Novel exercise parameter inversely associated with risk of HF and mortality
Inverse association of pulse pressure augmentation during exercise with heart failure and death
Introduction and methods
In individuals with suspected coronary artery disease (CAD), resting peak exercise values for systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) are measured during stress testing, however, the significance of PP augmentation in response to exercise remains relatively unknown . Previous studies showed a lower PP rise with exercise among individuals with a history of anterior myocardial infarction (MI)  or mortality . However, these data did not account for resting PP and did not include data on non-fatal outcomes like heart failure (HF). Therefore, this study assessed the relationship between the novel exercise parameter - pulse pressure stress index (P2SI) - and incident HF, MI and all-cause mortality among participants of the Henry Ford ExercIse Testing (FIT) Project.
The FIT project is a large, real-world cohort study consisting of patients aged >18 years who underwent physician-referred treadmill stress testing at Henry Ford Health System-affiliated hospitals and ambulatory care centers in Detroit, Michigan between 1991 and 2009. Subjects with a history of CAD, HF or atrial fibrillation (AF), and those below the 1st or above the 99th percentile of P2SI were excluded, leaving a study population of 55,524 participants.
PP was measured as the difference between SBP and DBP, respectively, and P2SI was defined as PP peak exercise during stress testing divided by resting PP. Participants were divided into quartiles according to their P2SI variability: Q1 (0.90-1.59 mmHg), Q2 (1.60-1.95 mmHg), Q3 (1.96-2.37 mmHg) and Q4 (2.38-4.09 mmHg).
The primary outcomes of the study were all-cause mortality, MI and incident HF.
- The incidence rates of HF, MI and all-cause mortality progressively increased with decreasing P2SI, with 13.3, 7.7 and 18.7 rates per 1000 person-years, respectively, in P2SI Q1 (P<0.001).
- The optimal P2SI cut-off for prediction of incident outcomes was 1.9 mmHg for all-cause mortality, 1.9 mmHg for MI and 1.8 mmHg for HF. Therefore Q3 (2.0-2.4 mmHg) was chosen as reference category as prediction of incident outcomes.
- After multivariable adjustment, subjects in Q1 and Q2 had a significantly higher risk of HF (Q1 HR: 1.47, 95%CI: 1.21-1.78, P-trend<0.001; Q2 HR: 1.27, 95%CI:1.09-1.49, P-trend<0.001) and all-cause mortality (Q1 HR: 1.33, 95%CI: 1.17-1.50; Q2 HR: 1.11, 95%CI: 1.01-1.23), compared to those in Q3, whereas subjects in Q4 did not show a difference in risk (HF HR: 0.94, 95%CI: 0.79-1.12; all-cause mortal HR: 0.93, 95%CI: 0.83-1.04) (P-trend<0.001). There was no association seen between P2SI and MI.
- After multivariable adjustment, P2SI was inversely associated and approximately linearly associated with both incident HF (linear HRadj: 0.81, 95%CI: 0.68-0.97) and all-cause mortality (linear HRadj: 0.79, 95%CI: 0.70-0.89).
- Results were similar after adjustment for exertional change in SBP or DBP, showing that P2SI was independently related to HF, MI and all-cause death.
- A similar or higher C-statistics for HF and all-cause mortality were observed with per cent HR achieved and number of metabolic equivalents achieved, compared with P2SI. After addition of these parameters, P2SI remained an independent predictor of both HF and all-cause mortality.
- In a post-hoc analysis of FIT participants with available LVEF information (n=13,134), the median LVEF of those in Q1 was 55% compared with 58% in Q4 (P<0.001). Similarly, 422 of this subsample had an LVEF <40%, with approximately 50% of these individuals being Q1 of versus 12% in Q4 (p<0.001).
In a large cohort study, poor augmentation of PP with exercise was inversely associated with risk of HF and all-cause mortality in individuals with suspected CAD, with a useful and simple threshold of <1.96 mmHg to identify incident HF and all-cause mortality. These results show that P2SI can be considered as a novel and readily quantifiable high-risk feature derived from exercise stress testing, which may be applied to any patient. Further research is needed to validate this new clinical parameter.