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

Lionel Tastet, Romain Capoulade, Mylène Shen, Marie-Annick Clavel, Nancy Côté, Patrick Mathieu, Marie Arsenault, Élisabeth Bédard, Alexe Tremblay, Marilie Samson, Yohan Bossé, Jean G Dumesnil, Benoit J Arsenault, Jonathan Beaudoin, Mathieu Bernier, Jean-Pierre Després, Philippe Pibarot, Lionel Tastet, Romain Capoulade, Mylène Shen, Marie-Annick Clavel, Nancy Côté, Patrick Mathieu, Marie Arsenault, Élisabeth Bédard, Alexe Tremblay, Marilie Samson, Yohan Bossé, Jean G Dumesnil, Benoit J Arsenault, Jonathan Beaudoin, Mathieu Bernier, Jean-Pierre Després, Philippe Pibarot

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 β≥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.

Keywords: aging; aortic valve stenosis; apolipoprotein; echocardiography.

© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1
Figure 1
Hemodynamic progression rate of aortic valve stenosis according to tertiles of apoB/apoA‐I ratio. Comparison of progression of Vpeak in the entire cohort (n=159) (A), in patients with age <70 years (ie, median age for the entire cohort; n=80) (B), and in patients with age ≥70 years (n=79) (C) according to top tertile of apoB/apoA‐I ratio (ie, ≥0.62) vs bottom and middle tertiles (ie, <0.62). The box shows the 25th to 75th percentiles, the median line on the box shows the median value, and the error bars the 10th and 90th percentiles; circles are outliers; the numbers of the top of the graph are median (25th percentile to 75th percentile). apoA‐I indicates apolipoprotein A‐I; apoB, apolipoprotein B; Vpeak, peak aortic jet velocity.
Figure 2
Figure 2
Comparison of the change in severity class of aortic valve stenosis according to tertiles of apoB/apoA‐I ratio and age. Baseline aortic valve stenosis severity was similar when comparing patients with higher (top tertile) vs those with lower (bottom/middle [mid] tertiles) plasma level of apoB/apoA‐I ratio, in patients aged peak, peak aortic jet velocity.
Figure 3
Figure 3
Association of higher apoB/apoA‐I ratio with the worsening of AS severity class. Risk of the worsening of AS severity class (ie, change from mild to moderate or severe defined as Vpeak>3.0 m/s, or change from moderate to severe defined as Vpeak≥4.0 m/s) after 2 years of follow‐up according to top tertile vs bottom and middle (mid) tertiles of apoB/apoA‐I ratio, in the entire cohort, the patients aged <70 years, and the patients aged ≥70 years, respectively. In the entire cohort, the logistic regression analysis was adjusted for age, sex, and baseline Vpeak. In both age groups, the analyses were adjusted for sex and baseline Vpeak. CI indicates confidence interval; OR, odd ratio; apoA‐I, apolipoprotein A‐I; apoB, apolipoprotein B; Vpeak, peak aortic jet velocity.

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