Abstract
Aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism is a common genetic variant in Asians that is responsible for defective toxic aldehyde and lipid peroxidation metabolism after alcohol consumption. The extent to which low alcohol consumption may cause atrial substrates to trigger atrial fibrillation (AF) development in users with ALDH2 variants remains to be determined. We prospectively enrolled 249 ethnic Asians, including 56 non-drinkers and 193 habitual drinkers (135 (70%) as ALDH2 wild-type: GG, rs671; 58 (30%) as ALDH2 variants: G/A or A/A, rs671). Novel left atrial (LA) mechanical substrates with dynamic characteristics were assessed using a speckle-tracking algorithm and correlated to daily alcohol consumption and ALDH2 genotypes. Despite modest and comparable alcohol consumption by the habitual alcohol users (14.3 [8.3~28.6] and 12.3 [6.3~30.7] g/day for those without and with ALDH2 polymorphism, p = 0.31), there was a substantial and graded increase in the 4-HNE adduct and prolonged PR, and a reduction in novel LA mechanical parameters (including peak atrial longitudinal strain (PALS) and phasic strain rates (reservoir, conduit, and booster pump functions), p < 0.05), rather than an LA emptying fraction (LAEF) or LA volume index across non-drinkers, and in habitual drinkers without and with ALDH2 polymorphism (all p < 0.05). The presence of ALDH2 polymorphism worsened the association between increasing daily alcohol dose and LAEF, PALS, and phasic reservoir and booster functions (all Pinteraction: <0.05). Binge drinking superimposed on regular alcohol use exclusively further worsened LA booster pump function compared to regular drinking without binge use (1.66 ± 0.57 vs. 1.97 ± 0.56 1/s, p = 0.001). Impaired LA booster function further independently helped to predict AF after consideration of the CHARGE-AF score (adjusted 1.68 (95% CI: 1.06–2.67), p = 0.028, per 1 z-score increment). Habitual modest alcohol consumption led to mechanical LA substrate formation in an ethnic Asian population, which was more pronounced in subjects harboring ALDH2 variants. Impaired LA booster functions may serve as a useful predictor of AF in such populations.
Highlights
Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that catalyzes the oxidation of acetaldehyde, which is the main toxic product of ethanol metabolism that causes major organ damage after alcohol consumption [1,2]
The median alcohol intake was 14.1 g/day (IQR: 7.6~28.6 g/day) and the median alcohol consumption duration was 16.0 (5.0~30.0) years for habitual drinkers, daily alcohol use was comparable in habitual drinkers stratified by considering
left atrial (LA) mechanical impairment prior to overt structural remodeling, which was prominent in those harboring ALDH2 polymorphism, which acted as a key acetaldehyde catalyzer after alcohol consumption
Summary
Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that catalyzes the oxidation of acetaldehyde, which is the main toxic product of ethanol metabolism that causes major organ damage after alcohol consumption [1,2]. Restoration of ALDH2 deficiency can reportedly reverse the myocardial damage (e.g., fibrosis) caused by acetaldehyde toxicity that arises due to excessive alcohol consumption and was shown to reverse the extent of cardiac remodeling and mechanical dysfunction [2,6]. It was proposed that abstinence from alcohol consumption may reduce the recurrence of arrhythmias in regular consumers with atrial fibrillation [10]. These findings highlight the toxic effects of prolonged alcohol consumption on the atrial tissue. We demonstrated that mild-to-moderate alcohol consumption might be associated with sub-clinical left atrial (LA) mechanical dysfunction in a large population-based study reported in ethnic
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