Role of serum high density lipoprotein levels and functions in calcific aortic valve stenosis progression.

BACKGROUND Clinical and epidemiological data well defines the role of atherosclerotic risk factors in pathogenesis of aortic stenosis. Especially dyslipidemia with elevated total and LDL cholesterol levels exerts certain histopathological changes on calcified valve tissue. Exact role of HDL in this process is not known. OBJECTIVE To evaluate the lipid profiles of patients with mild aortic valve stenosis with special focus on HDL; HDL subspecies, serum apoA1 levels, HDL related PON1 and PAF-AH enzyme activities and to correlate this with disease progression rates. METHOD 42 patients (26 female; 16 male), with calcific aortic valve stenosis were enrolled in the study. Serum fasting lipid parameters, HDL subspecies (HDL2, HDL3), serum apoA1 levels and HDL related PON1 and PAF-AH enzyme activities were determined. All participants underwent detailed follow-up transthoracic echocardiography examination. RESULTS Among 42 study participants mean serum total cholesterol level was 195 ± 27.3 mg/dl, LDL-c level was 123 ± 19.1 mg/dl, HDL-c level was 44 ± 10.3 mg/dl and total cholesterol/HDL-c ratio was 4.64 ± 1.13. Basal peak aortic jet velocity (Vmax2) was 2.67 ± 0.39 m/sec, mean pressure gradient (Pmean2) was 15.6 ± 5.5 mmhg. Annual progression rate in peak aortic jet velocity (Vmax) was 0.23 ± 0.17 m/sec, in mean pressure gradient (Pmean) was 3 ± 2.1 mmhg. Annual progression rate in Pmean was most strongly correlated with serum HDL-c level and total/HDL-c ratio (r=-0.528 and 0.505; <0.001 and 0.001 respectively). Progression in Vmax values was positively correlated with serum LDL-c level and total/HDL-c ratio while negatively correlated with serum HDL-c levels (r=0.328, 0.499 and -0.464; P=0.034, 0.001 and 0.002 respectively). Among HDL subspecies HDL2 was the predominant type. HDL2 levels were found to be positively correlated with progression rates. There was no significant correlation between apolipoprotein A1 level and annual progression rate. Serum PON1 activity level was determined to be negatively correlated to doppler echocardiographic progression parameters while HDL related PAF-AH activity was independent of disease progression. CONCLUSION Present study demonstrated a positive correlation between disease progression and serum total cholesterol/HDL-c ratio. Serum HDL-c level was inversely correlated with hemodynamic progression. The majority of HDL was HDL2 subtype. Among HDL related enzymes PON1 enzyme activity exhibited an inverse correlation with disease progression.