Hemodynamic response to exercise and cardiovascular risk in patients with normal myocardial perfusion
J Lu, S L Carre, J Hainer, C L Da Silva, D Yang, D M Lopez, R Blankstein, S Dorbala, M F Di Carli, S Divakaran, J M BrownAbstract
Introduction
A hypertensive response to exercise (HRE) has been associated with adverse cardiovascular (CV) outcomes in select populations, but its prognostic value in patients with normal myocardial perfusion remains unclear.
Purpose
To evaluate whether HRE is associated with incident CV events in a low-risk exercise SPECT population and identify exercise-derived predictors of risk.
Methods
This single-center study included all patients undergoing Bruce protocol exercise SPECT from 2006-2024. Exclusion criteria were prior stroke, myocardial infarction (MI), heart failure (HF), left ventricular ejection fraction <40%, or abnormal myocardial perfusion (summed stress score ≥ 3). The primary outcome was a composite of incident MI, stroke, HF hospitalization, or CV death. HRE was defined as systolic blood pressure (BP) ≥210 mmHg in men, ≥190mmHg in women, or diastolic BP ≥110 mmHg. Hypotensive response was defined as peak systolic BP < rest systolic BP. Normotension was defined as BP <130/80 mmHg. Hemodynamic gain index (HGI) was calculated as the percent change in the product of systolic BP and heart rate from rest to peak exercise. Associations with CV outcomes were assessed using multivariable Cox proportional hazards and Fine-Gray competing risks models adjusting for age, race, sex, BMI, diabetes, and hypertension.
Results
Among 9105 included patients (mean age 60.6±11y; 49% Male; 77% White) followed for 8.9±5.6y, HRE was present in 1200 (13%). Those with HRE had higher BMI (30.9 vs 28.6) and were more often female (64% vs 49%) and with more hypertension (74% vs 59%) and diabetes (22% vs 16%) (p<0.01 for all). CV event rates were similar (HRE 6.7 vs no HRE 7.3 per 1000 person-years), and HRE was not independently associated with CV events (HR 0.89, 95% CI 0.69–1.15). Among patients with normal resting BP, HRE was associated with lower risk (HR 0.35, 95% CI 0.14–0.84), with no effect modification by clinical hypertension history. Achieved METS <10 (HR 2.02, 95% CI 1.64–2.49), higher SBP to METs ratio (HR 1.25 per unit, 95% CI 1.16-1.34) and hypotensive response (HR 1.64, 95% CI 1.08-2.50) were associated with increased risk, whereas higher HGI (HR 0.53 per unit increase, 95% CI 0.46-0.62) was associated with lower risk. Competing risk analysis yielded similar results.
Conclusion
In this low-risk exercise SPECT cohort, HRE was not independently associated with adverse CV outcomes and may instead reflect preserved hemodynamic reserve rather than pathologic risk, particularly in patients with controlled baseline blood pressure. In contrast, absolute exercise capacity and fitness-adjusted systolic BP provide stronger prognostic discrimination in this population.