Abstract
BackgroundCompared to individuals without type 2 diabetes mellitus, the relative increase in cardiovascular mortality is much higher in women than in men in individuals with type 2 diabetes mellitus.MethodsWe evaluated data from 7443 individuals (3792 women, 50.9%), aged 20 to 81 years, from two independent population-based investigations, SHIP-0 and MONICA/KORA S3. We analyzed the longitudinal sex-specific associations of lipoprotein(a) with cardiovascular mortality in individuals with and without type 2 diabetes mellitus using Cox regression.ResultsDuring a median follow-up of 20.5 years (136,802 person-years), 657 participants (404 men and 253 women) died of cardiovascular causes. Among individuals without type 2 diabetes mellitus, men had a significantly higher risk for cardiovascular mortality compared to women in unadjusted model and after adjustment. On the other hand, in participants with type 2 diabetes mellitus, the risk for cardiovascular mortality was not different between men and women in the unadjusted model and after adjustment for age, body mass index, low-density lipoprotein-cholesterol, fasting status and study sample (SHIP-0, MONICA/KORA S3). Further adjustment for lipoprotein(a) concentrations had no impact on the hazard ratio (HR) for cardiovascular mortality comparing men versus women in individuals without type 2 diabetes mellitus [HR: 1.94; 95% confidence interval (CI) 1.63 to 2.32; p < 0.001]. In individuals with type 2 diabetes mellitus, however, further adjustment for lipoprotein(a) led to an increased risk for cardiovascular mortality in men and a decreased risk in women resulting in a statistically significant difference between men and women (HR: 1.53; 95% CI 1.04 to 2.24; p = 0.029).ConclusionsWomen are described to have a stronger relative increase in cardiovascular mortality than men when comparing individuals with and without type 2 diabetes mellitus. Higher lipoprotein(a) concentrations in women with type 2 diabetes mellitus than in men with type 2 diabetes mellitus might partially explain this finding.
Highlights
Compared to individuals without type 2 diabetes mellitus, the relative increase in cardiovascular mor‐ tality is much higher in women than in men in individuals with type 2 diabetes mellitus
On the other hand, when individuals with type 2 diabetes mellitus (T2DM) are compared to individuals without T2DM, the relative increase in CV mortality is much higher in women than in men [2, 3]
Lipoprotein(a) (Lp[a]), which is synthesized in the liver, is a low-density lipoprotein (LDL)-like particle where the apolipoprotein B-100 is covalently bound to an additional apolipoprotein, the apolipoprotein(a) [10]
Summary
Compared to individuals without type 2 diabetes mellitus, the relative increase in cardiovascular mor‐ tality is much higher in women than in men in individuals with type 2 diabetes mellitus. The leading causes of death in patients with type 2 diabetes mellitus (T2DM) are cardiovascular diseases (CVD) with the risk of cardiovascular (CV) mortality being twofold that of individuals without T2DM [1]. On the other hand, when individuals with T2DM are compared to individuals without T2DM, the relative increase in CV mortality is much higher in women than in men [2, 3]. Several meta-analyses [4,5,6,7,8] showed that women with T2DM have a higher relative increase in the risk for incident fatal and non-fatal coronary heart disease and stroke than men with T2DM when compared with individuals without T2DM. The blood concentrations of Lp(a) are considered to be genetically determined by variations in the Lp(a) gene [28], previous studies [17, 18, 20, 22, 23, 26, 27, 29] have reported an inverse association of Lp(a) with dysglycemic conditions including T2DM
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