Increased concentrations of ADP-ribosylation factor-like protein 5B are associated with a higher risk of incident coronary heart disease.
Cohort (n=2,856)
Yes
Do specific plasma protein concentrations associate with incident coronary heart disease in older adults?
Proteomic profiling identified 11 proteins associated with incident CHD, with MMP12 showing a strong observational association with increased risk but a causal protective effect in Mendelian randomization, highlighting the complex role of proteins in atherosclerosis.
Effect estimate: HR 1.24 (95% CI 1.12-1.38)
p-value: p=2.3×10-5
Systematic profiling of plasma proteins in population studies offers a complementary approach to discovery of novel risk factors and may provide new insights into the causes of coronary heart disease. To explore relationships between the circulating proteome and coronary heart disease (CHD), we evaluated associations of 4780 plasma proteins with incident CHD in the Cardiovascular Health Study (CHS, N=2856, 575 CHD events) and replicated significant associations in the Atherosclerosis Risk in Communities Study (ARIC, N = 10456; 1375 events). We find that 11 proteins significantly associate with incident CHD after adjusting for risk factors; and eight significantly replicated in ARIC. Several proteins correlate with carotid intimal medial thickness and CHD associations are attenuated in participants without subclinical atherosclerosis. Macrophage metalloelastase (MMP12) is the strongest observed association (Hazard Ratio, 1.31; 95% Confidence Interval, 1.19-1.44). Mendelian randomization (MR) identifies a causal relationship between higher MMP12 and lower CHD (Odds Ratio, OR 0.94) and ischemic stroke (OR 0.90) risk, while reverse MR found that genetic propensity to CHD increased MMP12. Taken together, multivariable MR confirms a direct protective effect of higher plasma MMP12 on CHD risk and a genetic effect of atherosclerosis and CHD on elevating MMP12. Proteomic analyses reveal associations with incident CHD and genomic evidence suggests that therapeutic MMP12 inhibition may confer adverse cardiovascular effects.
Huber et al. (Sat,) conducted a cohort in Coronary Heart Disease (n=2,856). Increased concentrations of ADP-ribosylation factor-like protein 5B are associated with a higher risk of incident coronary heart disease.