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Multicenter Study
. 2025 Jul 14;32(9):724-732.
doi: 10.1093/eurjpc/zwae382.

Traditional risk factors, optimal cardiovascular health, and elevated lipoprotein(a)

Alexander C Razavi  1 , Mikaila P Reyes  2 , John T Wilkins  3 , Moyses S Szklo  4 , Michael Y Tsai  5 , Seamus P Whelton  6 , Laurence S Sperling  1 , Sotirios Tsimikas  7 , Harpreet S Bhatia  7
Affiliations
Multicenter Study

Traditional risk factors, optimal cardiovascular health, and elevated lipoprotein(a)

Alexander C Razavi et al. Eur J Prev Cardiol. .

Abstract

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

Methods and results: There were 6676 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, and 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. The mean age was 62.1 years, 53% were women, and 61% were non-white. The median Lp(a) was 17 (interquartile range 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 [hazard ratio (HR) = 0.45, 95% confidence interval (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).

Keywords: American Heart Association; Cardiovascular disease; Cholesterol; Lifestyle; Lipoprotein(a); Prevention.

Plain language summary

Participants without clinical atherosclerotic cardiovascular disease (ASCVD) who achieved an optimal Life’s Simple 7 (LS7) score had ASCVD risk reduction regardless of lipoprotein(a) [Lp(a)] level.Compared to a poor LS7 score, an optimal LS7 score conferred a 55–88% lower ASCVD risk regardless of Lp(a) level.These results emphasize the importance of a healthy lifestyle and optimal ASCVD risk factor control among patients with elevated Lp(a).

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Conflict of interest statement

Conflict of interest: H.S.B. is a consultant/advisor for Kaneka, Novartis, Arrowhead, and Abbott. S.T. is a co-inventor and receives royalties from patents owned by UCSD, is a co-founder and has an equity interest in Oxitope and Kleanthi Diagnostics, and is a consult to Novartis and has a dual appointment at UCSD and Ionis Pharmaceuticals. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies. The other co-authors have nothing to disclose.

Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
(A–C) Association between traditional risk factors and atherosclerotic cardiovascular disease events, per standard deviation change and stratified by (A) Lp(a) <30 mg/dL, (B) Lp(a) 30–49 mg/dL, (C) Lp(a) ≥50 mg/dL.
Figure 2
Figure 2
(A-C) Cumulative incidence of ASCVD according to Life's Simple 7, stratified by, A) Lp(a) <30 mg/dL, B) Lp(a) 30-49 mg/dL, and C) Lp(a) ≥50 mg/dL.
See this image and copyright information in PMC

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