All-cause and cardiovascular mortality in relation to changing heart rate during treatment of hypertensive patients with electrocardiographic left ventricular hypertrophy.

BACKGROUND: Although higher heart rate (HR) at baseline has been associated with an increased risk of cardiovascular (CV) and all-cause mortality, the relationship of in-treatment HR over time to mortality in hypertensive patients with ECG left ventricular hypertrophy (LVH) has not been examined.

METHODS AND RESULTS: Heart rate was evaluated over time in 9190 hypertensive patients treated with losartan- or atenolol-based regimens and followed with annual ECGs. During a mean follow-up of 4.8 ± 0.9 years, 814 patients (8.9%) died, 438 (4.8%) from CV causes. In univariate Cox analyses, every 10 bpm higher HR on in-treatment ECGs was associated with a 25% increased risk of CV death [95% confidence interval (CI): 14-32%] and a 27% greater risk of all-cause mortality (95% CI: 21-34%). In an alternative analysis, persistence or development of a HR ≥ 84 bpm (upper quintile of baseline HR) was associated with an 89% greater risk of CV death (95% CI: 49-141%) and a 97% increased risk of all-cause mortality (95% CI: 65-135%). After adjusting for treatment with losartan vs. atenolol, baseline risk factors for death, baseline HR, baseline and in-treatment systolic and diastolic pressure, incident myocardial infarction, and the known predictive value of baseline and in-treatment QRS duration and ECG LVH, higher in-treatment HR in time-varying multivariable Cox models remained strongly predictive of mortality: every 10 bpm higher HR was associated with a 16% increased adjusted risk of CV mortality (95% CI: 6-27%) and a 25% greater risk of all-cause mortality (95% CI: 17-33%), with persistence or development of a HR ≥ 84 associated with a 55% greater risk of CV death (95% CI: 16-105%) and a 79% greater adjusted risk of all-cause mortality (95% CI: 46-121%).

CONCLUSION: Higher in-treatment HR on serial ECGs predicts greater likelihood of subsequent CV or all-cause mortality, independent of treatment modality, blood pressure lowering, regression of ECG LVH and changing QRS duration in hypertensive patients with ECG LVH. These findings support the value of serial assessment of HR for improved risk stratification in hypertensive patients.

CLINICAL TRIALS REGISTRATION: https://clinicaltrials.gov/ct/show/NCT00338260?order=1cp.