AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
A Proteomics-Derived HDL Biomarker Score Associates with Subclinical Atherosclerosis in South Asian Americans: The MASALA Study
By Seth L, Joshi PH, Melander O et al.
Introduction: South Asian (SA) ancestry is associated with an increased atherosclerotic cardiovascular disease (ASCVD) risk beyond traditional risk factors and is recognized in prevention guidelines as a risk-enhancing factor. Although high-density lipoprotein cholesterol concentration (HDL-C) is an established ASCVD risk marker, emerging evidence suggests that the proteomic composition of HDL particles more directly reflects HDL function and better captures ASCVD risk beyond HDL-C alone, which may be particularly relevant in SAs, who have a higher proportion of less protective HDL particles with impaired functionality. We determined the association of HDL proteome-derived markers with subclinical atherosclerosis in SA adults. Methods: The Mediators of Atherosclerosis in SAs Living in America (MASALA) cohort includes 1164 SA adults (mean age 56 years, 52% male), among whom 822 participants had all exposures, outcomes, and covariates measured. The primary exposure was a proteomics-derived biomarker score (pCAD) of five proteins on apolipoprotein A-I-containing (HDL) particles previously linked to coronary artery disease in non-SA populations. The primary outcome was the prevalence of coronary artery calcium (CAC) >0. We evaluated the association between pCAD and CAC>0 using multivariable modeling adjusted for age, sex, study site, education level, income, BMI, HbA1c, systolic blood pressure, smoking, diabetes medication, antihypertensive use, lipid-lowering medication use, HDL-C, total cholesterol, and hsCRP. Spearman correlations characterized inter-protein and cardiometabolic relationships. Jonckheere-Terpstra trend tests assessed monotonic associations by pCAD quartiles. Results: Among the cohort, 46.8% had CAC>0. Increasing pCAD quartiles was associated with lower HDL-C (overall: r = –0.76; male: r = –0.66, female: r = –0.74), higher triglycerides (overall: r = 0.58; male: r = 0.58, female: r = 0.56), and waist circumference (overall: r = 0.28; male: r = 0.16, female: r = 0.19) but not LDL (overall: r = -0.01; male: r = -0.03, female: r= 0.09). The prevalence of CAC>0 increased monotonically by pCAD quartile (Q1: 38.1%, Q4: 56.1%, p<.0001), and each 1-SD increase in pCAD score was associated with increased odds of CAC>0 in both unadjusted (OR 1.39, 95% CI 1.23 - 1.57; p<0.001) and fully adjusted models including HDL-C (OR 1.39, 95% CI 1.03 - 1.86; p=0.03). There was no interaction by sex. Conclusion: In the MASALA study population, a higher pCAD score was independently associated with CAC>0 after adjustment for traditional ASCVD risk factors. These findings provide insights into metabolic drivers of ASCVD risk in South Asian adults, suggesting a role for HDL dysfunction in this high-risk population. Future studies should assess associations with additional measures of HDL function and validate these findings using incident ASCVD events and independent cohorts.