TY - JOUR
T1 - 10-Year Associations Between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients With Stable Coronary Heart Disease
T2 - A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy
AU - Carlsson, Axel C.
AU - Ruge, Toralph
AU - Kjøller, Erik
AU - Hilden, Jørgen
AU - Kolmos, Hans Jørn
AU - Sajadieh, Ahmad
AU - Kastrup, Jens
AU - Jensen, Gorm Boje
AU - Larsson, Anders
AU - Nowak, Christoph
AU - Jakobsen, Janus Christian
AU - Winkel, Per
AU - Gluud, Christian
AU - Ärnlöv, Johan
N1 - © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.METHODS AND RESULTS: CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all-cause mortality. Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C-reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs. After adjustments, higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05-1.22; P=0.001 for TNFR1; hazard ratio, 1.16; 95% confidence interval, 1.08-1.24; P<0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).CONCLUSIONS: Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.
AB - BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.METHODS AND RESULTS: CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all-cause mortality. Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C-reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs. After adjustments, higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05-1.22; P=0.001 for TNFR1; hazard ratio, 1.16; 95% confidence interval, 1.08-1.24; P<0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).CONCLUSIONS: Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.
U2 - 10.1161/JAHA.117.008299
DO - 10.1161/JAHA.117.008299
M3 - Journal article
C2 - 29686027
VL - 7
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
SN - 2047-9980
IS - 9
M1 - e008299
ER -