Influence of high-density lipoprotein cholesterol and rheological factors on the sex difference in cardiovascular disease.

Background: It is well established that the incidence of cardiovascular disease among men is higher than that among women.

Objective: To determine whether differences between men and women in terms of a range of conventional and rheological risk factors could explain this sex difference.

Design: This was a population-based cohort study (the Edinburgh Artery Study).

Methods: Men and women aged 55-74 years (n = 1592) were selected at random from the general population of Edinburgh and followed up for 5 years. Baseline cardiovascular risk factors were measured and related to incidence of disease among men and women.

Results: Men had higher levels of cigarette smoking, haematocrit and blood viscosity and lower levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and plasma fibrinogen than did women. The incidences of cardiovascular events among men and women were 48.3 and 26.1 per 1000 person-years, respectively. Adjustment for level of HDL cholesterol reduced the male:female ratio for sex-specific incidence rates of cardiovascular events from 1.80 [95% confidence interval (CI) 1.43-2.27] to 1.34 (95% CI 1.04-1.73). This reduction was partially reversed after further adjustment for the other cardiovascular risk factors. The impact of blood viscosity, plasma viscosity and plasma level of fibrinogen on the risk of cardiovascular disease was higher for men than it was for women (multivariate relative risk for blood viscosity were 1.24, 95% CI 1.08-1.43, for men and 0.81, 95% CI 0.61-1.06, for women).

Conclusions: Levels of HDL cholesterol levels in women being higher than those in men may explain some, but not all, of the sex difference in incidence of cardiovascular disease. Greater susceptibility of men to rheological factors might also be important.