4 and 1.7 events per 1000 person years, respectively). In multivariable models adjusted for established HF risk factors (age, sex, race/ethnicity, body mass index, systolic blood pressure, antihypertensive treatment, heart rate, diabetes mellitus, history of myocardial infarction, current smoker, and former smoker status), individuals in the highest quartile of FMD (reflecting better endothelial function) had a lower HF risk compared with individuals in the lowest quartile hazard ratio 0.53, 95% confidence interval (CI) 0.31–0.95. Lower risk according to higher FMD was particularly evident for HFrEF, but not for HFpEF (hazard ratio per standard deviation increase 0.79, 95% CI 0.64–0.97 vs. 0.99, 95% CI 0.78–1.26, respectively). Results remained similar after adjustment for baseline natriuretic peptide levels. The addition of FMD to established HF risk factors generally rendered no or only modest improvement in C‐statistics C‐statistics for model with established HF risk factors: 0.774, and with the addition of FMD: 0.776 (delta C 0.002, 95% confidence interval −0.002 to 0.006).
Conclusions
Endothelial dysfunction was independently associated with HF in this community cohort, suggesting a pathophysiological contribution of endothelial function to the development of HF, in particular HFrEF. However, the value of FMD measurements for HF risk prediction seems limited.
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