Determinants of ventilatory thresholds obtained by cardiopulmonary exercise testing in a large cohort: implications for exercise prescription, risk stratification and clinical management

Background Ventilatory thresholds (VTs: VT1 and VT2), derived from cardiopulmonary exercise testing (CPET), are crucial metabolic markers, but the factors influencing them—particularly the delta between VT1 and VT2 (∆VT1-VT2)—remain underexplored. This study aimed to identify and quantify the determinants of VT1, VT2, and ∆VT1-VT2. Methods We analysed data from 865 individuals (mean age 44±17 years; 83% male) undergoing standardised CPET, incorporating clinical and echocardiographic evaluations. The cohort included healthy subjects and cardiac patients. VT1, VT2, and ∆VT1-VT2 were evaluated across subgroups and age strata. A multivariate regression and decision tree analysis were conducted to identify independent predictors of VTs. Results Cardiac patients exhibited significantly reduced VO2peak (1901.9±631.8 vs. 2409.9±717.8 mL/min) and ventilatory efficiency compared to healthy individuals (all p<0.001). VT1 and VT2 values declined with age, and ∆VT1-VT2 was lower in patients (28±15 vs. 37±14 bpm, p<0.001) and declined with age (43±12 bpm in ≤35 years vs. 24.4 ± 12.0 bpm in ≥55 years). Betablocker use and age significantly influenced VT1 and VT2 and ∆VT1-VT2 (p<0.001); weight significantly affected VT1 (p<0.001); powerMAX, and BMI significantly influenced VT2. The ∆VT1-VT2 was significantly predicted by Ejection Fraction (EF) and powerMAX (p<0.001). Conclusion This study identifies distinct predictors of ventilatory thresholds and introduces ∆VT1-VT2 as a valuable marker of metabolic flexibility and endurance potential. These findings have important implications for personalised exercise prescription, risk stratification, and monitoring in both clinical and athletic settings.