Coronary heart disease (CHD) is the primary cause of mortality in most developed countries. The thorough assessment of plasma protein levels in a well-characterized cohort might lead to the discovery of novel pharmacological targets for CHD prevention. In the Cardiovascular Health Study, plasma levels of 1,298 proteins were evaluated using SomaScan aptamers in 3,185 patients. Researchers examined the longitudinal relationships of protein levels with the primary event of incident CHD (acute MI or death from CHD) and a secondary outcome of angina, coronary revascularization, acute MI, or death from CHD after removing people with prevalent MI. Primary analyses controlled demographics, smoking, diabetes, hypertension, BMI, blood pressure, and LDL cholesterol. A statistically significant p-value of < 7.6 x 10-5 (adjusted for the number of main components explaining 95% of protein variation) was used. Then explored the biggest known genomic studies for possible protein quantitative trait loci among important proteins, and they examined published GWAS for probable causal links using Mendelian randomization.

The mean age at baseline was 74 years among the 2,868 individuals, with 62% (1,784) female and 16% (456) self-identifying as Black. About 576 (20%) patients experienced an incident CHD event after a median follow-up duration of 15 years (IQR 10-21). About 10 proteins were linked to incident CHD, while an additional 27 were linked to the secondary outcome. Adjusting for aspirin and statin usage, renal function, or established cardiac biomarkers (NT-proBNP, high-sensitive cardiac troponin T, C-reactive protein) had minimal effect on relationships while censoring at a shorter follow-up period enhanced the size of protein-outcome connections. In a sample of community-dwelling older persons, 37 proteins were linked with the incidence of CHD. Mendelian randomization analyses on two samples are now underway, and proteomic analyses on an additional ~3,700 proteins are planned.