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

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

Sarah O Nomura  1 , Harpreet S Bhatia  2 , Parveen K Garg  3 , Amy B Karger  1 , Weihua Guan  4 , Jing Cao  5 , Michael D Shapiro  6 , Michael Y Tsai  1
Affiliations

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

Sarah O Nomura et al. Am J Prev Cardiol. .

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.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image, graphical abstract
Graphical abstract
Fig. 1
Fig. 1
Combined associations of high-sensitivity c-reactive protein, lipoprotein(a) and total homocysteine with incident coronary heart disease in the Multi-Ethnic Study of Atherosclerosis. Abbreviations: high-sensitivity c-reactive protein, hs-CRP; coronary heart disease (CHD) total plasma homocysteine, tHcy; lipoprotein(a), LPA. Cox proportional hazards regression survival curves adjusted for age, sex, race/ethnicity, hypertension, hypertension medication usage, diabetes, pack-years smoking, HDL-C, total cholesterol, triglycerides (log-transformed), BMI and eGFR. Low hs-CRP <2 mg/dL; High hs-CRP ≥2 mg/dL; Low Lp(a) <50 mg/dL; High Lp(a) ≥50 mg/dL; Low tHcy <12 µmol/L; High tHcy=≥12 µmol/L.
Fig. 2
Fig. 2
Combined associations of high-sensitivity c-reactive protein, lipoprotein(a) and total homocysteine with incident stroke in the Multi-Ethnic Study of Atherosclerosis. Abbreviations: high-sensitivity c-reactive protein, hs-CRP; total plasma homocysteine, tHcy; lipoprotein(a), LPA. Cox proportional hazards regression survival curves adjusted for age, sex, race/ethnicity, hypertension, hypertension medication usage, diabetes, pack-years smoking, HDL-C, total cholesterol, triglycerides (log-transformed), BMI and eGFR. Low hs-CRP <2 mg/dL; High hs-CRP ≥2 mg/dL; Low Lp(a) <50 mg/dL; High Lp(a) ≥50 mg/dL; Low tHcy <12 µmol/L; High tHcy=≥12 µmol/L.
See this image and copyright information in PMC

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