Lipoprotein(a), high-sensitivity c-reactive protein, homocysteine and cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis

Sarah O Nomura; Harpreet S Bhatia; Parveen K Garg; Amy B Karger; Weihua Guan; Jing Cao; Michael D Shapiro; Michael Y Tsai

doi:10.1016/j.ajpc.2024.100903

Lipoprotein(a), high-sensitivity c-reactive protein, homocysteine and cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis

Am J Prev Cardiol. 2024 Dec 11:21:100903. doi: 10.1016/j.ajpc.2024.100903. eCollection 2025 Mar.

Authors

Sarah O Nomura¹, Harpreet S Bhatia², Parveen K Garg³, Amy B Karger¹, Weihua Guan⁴, Jing Cao⁵, Michael D Shapiro⁶, Michael Y Tsai¹

Affiliations

¹ Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware St SE, Minneapolis, MN 55455, USA.
² Division of Cardiovascular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
³ Division of Cardiology, University of Southern California Keck School of Medicine, 1975 Zonal Ave., Los Angeles, CA 90033, USA.
⁴ School of Public Health Biostatistics Division, University of Minnesota, 420 Delaware St SE, MN, 55455, USA.
⁵ Department of Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
⁶ Center for the Prevention of Cardiovascular Disease, Section on Cardiovascular Medicine, Wake Forest University School of Medicine, 475 Vine Street, Winston-Salem, North Carolina 27101, USA.

Abstract

Background and aims: Elevated lipoprotein(a) [Lp(a)], high-sensitivity C-Reactive Protein (hs-CRP), and total homocysteine (tHcy) are associated with atherosclerotic cardiovascular disease (ASCVD) risk. This study investigated the individual and joint associations of Lp(a), hs-CRP and tHcy with coronary heart disease (CHD) and stroke.

Methods: This study was conducted in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (2000-2017) (CHD analytic N = 6,676; stroke analytic N = 6,674 men and women). Associations between Lp(a) (<50 vs. ≥50 mg/dL), hs-CRP (<2 vs. ≥2 mg/L) and tHcy (<12 vs. ≥12 µmol/L) and CHD and stroke incidence were evaluated individually and jointly using Cox proportional hazards regression.

Results: Individually, elevated tHcy was associated with CHD and stroke incidence, Lp(a) with CHD only and hs-CRP with stroke only. In combined analyses, CHD risk was higher when multiple biomarkers were elevated [hs-CRP+Lp(a), hazard ratio (HR)=1.39, 95 % confidence interval (CI): 1.06, 1.82; hs-CRP+ tHcy, HR = 1.34, 95 % CI: 1.02, 1.75; Lp(a)+ tHcy HR = 1.58, 95 % CI: 1.08, 2.30; hs-CRP+Lp(a)+ tHcy HR = 2.02, 95 % CI: 1.26, 3.24]. Stroke risk was elevated when hs-CRP and either Lp(a) (HR = 1.51, 95 % CI: 1.02, 2.23) or tHcy (HR = 2.10, 95 % CI: 1.44, 3.06) was also high, when all three biomarkers were elevated (HR = 2.99, 95 % CI: 1.61, 5.58), or when hs-CRP and tHcy (HR = 1.79, 95 % CI: 1.16, 2.76) were both high.

Conclusions: Risk of ASCVD was highest with concomitant elevation of tHcy, hs-CRP and Lp(a). Inclusion of tHcy and consideration of biomarker combination rather than individual biomarker levels may help better identify individuals at greatest risk for ASCVD events.

Keywords: Coronary heart disease; High-sensitivity c-reactive protein; Homocysteine; Lipoprotein(a); Stroke.