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.