Alcohol and cardiovascular disease: inter-organ crosstalk, microvascular dysfunction, and cardiovascular ageing.

Abstract

Alcohol-related cardiovascular risk is being fundamentally reappraised. Observational associations suggesting cardioprotection with light-to-moderate drinking have been challenged by contemporary cohort analyses, Mendelian-randomization studies, biomarker-informed investigations, and updated public-health guidance. Uncertainty nevertheless persists at very low exposure levels and for selected coronary or all-cause outcomes. Alcohol is therefore best viewed as a dose-, pattern-, and host-dependent cardiovascular stressor. Acute or binge drinking, sustained heavy intake, chronic intake with episodic binges, and withdrawal produce overlapping but distinct phenotypes, including hypertension, atrial fibrillation, ventricular arrhythmias, sudden death, alcohol-associated cardiomyopathy, heart failure, stroke, and vascular disease. A systems-cardiology framework is presented in which direct myocardial injury, electrical instability, haemodynamic and autonomic stress, vascular and microvascular dysfunction, and disrupted inter-organ signalling interact. Ethanol and acetaldehyde toxicity, redox imbalance, microbial and inflammatory mediators, neurohumoral activation, and metabolic or electrolyte disturbances can impair endothelial signalling, mitochondrial energetics, excitation-contraction coupling, electrical stability, and repair. Pathway dominance varies across exposure patterns and susceptible hosts; coronary microvascular dysfunction may represent a convergence pathway rather than an obligatory mediator. Cumulative injury can diminish perfusion, contractile, electrical, autonomic, and exercise reserve. Alcohol-related cardiovascular ageing is proposed as a unifying cumulative phenotype encompassing mitochondrial dysfunction, oxidative and nitrative stress, inflammageing, senescence, impaired repair, circadian and epigenetic dysregulation, fibrosis, and ventriculo-arterial uncoupling, although direct human evidence remains incomplete. Age, biological sex, genetics, comorbidities, sleep-circadian disruption, nutrition, medications, and polysubstance misuse may modify pathway dominance and reversibility. Structured exposure assessment and alcohol reduction or abstinence, when indicated, are actionable components of cardiovascular prevention and care.