Shifting away from sedentary time, and FITTing exercise into the treatment of hypertension

Exercise not only prevents the development of hypertension but also decreases the levels of blood pressure (BP) in those who already have hypertension [1]. Indeed, several meta-analyses of randomized controlled trials (RCTs) have shown that aerobic exercise leads to significant decreases in systolic and diastolic BP in both normotensive and hypertensive individuals, with the beneficial effects being apparently more pronounced among the latter [2–5]. International societies, such as the European Society of Hypertension and the European Society of Cardiology [6], the Eight Joint National Committee [7] through endorsement of the recommendations provided by the American Heart Association /American College of Cardiology 2013 Lifestyle Work Group [8], the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research, Council on Cardiovascular and Stroke Nursing, Council on Epidemiology and Prevention, and Council on Nutrition, Physical Activity [9], the Canadian Hypertension Education Program [10], The American College of Sports Medicine [11], and the Australian Association for Exercise and Sports Science [12], all recommend exercise for the prevention and first-line treatment of hypertension in adults. However, the recommendations provided by these professional associations are not exactly similar with regard to the following practical questions: how often, how hard, how long, and what kind of exercise should be undertaken by patients with hypertension? In other words, and respectively, what are the recommended frequency, intensity, time, and type (FITT) of exercise? The differences and similarities as well as the potential reasons underlying these have been recently examined and discussed in detail by Pescatello et al.[13] who noted that the consensual agreement across the various professional organizations was that at least 30 min/day of moderate-intensity aerobic exercise on most, preferably all, days of the week, to total a volume of 150 min/week or more, should be prescribed to adults with pre to established hypertension. Aerobic exercise (e.g. walking, jogging, cycling, and swimming) is the type of exercise recommended by all associations. Most recommend also dynamic resistance training (e.g. machine weights, free weights, resistance bands, and functional body weight exercises) [6,9–12], though only one recommends isometric resistance training (a form of weight training involving sustained muscular contraction without change in muscle length) as adjuvant options [10]. Discussions around what is the best FITT to decrease BP levels in individuals with (newly diagnosed or pharmacologically treated) hypertension are likely to continue as more and better evidence accrues to fill in the gaps of the current literature (for further discussion see [13,14]). However, there are some additional questions that, thus far, have been left unanswered. The first one relates to what extent exercise prevents the development of cardiovascular disease (CVD) and mortality among individuals with hypertension? Exercise-induced decreases in BP and/or other risk factors are thought to constitute mechanisms through which exercise (i.e. physical activity that is planned, structured, and purposeful) may reduce the risk of CVD and all-cause mortality among patients with hypertension [15]. However, despite the large evidence available to support the benefits of physical activity and exercise on BP and mortality in the general population, the extent to which physical activity and/or exercise prevent incident CVD and mortality in individuals with hypertension is less clear. Up to now, the evidence with this regard derives from observational cohort studies only. A meta-analysis of six such studies concluded that individuals with hypertension who were more active had lower cardiovascular (16–67%) and all-cause (17–57%) mortality compared with their inactive peers [16]. The definition of hypertension was not consistent across the studies included in this review. Also, individuals’ levels of physical (in)activity were operationalized differently and relied on self-reports in all studies, which may thus have introduced some form of differential recall bias in the association estimates. This issue of the Journal of Hypertension features an interesting prospective cohort study that investigates the association between objectively measured levels of physical activity and all-cause mortality among individuals with hypertension from the 2003 to 2006 National Health and Nutrition Examination Survey (NHANES) [17]. Among the 2035 individuals with hypertension (defined as currently taking blood pressure-lowering medication or having an average of four BP measurements ≥140/90 mmHg) included in this study, 322 died over the course of follow-up (median of 80 months, incidence rate of 2.02 per 1000 person-months). Crude estimates indicated a 40% mortality risk reduction for every 60 min/day increase in total levels of physical activity (i.e. physical activity accrued at any intensity). After adjustment for confounders, the strength of this association was attenuated to 23% risk reduction. Noteworthy, further adjustments for variables that could explain the beneficial effects of physical activity on all-cause mortality, such as weight status, low-grade inflammation, and comorbid illnesses, only attenuated the risk reduction estimate slightly, to 19%. These estimates did not differ significantly between the sexes. The author also provided estimates for the association between physical activity levels and cardiovascular-specific mortality: 17% risk reduction in analyses adjusted for covariates. However, this estimate may have resulted from underpowered analyses as only 75 such cases were considered in these analyses (defined based on the International Classification of Diseases-10 codes related to diseases of the heart but not accounting for the 20 individuals who died because of cerebrovascular diseases). One key addition of this article to the field was the objective measurement of physical activity via accelerometers. Here the relationship with mortality was examined not only with total physical