Association Between an Exaggerated Exercise Blood Pressure Response and Mortality and Cardiovascular Events in Older Adults with Known or Suspected Coronary Artery Disease

Abstract

To the Editor: The relationship between exercise-induced hypertension and cardiovascular outcomes remains controversial. Several studies have shown an association between an exaggerated rise in systolic blood pressure (SBP) during exercise with the subsequent development of cardiovascular events,1-3 whereas others evaluating individuals with known or suspected coronary artery disease (CAD) differ in their findings.4-7 The purpose of this study was to examine the association between exercise-induced hypertension and all-cause mortality and cardiovascular events in elderly adults with known or suspected CAD. From March 1, 1995, to June 28, 2013, 6,104 community-based individuals aged 65 and older with known or suspected CAD underwent treadmill exercise echocardiography. Those who had received beta-blockers within 48 hours before the tests (because of their blunting effect on exercise-induced rise in SBP) and those in whom SBP did not increase with exercise above baseline values (because of the association between an exercise-induced hypotensive response and worse prognosis) were excluded.8 The final study population consisted of 4,511 individuals. The Comité Ético de Investigación Clínica de Galicia approved the investigation. Exercise echocardiography was performed as previously described.9 Blood pressure was measured at rest and at each stage of the protocol. Peak SBP was defined as maximum SBP obtained during exercise. An exaggerated exercise-induced SBP response (EESBPR) was defined as a peak SBP greater than 220 mmHg.6 Outcomes were all-cause mortality, myocardial infarction (MI), and stroke. Median follow-up was 3.6 years (interquartile range 0.2–8.1 years). Cox proportional hazards models were used to assess the association between EESPBR and outcomes. Covariates were sex, age, cardiovascular risk factors, prior MI, prior coronary revascularization, antihypertensive drugs, atrial fibrillation, left ventricular ejection fraction, baseline SBP, peak heart rate, exercise-induced chest pain, ischemic electrocardiographic changes, exercise workload, and echocardiographic ischemia. Two thousand five hundred twenty-nine participants (56.1%) were male, and 2,770 (61.4%) had a history of hypertension. EESBPR developed in 165 (3.7%). Participants with EESBPR were more likely to have resting hypertension and less likely to have previously diagnosed CAD. There were no significant differences between the groups regarding resting heart rate or likelihood of submaximal tests. During follow-up, 1,104 participants died. Annualized mortality was 3.5% in participants with EESBPR and 5.3% in those without (p = .002, Figure 1). Four hundred sixty-four participants experienced MI, and 145 had at least one stroke of any type. Annualized rates of MI, stroke of any type, ischemic stroke, and hemorrhagic stroke were 2.3%, 0.7%, 0.7%, and 0.1% in participants with EESBPR and 2.3%, 0.84, 0.6% and 0.2% in those without, respectively (P > .05 for all comparisons). In Cox regression analysis, EESBPR remained independently associated with lower risk of all-cause mortality (hazard ratio = 0.64, 95% confidence interval = 0.46–0.89, P = .008). There were no significant associations between EESBPR and MI, stroke of any type, ischemic stroke, or hemorrhagic stroke after multivariate adjustments. EESBPR was associated with longer survival in a series of elderly adults referred for exercise echocardiography for clinical reasons; no significant association was found between EESBPR and subsequent risk of MI or stroke in this population. Some prior studies performed in asymptomatic healthy subjects found that an exercise-induced BP response was associated with higher risk of cardiovascular events.1-3 Although these studies contrast with the current results, there are important differences in participant characteristics, in the definition of the variables evaluated, and in the technique used. Individuals with a history of CAD were generally excluded, and there was no consensus on normal values for exercise-induced SBP response. Nevertheless, other studies, particularly those evaluating individuals with known or suspected CAD, did not find an association between exercise-induced hypertension and worse prognosis.4-7 Furthermore, the current investigation complements and expands the results of a previous study10 that found that an increase in SBP during exercise was associated with longer survival in a group of 382 individuals aged 75 years old. Discrepancies between studies may be due, at least in part, to the different physiopathological pathways leading to an exercise-induced rise in SBP. An increase in cardiac output or an insufficient decrease in systemic vascular resistance may provoke EESBPR, and the theoretical effects of both mechanisms on outcome are opposite (beneficial for the former, detrimental for the latter). It may be that the predominant mechanism leading to the survival benefit observed in elderly adults with known or suspected CAD who exhibit EESBPR would be an enhanced exercise-induced increase in cardiac output. Conflict of Interest: The authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: MCBM: study concept and design, acquisition of subjects and data, data analysis and interpretation, preparation of manuscript. ABM, JP: study concept and design, acquisition of subjects and data, data analysis and interpretation, review of manuscript. Sponsor's Role: The study had no external funding.