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Dear Authors and Editorial Team,
The inverse association between resting heart rate (RHR) and longevity has been the subject of many studies, both in humans and across species . The article by Zhao et al., titled, “Effect of resting heart rate on the risk of all-cause death in Chinese patients with hypertension: analysis of the Kailuan follow-up study” determines that resting heart rate > 76 beats-per-minute (bpm) is a predictor of mortality in Chinese hypertensive patients as well . I applaud the authors for thoroughly adjusting for confounding factors and offering explanations for the association, but would like to bring to discussion key points that may help contextualize the findings.
Firstly, several studies have established that women have higher RHR than men and tend to have weaker associations between RHR and mortality . Thus, it may be important to develop sex-specific quintiles when categorizing heart rate as women paradoxically also have higher life expectancy than men. Fortunately, this study has a large proportion of men which reduces misclassification bias but may also in turn reduce generalizability of the results to women.
There are peculiarities among the baseline characteristics by quintile of RHR that may warrant further attention. There seems to be markedly unequal sample sizes across the quintiles (e.g. Q2 = 7589 vs. Q1=10349), suggesting that there may be room to adjust the categories. Furthermore, there is a distinct...
There are peculiarities among the baseline characteristics by quintile of RHR that may warrant further attention. There seems to be markedly unequal sample sizes across the quintiles (e.g. Q2 = 7589 vs. Q1=10349), suggesting that there may be room to adjust the categories. Furthermore, there is a distinct pattern seen across several characteristics (i.e. physical exercise, smoking, drinking, antihypertensive medication use, history of myocardial infarction, and history of stroke) from Q1 to Q2 to Q3 [2; see Table 1]. There is a decrease from Q1 to Q2, followed by an increase from Q2 to Q3. Observing that Q1 has a higher average age than other quintiles, we speculate that Q1 is comprised of a mix of healthy, young individuals as well as older, unhealthy individuals who have lower RHR due to 1) use of rate control medication other than beta blockers, 2) undiagnosed heart failure (heart failure with preserved ejection fraction), or 3) other cardiac-related illness/therapies . Furthermore, several comorbidities contribute to changes in heart rate, namely thyroid disorders, anemias, chronic inflammatory processes, and psychological illness. These are often associated with hypertension or diabetes diagnosis and thus should be accounted for in the analysis.
Both RHR and blood pressure fluctuate in the short- and long-term and have garnered attention in recent years due to potential prognostic value . Furthermore, because RHR and blood pressure were measured in different positions, orthostatic variability may also become a confounding factor. Future studies should aim to measure RHR and blood pressure at each visit and treat variability as independent predictors of cardiovascular disease or all-cause mortality. It may be worthwhile to also stratify study populations by ejection fraction status or heart failure status. For those with left ventricular hypertrophy due to long-standing hypertension, increasing diastolic dysfunction may lead to compensatory increases in heart rate and contractility, possibly in part explaining the association between RHR and all-cause mortality in hypertensive patients. We also propose stratifying analysis in future studies by hypertension subtype (e.g. isolated systolic hypertension, isolated diastolic hypertension, systo-diastolic hypertension) to better classify individuals on the basis of physiological natural history of blood pressure.
Overall, I believe this article makes a strong case for the association between RHR and all-cause mortality. Further studies are necessary to better quantify the association and develop thresholds for pharmacologic interventions.
Aayush Visaria, MPH
1. Levine, H.J., 1997. Rest heart rate and life expectancy. Journal of the American College of Cardiology, 30(4), pp.1104-1106.
2. Zhao, M.X., Zhao, Q., Zheng, M., Liu, T., Li, Y., Wang, M., Yao, S., Wang, C., Chen, Y.M., Xue, H. and Wu, S., 2020. Effect of resting heart rate on the risk of all-cause death in Chinese patients with hypertension: analysis of the Kailuan follow-up study. BMJ open, 10(3), p.e032699.
3. Palatini, P., 2001. Heart rate as a cardiovascular risk factor: do women differ from men?. Annals of medicine, 33(4), pp.213-221.
4. Williams, B., Mancia, G., Spiering, W., Agabiti Rosei, E., Azizi, M., Burnier, M., Clement, D.L., Coca, A., De Simone, G., Dominiczak, A. and Kahan, T., 2018. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). European heart journal, 39(33), pp.3021-3104.
5. Mancia, G., 2012. Short-and long-term blood pressure variability: present and future. Hypertension, 60(2), pp.512-517.