Resting heart rate: a risk marker or a treatment target? What the trials that lowered it found

A faster resting pulse is one of the most consistent warning signs in population studies: people whose heart beats faster at rest die earlier, on average, than people whose heart beats slower. That raises an obvious question. If the number goes with the risk, does pushing the number down lower the risk? Several large trials tested exactly that with ivabradine, a drug that slows the heart at the sinus node and does not share the other actions of beta-blockers. Their answers differ sharply depending on who was in the trial, and that difference is the most useful thing to know about this marker.

This article is the second look at the topic. The basics of what resting heart rate and heart-rate variability measure are in our earlier piece on resting heart rate and HRV.

What the cohorts show

• A 2016 meta-analysis pooled 46 prospective cohort studies of the general population. For death from any cause, the analysis covered 1,246,203 people, and each 10 beats per minute higher resting heart rate was associated with a 9% higher risk. For cardiovascular death, it covered 848,320 people, and the corresponding figure was 8%. Compared with the lowest category, a resting rate above 80 beats per minute was associated with a 45% higher risk of death from any cause. The authors reported substantial heterogeneity between studies and signs of publication bias.

• A Norwegian cohort of about 29,000 adults without known cardiovascular disease measured resting heart rate twice, around ten years apart. People whose rate rose from below 70 to above 85 beats per minute had roughly twice the risk of dying from ischaemic heart disease over the following years compared with people who stayed below 70, although the lower end of the confidence interval was close to no difference. Overall, a fall in heart rate between the two measurements did not show a general mortality benefit.

These are observational findings. They describe an association: a faster resting rate travels together with a higher risk. They do not say the rate itself causes the risk. A fast resting rate can reflect low fitness, illness, or other conditions that carry their own risk.

A hint from genetics

One way to get closer to cause is to look at genetic variants that nudge resting heart rate up or down from birth. A 2016 genome-wide study of up to 265,046 people found 64 regions of the genome associated with resting heart rate. Using those variants, that study reported that a genetically predicted increase of 5 beats per minute was associated with a 20% higher risk of death, and the authors framed this as shared genetic predictors of heart rate and mortality. A larger 2023 analysis from the same group did not find a genetic association between resting heart rate and death from any cause, and judged the earlier mortality result most likely a false positive. Neither analysis is a trial in which someone's heart rate was lowered and outcomes were counted.

The trials that lowered heart rate on purpose

Ivabradine slows the heart by acting on its natural pacemaker, the sinus node, without the other effects of beta-blockers. That made it a sharper test than a beta-blocker of whether heart rate itself is the target. It is not a pure test: the trials also recorded effects other than a slower pulse, such as temporary visual disturbances. Three large randomised, placebo-controlled trials used it, all funded by the manufacturer.

Heart failure with reduced pumping function (SHIFT, 2010). The trial enrolled 6,558 people with symptomatic heart failure, an ejection fraction of 35% or lower, a normal (sinus) rhythm with a resting rate of at least 70 beats per minute, and a hospital admission for heart failure in the previous year. Most were already on standard treatment, including a beta-blocker where tolerated. Over a median of about 23 months, the combined outcome of cardiovascular death or hospital admission for worsening heart failure occurred in 24% on ivabradine and 29% on placebo. The difference came mainly from fewer heart-failure admissions and fewer deaths from heart failure. Symptomatic slow heart rate occurred in 5% on ivabradine versus 1% on placebo, and temporary visual disturbances in 3% versus 1%. A separate analysis of the same trial found that the benefit disappeared statistically once the analysis adjusted for how much heart rate had fallen, which is what one would expect if the slower rate was doing the work.

Coronary disease with a weakened left ventricle (BEAUTIFUL, 2008). In 10,917 people with coronary artery disease and an ejection fraction below 40%, ivabradine lowered heart rate by about 6 beats per minute compared with placebo, but did not change the main combined outcome of cardiovascular death, admission for heart attack or admission for heart failure. In the prespecified group with a resting rate of 70 or more, the main outcome did not change either; fewer hospital admissions for heart attack were seen only among secondary outcomes.