activity but also with time spent in sedentary, light, and moderate-to-vigorous intensity activities (MVPA). Notably, an individual can be both highly sedentary (defined as any waking activity sitting that demands no more than 1.5 times of an individual's resting metabolic rate, while in a sitting or reclining position [18]), and still meet physical activity guidelines regarding regular participation in MVPA [19]. This explains why sedentary behaviours have been linked to poorer haemodynamic [20], metabolic [21] and cardiovascular outcomes [22], even after statistical adjustment for MVPA. In other words, time spent in MVPA does not fully mitigate the health risks associated with high levels of sedentary time, emphasizing the importance of measuring and considering time spent in activities across the intensity spectrum. In the Loprinzi study, the associated covariate adjusted estimates (60 min/day increase for total, sedentary, and light; 10 min/day increase for MVPA) in all-cause mortality were − 19, +11, −19, and −15%, respectively [17]. When only bouted MVPA (i.e. MVPA accrued in bouts of at least 10 min duration) was considered, the estimate was slightly stronger: 17% risk reduction for every 10 min/day. Use of objective monitors addresses many of the concerns raised in previous studies in relation to differential bias. However, there are limitations to take into consideration when interpreting these findings. Hip-worn single-axis accelerometers, like the ones used in the study by Loprinzi [17], predominantly assess ambulatory activities; other relevant activities may be missed or misclassified [23]. Conclusions regarding the impact of the intensity levels are dependent on processing decisions [24], and, as the monitor is not posture based, misclassification between low-intensity activities (e.g. sitting and standing) is likely [25]. Given the potential cardiometabolic benefits observed with time spent standing [21], collection of further evidence using postural-based monitors is recommended. An element not considered in the Loprinzi study was the interdependencies of activities. That is, given time is fixed (a 24-h day, or in the current study, waking hours), more time spent in one activity necessarily means less time is spent in other(s). This mix, or ‘composition,’ of relative time spent in activities of various intensities impacts on health. Analytic approaches to address these interdependencies have recently been used with the NHANES dataset, with findings related to a variety of cardiovascular risk factors, including BP [26], highlighting the importance of maintaining time in, or shifting time to MVPA [26,27]. However, given the challenges associated with increasing MVPA levels, it is encouraging to note that benefits can potentially be achieved with shifting time away from sedentary to light intensity activities [26,27], particularly for those that are less active [28]. Notably, randomized controlled trials in general adult populations have demonstrated that large (>2 h) shifts away from sedentary time are both feasible and acceptable [29]. The potential for such interventions in adults with hypertension is a key area for future research. A second most pertinent question relates to how do any beneficial effects of exercise on CVD and mortality among individuals with hypertension compare with the beneficial effects of pharmacotherapy? There is only one study thus far that has tried to quantify the joint and independent effects of physical activity and pharmacological treatment on all-cause mortality risk [30]. Based on a large-scale analysis of NHANES data, the authors found that, among individuals with hypertension, being physical active (defined as participating in one or more periods of moderate or vigorous physical activity per week) reduced the risk of mortality, regardless of receiving pharmacologic treatment or not, and regardless of its control status, as compared with being inactive [30]. These findings suggest that exercising as little as 1 day/week may be critical for reducing premature mortality in adults with hypertension, especially for those in whom pharmacologic treatment does not produce the desirable level of BP control. However, this contention still needs to be supported by RCTs. Indeed, the lack of RCTs comparing the effectiveness of exercise vs. pharmacological treatment on morbidity and mortality outcomes among individuals with (pre)hypertension is, to say the least, remarkable, especially considering the numerous comparisons between pharmacological treatments available. Noteworthy, a recent network meta-analysis of major pharmacological and physical activity RCTs showed that both types of interventions seemed to be similarly effective in the prevention of mortality among patients with coronary heart disease and (pre)diabetes [31]. In addition this study showed that physical activity interventions may be considerably more effective for the secondary prevention of stroke mortality, and only less effective than diuretics in the prevention of heart failure mortality [31]. From the 305 RCTs revised, only 57 were on physical activity interventions and, with the exception of mortality prevention in the context of type 2 diabetes (where exercise had been compared with biguanides and α glucosidase inhibitors though not to glinides and thiazolidinediones), no head-to-head comparisons between exercise and pharmacological treatments such, as β-blockers, ACE-inhibitors, angiotensin receptor blockers, antiplatelets, and statins had ever been reported. Clearly, this constitutes an urgent research agenda point. Given the limited resources, an efficient way to proceed would be to include exercise/replacement of sedentary behaviour interventions as an active comparator in (new) drug trials [31]. We owe the physicians, healthcare systems and, above all, the patients, with this piece of information, to enable fully informed decisions tailored to patients’ treatment needs and preferences. ACKNOWLEDGEMENTS G.N.H is supported by a National Health and Medical Research Council [#108029] Career Development Fellowship. Conflicts of interest There are no conflicts of interest.

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