Incidence and risk factors of atherosclerotic cardiovascular accidents in predialysis chronic renal failure patients: a prospective study

BACKGROUND: Accelerated atherosclerosis resulting in an abnormally high incidence of coronary and cerebrovascular occlusive accidents has been repeatedly reported in dialysis patients, but incidence and risk factors of such complications in chronic renal failure (CRF) predialysis patients are debated. METHODS: We prospectively assessed the incidence of first myocardial and cerebral infarction episodes in a cohort of 147 CRF patients (99 male) followed from January 1985 to December 1994. Relevant clinical and laboratory risk factors for atherogenesis were determined at yearly intervals. They included blood pressure, smoking, blood lipids, fibrinogen, and homocysteine which were compared in patients with (CVA+) or without (CVA-) occurrence of cardiovascular (CV) atherosclerotic accidents. RESULTS: Incidence of CV accidents was nearly three times higher in CRF patients than in the French general population in both genders. In particular, incidence of myocardial infarction in male patients aged 45-55, 55-65 and > 65 years was 7.6, 18.2, and 27.8/1000 patient-years, respectively, compared to 3.4, 8.9, and 10.4/1000 subject-years in the general population. Although age and degree of renal failure at onset of CV events or at end of follow-up did not differ between CVA+ and CVA- groups, cigarette smoking (24.5 SD 24.3 vs 8.2 14.7 pack-years, P < 0.0001) and systolic blood pressure (159 19 vs 148 19 mmHg, P < 0.001) were markedly higher in CVA+ patients. Similarly, mean plasma HDL-cholesterol was lower, whereas LDL-cholesterol, triglycerides, apoB, Lp(a), fibrinogen, and homocysteine levels all were significantly higher in CVA+ than in CVA- patients. Multivariate Cox analysis identified cigarette smoking, systolic pressure, HDL cholesterol, and fibrinogen as independent risk factors for developing CV accidents. CONCLUSIONS: Incidence of atherosclerotic CV complications is abnormally high in predialysis CRF patients, suggesting that the uraemic state per se is associated with atherogenesis. As several of the identified clinical and metabolic risk factors for such accidents are potentially remediable by specific therapeutic interventions, prophylactic measures should be initiated long before start of renal replacement therapy.