Association of plasma trimethylamine N-oxide levels with atherosclerotic cardiovascular disease and factors of the metabolic syndrome

Gut Microbiota-Derived Metabolites and Cardiovascular Disease Risk: A Systematic Review of Prospective Cohort Studies

“…We excluded 52 reports for reasons indicated in Figure 1 and finally 21 studies were deemed eligible for inclusion in the present systematic review. Of them, 19 included prospective cohorts [18][19][20]22,[24][25][26][27][28][29][30][31]36,[38][39][40][41], one study included one nested case-control study [23] and one study included two nested case-control studies [21]. All of the included studies were of high quality with a mean of 8.9 points in the Newcastle-Ottawa scale (range: 7-9) (Tables S2 and S3).…”

“…The main characteristics of the 21 selected articles [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]36,[38][39][40][41][42] are summarized in Table 1. Most of them (n = 18) were published in the last five years (2022-2018), while none were published before 2015.…”

“…All studies used a cohort design except two that included a nested case-control design [21,23]. There was one article that included three cohorts [19] whereas two articles included two cohorts as the discovery and replication sample analyses [28,40]. The minimum and maximum follow-up was 1 month and 28 years, respectively, while in most of the studies the average follow-up was up to 10 years.…”

“…In 14 articles participants were free of CVD at baseline [18,[21][22][23][24][27][28][29][30][31][32]36,39,40] but two of them were conducted in patients with type 2 diabetes (T2D) [18,22] and two studies in chronic kidney disease (CKD) patients [31,32]. On the other hand, in seven articles participants had at least one CVD condition [19,20,25,26,38,41,42]. The main outcome in most of the studies was all-cause and CVD mortality, followed by incident MACE, AF, HF, stroke, and additional CV outcomes.…”

“…Since the discovery of a relationship between the gut microbiota-dependent metabolite TMAO and CVD, in 2011 [8], nine systematic reviews of prospective studies published up to 2020, suggest a strong association between elevated circulating levels of TMAO with risk of several CV outcomes [9][10][11][12][13][14][15][16][17]. Since then, the number of prospective TMAO profiling studies on CVD risk has substantially increased [18][19][20][21][22][23][24][25][26][27]. However, less evidence exists on other microbial-related metabolites in relation to incident CVD.…”