Traditional Risk Factors, Optimal Cardiovascular Health, and Elevated Lipoprotein(a).

Aims: To assess the association of traditional risk factor burden and Life's Simple 7 (LS7) score with incident atherosclerotic cardiovascular disease (ASCVD) across Lp(a) levels.

Methods: There were 6,676 participants without clinical ASCVD from the Multi-Ethnic Study of Atherosclerosis who underwent Lp(a) testing and were followed for incident ASCVD events (coronary heart disease and stroke). Low, intermediate, and elevated Lp(a) were defined as <30, 30-49, and >50 mg/dL, respectively. Cox proportional hazards regression assessed the association of traditional risk factors and LS7 score (poor: 0-8, average: 9-10, optimal: 11-14) with incident ASCVD across Lp(a) groups during a median follow-up of 17.7 years, adjusting for demographics and time-varying statin and aspirin therapy.

Results: The mean age was 62.1 years, 53% were women, and 61% were non-white. The median Lp(a) was 17 (IQR 8-41) mg/dL, 13% had Lp(a) 30-49 mg/dL, and 20% had Lp(a) >50 mg/dL. Individuals with Lp(a) >50 mg/dL had higher absolute event rates across all LS7 categories. There was no significant interaction between Lp(a) and LS7 score on incident ASCVD (p-interaction=0.60). Compared to a poor LS7 score, optimal LS7 conferred a lower risk for incident ASCVD among individuals with Lp(a) <30 (HR=0.45, 95% CI: 0.28-0.71), Lp(a) 30-49 (HR=0.12, 95% CI: 0.02-0.89), and Lp(a) >50 mg/dL (HR=0.35, 95% CI: 0.13-0.99).

Conclusion: Participants without clinical ASCVD who achieved an optimal LS7 score had ASCVD risk reduction regardless of Lp(a) level. These results emphasize the importance of a healthy lifestyle and ASCVD risk factor control among individuals with elevated Lp(a).