Total cholesterol as a risk factor for coronary heart disease and stroke in women compared with men: A systematic review and meta-analysis

Sanne A.E. Peters, Yankuba Singhateh, Diana Mackay, Rachel R. Huxley, Mark Woodward

Raised total cholesterol is a strong risk factor for cardiovascular disease (CVD). It remains unknown whether sex differences exist in the relationship between total cholesterol and CVD outcomes. PubMed was searched in December 2014 for cohort studies reporting on the relationship between total cholesterol and coronary heart disease (CHD) and total stroke, separately in men and women. Random effects meta-analyses with inverse variance weighting were used to obtain adjusted pooled sex-specific relative risks (RR) and women-to-men ratio of RRs (RRRs). Data from 97 cohorts, 1,022,276 individuals, and 20,176 CHD and 13,067 stroke cases were included. The pooled RR (95% confidence interval) for CHD associated with a 1-mmol/L increase in total cholesterol was 1.20 (1.16; 1.24) in women and 1.24 (1.20; 1.28) in men, resulting in a RRR of 0.96 (0.93; 0.99). Corresponding RRs for the risk of total stroke were 1.01 (0.98; 1.05) in women, and 1.03 (1.00; 1.05) in men, with a pooled RRR of 0.99 (0.93; 1.04). Pooled RRRs (95% CI) comparing individuals in the highest TC category to those in the lowest, such as the highest versus lowest third, were 0.87 (0.79; 0.96) for CHD and 0.86 (0.76; 0.97) for total stroke. Raised total cholesterol is a strong risk factor for CHD, with evidence of a small, but significantly stronger, effect in men compared to women. Raised total cholesterol had little effect on the risk of total stroke in both sexes.