Serum albumin, cardiometabolic and other adverse outcomes: systematic review and meta-analyses of 48 published observational cohort studies involving 1,492,237 participants.

Objectives. A general body of evidence suggests that low serum albumin might be associated with increased risk of adverse cardiometabolic outcomes, but findings are divergent. We aimed to quantify associations of serum albumin with the risk of type 2 diabetes (T2D), cardiovascular disease (CVD), all-cause mortality, and other adverse outcomes using a systematic review and meta-analyses of published observational cohort studies. Design. MEDLINE, Embase, Web of Science, and manual search of relevant bibliographies were systematically searched to January 2020. Relative risks (RRs) with 95% confidence intervals (CIs) comparing top versus bottom thirds of serum albumin levels were pooled. Results. Fifty-four articles based on 48 unique observational cohort studies comprising of 1,492,237 participants were eligible. Multivariable adjusted RRs (95% CIs) comparing the top vs bottom third of serum albumin levels were: 1.03 (0.86-1.22) for T2D; 0.60 (0.53-0.67) for CVD; 0.74 (0.66-0.84) for coronary heart disease (CHD); 0.57 (0.36-0.91) for CHD death; 0.76 (0.65-0.87) for myocardial infarction; 0.66 (0.55-0.77) for all-cause mortality; 0.71 (0.61-0.83) for venous thromboembolism; 0.65 (0.48-0.88) for cancer mortality; and 0.62 (0.46-0.84) for fracture. Heterogeneity between contributing studies of T2D was partly explained by sample sizes of studies (p for meta-regression = .035). Conclusions. Elevated levels of serum albumin are associated with reduced risk of vascular outcomes, all-cause mortality, certain cancers, and fracture. Inconsistent findings for T2D may be attributed to selective reporting by studies. Further research is needed to assess any potential causal relevance to these findings and the role of serum albumin concentrations in disease prevention.Systematic review registration: PROSPERO 2019: CRD42019125869.