Sex differences in Lp(a) levels and associated risk by age: Copenhagen (Simony et al., Atherosclerosis 2022)

Background And Aims: Lipoprotein(a) is a well-known causal risk factor for cardiovascular morbidity and mortality. Little is known about the effect of age and sex on lipoprotein(a) levels, and it is largely unknown if the same elevation in lipoprotein(a) confers the same increase in risk in women and men. We investigated whether lipoprotein(a) levels and lipoprotein(a) associated risks of morbidity and mortality by age are similar in women and men.

Methods: We included 37,545 women and 32,497 men from the Copenhagen General Population Study.

Results: Plasma lipoprotein(a) increased with age, and in women we found an additional increase around age 50 (age by sex interaction p = 8∙10-7). In women, levels were 27% higher after menopause (p = 4∙10-61) and 12% lower during hormone replacement therapy (p = 2∙10-19). Adjustment for estimated Glomerular Filtration Rate in both sexes and plasma estradiol in women resulted in attenuated sex differences in lipoprotein(a) levels. In sex and age stratified multivariable adjusted models, lipoprotein(a) >40 mg/dL(83 nmol/L) versus <10 mg/dL(18 nmol/L) was associated with increased risk of myocardial infarction, ischemic heart disease, aortic valve stenosis, and heart failure (men only), but not statistically significant with risk of ischemic stroke, cardiovascular mortality, or all-cause mortality.

Conclusions: Lipoprotein(a) levels increased modestly around age 50 selectively in women; however, risk of morbidity and mortality for high lipoprotein(a) was similar in women and men above age 50. This implies that elevated lipoprotein(a) above age 50 is a relatively more common cardiovascular risk factor in women, pointing toward repeat measurements in women above age 50.