Risk of coronary heart disease is associated with triglycerides and high-density lipoprotein cholesterol in women and non high-density lipoprotein cholesterol in men

BACKGROUND: Although the physiologic interrelationships between triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) are not fully understood, studies typically are adjusted for one when one is examining the role of the other. If the mechanism of coronary heart disease (CHD) risk is mediated through the other, then controlling for the second factor may mask the true effect of the first. We investigated the relationship between the combined effect of increased (up arrow) TG and decreased (down arrow) HDL-C compared with isolated up arrow TG or isolated down arrow HDL-C on CHD risk in men and women and compared these down arrow TG/up arrow HDL-C categories to non-HDL cholesterol (non-HDL-C). METHODS: Subjects (936 women and 746 men) from the San Luis Valley Study were grouped on the basis of 4 sex-specific NCEP-ATP III cutpoints (up arrow TG >= 150 mg/dL, and down arrow HDL-C, <40 and <50 mg/dL for men and women, respectively). Descriptive statistics and survival analyses were used. The reference group was down arrow TG/up arrow HDL-C (TG < 150, and HDL-C >50 and >40 mg/dL for women and men, respectively). Non-HDL-C was analyzed as a continuous variable. RESULTS: Among women, all groups had greater risk of CHD compared with the down arrow TG/up arrow HDL-C reference in univariate analysis: down arrow TG/down arrow HDL-C HR = 2.82 [95% confidence interval 1.12-7.1], up arrow TG/up arrow HDL-C HR = 3.82 [1.50-9.74], up arrow TG/down arrow HDL-C HR= 4.32 [1.91-9.80]. The risk remained significant in the down arrow TG/down arrow HDL-C group (HR= 3.27 [1.26-8.50] and marginally significant in other groups in multivariable analysis. Neither up arrow TG nor down arrow HDL-C was related to CHD risk in men. Non-HDL cholesterol was significantly related to CHD in men but not in women. CONCLUSIONS: The CHD risk associated with down arrow HDL-C in women was >2- to 4-fold elevated depending on TG levels. Non-HDL cholesterol was a significant predictor of CHD in men. Examining the combined effects of risk factors that share physiologic pathways may reveal important associations that can be otherwise obscured. Further dissection of gender specific pathways that affect HDL-C and TG and non-HDL cholesterol are important in understanding CHD risk. Published by Elsevier Inc. on behalf of National Lipid Association.