ABSTRACT
BACKGROUND: Previous studies reported that middle-aged patients with atherogenic lipoprotein-lipid profile exhibit faster progression of aortic valve stenosis (AS). The ratio of apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) reflects the balance between atherogenic and anti-atherogenic lipoproteins. The aim of this study was to examine the association between apoB/apoA-I ratio and AS hemodynamic progression and to determine whether this association varies according to age. METHODS AND RESULTS: A total of 159 patients (66±13 years, 73% men) with AS were prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study. Hemodynamic progression of AS was determined by the change in peak aortic jet velocity (Vpeak) measured by Doppler-echocardiography between baseline and 2-year follow-up. Patients in the top tertile of apoB/apoA-I ratio (≥0.62) had a faster progression rate of AS compared with those in the bottom/mid tertiles (Vpeak progression: 0.30 [0.09-0.49] versus 0.16 [0.01-0.36] m/s, P=0.02). There was a significant interaction (P=0.007) between apoB/apoA-I ratio and age. Among younger patients (ie, aged <70 years; median value of the cohort), those in the top tertile of apoB/apoA-I ratio had a 3.4-fold faster AS progression compared with those in the bottom/mid tertiles (Vpeak progression: 0.34 [0.13-0.69] versus 0.10 [-0.03-0.31] m/s, P=0.002), whereas there was no significant difference between tertiles in the subgroup of older patients (P=0.83). After comprehensive adjustment, higher apoB/apoA-I ratio was significantly associated with faster AS progression in the subset of younger patients (all, standardized ß≥0.36; P≤0.01). CONCLUSIONS: Higher apoB/apoA-I ratio is significantly associated with faster hemodynamic progression of AS in the younger patients. These findings suggest that atherogenic lipid factors may play a crucial role in the pathogenesis of AS in younger patients, but may be are less important in older patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01679431.
Subject(s)
Aortic Valve Stenosis/blood , Aortic Valve Stenosis/physiopathology , Aortic Valve/pathology , Apolipoprotein A-I/blood , Apolipoprotein B-100/blood , Calcinosis/blood , Calcinosis/physiopathology , Hemodynamics , Age Factors , Aged , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Aortic Valve Stenosis/diagnostic imaging , Biomarkers/blood , Calcinosis/diagnostic imaging , Disease Progression , Echocardiography, Doppler , Female , Humans , Male , Middle Aged , Prospective Studies , Risk Assessment , Risk Factors , Time Factors , Ventricular Function, LeftABSTRACT
AIMS: Hypertension is highly prevalent in patients with aortic stenosis (AS) and is associated with worse outcomes. The current prospective study assessed the impact of systolic hypertension (SHPT) on the progression of aortic valve calcification (AVC) measured by multidetector computed tomography (MDCT) in patients with AS. METHODS AND RESULTS: The present analysis includes the first series of 101 patients with AS prospectively recruited in the PROGRESSA study. Patients underwent comprehensive Doppler echocardiography and MDCT exams at baseline and after 2-year follow-up. AVC and coronary artery calcification (CAC) were measured using the Agatston method. Patients with SHPT at baseline (i.e. systolic blood pressure ≥140 mmHg; n = 37, 37%) had faster 2-year AVC progression compared with those without SHPT (i.e. systolic blood pressure <140 mmHg) (AVC median [25th percentile-75th percentile]: +370 [126-824] vs. +157 [58-303] AU; P = 0.007, respectively). Similar results were obtained with the analysis of AVC progression divided by the cross-sectional area of the aortic annulus (AVCdensity: +96 [34-218] vs. +45 [14-82] AU/cm2, P = 0.01, respectively). In multivariable analysis, SHPT remained significantly associated with faster progression of AVC or AVCdensity (all P = 0.001). There was no significant difference between groups with respect to progression of CAC (+39 [3-199] vs. +41 [0-156] AU, P = 0.88). CONCLUSION: This prospective study shows for the first time that SHPT is associated with faster AVC progression but not with CAC progression in AS patients. These findings provide further support for the elaboration of randomized clinical trials to assess the efficacy of antihypertensive medication to slow the stenosis progression in patients with AS.
