Nocturnal Heart Rate and Inflammation

Increased resting heart rate (HR) is associated with adverse cardiovascular outcomes in populations with and without cardiovascular risk factors.1, 2, 3 Higher HR often coexists with higher blood pressure (BP), obesity, and metabolic disturbances, but the association of higher HR with cardiovascular risk remains even after adjustments for these factors. The exact mechanisms behind the association of higher HR with poor outcomes remain uncertain, and whether HR is a causative risk factor for atherosclerosis and cardiovascular disease (CVD) or merely an epiphenomenon of pathophysiological conditions is still debated. In animal studies, HR reduction has been shown to improve vascular function and prevent atherosclerosis,1, 2, 3 but human studies showing a modulation of cardiovascular risk by HR reduction are scarce.

HR measured in out‐of‐office settings (ie, home BP and ambulatory BP monitoring), instead of in an office/clinic, may more accurately represent HR in daily life and therefore reflect both cardiovascular burden and metabolic disturbances more precisely.4, 5 Particularly, nocturnal HR, when compared with daytime HR, is more closely associated with poor cardiovascular and noncardiovascular outcomes, although the findings are inconsistent.6, 7, 8, 9 Some plausible, albeit speculative, explanations for this phenomenon could be considered. First, physiologically, HR is reduced during sleep.10 Myocardiocytes and systemic arteries may be particularly vulnerable during sleep,3 as they are adversely affected when HR is elevated via increased oxygen consumption, which may predispose individuals to arrhythmias, higher cyclic stretch, and elastin fatigue. Second, in terms of physical and mental activity as well as body position, nocturnal HR, compared with office or daytime HR, is more standardized as a result of the reduced influence of environmental stimuli.11, 12 Third, nocturnal HR, compared with office or daytime HR, could reflect concurrent pathophysiology, such as sympathovagal imbalance and disturbed breathing during sleep.11, 12 Moreover, although the association between higher HR and increased inflammation is already known,13, 14 in the current issue of The Journal of Clinical Hypertension, Hartaigh and colleagues15 extend that evidence by demonstrating that nocturnal HR is more closely associated with inflammation than daytime HR.

This cross‐sectional analysis in treated hypertensive patients (368 Caucasians, mean age 61 years, 53% women, 51% taking β‐blockers) demonstrated that both daytime HR (β [standard error: SE]: 0.02 [0.01]) and nocturnal HR (β [SE]: 0.04 [0.01], both P<.05) were associated with leukocyte counts, independently of age, sex, smoking status, body mass index, 24‐hour ambulatory BP, glucose and lipid parameters, mediation, and pre‐existing CVD. When daytime HR and nocturnal HR were entered into the same model, only nocturnal HR was associated with leukocyte counts (β [SE]: 0.06 [0.03]) and C‐reactive protein (β [SE]: 0.20 [0.07], both P<.05). The relationship between the ratio of nocturnal HR and daytime HR (ie, nocturnal HR/daytime HR) and inflammation was not assessed. Although these results are statistically significant, the effect sizes were small. The nature of cross‐sectional analysis may limit the exploration of the association between nocturnal HR and inflammation and preclude any causal inference. Further clinical implications depend on whether interventions to suppress (nocturnal) HR using an I(f) current inhibitor having no relevant effects on left ventricular contractility, BP, and atrioventricular conduction can reduce inflammatory activity, and whether such interventions can prevent the development of atherosclerosis and CVD. Another limitation is that there may be a common cause between higher nocturnal HR and inflammation. Both nocturnal HR and inflammation are susceptible to lower socioeconomic factors, adverse stressors, diet (eg, omega‐3 polyunsaturated fatty acids), and sleep‐disordered breathing1, 2, 3, 16, 17, 18, 19, 20, 21; these factors are uncontrolled confounders in this study. In spite of the limitations, Hartaigh's study demonstrates that measuring nocturnal HR instead of daytime HR is more precise for assessing individual inflammatory states in hypertensive patients.

How can researchers expand the clinical significance of nocturnal HR? The primary advantage of measuring resting HR in clinical settings is that HR is a familiar and accessible clinical variable. By contrast, how about nocturnal HR? Currently, the optimal nocturnal HR for a given individual, which may differ based on individual clinical characteristics, is unclear. Moreover, nocturnal HR measures via ambulatory BP monitoring are not readily available, since cost and relative cumbersomeness to patients are limitations for ambulatory BP monitoring. However, programmed home BP measurement devices that can measure nocturnal BP and HR automatically have now been developed.22, 23 In addition, newly available technologies such as smartphone‐based single‐lead electrocardiography (ECG), hand‐held ECG, and ECG patch monitoring are diffusing swiftly into medical practice. These devices are inexpensive, accessible, and easy to use, so patients can readily use them even during sleep and over long periods.24 These technologies will start a new era in heart rhythm (not only atrial fibrillation) research and a transition from population‐level health care to personalized preventive medicine. The most important and challenging issue that lies ahead is to assess whether higher (nocturnal) HR is simply a marker of concurrent pathophysiology or related in a causal pathway to pathogenesis in CVD. If higher (nocturnal) HR is a marker, not only statistical significance but also indications of clinical meaningfulness to the refinement and improvement of risk assessment methods is warranted.25 These assessments are fundamental to future HR research.

Disclosure

There is no relationship with industry to declare, and none of the authors have competing financial interests or conflicts of interest.