Association of plasma propionate concentration with coronary artery disease in a large cross-sectional study

Microbiome has been linked to the pathogenesis of coronary artery disease (CAD) but data providing direct evidence for an association of short-chain fatty acids (SCFA) with CAD are lacking. This study aimed to evaluate the role of propionate, the most important SCFA in patients with CAD.

We performed a cross-sectional study enrolling patients admitted for invasive coronary angiography in two university hospitals in Germany. Patients with known or suspected CAD and risk factors for cardiovascular disease were prospectively recruited. Blood sampling was performed after overnight fasting and before invasive procedures. Measurement of propionate was performed by liquid chromatography.

The study included 1,253 patients (median [IQR], 67 [58-76] years; 799 men [64%]). A total of 739 had invasively confirmed CAD with at least one coronary artery stenosis ≥50% and 514 had exclusion of CAD. CAD patients had significant lower levels of propionate (median 5.75 μM, IQR, 4.1-7.6) compared to the non-CAD groups 6.53 μM (4.6-8.6, p < 0.001). Multivariate linear regression analysis revealed an odds ratio of 0.94 (CI 0.90-0.98, p = 0.002) for propionate as predictor of CAD. The odds ratio was further decreased to 0.45 (CI 0.31-0.65, p < 0.001) when comparing patients in the lowest quartile of propionate with those with higher levels of propionate.

The study provides large-scale in vivo data for the association of propionate to manifest coronary artery disease, independent of other traditional cardiovascular risk factors.