Serum/plasma biomarkers and the progression of cardiometabolic multimorbidity: a systematic review and meta-analysis.

Background: The role of certain biomarkers in the development of single cardiometabolic disease (CMD) has been intensively investigated. Less is known about the association of biomarkers with multiple CMDs (cardiometabolic multimorbidity, CMM), which is essential for the exploration of molecular targets for the prevention and treatment of CMM. We aimed to systematically synthesize the current evidence on CMM-related biomarkers. Methods: We searched PubMed, Embase, Web of Science, and Ebsco for relevant studies from inception until August 31st, 2022. Studies reported the association of serum/plasma biomarkers with CMM, and relevant effect sizes were included. The outcomes were five progression patterns of CMM: (1) no CMD to CMM; (2) type 2 diabetes mellitus (T2DM) followed by stroke; (3) T2DM followed by coronary heart disease (CHD); (4) T2DM followed by stroke or CHD; and (5) CHD followed by T2DM. Newcastle-Ottawa Quality Assessment Scale (NOS) was used to assess the quality of the included studies. A meta-analysis was conducted to quantify the association of biomarkers and CMM. Results: A total of 68 biomarkers were identified from 42 studies, which could be categorized into five groups: lipid metabolism, glycometabolism, liver function, immunity, and others. Lipid metabolism biomarkers were most reported to associate with CMM, including TC, TGs, HDL-C, LDL-C, and Lp(a). Fasting plasma glucose was also reported by several studies, and it was particularly associated with coexisting T2DM with vascular diseases. According to the quantitative meta-analysis, HDL-C was negatively associated with CHD risk among patients with T2DM (pooled OR for per 1 mmol/L increase = 0.79, 95% CI = 0.77-0.82), whereas a higher TGs level (pooled OR for higher than 150 mg/dL = 1.39, 95% CI = 1.10-1.75) was positively associated with CHD risk among female patients with T2DM. Conclusion: Certain serum/plasma biomarkers were associated with the progression of CMM, in particular for those related to lipid metabolism, but heterogeneity and inconsistent findings still existed among included studies. There is a need for future research to explore more relevant biomarkers associated with the occurrence and progression of CMM, targeted at which is important for the early identification and prevention of CMM.