Low TGF-β1 serum levels are a risk factor for atherosclerosis disease in ESRD patients

Abstract

Background. It is thought that transforming growth factor-β1 (TGF-β1) might be a key inhibitor of atherogenesis in nonuremic patients. We evaluated the intra- and post-dialytic serum levels of TGF-β1 in uremic patients to assess if TGF-β1 is an independent risk factor for cardiovascular diseases, and if any correlation exists between TGF-β1 and any yet known atherosclerotic risk factors. Methods. We studied 155 patients who were on regular hemodialysis, with or without clinically significant atherosclerotic vascular disease. Forty-one apparently healthy people were enrolled as a control group. TGF-β1 was evaluated during the midweek dialysis session, at times 0, 30, and 120 minues, at the end of the session, and 3 hours after the session's end. All hitherto known atherosclerotic risk factors also were evaluated. The investigation was performed over a 24-month follow-up. Results. TGF-β1 values (mean ± SD) in dialysis patients were 26.64 ± 7.0 ng/mL (N = 155) compared with 42.31 ± 6.0 ng/mL in the control group (N = 41, P < 0.0001). A weak inverse correlation emerged between TGF-β1 and age (r = -0.28), TGF-β1 and lipoprotein(a) [Lp(a); r = -0.35], TGF-β1 and C-reactive protein (CRP; r = -0.27), and TGF-β1 and plasminogen activator inhibitor-1 (PAI-1; r = -0.41). TGF-β1 also correlated with albumin (r = 0.31). In the coronary heart disease (CHD) group (N = 32) the TGF-β1 was 26.2 ± 4.9 ng/mL; in the cerebrovascular disease (CVD) group (N = 8) it was 26.7 ± 3.7 ng/mL and in the peripheral vascular disease (PVD) group (N = 9) it was 25.4 ± 1.7 ng/mL. In dialysis patients with no cardiovascular disease (N = 80) TGF-β1 was 35.1 ± 6.8 ng/mL (P < 0.0001 vs. CHD, CVD and PVD patients). TGF-β1 was significantly lower among those patients with triple coronary vessel disease than with the other CHD patients. The Cox analysis demonstrated that a 1 ng/mL reduction in TGF-β1 concentration was associated with a 9% increase in the relative risk of a cardiovascular event. Conclusions. TGF-β1 was significantly reduced in hemodialysis patients, in particular in those with severe cardiovascular disease. Baseline TGF-β1, diabetes mellitus and serum albumin levels proved to be the only independent contributors to atherosclerotic risk in dialysis patients.