Effects of Exercise and Stress Management Training on Nighttime Blood Pressure Dipping in Patients with Coronary Heart Disease: A Randomized Controlled Trial

Abstract

INTRODUCTION

Blunted nighttime blood pressure (BP) dipping, typically defined as <10% fall in average BP from daytime to nighttime, is a strong prognostic indicator of cardiovascular morbidity and mortality for both hypertensive and non-hypertensive individuals^1–4. Blunted nighttime BP dipping also appears to be unusually common in patients with coronary heart disease (CHD), with a non-dipping pattern approximately twice as common as in age-matched controls.^5–7 For vulnerable CHD patients, blunted nighttime BP dipping may exacerbate their heightened risk of adverse cardiovascular disease (CVD) events. As a result, there have been a number of different approaches designed to enhance BP dipping in various CVD populations.

Chronotherapy is one successful approach to enhancing nighttime BP dipping. For patients with hypertension, bedtime dosing of antihypertensive medications, rather than typical morning dosing, lowers nighttime BP^8–10. Nighttime dosing of melatonin, a hormone involved in diurnal regulation, also may enhance BP dipping through multiple physiological pathways¹¹. Lifestyle factors including physical activity and psychological stress also affect the nocturnal decline in BP. For example, greater daytime physical activity has been related to enhanced nighttime BP dipping¹², but the evidence is equivocal with regard to whether dipping is improved with exercise training ^13–16. Psychological stress also has been linked to a blunted fall in nighttime BP¹⁷, suggesting that behavioral interventions designed to reduce stress may also enhance dipping. However, to our knowledge, no study to date has evaluated whether stress reduction may improve BP dipping in CHD patients. The present report from the Smart Heart trial¹⁸ examined the effects of a 16-week stress management (SM) intervention and aerobic exercise (EX) compared to Usual Care (UC) on nighttime BP dipping in patients with CHD. The primary results of the trial, which showed that both active interventions improved biomarkers of cardiovascular risk, have been reported previously.¹⁸ To assess BP dipping, 24-hour ABPM was performed before and after the interventions. We hypothesized that both EX and SM would result in enhanced nighttime BP dipping compared to UC.

METHODS

RESULTS

One hundred and thirty-four individuals were randomized to participate in the intervention including 44 to SM, 48 to EX, and 42 to UC, as previously reported (Table 1).¹⁸ The flow of participants from recruitment through post-intervention assessments is illustrated in Figure 1.

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Figure 1

Flow of participants from initial recruitment to end of treatment. SM = Stress Management training; EX = Exercise training; UC = Usual Care; ITT = intention-to-treat.

We did not observe any baseline imbalance in daytime or nighttime ambulatory BPs (all p’s>.774), SBP dipping (P = .853), or DBP dipping (P = .951). At baseline, 124 participants provided BP dipping data. Of these 64 (52%) were considered ‘dippers’ (≥ 10% mean SBP dip from daytime to nighttime).

Nocturnal Blood Pressure Dipping Changes

Examination of planned treatment contrasts demonstrated that the EX and SM groups exhibited a strong trend towards greater improvements in SBP dipping compared with the UC condition (P = .052). SBP dipping improvements from pre-to post-treatment were 3.2 (SE = 1.5) % for SM, 1.7 (SE = 1.5) % for EX, and −0.7 (SE = 1.4) % for UC (Table 2). As shown in Figure 2, this corresponded to mean post-treatment SBP dipping values of 12.9 (SE = 1.5) % for SM, 11.1 (SE = 1.4) % for EX, and 8.6 (1.4) % for UC.

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Figure 2

Post-intervention nighttime systolic (SBP) and diastolic (DBP blood pressure dipping (%) following 16 weeks of Exercise (EX) training, Stress Management (SM) training, and Usual Care (UC).

Table 2

Post intervention ambulatory blood pressures following 16 weeks of Exercise (EX) training, Stress Management (SM) training, and Usual Care (UC).

	UC (N = 42)	EX (N = 48)	SM (N = 44)
Daytime SBP (mm Hg)	130 ± 2	131 ± 2	132 ± 2
Nighttime SBP (mm Hg)	119 ± 2	117 ± 2	115 ± 2
SBP Dip (%)	9 ± 1	11 ± 1	13 ± 2
Daytime DBP (mm Hg)	75 ± 1	74 ± 1	75 ± 1
Nighttime DBP (mm Hg)	68 ± 1	64 ± 1	65 ± 1
DBP Dip (%)	9 ± 2	14 ± 2	13 ± 2

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Examination of changes in DBP dipping demonstrated a similar pattern of findings, with the treatment groups demonstrating greater improvements in DBP dipping compared with the UC condition (P = .031). DBP dipping improvements from pre-to post-treatment were 1.2 (SE = 1.9) % for SM, 2.5 (SE = 1.9) % for EX, and −3.0 (SE = 1.8) % for UC, corresponding to mean post-treatment DBP dipping values of 13.2 (SE = 1.9) % for SM, 14.0 (SE = 1.9) % for EX, and 8.8 (1.8) % for UC (Figure 2; Table 2).

