Association between Intestinal Flora Metabolites and Coronary Artery Vulnerable Plaque Characteristics in Coronary Heart Disease

Abstract

Aims/Background The incidence of coronary heart disease (CHD) has been increasing annually. Patients with severe conditions may die from myocardial infarction, heart failure or malignant arrhythmia. Intestinal flora plays an important role in various metabolic processes, such as atherosclerosis, tumour formation, and inflammation. However, its direct role in promoting plaque vulnerability must be further explored and validated. Therefore, this study aims to explore the relationship between changes in intestinal flora, its metabolites in CHD patients and the vulnerability characteristics of coronary plaques. Methods This study recruited 180 subjects, among these, 90 CHD patients diagnosed between January 2023 and January 2024 were selected as the CHD group and 90 healthy volunteers were selected as the control group following a principle of 1:1 ratio. The differences in intestinal flora composition, metabolite levels, and blood biochemical indexes were compared between the two study groups. Based on the coronary angiography (CAG) and intravascular ultrasound (IVUS) results, the CHD group was divided into two sub-groups for stratified comparative analysis: the stable plaque group (n = 49) and the vulnerable plaque group (n = 41). Results The CHD group had reduced intestinal Bifidobacteria and lactic acid bacteria counts and higher intestinal Escherichia coli and Enterococcus levels than the control group (p < 0.05). Moreover, trimethylamine-N-oxide (TMAO) and phenylacetylglutamine (PAGln) levels were significantly higher in the CHD group compared to the control group (p < 0.05). Similarly, the CHD group exhibited substantially elevated serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels compared to the control group. However, compared to the control group, the high-density lipoprotein cholesterol (HDL-C) levels were significantly lower in the CHD group (p < 0.05). Furthermore, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum urea nitrogen (BUN), and serum creatinine (Scr) were comparable in the two experimental groups (p > 0.05). Similarly, intestinal Bifidobacteria, lactic acid bacteria, Escherichia coli, and Enterococcus compositions were comparable in CHD patients with vulnerable plaque and those with stable plaque (p > 0.05). Moreover, CHD patients with vulnerable plaque had elevated TMAO and PAGln levels than those with stable plaque (p < 0.05). However, TG, TC, HDL-C, LDL-C, ALT, AST, BUN, and Scr levels were comparable between CHD patients with a vulnerable plaque and those with stable plaque (p > 0.05). Multivariate regression analysis showed that diabetes, elevated TMAO levels, and elevated PAGln levels were potential risk factors for coronary plaque vulnerability (p < 0.05). Conclusion In summary, CHD patients exhibit significant intestinal flora imbalance, with elevated TMAO and PAGln metabolite levels, which are related to the characteristics of plaque instability.

Keywords: atheromatous plaque; coronary disease; fibroatheromatous plaque; intestinal flora; metabolome.