Key result
Lp(a), smoking, and diabetes independently compound post-ACS MACE risk, reaching ~20% at 4 years.
Why the study?
Lipoprotein(a), smoking, and diabetes may convey cardiovascular risk through shared atherogenic, thrombogenic, and inflammatory mechanisms. However, the degree to which these factors are additive or interactive risk factors for MACE after ACS was uncertain.
Are lipoprotein(a), smoking, and diabetes additive or interactive risk factors for major adverse cardiovascular events in patients with recent acute coronary syndrome on optimized statin therapy?
Observational (n=9,462)
Yes
Are lipoprotein(a), smoking, and diabetes additive or interactive risk factors for major adverse cardiovascular events in patients with recent acute coronary syndrome on optimized statin therapy?
Following acute coronary syndrome, lipoprotein(a), smoking, and diabetes act as additive rather than interactive risk factors for major adverse cardiovascular events, with Lp(a) remaining an independent predictor after adjustment for smoking and diabetes.
Answers are grounded in this paper and cite their sources.
Supports additive post-ACS risk stratification with Lp(a); leaves open whether Lp(a) lowering modifies outcomes in smokers or diabetics.
Background There is growing recognition that lipoprotein(a) [Lp(a)] increases cardiovascular risk through atherogenic, thrombogenic, and inflammatory properties. Conventional risk factors of smoking and diabetes may also convey risk through these mechanisms. The degree to which Lp(a), smoking, and diabetes are additive or interactive risk factors is uncertain. Purpose We determined whether Lp(a), smoking, and diabetes are additive or interactive risk factors for major adverse cardiovascular events (MACE) in a post hoc analysis of the placebo group of the ODYSSEY OUTCOMES trial. Methods ODYSSEY OUTCOMES compared the effects of alirocumab or placebo in patients with recent acute coronary syndrome on optimized statin therapy. Baseline Lp(a) was measured by immunoassay in mass units and categorized by quartile. Smoking was categorized as current versus prior or never. Presence of diabetes was determined from history, laboratory, and prescription data. MACE (cardiovascular death, myocardial infarction, ischemic stroke, hospitalization for unstable angina, and ischemia-driven coronary revascularization) were determined over median (Q1, Q3) follow-up of 2.8 (2.3, 3.4) years. Cox regression models were adjusted for age, sex, geographic region, LDL-C, and systolic blood pressure and evaluated the association of Lp(a) with MACE, without and with further adjustment for smoking and diabetes. Results In 9462 patients assigned to placebo, median (Q1-Q3) Lp(a) was 21.6 (6.6-60.1) mg/dL, 24.1% were current smokers, and 29.1% had diabetes. The 4-year Kaplan-Meier cumulative incidence of MACE was 19.7% (1474 events). Lp(a) ≥median was associated with greater risk of MACE than Lp(a) Conclusions Lp(a), smoking, and diabetes are additive but not interactive risk factors for MACE after ACS. Lp(a) remains an independent risk factor for MACE after adjustment for both smoking and diabetes.
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Schwartz et al. (2026) conducted an observational in Recent acute coronary syndrome (n=9,462). Lipoprotein(a) [Lp(a)] ≥median, smoking, and diabetes vs. Lp(a) <median, prior/never smoking, no diabetes was evaluated on Major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, ischemic stroke, hospitalization for unstable angina, and ischemia-driven coronary revascularization). Lp(a), smoking, and diabetes were additive, independent risk factors for MACE after ACS over 2.8 years (4-year cumulative MACE incidence 19.7%, 1474 events).
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