PRoFESS: Impact of resting heart rates on recurrent stroke, cardiovascular outcomes, disability and cognitive decline in 20.165 patients after ischemic stroke

List of Authors: Prof. Michael Böhm / GermanyCo-authors: Michael Böhm, Daniel Cotton, Lydia Foster, Florian Custodis, Ulrich Laufs, Ralph Sacco, Philip Bath, Salim Yusuf, Hans-Christoph Diener

Background
Recurrent stroke is a frequent and disabling event. High heart rates are associated with cardiovascular risk. We investigated the effects of resting heart rates on cardiovascular and neurological outcomes after recurrent stroke in the high risk population of the PRoFESS study.

Methods and Results
20165 patients after ischemic stroke (mean age 66.1, SD 8.6 years) assigned to the treatment arms of the PRoFESS trial were pooled divided by quintiles of baseline heart rate and analyzed according to cardiovascular and functional outcomes after stroke. Recurrent stroke and major cardiovascular outcomes like myocardial infarction, death from cardiovascular cause and noncardiovascular death were examined. Predefined endpoints were disability after recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed with the mini-mental state examination (MMSE) score at 4 weeks after randomization and at the penultimate visit. Patients in the two highest quintiles of heart rates (76-82 and > 82 bpm) were at higher risk for total death (hazard ratio [HR] 1.42, 95% CI, 1.19-1.69 and [HR] 1.74, 95% CI, 1.48-2.06) compared to the lowest quintile. Similar results were observed for vascular death and noncardiovascular death. Risks of recurrent stroke (HR 1.11, 95% CI, 0.96-1.29), and MI were not significantly different in patients with higher baseline heart rates. In patients with recurrent stroke, an association of lower heart rates to better outcomes (Barthel) was observed across all heart rate groups. In addition, there was a significant association of baseline heart rates to significant cognitive decline, defined as defined as a ≥ 2 point decrease in MMSE score between one month and penultimate visit.

Interpretation
Our data show that heart rate is associated with mortality but not recurrent strokes or MI in patients after stroke. Low heart rates are associated with better neurological functional outcomes after ischemic stroke. Therefore, higher heart rates could be associated with larger strokes or impaired recovery after stroke and represent a general marker of survival in these patients. 

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