Oral microbiome and metabolome profiling for perioperative cardiovascular risk stratification in high-risk older patients undergoing non-cardiac surgery: protocol for the prospective multicenter MEPCOM cohort study

Older patients undergoing major non-cardiac surgery are particularly vulnerable to postoperative cardiovascular adverse events because of multimorbidity, reduced physiological reserve, chronic low-grade inflammation, and subclinical cardiovascular disease. Current perioperative risk scores, which rely mainly on conventional clinical variables, may not adequately capture occult cardiovascular vulnerability or geriatric vulnerability in this population. The MEPCOM study aims to investigate the association between preoperative oral microbiome and metabolome profiles and 30-day postoperative cardiovascular adverse events in high-risk older patients undergoing non-cardiac surgery, and to develop a non-invasive oral microbiome-based predictive model for perioperative cardiovascular risk stratification. This is a prospective, multicenter cohort study. We will enroll 2100 patients aged ≥ 60 years who are at high cardiovascular risk and scheduled for elective major non-cardiac surgery. Preoperative samples, including saliva, tongue coating and dental plaque, will be collected and analyzed using full-length 16S rRNA sequencing and untargeted metabolomics. Baseline clinical data, geriatric-related variables, oral health information, and perioperative characteristics will be collected, and patients will be followed up for 30 days postoperatively to record CVEs, defined as a composite endpoint including all-cause mortality, myocardial infarction, myocardial injury, stroke, heart failure, and others. Bioinformatics and integrated analyses will be conducted to explore the relationships between microbial/metabolite characteristics and CVEs. Machine learning algorithms, including random forest and LASSO regression, will be employed to construct a predictive model, with its discriminative ability, calibration, and clinical utility assessed using an independent internal validation set and an external validation cohort. The study has been approved by the Biomedical Ethics Committee of West China Hospital, Sichuan University on 9 September 2025 [Approval No. 2025 Review (1603)] as the primary ethical review authority. All participating centers will obtain approval from their respective local responsible ethics committees in compliance with relevant regulatory requirements. Written informed consent will be obtained from all participants. Results will be published in peer-reviewed international journals. Chinese Clinical Trial Registry, ChiCTR2500109657. Registered on 23 September 2025.