Abstract 5532: Apoptosis, Interstitial Collagen and Diastolic Function in Essential Hypertension

Abstract

Introduction: Sustained hypertension (HT) leads to left ventricular hypertrophy (LVH) and left ventricular dilatation, processes associated with loss of cardiac myocytes through apoptosis. Nevertheless, the relationship of apoptosis, myocardial fibrosis and diastolic function remains unknown. Therefore, the aims of the present study were to analyze the relationship between aminoterminal propeptide levels of type III procollagen (PIIINP), sFas, soluble TNF receptor 1 (sTNF-R1) and diastolic function in essential HT. Hypothesis: We assessed the hypothesis that increased cardiac collagen turnover would be associated with LVH, diastolic dysfunction and apoptosis even in asymptomatic HT. Methods: The asymptomatic hypertensive group consisted of 253 Caucasian patients (mean age 60±13 years, 139 males) from 11 hospitals. A routine physical examination, laboratory analyses, and echo-Doppler study were performed. Results: Serum concentrations of PIIINP were higher in hypertensive patients compared to control group [4.18 (3.55 – 5.04 μ g/L) vs. 3.54 (2.98 – 4.54 μ g/L), p=0.006] and also plasma levels of sFas and sTNF-R1 [1.40 (1.13 – 1.69 ng/mL) vs. 1.00 (0.84 – 1.27 ng/mL), p<0.0001; 385 (291 – 545 pg/mL) vs. 236 (194 – 302 pg/mL), p<0.0001]. Log-transformed concentrations of anti-apoptotic cytokines were correlated between them (r=0.404, p<0.0001). Moreover, serum PIIINP concentrations were associated with log-transformed sFas (r=0.386, p<0.0001) and sTNF-R1 (r=0.298, p<0.001). Then, multivariate analyses included sFas (p<0.0001) and sTNF-R1 (p<0.0001) as independent factors of serum procollagen levels. Finally, marker concentrations were significantly correlated with diastolic parameters. Conclusions: This study showed increased circulating levels of PIIINP, sFas and sTNF-R1 in our group of asymptomatic hypertensive patients. Furthermore, sFas and sTNF-R1 are independent factors of serum type III procollagen, and diastolic parameters showed a highly significant relationship with myocardial fibrosis and anti-apoptotic cytokines.