Mirzaei Sahereh, DeVon Holli A, Cantor Rita M, Cupido Arjen, Fernandes Silva Lilian, Laakso Markku, Lusis Aldons J
Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
School of Nursing, University of California, Los Angeles, Los Angeles, CA, United States.
Front Microbiol. 2024 Aug 1;15:1411328. doi: 10.3389/fmicb.2024.1411328. eCollection 2024.
An association between gut microbes and cardiovascular disease (CVD) has been established, but the underlying mechanisms remain largely unknown.
We conducted a secondary analysis of the cross-sectional data obtained from the Metabolic Syndrome in Men (METSIM) population-based cohort of 10,194 Finnish men (age = 57.65 ± 7.12 years). We tested the levels of circulating gut microbe-derived metabolites as predictors of CVD, ischemic cerebrovascular accident (CVA), and myocardial infarction (MI). The Kaplan-Meier method was used to estimate the time from the participants' first outpatient clinic visit to the occurrence of adverse outcomes. The associations between metabolite levels and the outcomes were assessed using Cox proportional hazard models.
During a median follow-up period of 200 months, 979 participants experienced CVD, 397 experienced CVA, and 548 experienced MI. After adjusting for traditional risk factors and correcting for multiple comparisons, higher plasma levels of succinate [quartile 4 vs. quartile 1; adjusted hazard ratio, aHR = 1.30, (confidence interval (CI), 1.10-1.53) = 0.0003, adjusted = 0.01] were significantly associated with the risk of CVD. High plasma levels of ursodeoxycholic acid (UDCA) (quartile 3 vs. quartile 1); [aHR = 1.68, (CI, 1.26-2.2); = 0.0003, adj. = 0.01] were associated with a higher risk of CVA. Furthermore, as a continuous variable, succinate was associated with a 10% decrease in the risk of CVD [aHR = 0.9; (CI, 0.84-0.97); = 0.008] and a 15% decrease in the risk of MI [aHR = 0.85, (CI, 0.77-0.93); = 0.0007].
Gut microbe-derived metabolites, succinate, and ursodeoxycholic acid were associated with CVD, MI, and CVA, respectively. Regulating the gut microbes may represent a potential therapeutic target for modulating CVD and CVA.
肠道微生物与心血管疾病（CVD）之间的关联已被确立，但其潜在机制仍大多未知。
我们对从基于人群的男性代谢综合征（METSIM）队列研究中获取的横断面数据进行了二次分析，该队列研究包含10194名芬兰男性（年龄 = 57.65 ± 7.12岁）。我们检测了循环中源自肠道微生物的代谢产物水平，以作为CVD、缺血性脑血管意外（CVA）和心肌梗死（MI）的预测指标。采用Kaplan-Meier方法估算从参与者首次门诊就诊到出现不良结局的时间。使用Cox比例风险模型评估代谢产物水平与结局之间的关联。
在中位随访期200个月期间，979名参与者发生了CVD，397名发生了CVA，548名发生了MI。在调整传统风险因素并校正多重比较后，较高的琥珀酸血浆水平[四分位数4与四分位数1相比；调整后风险比，aHR = 1.30，（置信区间（CI），1.10 - 1.53）；P = 0.0003，调整后P = 0.01]与CVD风险显著相关。较高的熊去氧胆酸（UDCA）血浆水平（四分位数3与四分位数1相比）；[aHR = 1.68，（CI，1.26 - 2.2）；P = 0.0003，校正后P = 0.01]与较高的CVA风险相关。此外，作为连续变量，琥珀酸与CVD风险降低10%[aHR = 0.9；（CI，0.84 - 0.97）；P = 0.008]和MI风险降低15%[aHR = 0.85，（CI，0.77 - 0.93）；P = 0.0007]相关。
源自肠道微生物的代谢产物琥珀酸和熊去氧胆酸分别与CVD、MI和CVA相关。调节肠道微生物可能是调节CVD和CVA的潜在治疗靶点。
