Abstract

Although hemodynamic responses to exercise have been studied for decades, comprehensive and definitive prognostic markers are lacking. The present study aimed to assess the association between a new hemodynamic index and all-cause mortality in men. Treadmill exercise testing was performed between 1987 and 2012 in 11,455 men aged 58.5 ± 11 years who were prospectively followed for 9.8 ± 5.8 years. Heart rate (HR) and systolic blood pressure (SBP) responses were used to develop a hemodynamic gain index (HGI) = [(HRpeak × SBPpeak) - (HRrest × SBPrest)]/(HRrest × SBPrest). Multivariable Cox hazard models adjusted for established cardiometabolic diseases, risk factors, cardiorespiratory fitness, and medications were analyzed for HGI and all-cause mortality. During the follow-up, 2,804 participants (24.5%) died, and mean HGI was 1.68 ± 0.83 bpm/mm Hg. In a continuous model, every 1 unit higher in HGI was associated with a 23% (hazard ratio 0.77, 95% confidence interval 0.71-0.82, p <0.001) reduced risk of mortality. In a categorical model, compared with participants <25th percentile (HGI <1.1), participants who were between the 25th and 50th (HGI 1.1-1.59), 50th to 75th (HGI 1.6-2.1) and >75th percentile (HGI >2.1) exhibited 12%, 24%, and 36% reductions in mortality risk (p trend <0.001), respectively. The inverse association between HGI and death was significant across wide-range of age groups and among participants with varied chronic conditions. In conclusion, these novel findings indicate that higher HGI is inversely and independently associated with lower risk of all-cause mortality in men, suggesting its potential prognostic value for risk stratification in clinical and research settings.

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