Sex differences of lipoprotein(a) levels and associated risk of morbidity and mortality by age: The Copenhagen General Population Study

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