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To investigate the association of the cardiovascular risk factor lipoprotein (Lp)(a) and vascular complications in patients with type 1 diabetes. RESEARCH DESIGN AND METHODSPatients with type 1 diabetes receiving regular care were recruited in this observational cross-sectional study and divided into four groups according to their Lp(a) levels in nmol/L (very low <10, low 10-30, intermediate 30-120, high >120). Prevalence of vascular complications was compared between the groups. In addition, the association between metabolic control, measured as HbA 1c , and Lp(a) was studied. RESULTSThe patients (n 5 1,860) had a median age of 48 years, diabetes duration of 25 years, and HbA 1c of 7.8% (61 mmol/mol). The median Lp(a) was 19 (interquartile range 10-71) nmol/L. No significant differences between men and women were observed, but Lp(a) levels increased with increasing age. Patients in the high Lp(a) group had higher prevalence of complications than patients in the very low Lp(a) group. The age-and smoking-status-adjusted relative risk ratio of having any macrovascular disease was 1.51 (95% CI 1.01-2.28, P 5 0.048); coronary heart disease, 1.70 (95% CI 0.97-3.00, P 5 0.063); albuminuria, 1.68 (95% CI 1.12-2.50, P 5 0.01); and calcified aortic valve disease, 2.03 (95% CI 1.03-4.03; P 5 0.042). Patients with good metabolic control, HbA 1c <6.9% (<52 mmol/mol), had significantly lower Lp(a) levels than patients with poorer metabolic control, HbA 1c >6.9% (>52 mmol/mol). CONCLUSIONSLp(a) is a significant risk factor for macrovascular disease, albuminuria, and calcified aortic valve disease in patients with type 1 diabetes. Poor metabolic control in patients with type 1 diabetes is associated with increased Lp(a) levels.Lipoprotein(a) [Lp(a)] is an established cardiovascular risk factor that is receiving increasing attention (1). Lp(a) is an LDL particle to which an apolipoprotein(a) is covalently bound to the apolipoprotein B. LDL and Lp(a) particles are both atherogenic, but the strong capacity of Lp(a) to carry oxidized phospholipids has been proposed as an additional proatherogenic property compared with LDL-cholesterol (LDL-C) (2). Plasma levels of Lp(a) have a skewed distribution that ranges up to three orders of magnitude

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Background Patients with familial hypercholesterolemia (FH) display high levels of low‐density lipoprotein cholesterol (LDL‐c), endothelial dysfunction, and increased risk of premature atherosclerosis. We have previously shown that red blood cells (RBCs) from patients with type 2 diabetes induce endothelial dysfunction through increased arginase 1 and reactive oxygen species (ROS). Objective To test the hypothesis that RBCs from patients with FH (FH‐RBCs) and elevated LDL‐c induce endothelial dysfunction. Methods and results FH‐RBCs and LDL‐c >5.0 mM induced endothelial dysfunction following 18‐h incubation with isolated aortic rings from healthy rats compared to FH‐RBCs and LDL‐c <2.5 mM or RBCs from healthy subjects (H‐RBCs). Inhibition of vascular but not RBC arginase attenuated the degree of endothelial dysfunction induced by FH‐RBCs and LDL‐c >5.0 mM. Furthermore, arginase 1 but not arginase 2 was elevated in the vasculature of aortic segments after incubation with FH‐RBCs and LDL‐c >5.0 mM. A superoxide scavenger, present throughout the 18‐h incubation, attenuated the degree of endothelial dysfunction induced by FH‐RBCs and LDL‐c >5.0 mM. ROS production was elevated in these RBCs in comparison with H‐RBCs. Scavenging of vascular ROS through various antioxidants also attenuated the degree of endothelial dysfunction induced by FH‐RBCs and LDL‐c >5.0 mM. This was corroborated by an increase in the lipid peroxidation product 4‐hydroxynonenal. Lipidomic analysis of RBC lysates did not reveal any significant changes across the groups. Conclusion FH‐RBCs induce endothelial dysfunction dependent on LDL‐c levels via arginase 1 and ROS‐dependent mechanisms.