This study was aimed to determine prevalence of several classical and non-classical cardiovascular risk factors, and to test their association with cardiovascular events in three groups of end stage renal disease (ESRD). A total of 35 chronic renal failure, 50 hemodialysed and 30 renal transplant recipient patients, and 31 healthy subjects were included. Hypertension, elevated plasma concentrations of tHcy, fibrinogen, CRP, and lipoprotein(a) were highly prevalent in ESRD patients. Whereas, smoking, hypertriglyeeridemia, hypercholesterolemia, hypoHDLemia, and hypoalbuminemia arc less common. In univariate analysis, cardiovascular events were associated with age, hypertension, and the top quartile of tHcy and CRP values. When controlling for several potential confounding factors, cardiovascular events remained associated with age, hypertension (OF, 5.65; 95% CI, 1.55-20.59; P=0.01), and the top quartile of tHcy (OR, 6.14; 95% CI, 1.93-19.56; P=0.002) and CRP (OR, 2.94; 95% CI, 0.90-9.56; P=0.07).

An abnormally high mortality from atherosclerotic cardiovascular (CV) accidents has long been reported in patients on maintenance hemodialysis (HD). However, incidence of such complications had not been so far evaluated in chronic renal failure (CRF) patients not yet on dialysis. In a cohort study bearing on 232 predialysis CRF patients, followed as out-patients at Necker hospital, incidence of first myocardial infarction (MI) was three times higher than in the French general population in every age group and in both genders, with a mean (+/- SEM) age at onset of MI of 62.9 +/- 1.2 years. In a retrospective cooperative study involving 748 patients treated in 9 hemodialysis centers in the Ile-de-France area, incidence of first MI episodes did not differ before acid after start of HD therapy acid was similar to that observed in the cohort study. Mean age of patients at first MI, before and after start of HD, was respectively 62.4 +/- 1.6 and 63.7 +/- 1.5 years, a not significant difference. In conclusion, two epidemiologic studies confirm the existence of accelerated atherosclerosis in CRF patients, the incidence of MI being 3 times higher in uremic patients than in the general population in every age group and in both genders. The fact that incidence of first MI episodes and age at onset was similar in predialysis and in dialyzed patients suggests that the uremic stale per se is a main determinant of such accelerated atherosclerosis. It results that therapeutic measures aimed at preventing development of atherosclerosis should be initiated from the early stage of CRF, long before start of renal replacement therapy.

Atherosclerosis, a common and complex disease, results from multiple interactions among injurious stimuli and the healing or reparative responses of the arterial wall. After endothelial injury, direct cell-cell interaction, and secretion of chemotactic and growth factors resulting from endothelial cell dysfunction, induce recruitment of monocytes to subintimal regions, smooth muscle cell proliferation, and increased synthesis of matrix proteins. The recruited monocytes become macrophages, accumulate lipid, and ultimately become foam cells. Together with accompanying T lymphocytes, these changes represent the fatty streak, an early histopathological change indicating atherosclerosis. Progression of this atherosclerotic lesion is marked by the accumulation of alternating layers of smooth muscle cells and lipid-laden macrophages. The advanced lesions of atherosclerosis compromise the lumen diameter and, thus, reduce the blood flow in arteries and ultimately participate in the mechanisms that lead to occlusion of the involved arteries.

Disturbances of the lipid metabolism in chronic renal failure (CRF) are characterized by an accumulation of serum VLDL, IDL, and remnants and also by a decrease of the HDL pool, especially for HDL2. CRF is also associated with a decrease of apolipoproteins (apo) AI and AII in relation to a preferential decrease of lipoparticles (Lp) AI-AII by comparison with the anti-atherogenic Lp AI containing no All. It is furthermore characterized by a marked increase of apo CIII, which is disproportionate with respect to the increase of apo CII and the variation of apo E, in relation with an accumulation of Lp B-CIII (and also Lp B-E and Lp B-C-E for hemodialyzed patients) in the whole spectrum of low density lipoproteins. The abnormal distribution of apo into the various classes of lipoproteins is the consequence firstly of the relative inefficacy of the lipolytic process implicated in TG-rich lipoprotein metabolism (LPL dysfunction), and secondly of the abnormal reverse cholesterol transport (anomalies of CETP and LCAT). The hormonal, nutritional, and iatrogenic factors implicated in the uremic dyslipoproteinemia are described and the implications of such abnormalities on cardiovascular disease and on the progression of renal disease are discussed.