Abstract
Background: Evidence suggests that the total bilirubin has a protective effect on coronary heart disease (CHD), but the dose-response relationship remains controversial, and there is no meta-analysis to assess the relationship.Methods: As of October 1, 2021, relevant literature was selected from four databases (PubMed, Web of Science, Cochrane Library, and Embase) by using a retrieval strategy. The dose-response curve between the total bilirubin and CHD was fitted by a restricted cubic spline. Stata 12.0 was used for statistical analysis.Results: A total of 170,209 (6,342 cases) participants from 7 prospective studies were analyzed in our meta-analysis. We calculated the pooled relative risks (RRs) and 95% CIs for the association between serum bilirubin level and risk of CHD using random-effects models. Compared with the first quantile, the bilirubin level in the third quantile had a protective effect on the risk of CHD (RR, 0.90; 95% CI, 0.82–0.99). The restricted cubic spline functions depicted a U-type curve relationship between bilirubin (3.42–49 μmol/L) and CHD (P linear < 0.001). When the bilirubin level was in the range of 3.42–13μmol/L, the protective effect of bilirubin on CHD was enhanced with increasing bilirubin levels. When the bilirubin level exceeded 13μmol/L, the protective effect of bilirubin weakened, and a dangerous effect gradually appeared with further increases in bilirubin levels.Conclusions: Compared with a low bilirubin level, a high bilirubin level has a protective effect on the risk of CHD, and there was a U-shaped dose-response relationship between them.
Highlights
Coronary heart disease (CHD) accounts for one-third to one-half of cardiovascular diseases and is the most common heart disease [1]
Recent studies have shown that bilirubin has a certain clinical value in the diagnosis and prognosis of stroke [8], diabetes [9], peripheral arterial disease [10], Parkinson’s disease [11], and heart failure [12], so it may be used as a new marker for cardiovascular and cerebrovascular diseases in clinical practice
Our results showed that compared with the first quantile, the bilirubin level in the third quantile has a protective effect on the risk of CHD; at the same time, dose-response meta-analysis showed that the protective effect was U-type
Summary
Coronary heart disease (CHD) accounts for one-third to one-half of cardiovascular diseases and is the most common heart disease [1]. There is evidence that bilirubin has antioxidant activity, and its antioxidant effect is stronger than that of bilirubin αtocopherol [7]. It plays an important role in the occurrence and development of oxidative stress diseases. Recent studies have shown that bilirubin has a certain clinical value in the diagnosis and prognosis of stroke [8], diabetes [9], peripheral arterial disease [10], Parkinson’s disease [11], and heart failure [12], so it may be used as a new marker for cardiovascular and cerebrovascular diseases in clinical practice. Evidence suggests that the total bilirubin has a protective effect on coronary heart disease (CHD), but the dose-response relationship remains controversial, and there is no meta-analysis to assess the relationship
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