SEX DIFFERENCES IN THE ASSOCIATION BETWEEN LIPOPROTEIN (A) AND MYOCARDIAL INFARCTION IN PATIENTS WITH NO ATHEROSCLEROTIC CARDIOVASCULAR DISEASE: THE MASS GENERAL BRIGHAM LP(A) REGISTRY

Abstract

Therapeutic Area: ASCVD/CVD in Women Background: Lipoprotein (a) [Lp(a)] is a risk factor for atherosclerotic cardiovascular disease (ASCVD). However, sex based differences in the association of Lp(a) with myocardial infarction (MI) have not been well established, particularly for those without prior ASCVD. Our aim was to evaluate the association of Lp(a) with MI among females and males without prior ASCVD. Methods: Patients without known ASCVD, defined as no history of MI, coronary revascularization, or ischemic stroke, were identified in the Mass General Brigham Lp(a) registry – a retrospective cohort of patients who had Lp(a) measured as part of routine care from 2000-2019. Lp(a) percentile groups were categorized as 1st-50th (reference), 51st-70th, 71st-90th, and 91st-100th. The primary outcome was a composite of fatal or non-fatal MI. Analyses were adjusted for age, race, hypertension, hyperlipidemia, diabetes mellitus, chronic kidney disease, and smoking. Results: A total of 6,238 patients were included, of whom 45% were female. Median age was 55 in females and 54 in males. Females had higher median total cholesterol, LDL-C, and HDL-C, while males had higher rates of diabetes mellitus, atrial fibrillation, and smoking. Females had a lower rate of statin use at baseline than males. Median Lp(a) was 33.2 nmol/L in females and 28.9 nmol/L in males. Higher Lp(a) percentile group was associated with an increased incidence of fatal or non-fatal MI, with females in the 91st-100th percentile group (>217 nmol/L) having an adjusted hazard ratio (HR) of 2.57 (95% CI 1.35-4.88) and males having an adjusted HR of 3.35 (95% CI 1.94-5.78). Kaplan Meier curves for the cumulative incidence of fatal or non-fatal MI showed a significant overall difference between Lp(a) percentile groups for both sexes (p <0.001), with no interaction by sex (p-interaction = 0.14). The annual incidence rate (per 1,000) for MI was 8.49 in males in the 91st-100th percentile group (vs. 2.52 in reference group) and 5.66 in females in the 91st-100th percentile group (vs. 1.67 in reference group). Conclusions: Among individuals with no prior ASCVD, elevated Lp(a) is associated with higher rates of MI in both females and males.