Data_Sheet_1_Serum/plasma biomarkers and the progression of cardiometabolic multimorbidity: a systematic review and meta-analysis.docx

BackgroundThe 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.
MethodsWe 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.
ResultsA 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.
ConclusionCertain 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.

背景 部分生物标志物在单一心血管代谢疾病（cardiometabolic disease, CMD）发生发展中的作用已得到广泛研究，但针对生物标志物与多种心血管代谢疾病即心血管代谢共病（cardiometabolic multimorbidity, CMM）之间关联的研究相对匮乏，而此类研究对于探索CMM防治的分子靶点至关重要。本研究旨在系统梳理当前关于CMM相关生物标志物的研究证据。

方法 本研究检索了PubMed、Embase、Web of Science及Ebsco数据库建库至2022年8月31日期间发表的相关研究，纳入报道血清/血浆生物标志物与CMM关联且提供有效效应量的文献。本研究的结局指标涵盖CMM的5种进展模式：（1）无CMD进展为CMM；（2）2型糖尿病（type 2 diabetes mellitus, T2DM）后继发脑卒中；（3）T2DM后继发冠心病（coronary heart disease, CHD）；（4）T2DM后继发脑卒中或CHD；（5）CHD后继发T2DM。采用纽卡斯尔-渥太华质量评价量表（Newcastle-Ottawa Quality Assessment Scale, NOS）对纳入研究的质量进行评估，并通过荟萃分析量化生物标志物与CMM的关联强度。

结果 本研究从42项文献中共筛选出68种生物标志物，可分为五大类：脂代谢类、糖代谢类、肝功能类、免疫类及其他类。其中脂代谢类生物标志物与CMM的关联报道最多，包括总胆固醇（total cholesterol, TC）、甘油三酯（triglycerides, TGs）、高密度脂蛋白胆固醇（high-density lipoprotein cholesterol, HDL-C）、低密度脂蛋白胆固醇（low-density lipoprotein cholesterol, LDL-C）及脂蛋白(a)（lipoprotein(a), Lp(a)）。另有多项研究报道空腹血浆葡萄糖与CMM存在关联，尤其与合并血管疾病的T2DM患者相关。定量荟萃分析结果显示，在T2DM患者中，HDL-C水平与CHD发病风险呈负相关（每升高1 mmol/L，合并比值比pooled OR=0.79，95%置信区间CI=0.77~0.82）；而在女性T2DM患者中，TGs水平高于150 mg/dL时，其CHD发病风险呈正相关（pooled OR=1.39，95% CI=1.10~1.75）。

结论 部分血清/血浆生物标志物与CMM的进展存在关联，其中脂代谢相关生物标志物的关联最为显著，但纳入研究间仍存在异质性且研究结果不完全一致。未来仍需开展更多研究，探索与CMM发生及进展相关的新型生物标志物，这对于CMM的早期识别与防治具有重要意义。