The Mediating Role of Systemic Inflammation in the Effects of Fetal Famine Exposure on Cardiovascular Disease in Adults: A Cohort Study.

BACKGROUND:A few studies have reported the association between famine exposure during fetal development and risk of CVD, but no mechanisms have been explored. OBJECTIVES:The objective of this study was to examine risk of CVD in adulthood after exposure to famine during the fetal stage and explore the mediating role of systemic inflammation. METHODS:A total of 59,416 participants of the Kailuan Study without CVD were included. All participants were divided into 3 groups based on date of birth, including the unexposed group (1963-1974), the fetal-exposed group (1959-1962), and the childhood-exposed group (1949-1958). Systemic immune-inflammation index (SII) (neutrophils × platelets / lymphocytes) and systemic inflammatory response index (SIRI) (neutrophils × monocytes / lymphocytes) are 2 novel systemic inflammation indexes that represent the level of systemic inflammation. Time-weighted Cox regression was used to test the effect of famine exposure on risk of CVD, and a mediation model was used to calculate the role of systemic inflammation. RESULTS:During a median follow-up period of 12.36 (12.69, 13.16) y, a total of 3772 cases of CVD were documented. Compared with unexposed participants, the fetal-exposed group had an increased risk of CVD (HR: 1.19; 95% CI: 1.04, 1.38) and stroke (HR: 1.28; 95% CI: 1.09, 1.51) but not MI. No association was observed in the childhood-exposed group. In mediation analysis, SII mediated an estimated 24.43% of the association between fetal exposure and CVD (24.61% for stroke and 23.27% for MI). For SIRI, this percentage was 30.20% for CVD (29.94% for stroke and 31.25% of MI). CONCLUSIONS:Fetal exposure to famine may increase risk of CVD in adulthood. Systemic inflammation may play an intermediary role in the effect of fetal famine exposure on CVD.