INCREASED PLASMA APOLIPOPROTEIN(A) LEVELS IN IDDM PATIENTS WITH DIABETIC NEPHROPATHY

OBJECTIVE - The relative mortality from cardiovascular disease (CVD) i s increased 40-fold in IDDM patients suffering from diabetic nephropat hy as compared with nondiabetic subjects on average. We assessed the p otential contribution of dyslipidemia in general and elevated serum ap olipoprotein(a) [apo(a)] in particular to CVD in nephropathic patients with IDDM. RESEARCH DESIGN AND METHODS - We investigated 199 IDDM pat ients with diabetic nephropathy and 192 normoalbuminuric IDDM patients marched for ses, age, diabetes duration, and BMI. RESULTS - The preva lence of CVD was 30 and 12% in patients with and without nephropathy r espectively (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 pathogen icity) was 38% (31-45) vs. 22% (16-28) in patients with and without ne phropathy, respectively (P < 0.0005). in nephropathic patients, the pr evalence of plasma apo(a) > 300 U/l was raised in patients with CVD (4 8%, 36-61%) as compared with patients without (34%, 26-42%) (P = 0.05) . Furthermore, the serum concentrations of the following apolipoprotei ns and lipids were higher in patients with nephropathy as compared wit h 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 triglycerid es 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 t hat plasma apo(a) concentration > 300 U/l is an independent risk facto r 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 d iabetic nephropathy.