Gallstone Disease (GSD) is a multifactorial risk factor for various complications. This study aimed to examine the relationship between GSD and Cardiovascular Disease (CVD) incidence through a systematic review and meta-analysis approach. A thorough search was conducted across Web of Science, Scopus, MEDLINE/PubMed, Cochrane Library, and Embase databases. Only studies published between 1980 and December 2023 were included. Chi-square, I2, and forest plots were used to assess heterogeneity. Begg's and Egger's tests were used to evaluate publication bias. Statistical significance was considered at p <0.05, and all analyses were performed using Stata 17. This meta-analysis involved 21 studies and comprised 2,138,282 participants; there has been a significant association found between GSD and an increased risk of CVD (with a relative risk of 1.46, 95% confidence interval: 1.32-1.63, p <0.001). The analysis found no evidence of publication bias based on Begg's test (p =0.085) and Egger's test (p =0.231). Subgroup analysis of the studies showed a higher risk of CVD in studies with a sample size of less than 10,000 participants, conducted in 2016 or later, utilizing a cross-sectional design, in Asian countries; the analysis had a moderate quality score, with a follow-up period of equal to or less than ten years. There has been a significant association found between GSD and an increased risk of incidence of CVD. Taking proactive steps to implement targeted interventions for individuals with gallstone disease could potentially reduce the risk of cardiovascular disease within this population.
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