Resting heart rate and decline in cognitive function: observations from the ONTARGET/TRANSCEND studies

Abstract

Background: Higher resting heart rate (RHR), even within the normal range, has been associated with adverse cardiovascular outcomes. Recently, RHR was shown predictive of cognitive decline among patients with ischaemic stroke. It is not known whether RHR is linked with cognitive decline in a broader population Purpose: We hypothesised that RHR is independently associated with decline in cognitive function in patients with elevated cardiovascular risk Methods: We conducted a post hoc analysis of patients enrolled in parallel multicentre trials that randomised participants with vascular disease or diabetes mellitus to telmisartan, ramipril, or their combination; and to telmisartan or placebo in those intolerant of angiotensin converting enzyme inhibitors. Cognitive function was evaluated by Mini-Mental State Examination (MMSE) at randomisation, 2 years, and at final follow-up (median 4.7 years). Cognitive decline was defined as a fall of ≥ 3 points from baseline to either follow-up MMSE. RHR was categorised by quartiles (<60, 60-66, 67-74, and ≥75bpm). Multiple logistic re-gression was performed with adjustment for baseline covariates including demographics, cardiovascular comorbidities, tobacco use, alcohol consumption, pharmacotherapy (including negative chronotropes), physical activity level, ethnicity education level, depressive symptoms, dietary habits, blood pressure, anthropometrics, renal function, serum lipid concentrations, left ventricular hypertrophy and baseline MMSE score. Results: In 27 860 subjects with baseline and follow-up MMSE, mean age was 66±7.1 years and 8146 (29%) were female. Baseline MMSE score in ascending RHR groups was 27.8±2.60; 27.7±2.80; 27.6±2.92; and 27.4±3.22. Over follow-up, 4699 (17%) subjects exhibited cognitive decline. Compared with RHR <60bpm, the adjusted odds ratios (95% CI) for cognitive decline were 1.04 (0.940-1.15) for RHR 60-66; 1.16 (1.05-1.28) for HR of 67-74; and 1.15 (1.04-1.28) for HR ≥75bpm respectively. For every 10bpm increase in RHR, the unadjusted and adjusted odds ratios (95% CI) for cognitive decline were 1.08 (1.05-1.11); and 1.04 (1.01-1.08) respectively. Conclusions: RHR is independently associated with cognitive decline and may be an important risk marker. Further research is needed to determine the nature of this association and whether RHR represents a therapeutic target to prevent cognitive decline.