DISCUSSION

Few studies have examined nighttime BP dipping in patients with CHD. Mousa and colleagues first described this phenomenon in a study of 68 men with documented CHD who exhibited a significantly blunted nighttime BP dipping compared to 68 age-matched healthy men.⁵ Our prior work described similar findings in a study comparing 54 postmenopausal women with documented CHD with 48 age-matched control women.⁶ Most recently, in a study of 401 patients with CVD, including those with CHD and others who had experienced an ischemic stroke, Cai et al. reported that blunted nighttime BP dipping was related to greater risk of a cardiovascular event.⁷ The present study provides further evidence that patients with CHD are prone to exhibit a non-dipping nighttime BP pattern, potentially placing them at higher risk for adverse CVD events. In this sample, almost half of subjects were considered ‘non-‘dippers’ (≥ 10% mean SBP dip from daytime to nighttime). The present findings also demonstrate that two behavioral interventions, exercise and stress management training, may augment nighttime BP dipping, which may help reduce the risk of adverse CVD events associated with blunted BP dipping.

Because sleep quality is directly related to the magnitude of nighttime BP dipping ^{6, 24–26}, one mechanism by which both the exercise and stress management training interventions may have enhanced BP dipping is by improving sleep quality. This possibility is supported by our finding that augmentation of nighttime BP dipping was achieved through post-intervention declines in nighttime BP, with little changing in daytime BP. No clinical trials have evaluated the effects of sleep medications on nighttime BP dipping. Nighttime dosing of melatonin, however, a hormone involved in diurnal regulation, appears to enhance nighttime BP dipping, possibly in part by improving sleep quality¹¹. Stress is considered to be one of the most common causes of insomnia,²⁷ and exercise training may be an effective treatment for insomnia in a variety of patient populations.^28–30 As previously reported, participants in the present study who underwent stress management or exercise training showed a reduction in psychological distress,¹⁸ which may have had a beneficial effects on their sleep quality.

These findings provide further evidence for the value of stress management and exercise training in improving cardiovascular health, and support previous reports that increased levels of physical activity may benefit BP dipping. ^14–16 The mechanisms by which exercise may promote lower nighttime BP and augmented BP dipping have yet to be elucidated. Both exercise and stress management training have been shown to produce favorable changes in physiological regulatory systems, including improved vascular endothelial vasodilatory function.¹⁹ Interestingly, impaired endothelial function has been linked both to nighttime hypertension and insomnia^{31, 32}. Although exercise did not result in improved heart rate variability (HRV) measured during supine deep breathing, stress management training did improve HRV compared to Usual Care.¹⁹ Reduced HRV is indicative of low parasympathetic activity, and has been associated with blunted nighttime BP dipping.³³ In contrast, reduced resting sympathetic activity is related to enhanced nighttime BP dipping.^{24, 26, 34}

The present study has several limitations. These include a relatively small sample size for a clinical trial that was not powered specifically to examine the effects of exercise and stress management training on nighttime BP dipping. Due in part to the sample size limitation, the study was not designed to address mechanisms responsible for intervention effects on BP dipping. Nonetheless, our observations suggest that over the course of 16-weeeks, two behavioral interventions, exercise and stress management training, can enhance nighttime BP dipping in CHD patients, who are both prone to exhibit blunted dipping and are at heightened risk of adverse clinical events.

Enhancing nocturnal blood pressure dipping by pharmacological chronotherapy has been shown to reduce subsequent cardiovascular events⁹. A small sub-study of the HOPE trial first showed that nighttime dosing of Ramipril reduced cardiovascular morbidity and mortality in patients with peripheral arterial disease³⁵. The MAPEC trial subsequently provided compelling evidence that in patients with hypertension, restoration of a normal nighttime “dipper” profile reduced the risk of CVD, stroke and new onset diabetes³⁶. Nighttime dosing of antihypertensive medications typically augments BP dipping by lowering nighttime BP. Compared to usual care controls, this same phenomenon was evident for DBP dipping for the behavioral interventions. Because both exercise and stress management training improved other biomarkers of CVD risk, in addition to nighttime BP dipping, and also reduced psychological distress, these behavioral interventions also should reduce the risk for worse CHD outcomes ¹⁸. For exercise training, the supportive evidence is already compelling, and recent evidence indicates that enhancing traditional cardiac rehabilitation with stress management training can further reduce risk of adverse clinical events in cardiac patients.³⁷

Acknowledgments

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