Narrowing sex differences in lipoprotein cholesterol subclasses following mid-life: the very large database of lipids (VLDL-10B)

Abstract

Background: Women have less risk of atherosclerotic cardiovascular disease compared with men up until midlife (ages 50 to 60), after which the gap begins to narrow post menopause. We hypothesized that the average lipid profile of women undergoes unfavorable changes compared with men after midlife.

Methods and results: We examined lipids by sex and age in the Very Large Database of Lipids 10B (VLDL 10B) study. The analysis included 1 350 908 unique consecutive patients clinically referred for lipoprotein testing by density gradient ultracentrifugation from 2009 to 2011. Ratio variables were created for density subclasses of LDL-C, HDL-C, and VLDL-C (LLDR, LHDR, LVDR, respectively). Men showed higher median LDL-C values than women for ages 20 to 59, with the greatest difference in their 30s: 146 mg/dL in men versus 130 mg/dL in women. In contrast, women consistently had higher values after midlife (age 60), for example ages 70 to 79: 129 mg/dL in women versus 112 mg/dL in men. After age 50, women had higher LDL-C each decade, for example 14% higher from their 30s to 50s, while HDL-C concentrations did not differ. Women had more buoyant LDL-C and HDL-C (lower LLDR and LHDR) than men at all ages but the gap closed in higher age groups. In contrast, women had a generally denser VLDL-C (higher LVDR) leading into midlife, with the gap progressively closing in higher age groups, approximating that of men in their 60s and 70s.

Conclusion: The narrowing sex differential in cardiovascular disease risk after midlife is mirrored by a higher total atherogenic lipoprotein cholesterol burden in women and a closer approximation of the less favorable density phenotype characteristic of men.

Keywords: aging; lipids; menopause; prevention; statins.

Figure 1.

Relationship of LLDR (top), LHDR (middle), and LVDR (bottom) with concentrations of TG (left) and HDL‐C (right). HDL‐C indicates high‐density lipoprotein cholesterol; LHDR, logarithmic HDL density ratio; LLDR, logarithmic LDL density ratio; LVDR, logarithmic VLDL density ratio; TG, triglycerides.

Figure 2.

Median and interquartile ranges for selected characteristics. HDL‐C indicates high‐density lipoprotein cholesterol; LHDR, logarithmic HDL density ratio; LLDR, logarithmic LDL density ratio; LVDR, logarithmic VLDL density ratio.

Figure 3.

LDL‐C and density through late life, by sex. Lower panel shows median LDL‐C (directly measured) with interquartile range, by sex through life. Middle panel shows the ratio of dense subclasses (darker) to buoyant subclasses (lighter) at select ages to highlight the pre‐, peri‐, and post‐menopausal time periods. Upper panel shows density relative to men, age 30 to 39. Upper panel shows LLDR or density expressed as color saturation. Darker, or more saturated purple reflects higher LLDR. As shown, while LDL‐C is higher for women than for men from age 60 and beyond, this is driven by a greater proportion of the buoyant subclasses leading to a preservation of the advantageous density phenotype. With advanced age, sex differences in density narrow. LDL‐C indicates low‐density lipoprotein cholesterol; LLDR, logarithmic LDL density ratio.