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Exercise in the era of polypills


MANY years ago, I established and managed Australia’s first tertiary hospital-based Exercise Physiology service, in the Cardiac Transplant Unit at Royal Perth Hospital. Alongside clinical exercise testing and prescription, we did a lot of research to assess and optimise our exercise interventions, and their outcomes, for patients with cardiovascular diseases.

After a few years, I was invited to present these findings at a Cardiology Department morning meeting. It did not go very well. Around 15 minutes into my talk, a senior colleague interrupted, saying: “This is pointless. Prevention should consist of making sure patients take their statins”. And then walked out.

This anecdote came back to me recently when I read the results of the SECURE trial, which concluded that treatment with a polypill containing aspirin, ramipril and atorvastatin after myocardial infarction significantly lowered the risk of major adverse cardiovascular events relative to usual care. SECURE reinforces some recent results of polypill use in primary prevention settings.

So, if risk factors for our most common and costly diseases can be managed effectively by drugs (even in a primary prevention setting), what is the role of exercise in cardiovascular disease prevention?

The first thing to say is that exercise does many things apart from having effects on the cardiovascular system. Benefits exists for mental health, musculoskeletal function, sarcopenia, and the risk of falls, to name a few. But if we do confine our discussion to cardiovascular risk, the impacts of exercise in a primary prevention context are, on average, relatively modest compared with the effects of optimal medication (eg, for lipids and blood pressure).

Nonetheless, exercise has cardiovascular benefits that are independent of risk factor reduction. In fact, modification of traditional cardiovascular risk factors in response to exercise contributes less than 50% to the observed reduction in cardiovascular events attributable to increasing physical activity. This “risk factor gap” may be partly explained by direct effects of exercise on cardiovascular function and health. For example, we have shown that exercise enhances artery endothelial function (and hence reduces atherosclerotic development and progression) by virtue of direct effects of repetitive episodic increases in arterial blood flow and shear stress. There are also well established impacts of exercise training on inflammation and autonomic balance.

But practitioners treat individuals, not populations, and there is increasing focus on characterising the sources of variability between people in their responsiveness. Recently, we reported results of an experiment we called Studies of Twin Responses to Understand Exercise as a THerapy (STRUETH). In this randomised crossover trial, we asked 72 individuals to undertake 3 months of endurance style exercise training (eg, walking, running, cycling) and 3 months of resistance type training (eg, weight lifting). The order of these modes of exercise was randomised, and the 3-month periods of centre-based and supervised exercise training were separated by a 3-month wash-out period. The volume or load of exercise undertaken was matched for all individuals. Outcomes included cardiac magnetic resonance imaging scans (here, here), artery function and health (here, here, here), cardiopulmonary fitness, muscular strength, body composition, and cardiovascular risk factors (here, here).

Our findings indicate that different modes of exercise induced distinct group mean changes. For example, endurance training, on average, had greater effects on fitness than resistance training, while resistance training had, on average, greater effects on muscle mass and strength. Such findings were not surprising, and largely reinforced the specificity principle of exercise training. But the interesting thing was the range of responses – there were subjects who benefitted greatly from either type of training, and there were some who only responded modestly, or not at all.

So despite the intensity, duration and frequency of exercise being matched between people, with about 95% training compliance, there were responders and non-responders to each form of training. In terms of cardiovascular risk factors and group average responses, our findings indicated that exercise had modest effects. But for each risk factor (weight, waist circumference, BP, glucose, insulin, low-density lipoprotein and high-density lipoprotein levels) a large proportion of individuals nonetheless responded positively to each form of training.

The good news is that there were very few “recalcitrant” non-responders, in that those who had modest responses to one form of training usually responded well when they switched to the alternative mode. This suggests that there is a form of exercise that benefits almost everyone, but it may not be the first one they try.

In a way, none of this will be surprising to GPs, who in their daily practice see variable responses between individuals (eg, in terms of drug efficacy) and modify therapy to optimise outcomes. Just as a GP may increase the drug dose (equivalent to increasing exercise intensity) or change from one type of drug to another (equivalent to changing exercise modality), our data emphasise the importance of considering exercise as an intervention that should be personalised for optimal health gain.

It is important to note that of the 72 STRUETH participants, 50 (25 pairs) were monozygotic twins and 22 (11 pairs) were dizygotic. This gave us some insight into the extent to which physiological adaptations to exercise were inherited (here, here, here, here). The answer, generally, was that environmental factors contributed more to exercise responses than did genetics.

Take home messages for GPs include:

  • that exercise has myriad beneficial effects, including cardiovascular benefits that exceed those attributable to effects on traditional risk factors;
  • that exercise effects are idiosyncratic – some individuals will respond more than others and this is a biological issue (not simply due to differences in adherence);
  • that exercise is not one-size-fits-all – different prescriptions have distinct physiological effects and exercise should be individualised if it is to be optimised; and
  • that doing something is better than doing nothing, but if whatever you’re doing isn’t working after a while (eg, 1 month), it’s likely that doing something different will work better and the benefits will start to show.

Daniel J Green is Winthrop Professor in the School of Human Sciences (Exercise and Sport Science) at the University of Western Australia.

 

 

The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight+ unless so stated.

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