Association between insulin-like growth factor-1 and cardiovascular events: a systematic review and dose-response meta-analysis of cohort studies

Background Insulin-like growth factor-1 (IGF-1) has increasingly been reported as linked to cardiovascular (CV) events; however, reported results have been inconsistent, and no meta-analysis has been undertaken to quantitatively assess this association. Methods We searched PubMed, Embase, and Web of Science databases for cohort articles published up to December 1, 2020. Fixed or random-effects models were used to estimate the summary relative risks (RRs) and 95% confidence intervals (CIs) of CV events in relation to IGF-1. Restricted cubic splines were used to model the dose-response association. Results We identified 11 articles (thirteen cohort studies) covering a total of 22,995 participants and 3040 CV events in this meta-analysis. The risk of overall CV events reduced by 16% from the highest to the lowest IGF-1 levels (RR 0.83, 95% CI 0.72-0.95), while the occurrence of CV events reduced by 28% (RR 0.72, 95% CI 0.56-0.92), but not for CV deaths, however (RR 1.00, 95% CI 0.65-1.55). We also found linear associations between IGF-1 levels and CV events. With each per 45 mu g/mL IGF-1 increase, the pooled RRs were 0.91 (95% CI 0.86-0.96), 0.91 (95% CI 0.85-0.97) and 0.91 (95% CI 0.84-0.98) for overall CV events, for the occurrence of CV events, and for CV deaths, respectively. Conclusions Our findings based on cohort studies support the contention that any increase in IGF-1 is helpful in reducing the overall risk of CV events. As an important biomarker for assessing the likelihood of CV events, IGF-1 appears to offer a promising prognostic approach for aiding prevention.