Digital Therapeutics and Lifestyle: The Start of a new era in the Management of Arterial Hypertension?

Luis M. Ruilope; Pedro L. Valenzuela; Alejandro Lucia

Disclosures

Eur Heart J. 2021;42(40):4123-4125. 

Nearly a third of adults worldwide have hypertension, defined as a clinic blood pressure (BP) ≥140/90 mmHg according to the most recent European [European Society of Cardiology (ESC)/European Society of Hypertension (ESH)] guidelines,[1] and this condition remains one of the leading causes of premature mortality worldwide.[2]

The 'westernized way' of life—usually characterized not only by physical inactivity and unhealthy dietary habits leading to a real pandemic of overweight/obesity, but also by frequent disruption of circadian rhythms with poor sleep patterns as well as by high amounts of psychosocial stress—is likely to increase the prevalence of hypertension in the years to come.[3] In contrast, 'non-westernized' populations (e.g. hunter–gatherers such as the Hadza, or foragers–horticulturalists such as the Tsimané or Yanomani) who still follow lifestyles similar to those that have characterized human evolution (with very high amounts of daily physical activity and sleep–wake cycles corresponding to natural dark–light exposure, among others) show a very low prevalence of hypertension, with virtually no evidence of age-related increases in BP and overall cardiovascular disease (CVD) risk despite having no access to any type of pharmacological treatment whatsoever.[3] On the other hand, the ESC/ESH guidelines consider an optimal lifestyle (i.e. 150–300 min/week of moderate–vigorous physical activity, dynamic resistance such as lifting weights on 2–3 days/week, increased consumption of vegetables, fresh fruits, fish, nuts, and unsaturated fatty acids, sodium intake <2000 mg/day, keeping a body mass index ~20–25 kg/m2, moderate alcohol intake, and avoiding smoking) as the only treatment needed for people at low CVD risk with mild hypertension (grade I, defined as office BP 140–159/90–99 mmHg) during the first 3–6 months following diagnosis.[1] Indeed, prescription of antihypertensive drugs at baseline has no benefits on the incidence of CVD or mortality among low-risk individuals with mild hypertension and could actually increase the risk of adverse events (e.g. hypotension, electrolyte abnormalities, or acute kidney injury).[4]

Strong evidence in fact supports the benefits of an optimal lifestyle for the prevention or management of hypertension.[3] For instance, a network meta-analysis (n = 39 742 participants) found a similar effectiveness of exercise interventions and antihypertensive medication in reducing BP in individuals with hypertension.[5] The evidence is also solid for body weight reductions back to normal values in individuals with overweight or obesity,[6] for restriction of sodium intake in those who have been diagnosed with hypertension,[7] as well as for the Dietary Approaches to Stop Hypertension (DASH) diet in people with pre-hypertension or hypertension.[8] Moreover, although more research is needed, emerging evidence supports implementation of less 'conventional' approaches, particularly circadian entrainment and stress management strategies.[3]

In contrast to the different antihypertensive drugs, the biological mechanisms explaining the benefits of lifestyle intervention against hypertension are multisystemic. These include: prevention of obesity and insulin resistance, enhancements in vascular health—through an improved redox and inflammatory status, or a healthy pattern of vessel remodelling in those who exercise regularly (i.e. increase in the luminal diameter of conduit arteries and resistance arteries and in the capillary density of skeletal muscle tissue)—and reduced overactivation of the sympathetic nervous system (SNS).[3] Importantly, regular exercise can also contribute to the reduction of BP through 'non-traditional' mechanisms, such as the release of muscle-derived factors (usually, but not only, small peptides) collectively known as 'myokines' that are produced in the exercise milieu and can travel through the bloodstream to induce numerous beneficial effects, including, among others, reduced inflammation or vasorelaxation.[9]

Yet, a major problem of lifestyle changes in our modern societies is sustainability. There is meta-analytical evidence that the benefits of exercise intervention to reduce BP in young adults with pre-hypertension/hypertension are lost after 12 months.[10] Similarly, a recent network meta-analysis found that although different diets result in significant decreases in body weight and BP at 6 months, almost no benefits are observed after 12 months.[11] How can we enhance adherence to healthy lifestyle interventions among westerners in an efficient manner? One possibility is to take advantage of the current over-reliance on smartphones and other wearables, which can be used as a health tool. A new concept of individualized medical follow-up (the so-called mHealth) coupled with initiatives such as those by Google or Apple to turn their devices into mobile health centres might set the start of a new paradigm in medicine. Another initiative along the same lines is 'Digital therapeutics', which aim at facilitating disease management through the implementation of lifestyle changes. However, despite the rapidly increasing availability of mobile technologies designed for improving BP management, scientific evidence of their effectiveness is still scarce.[12,13]

In this issue of the European Heart Journal, a topical study by Kario et al.[14] reports the findings of HERB-DH1, a pivotal trial investigating the efficacy and safety of Digital therapeutics (a 12-week intervention followed by a 12-week follow-up) in patients with untreated essential hypertension (baseline office and ambulatory 24 h BP ≥140/90 mmHg and ≥130/80 mmHg, respectively). HERB mobile is a new interactive smartphone app that promotes intensive lifestyle modifications (i.e. decreasing salt intake, body weight control, exercise, improving sleep patterns, stress coping, and reducing alcohol intake) leading to a potential significant reduction in BP. The trial by Kario et al.[14] was developed in three steps: (i) an educational programme consisting of lectures and advice, which was followed by (ii) lifestyle interventions and thereafter by (iii) self-planning and evaluation with participants, who were subsequently encouraged to incorporate the different lifestyle modifications into their lives. The first part of the study demonstrated a significant fall in office, home, and 24 h BP in the intervention group compared with a control group that received lifestyle recommendations without the support from the mobile app, followed during the second part of the study by an improved BP control with the addition of antihypertensive medication. Of note, these effects occurred along with improvements in secondary outcomes such as larger reductions of salt intake and body weight.

The findings of Kario et al.[14] are interesting and add valuable information to the bulk of knowledge on how to attain adequate goals in arterial hypertension. However, besides the need for replicating these results in other cohorts, a few issues deserve consideration. One is the long-term sustainability of this intervention, with differences in BP between groups slightly reduced at 24 weeks. A major issue in this respect is intervention adherence. In this regard, in the study by Kario et al., participants showed a relatively optimal adherence, as reflected by a >95% engagement rate with the mobile app and with >90% of the participants completing the recommendations provided in steps (i) and (ii) of the trial. Future research should confirm whether adherence—and the benefits on BP—can be maintained in the long term. On the other hand, clinicians in charge must establish an adequate interaction with the patient to use the app correctly, which might represent a limitation in terms of time investment. Well-trained nurses could, in our opinion, be in charge of this new methodology. Finally, whether this novel approach can prevent the development of sustained hypertension in people with pre-hypertension—a major milestone in the field—remains to be determined.

More efforts are needed to efficiently implement healthy lifestyle changes for the prevention and management of arterial hypertension. Initiatives such as Digital therapeutics might pave the way for a new era in which the technology of the new millennium can be used—paradoxically—to help us return to a more 'traditional' (non-westernized) way of living (Graphical Abstract).

Graphical Abstract.

Graphical Abstract: BP, blood pressure; DASH, Dietary Approaches to Stop Hypertension. → promotes (increasing effect);—| inhibits (decreasing effect)

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