HYPERHOMOCYSTEINEMIA, HYPERFIBRINOGENEMIA, AND LIPOPROTEIN (A) EXCESSIN MAINTENANCE DIALYSIS PATIENTS - A MATCHED CASE-CONTROL STUDY

Maintenance dialysis patients experience an exceedingly high incidence of arteriosclerotic cardiovascular disease (CVD) events that are poor ly predicted by traditional CVD risk factor indices. We evaluated the prevalence of three non-traditional CVD risk factors, i.e. hyperhomocy steinemia, hyperfibrinogenemia, and lipoprotein (a) (Lp(a)) excess, an d combined hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess , in maintenance dialysis patients. Fasting total plasma homocysteine (Hey), fibrinogen, Lp(a), glucose, and total and HDL cholesterol level s, and traditional CVD risk factor (i.e. glucose tolerance, smoking, h ypertension, dyslipidemia) prevalences were assessed in 71 dialysis pa tients and 71 age, sex, and race matched Framingham Study controls fre e of clinical renal disease, with normal serum creatinine (less than o r equal to 1.5 mg/dl). Mean plasma Hey (23.7 vs. 9.9 mu M P = 0.0001), fibrinogen (457 vs. 309 mg/dl, P = 0.0001), and Lp(a) (30 vs. 17 mg/d l, P = 0.0070) levels were substantially increased in the dialysis pat ients. Matched odds ratios (with 95% confidence intervals), dialysis p atients/controls, for hyperhomocysteinemia, hyperfibrinogenemia, and L p(a) excess, alone or combined, were markedly greater in the dialysis patients, with no evidence of confounding by the traditional CVD risk factors: hyperhomocysteinemia, 105.0 (29.9-368.9); hyperfibrinogenemia , 16.6 (6.6-42.0); Lp(a) excess, 3.5 (1.5-8.4); all three combined 35. 0 (5.7-199.8). Given in vitro evidence that Hcy, Lp(a), and fibrinogen interact to promote atherothrombosis, combined hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess may contribute to the high incid ence of vascular disease sequelae experienced by dialysis patients, wh ich is inadequately explained by traditional CVD risk factors. Control led, prospective studies of well-characterized maintenance dialysis co horts are urgently required to substantiate this hypothesis.