ApoB/ApoA‐I Ratio is Associated With Faster Hemodynamic Progression of Aortic Stenosis: Results From the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) Study

Abstract

BackgroundPrevious 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 ResultsA 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 β≥0.36; P≤0.01).ConclusionsHigher 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.

ApoC-III is a novel inducer of calcification in human aortic valves

“…ApoA-I served as a second commercially available purified human apolipoprotein that we investigated for effects on calcification. The absence of in vitro calcification induction is consistent with prior findings, where apoA-I had an inverse relationship to risk for AS incidence ( 12 ) and hemodynamic AS progression ( 13 ). Furthermore, in vivo data suggested that injection of an apoA-I mimetic peptide to rabbits and mice led to a reduction in fibrosis and calcification ( 14 , 18 , 19 , 20 ).…”

“…Genetically, LPA is the only lipoprotein gene that has been associated with AV calcification ( 6 ). At the epidemiological level, apoB ( 7 ), lp(a) ( 8 , 9 ), and apoC-III ( 10 , 11 ) are associated with CAVD, and apoA-I has demonstrated an inverse relationship to risk for AS incidence ( 12 ) and its hemodynamic progression ( 13 ). Low-density lipoprotein cholesterol (LDL-C), oxidized phospholipids, and triglycerides are associated with onset of CAVD ( 10 , 14 , 15 ) and are introduced into the valvular matrix as components of lipoproteins.…”

Elevated Apolipoprotein B/A-1 Ratio is Associated With an Increased Risk of Aortic Stenosis: Experience From the AMORIS Cohort

“…There have been three previous studies on the association between apolipoproteins and AS. The mean apoB/apoA-1 ratio of 0.92 in this study was higher than in the three previous reports, which showed ratios ranging 0.53-0.70, and those patients were older than in the present study (Supplementary Table 1) [5,10,11]. Other manifestations of dyslipidaemia have also been associated with the risk of developing AS.…”

“…This study documented a strong association of the apoB/ apoA-I ratio and incident AS in those aged 65 years. In the PROGRESSA echocardiographic study of 159 patients followed for 2 years, a high apoB/apoA-1 ratio was significantly associated with a faster progression of AS in those aged ,70 years [11].…”

“…In Swedish subjects followed for 11 years, increased lipoprotein (a) level and elevated apoB/apoA-1 ratio were associated with surgery for AS in those with concomitant coronary artery disease [10]. In the Metabolic Determinants of the Progression of Aortic Stenosis (PRO-GRESSA) study, the top tertile of apoB/apoA-1 ratio was associated with faster progression of AS at a 2-year followup, particularly in young individuals [11]. A high apoB/ apoA-1 ratio has been reported in patients with degenerated aortic bioprosthesis [12].…”