Increased Plasma Apolipoprotein(a) Levels in IDDM Patients With Diabetic Nephropathy

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Abstract
OBJECTIVE The relative mortality from cardiovascular disease (CVD) is increased 40-fold in IDDM patients suffering from diabetic nephropathy as compared with nondiabetic subjects on average. We assessed the potential contribution of dyslipidemia in general and elevated serum apolipoprotein (a) [apo(a)] in particular to CVD in nephropathic patients with IDDM. RESEARCH DESIGN AND METHODS We investigated 199 IDDM patients with diabetic nephropathy and 192 normoalbuminuric IDDM patients matched for sex, age, diabetes duration, and BMI. RESULTS The prevalence of CVD was 30 and 12% in patients with and without nephropathy, respectively (P < 0.001). The level of apo(a) was significantly higher in patients with nephropathy, 189 (20–2,350) U/l as compared with the normoalbuminuric group, 103 (20–1,940) U/l (P < 0.005). The prevalence of plasma apo(a) > 300 U/l (at-risk level for cardiovascular pathogenicity) was 38% (31–45) vs. 22% (16–28) in patients with and without nephropathy, respectively (P < 0.0005). In nephropathic patients, the prevalence of plasma apo(a) > 300 U/l was raised in patients with CVD (48%, 36–61%) as compared with patients without (34%, 26–42%) (P = 0.05). Furthermore, the serum concentrations of the following apolipoproteins and lipids were higher in patients with nephropathy as compared with normoalbuminuric patients: apoB 1.33 ± 0.37 vs. 1.06 ± 0.26 g/l; total cholesterol 5.6 ± 1.2 vs. 4.8 ± 0.9 mmol/l; and triglycerides 1.22 (0.31–9.87) vs. 0.77 (0.28–3.05) mmol/l, P < 0.0001. Multiple logistic regression analysis of cardiovascular risk factors revealed that plasma apo(a) concentration > 300 U/l is an independent risk factor for coronary heart disease, odds ratio 1.86 (1.03–3.36) (P < 0.05). CONCLUSIONS Dyslipidemia and raised plasma concentrations of apo(a), particularly > 300 U/l, may contribute to the enhanced morbidity and mortality from CVD characteristically observed in IDDM patients with diabetic nephropathy.

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