Circulating lipoprotein (a) and all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis.

AIMS To investigate the association between circulating lipoprotein(a) (Lp(a)) and risk of all-cause and cause-specific mortality in the general population and in patients with chronic diseases, and to elucidate the dose-response relations. METHODS AND RESULTS We searched literature to find prospective studies reporting adjusted risk estimates on the association of Lp(a) and mortality outcomes. Forty-three publications, reporting on 75 studies (957,253 participants), were included. The hazard ratios (HRs) and 95% confidence intervals (95%CI ) for the top versus bottom tertile of Lp(a) levels and risk of all-cause mortality were 1.09 (95%CI: 1.01-1.18, I2: 75.34%, n = 19) in the general population and 1.18 (95%CI: 1.04-1.34, I2: 52.5%, n = 12) in patients with cardiovascular diseases (CVD). The HRs for CVD mortality were 1.33 (95%CI: 1.11-1.58, I2: 82.8%, n = 31) in the general population, 1.25 (95%CI: 1.10-1.43, I2: 54.3%, n = 17) in patients with CVD and 2.53 (95%CI: 1.13-5.64, I2: 66%, n = 4) in patients with diabetes mellitus. Linear dose-response analyses revealed that each 50 mg/dL increase in Lp(a) levels was associated with 31% and 15% greater risk of CVD death in the general population and in patients with CVD. No non-linear dose-response association was observed between Lp(a) levels and risk of all-cause or CVD mortality in the general population or in patients with CVD (Pnonlinearity > 0.05). CONCLUSION This study provides further evidence that higher Lp(a) levels are associated with higher risk of all-cause mortality and CVD-death in the general population and in patients with CVD. These findings support the ESC/EAS Guidelines that recommend Lp(a) should be measured at least once in each adult person's lifetime, since our study suggests those with higher Lp(a) might also have higher risk of mortality

Potential mediating role of iron biomarkers in the association of sex with glucose, insulin, and type 2 diabetes

This study investigated the mediating role of iron biomarkers in the association between biological sex and glucose metabolism and the incidence of type 2 diabetes (T2D). Using the data from the Prevention of REnal and Vascular ENd-stage Disease study, results showed that females had lower fasting plasma glucose (FPG) and insulin (FPI) levels than males. Iron biomarkers like ferritin, hepcidin, and soluble transferrin receptor (sTfR) were found to mediate the association between sex and FPG, as well as FPI to varying degrees, while transferrin saturation (TSAT) had a suppressive effect. The incidence of T2D was also lower in females, with ferritin mediating a significant portion of this difference. These findings suggest that iron biomarkers could partially explain the sex differences in glucose metabolism and T2D incidence, warranting further causal research