Person:

O'Donoghue, Michelle

Background: It is unknown whether short sleep duration, obstructive sleep apnea, and overnight shift work are associated with the risk of recurrent cardiovascular events in patients after an acute coronary syndrome. Methods and Results: SOLID‐TIMI 52 (The Stabilization of PLaques UsIng Darapladib‐Thrombolysis in Myocardial Infarction 52 Trial) was a multinational, double‐blind, placebo‐controlled trial that enrolled 13 026 patients ≤30 days of acute coronary syndrome. At baseline, all patients were to complete the Berlin questionnaire to assess risk of obstructive sleep apnea and a sleep and shift work survey. Median follow‐up was 2.5 years. The primary outcome was major coronary events (MCE; coronary heart disease death, myocardial infarction, or urgent revascularization). Cox models were adjusted for clinical predictors. Patients who reported <6 hours sleep per night had a 29% higher risk of MCE (adjusted hazard ratio, 1.29; 95% confidence interval, 1.12–1.49; P<0.001) compared with those with longer sleep. Patients who screened positive for obstructive sleep apnea had a 12% higher risk of MCE (1.12; 1.00–1.24; P=0.04) than those who did not screen positive. Overnight shift work (≥3 night shifts/week for ≥1 year) was associated with a 15% higher risk of MCE (1.15; 1.03–1.29; P=0.01). A step‐wise increase in cardiovascular risk was observed for individuals with more than 1 sleep‐related risk factor. Individuals with all 3 sleep‐related risk factors had a 2‐fold higher risk of MCE (2.01; 1.49–2.71; P<0.0001). Conclusions: Short sleep duration, obstructive sleep apnea, and overnight shift work are under‐recognized as predictors of adverse outcomes after acute coronary syndrome. Increased efforts should be made to identify, treat, and educate patients about the importance of sleep for the potential prevention of cardiovascular events. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01000727.

Background: Interleukin‐6 (IL‐6) is an inflammatory cytokine implicated in plaque instability in acute coronary syndrome (ACS). We aimed to evaluate the prognostic implications of IL‐6 post‐ACS. Methods and Results: IL‐6 concentration was assessed at baseline in 4939 subjects in SOLID‐TIMI 52 (Stabilization of Plaque Using Darapladib—Thrombolysis in Myocardial Infarction 52), a randomized trial of darapladib in patients ≤30 days from ACS. Patients were followed for a median of 2.5 years for major adverse cardiovascular events; cardiovascular death, myocardial infarction, or stroke) and cardiovascular death or heart failure hospitalization. Primary analyses were adjusted first for baseline characteristics, days from index ACS, ACS type, and randomized treatment arm. For every SD increase in IL‐6, there was a 10% higher risk of major adverse cardiovascular events (adjusted hazard ratio [adj HR] 1.10, 95% confidence interval [CI] 1.01‐1.19) and a 22% higher risk of cardiovascular death or heart failure (adj HR 1.22, 95% CI 1.11‐1.34). Patients in the highest IL‐6 quartile had a higher risk of major adverse cardiovascular events (adj HR Q4:Q1 1.57, 95% CI 1.22‐2.03) and cardiovascular death or heart failure (adj HR 2.29, 95% CI 1.6‐3.29). After further adjustment for biomarkers (high‐sensitivity C‐reactive protein, lipoprotein‐associated phospholipase A2 activity, high‐sensitivity troponin I, and B‐type natriuretic peptide), IL‐6 remained significantly associated with the risk of major adverse cardiovascular events (adj HR Q4:Q1 1.43, 95% CI 1.09‐1.88) and cardiovascular death or heart failure (adj HR 1.79, 95% CI 1.22‐2.63). Conclusions: In patients after ACS, IL‐6 concentration is associated with adverse cardiovascular outcomes independent of established risk predictors and biomarkers. These findings lend support to the concept of IL‐6 as a potential therapeutic target in patients with unstable ischemic heart disease.