Left ventricular-arterial coupling parameters predict incident cardiovascular events and mortality in UK Biobank

Ventricular-arterial coupling (VAC) is fundamental to cardiovascular efficiency, but its value for predicting cardiovascular disease (CVD) in the general population is unclear. This study aimed to evaluate the predictive value of three novel non-invasive VAC parameters—the ratio of arterial stiffness index to global longitudinal strain (ASI/GLS), estimated pulse wave velocity to GLS (ePWV/GLS), and left ventricular end-systolic volume to stroke volume (LVESV/LVSV)—for incident atrial fibrillation (AF), stroke, heart failure (HF), coronary heart disease (CHD), all-cause and CVD mortality. We analyzed UK Biobank participants free of baseline significant structural CVD or prior major cardiac surgery. VAC parameters were derived from arterial stiffness metrics and cardiac magnetic resonance (CMR). Associations were assessed using multivariable Cox or Fine-Gray models with false discovery rate (FDR) correction. Incremental prognostic value was evaluated using likelihood ratio tests, C-indices, and continuous net reclassification improvement (NRI). The study included 38,144 participants (mean age 63.5 ± 7.5 years; 47.2% men) with a median follow-up of 4.82 years. After adjustment for clinical features, all three VAC parameters were associated with increased risk of AF, stroke, HF, CHD, all-cause and CVD mortality (except ASI/GLS for CHD). For incident HF, the addition of VAC parameters yielded substantial incremental value, raising C-indices to 0.789–0.835 with NRIs of 11.0%–24.1%. Beyond some respective conventional CMR indices, all three VAC parameters remained independent predictors for incident stroke, whereas ePWV/GLS was specifically independent for incident AF (hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.10–1.29), HF (HR 1.26, 95% CI 1.11–1.43), and CHD (HR 1.11, 95% CI 1.001–1.23). Furthermore, while VAC parameters were independently associated with all-cause mortality regardless of LVEF, their associations with CVD mortality were largely attenuated by LVEF. In the general population, non-invasive VAC parameters predict various adverse cardiovascular outcomes. Incorporating ASI/GLS or ePWV/GLS into traditional risk assessment enhances prognostic value in specific clinical scenarios. VAC parameters predict incident cardiovascular events and mortality. Abbreviations: AF, atrial fibrillation; ASI, arterial stiffness index; CHD, coronary heart disease; CVD, cardiovascular disease; ePWV, estimated pulse wave velocity; GLS, left ventricular global longitudinal strain; HF, heart failure; LVESV, left ventricular end-systolic volume; LVSV, left ventricular stroke volume; VAC, ventricular-arterial coupling.