Defining lifelong exercise frequency and arterial stiffness changes in older adults: considerations for sex differences and exercise dose

Arterial stiffness parameters measure arterial elastic properties and represent an important determinant of cardiovascular health. The physiological underpinning of arterial stiffness, which has been rightfully popularized given its clinical relevance, requires some basic physiological knowledge. The historical Windkessel model provides a conceptual model for understanding the dampening effects of arterial function. During the cardiac cycle, incident arterial pressure waveforms are distributed centrally from the cardiac system toward peripheral arteries and reflected back toward the cardiac system. The presence of ageing and disease have been widely associated with increased arterial stiffness, such that arterial waveforms are propagated outward and reflected back at a faster rate. This phenomenon can result in the incident and reflective waves merging to cause higher systolic pressures and lower diastolic pressures. Remarkably, the exercise ‘dose–response’ relationship has shown that higher exercise ‘doses’ may reduce arterial stiffness. The extent to which exercise ‘dose’ components of frequency, intensity and duration contribute to reductions in central and peripheral arterial stiffness, however, is not completely understood. Furthermore, there are important distinctions in the modulation of arterial stiffness between individuals, and one thing is clear, sex matters. Most recently, the relationships among arterial stiffness, ageing and exercise ‘dose’ were described in an article in The Journal of Physiology (Shibata et al. 2018). The authors sought to test the hypothesis that high lifelong exercise ‘dose’ (e.g. 4–5 weekly exercise sessions of >30 min in duration) would be associated with a reduction in central arterial stiffness using subjects recruited largely from the Cooper Center Longitudinal Study database (with the exception of Masters athletes who were recruited separately to characterize the highest exercise ‘dose’ quartile). This established longitudinal study offers a unique clinical research advantage in characterizing physical activity and cardiovascular risk given the large sample size (>80,000 individuals) and follow-up period (>40 years). In the current study, older males and females (n = 102, >60 years old) were screened based on medical history, physical examination and detailed exercise training history. Eligible participants had detailed assessments for arterial stiffness (including pulse wave velocity, augmentation index and biological aortic age) and were stratified into four groups based on self-reported lifelong exercise ‘doses’, including: sedentary (0–1 exercise session/week), casual (2–3 exercise sessions/week), committed (4–5 exercise sessions/week) and competitive athletes (6–7 exercise sessions/week). The authors elegantly reported that life-long habitual activity (>25 years) at a frequency of 4–5 times per week was associated with lower central arterial stiffness but not peripheral arterial stiffness, which is reflective of large conduit and small resistance vessel structure, respectfully. To a similar extent, total arterial compliance, blood pressures and cardiac afterload, which are reflective of small resistance vessel function, were improved with even a modest (2–3 sessions per week) amount of lifelong exercise. As a result, the authors concluded that higher lifelong volumes of aerobic exercise may prevent adverse central arterial stiffness common with ageing. The association between lifelong habitual exercise and markers of vascular structure and function provides novel insight for therapeutic interventions to modulate the profound age-related declines in vascular health. The importance of the current study findings cannot be understated, since large epidemiological studies have demonstrated that age-associated declines in vascular function and structure are associated with all-cause and cardiac-related mortality, although it is unknown if the benefits observed in this study are different between men and women. Based on previous evidence, sex differences in response to long-term habitual exercise training in older adults is inconsistent, reporting that older women experience similar responses relative to older men (Endes et al. 2016), or no effect on vascular structure and function (Pierce et al. 2011). This has been attributed largely to sex differences in vascular ageing, the loss of circulating oestrogen following menopause in women and differences in cardiopulmonary fitness. The authors address this and acknowledge that there were no differences between the sedentary and exercise groups in the male/female ratio; however, there were only a small number of women in the exercise groups (i.e. male/female ratio in casual exercises of 18/7; committed exercises 20/5; competitive exercises 17/8), which may limit the generalizability of these results to both men and women. Higher cardiopulmonary fitness observed with increases in frequency of exercise paralleled the increased numbers of males versus females in these cohorts. As such, sex and cardiopulmonary fitness may have interacted and had a direct influence on the study findings. A future comparison between equal numbers of men and women matched on cardiopulmonary fitness may better address the association between habitual exercise and markers of vascular health, particularly if differential doses of habitual exercise are needed to confer the same benefits in older men versus women. Nonetheless, one key difference between these previous data and the current study is life-long participation in exercise compared to shorter durations (i.e. 5 years versus >25 years). Accordingly, this provides both novel and promising insight for favourable intervention to prevent cardiovascular disease if exercise started earlier in life can decrease the signs of vascular ageing in older women. Future research should consider potentially important sex differences when designing such clinical investigations to increase the widespread application of these data. This is especially critical in the design of studies and reporting of data that address important research gaps regarding potential interventions to reduce the burden of cardiovascular disease in men and women because the response of the intervention may be sex dependant. Perhaps reporting of data on both men and women separately might also allow future meta-analyses to pool data to strengthen our understanding of possible sex-based differences. The exercise dose–response relationship has shown unequivocally the benefits of greater exercise ‘doses’ on improving cardiovascular morbidity and mortality; however, the effect of exercise ‘dose’ on arterial stiffness is not completely understood. The current study findings are intriguing, with such a simple index sensitive enough to detect an association between a higher exercise dose and lower arterial stiffness; yet, we need to be prudent and consider the effects of exercise duration and intensity on cardiovascular health in older adults. The present study quantified exercise ‘dose’ solely in the self-reported frequency of exercise sessions lasting greater than 30 min, which limits our ability to understand the exercise dose–response relationship. In contrast, a systematic review and meta-analysis has demonstrated that longer duration aerobic exercise has a significant impact on reducing arterial stiffness in pre-hypertensive adults (Montero et al. 2014). As a further example, a recent study observed greater coronary artery calcification and atherosclerotic plaque in middle-aged men who performed higher duration and/or intensity exercise, based on a stronger index of metabolic equivalent (MET) minutes per week (>2000 MET-minutes per week) (Aengevaeren et al. 2017). The clinical significance of this finding may be rather benign, as the authors asserted, but nonetheless, it demonstrates that exercise duration and intensity are important mediators of arterial health. Likewise, exercise mode may result in a differential response with aerobic versus resistance exercise on central and peripheral arterial stiffness. While aerobic exercise has been frequently associated with declines in arterial stiffness, studies should delineate how resistance exercise and/or combined aerobic and resistance exercise modulate central and/or peripheral arterial stiffness, and again may have had a direct effect on the study findings. Lastly, in all cases, self-reporting bias and recall bias may be present when considering long-term physical activity behaviours. While a longitudinal study evaluating individual lifelong habitual exercise patterns with objective physical activity data (e.g. not subject to recall bias) remains impractical, future studies are needed to clearly delineate the exercise dose–response relationship with objective quantifications of the multiple exercise dose components (frequency, duration and intensity) in order to optimize exercise recommendations for arterial health among our ageing adult population. In summary, the current study provides novel insights into the associations between self-reported lifelong exercise frequency and arterial stiffness through middle age. Exercise frequency provides only one component of a more complex exercise ‘dose’, which should ideally extend to quantify objective exercise duration and intensity. Sex differences need to be considered in both the study design and reporting of study findings such that future clinical investigations can advance our understanding of arterial stiffness following exercise training. None to disclose. Both authors contributed to conception and drafting of the work. Both authors have read and approved the final version of this manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed. A.B. is supported by the Canadian Institute of Health Research Frederick Banting and Charles Best Canada Graduate Scholarships Doctoral Award.

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