Low Heart Rate on HR-Reducing Meds Bodes Higher CV, Death Risk: MESA Analysis

Veronica Hackethal, MD

January 19, 2016

CHICAGO, IL — Bradycardia per se does not increase mortality or cardiovascular risk overall, but it may be associated with those risks in persons taking medications that lower heart rate, suggests an analysis based on an ethnically diverse US population-based cohort[1].

"I think caution is in order if somebody has a reason to be on drugs that lower the heart rate, and their heart rate is consistently below 50 beats per minute," Dr Alain Bertoni (Wake Forest School of Medicine, Winston-Salem, NC) commented to heartwire from Medscape.

"We believe doctors should look carefully at people who have really slow heart rates when they're on these medications and consider the possibility that the dose needs adjustment or that other diseases that aren't well controlled need to be addressed," he said.

Bertoni is the senior author on the analysis from the Multi-Ethnic Study of Atherosclerosis (MESA) published January 19, 2016 in JAMA Internal Medicine with lead author Dr Ajay Dharod (Wake Forest University). The report defined heart-rate–lowering agents as beta-blockers, digitalis, nondihydropyridine calcium-channel blockers, and all other antiarrhythmic drugs.

Past studies have suggested that having a high resting heart rate can increase the risk of cardiovascular events, the authors explain. But the role of bradycardia is less clear, they write, especially in middle-aged and older people. Some studies suggest that bradycardia in healthy middle-aged nonathletes isn't associated with cardiovascular risk, and others have seen a J-curve relationship between heart rate and mortality.

The current MESA-cohort analysis included 6733 participants without clinical cardiovascular disease who were recruited from 2000 to 2002 in six regions of the US and were followed for more than a decade.

In participants taking heart-rate–lowering drugs (n=902) at baseline and those not on such medications (n=5831), bradycardia was not significantly associated with developing cardiovascular disease (HR 1.27, 95% CI 0.68–2.37; and HR 1.07, 95% CFI 0.71–1.63), respectively).

Consistent with past findings, a heart rate >80 bpm was associated with increased mortality (HR 1.49, 95% CI 1.08-2.05; P=0.01) compared with a reference group of persons with heart rate 60 to 69 bpm.

In multivariate analysis that included coronary artery calcification as a variable, mortality in participants on  heart-rate–lowering drugs followed a J-shaped curve in that it was significantly increased for a heart rate <50 bpm (HR 2.42, 95% CI 1.39–4.20; P=0.002) and >80 bpm (HR 3.55, 95% CI 1.65–7.65; P=0.001) compared with the reference range of 60 to 69 bpm.

In contrast, mortality in those not on  heart-rate–lowering meds showed a more linear pattern. Fully adjusted analyses showed no significant difference in mortality risk for participants who had bradycardia and were not on such meds (HR 0.71, 95% CI 0.41–1.09; P=0.12).

The study could not tease out whether the findings were due to underlying heart disease or to heart-rate–modifying drugs, Bertoni acknowledged.

"The current analysis does a good job in highlighting the complexity of this issue," Dr Jeffrey Goldberger (University of Miami, FL) said for heartwire . "We're never going to have a clear one-line statement on what it means to have bradycardia, because bradycardia's complex. It's not one physiologic entity across all patients," explained Goldberger, who is not associated with the current MESA analysis.

The study also raises an important question, he said. Recent data on the global epidemiology of cardiac death suggests a shift in underlying etiology, from fast arrhythmias to an increasing incidence of slower heart rhythms, he pointed out.

"It's worth trying to understand which patients with bradycardia may be at risk for cardiac events and what types of interventions could be done to improve their care," he concluded.

Neither Bertoni nor Dharod reported relevant financial relationships; disclosures for the coauthors are listed in the article. Goldberger said he has no relevant financial relationships.

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