Stable coronary disease without heart failure (SIGNIFY, 2014). This was the largest test: 19,102 people with stable coronary artery disease, no clinical heart failure, and a resting rate of at least 70. The dose was adjusted to aim for 55 to 60 beats per minute, and at three months the average rate was about 61 on ivabradine versus 71 on placebo. Over a median of about 28 months, cardiovascular death or non-fatal heart attack occurred in 6.8% on ivabradine and 6.4% on placebo, a difference that was not statistically significant. In the subgroup with angina that limited their activity, ivabradine was associated with more primary events than placebo. A slow heart rate was reported in 18.0% on ivabradine versus 2.3% on placebo.

Put together: in one well-defined group, people with heart failure and reduced pumping function who remain at a resting rate of 70 or more despite standard treatment, lowering heart rate further improved outcomes. In people with coronary disease but without heart failure, lowering the number by about ten beats did not.

What about beta-blockers

Beta-blockers also slow the heart, but they do several other things, so their trials cannot isolate heart rate. A 2009 meta-analysis of 23 randomised trials in heart failure, with 19,209 participants, more than 95% of whom had reduced pumping function, found that beta-blockers lowered the risk of death overall. Across trials, the size of the benefit tracked the size of the heart-rate reduction, about 18% lower risk of death for every 5 beats per minute, while the dose did not. This is a comparison between trials, not within them, and it again concerns people with heart failure.

And exercise

Regular exercise lowers resting heart rate. A 2018 meta-analysis of controlled trials in healthy people, covering 191 studies, found that all types of sport studied lowered resting heart rate, but only endurance training and yoga did so significantly in both men and women. Across studies, the drop was larger where the pre-training resting rate was higher and where the participants were younger on average. These trials measured heart rate, not survival, and do not show that the lower pulse produced by training is, by itself, the reason for any benefit. The link between fitness and longer life comes from cohort studies, covered in our article on VO2max and longevity.

What this means for reading your own number

• In the general population, resting heart rate is a risk marker: a faster rate is associated with higher risk, and the association holds across many large cohorts.

• It has been shown to be a treatment target only in a specific group: heart failure with reduced ejection fraction, in sinus rhythm, with a rate that stays at 70 or above on standard treatment. That decision belongs to a cardiologist.

• In people with stable coronary disease and no heart failure, lowering the rate with a drug did not improve outcomes, and in one subgroup it was associated with more events.

• For someone without a heart condition, a persistently fast resting rate is a reason to look for why it is fast, together with a clinician, rather than a number to push down on its own. The same logic applies to other markers that are strongly associated with risk, such as walking speed: a marker that predicts outcomes is not automatically a lever that changes them.

This material is for information only and does not replace a consultation with a doctor.

References

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• Nauman J, et al. Temporal changes in resting heart rate and deaths from ischemic heart disease. JAMA. 2011. PMID 22187277

• Eppinga RN, et al. Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality. Nature Genetics. 2016. PMID 27798624

• van de Vegte YJ, et al. Genetic insights into resting heart rate and its role in cardiovascular disease. Nat Commun. 2023. PMID 37532724

• Swedberg K, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010. PMID 20801500

• Böhm M, et al. Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet. 2010. PMID 20801495

• Fox K, et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL). Lancet. 2008. PMID 18757088

• Fox K, et al. Ivabradine in stable coronary artery disease without clinical heart failure (SIGNIFY). N Engl J Med. 2014. PMID 25176136

• McAlister FA, et al. Meta-analysis: beta-blocker dose, heart rate reduction, and death in patients with heart failure. Ann Intern Med. 2009. PMID 19487713

• Reimers AK, et al. Effects of exercise on the resting heart rate: a systematic review and meta-analysis of interventional studies. J Clin Med. 2018. PMID 30513777