BackgroundPatients with metabolic syndrome (MS) have a higher incidence of cardiovascular disease (CVD), but the possible mechanisms are not fully understood and further exploration of the possible factors influencing the high incidence of CVD in patients with MS is still needed.ObjectivesThis study aims to examine the association between fetal famine exposure and the risk of CVD in adulthood with MS.MethodsOf 13,744 MS patients free of CVD selected from the Kailuan Study in 2006 (referred as the baseline survey) were included in the study. China suffered a severe famine from 1959 to 1962, so the participants born during this period were classified as the uterine famine exposed group. All patients were born between January 1, 1949, and December 31, 1974. Based on the date of birth, all patients were divided into the no-exposed group (born between January 1, 1963, and December 31, 1974), uterine famine exposed group (born between January 1, 1959 and December 31, 1962), and childhood famine exposed group (born between January 1, 1949 and December 31, 1958). After following up to December 31, 2019, the weighted Cox regression analysis model was used to calculate the effect of early life famine exposure in MS individuals on the risk of CVD in adulthood.ResultsDuring the 12.12 years of follow-up, the incidence of CVD was 5.87%, 10.13%, and 10.90% in the no-exposed group, uterine famine exposed group, and childhood famine exposed group, respectively. Compared with participants in the no-exposed group, the CVD risk and stroke risk increased in participants in the uterine famine exposed group (for CVD, HR: 1.32, 95% CI 1.04–1.67; for stroke, HR:1.37, 95% CI 1.05–1.79), but not in childhood famine exposed group. However, the increased CVD risks were only observed in females or smokers. No increased MI risks were observed for participants in the uterine famine exposed group or childhood famine exposed group.ConclusionsOur findings suggested that exposure to famine during uterine life might increase the risk of CVD in adulthood in participants with MS.