COMMENTARIES

Central Artery Stiffness and Metabolic Syndrome: Is Lifestyle Modification Effective for Both?

Kunihiko Aizawa1,2 J Kevin Shoemaker2, and Robert J Petrella1,2,3, 1Aging, Rehabilitation & Geriatric Care Research Centre, Lawson Health Research Institute at Parkwood Hospital, 2School of Kinesiology, The University of Western Ontario, 3Schulich School of Medicine and Dentistry, The University of Western Ontario

Please address correspondence to:
Dr. Robert J Petrella:
Parkwood Hospital, Room B3002
801 Commissioners Rd. E
London, ON, N6C 5J1, Canada
Email: petrella@uwo.ca

Metabolic syndrome (MS), a constellation of cardiovascular disease (CVD) risk factors such as elevated blood pressure, impaired glucose regulation (IGR), central obesity, and atherogenic dyslipidemia, increases CVD risk more than 60% compared to individuals without MS [1]. Although the mechanisms responsible for this increase in CVD risk have not been elucidated yet, central artery stiffness, an independent predictor of all-cause and cardiovascular mortality [2], has recently emerged as one of the possible explanations underlying pathophysiological mechanisms [3]. Indeed, since each component of MS is associated with increased central artery stiffness [4], it seems highly plausible to assume that central artery stiffness is higher in individuals with MS than in those without MS.

          Previous studies examining the impact of MS on central artery stiffness have shown that the presence of MS increases central artery stiffness in subjects without CVD (healthy: [5-7]), with hypertension [8-12], and in population-based [13-16] subjects. Moreover, increased central artery stiffness in MS appears to be synergistic. However, the inclusion of subjects with hypertension (even untreated hypertension), type 2 diabetes mellitus (DM), and/or a history of CVD in those studies did not allow one to conclude that the presence of MS per se increases central artery stiffness. Therefore, we have conducted a cross-sectional study examining the impact of MS on carotid artery stiffness in middle-aged and older MS subjects who were at increased risk for CVD due to high-normal blood pressure (HNBP) and/or IGR but were considered normal [17].

          In that study, all the subjects had HNBP and/or IGR (impaired fasting glucose and/or impaired glucose tolerance) but none had hypertension, type 2 DM, or a history of CVD. Each component of MS and carotid artery stiffness by a Doppler ultrasound device were assessed. Interesting results we observed were that arterial distensibility of the carotid artery was significantly lower in subjects with MS (0.15 ± 0.01 1/mmHgx10-2) than in subjects without MS (0.18 ± 0.01 1/mmHgx10-2, p < 0.05), while the β stiffness index was similar between the groups. Furthermore, based on a multivariate regression analysis, carotid artery stiffness was independently associated with aging and resting heart rate but not with the presence of MS, suggesting that the presence of MS in this population may be just a sum of each MS component in terms of central artery stiffness. These results stand in contrast with a study that focused on a similar population as ours showing that, although aortic pulse wave velocity was higher in subjects with MS than in subjects without MS, the presence of MS was associated with a significant increased risk for aortic pulse wave velocity in normotensive subjects at risk for developing type 2 DM [18]. The discrepancy between the studies might have been due to differences in the subjects’ inclusion criteria and/or in the methods used for assessment of arterial stiffness. Nonetheless, our results indicate a need of early intervention, such as lifestyle modification, to reduce central artery stiffness in MS because arterial stiffness may be a possible mechanism of initiation and/or progression of CVD [19].

          As the common causes of MS are inadequate physical activity and poor diet [20], the AHA/NHLBI Scientific Statement recommends lifestyle modification as the initial therapy for the treatment of MS [21]. This strategy is supported by accumulating evidence showing that major chronic diseases such as CVD, stroke, and type 2 DM are heavily influenced by modifiable lifestyle factors including diet, physical activity, obesity, and smoking [22]. Therefore, incorporation of healthy lifestyle is expected not only to reduce CVD risk (MS components) but also reduce central artery stiffness, an important strategy for those at risk for CVD to prevent a CVD event as early as possible. However, there have been few studies examining the effect of lifestyle modification on central artery stiffness in MS.

          As a follow-up of our previous study, we have recently completed an intervention study examining the effect of a 24-week lifestyle modification on carotid artery stiffness in MS subjects with HNBP and/or IGR. Twenty-nine subjects without MS (MS-) and 34 subjects with MS (MS+) participated in the study. Similar to the previous study, each component of MS and carotid artery stiffness were assessed before, at 8 weeks, and following 24 weeks. Individualized lifestyle prescription for aerobic exercise and a Mediterranean-style diet was delivered to the subjects by each subject’s family physician every 8 weeks. The primary findings of the study were that carotid artery stiffness was reduced in MS+ following the 24-week intervention with accompanying improvements in several MS components (waist circumference, blood pressure, and glucose). Moreover, 13 MS+ subjects were free from MS following the intervention. If these results are translated into general populations, then the implication of preventing CVD events can be considerable.

          Several issues relating to lifestyle modification that can reduce the prevalence of MS and central artery stiffness require additional research. First, what mechanism(s) would be responsible for the reduction in central artery stiffness by lifestyle modification? Enhanced endothelial function may be one of mechanisms for this reduction. Since endothelial function has been shown an association with arterial stiffness [23-24] as well as recognized as an early step in the initiation/development of atherosclerosis, it may be feasible to consider that enhanced endothelial function has a direct as well as indirect (via reduced arterial stiffness) effect on reduced risk of CVD. Second, how long would the MS subjects who participated in the intervention studies be able to maintain reduced central artery stiffness after the discontinuation of active intervention? Whereas no study has examined this “de-training” effect in MS yet, available evidence from previous studies in healthy and high-risk individuals has indicated that arterial stiffness appears to return to pre-intervention level quickly (i.e. less than the duration of intervention: [25-27]). Thus, these data underscores the fact that permanent lifestyle change is required [28]. This raises another issue: how to maintain (or increase) adherence to lifestyle modification? One way to respond to this issue may be the use of family physicians for which our lifestyle modification strategy utilized in the intervention study. As the majority living in the community relies heavily on the direction provided by their family physicians to maintain their health, the results of our intervention study may show a window of opportunity for family physicians to target their patients at risk for CVD by lifestyle intervention. Lastly, is lifestyle intervention superior to pharmacological interventions to reduce central artery stiffness in MS? While evidence suggests that lifestyle modification seems to work better than pharmacological treatments in reducing the prevalence of MS (and the components of MS: [29]), a future study is required to answer this issue.

          In summary, from our experience lifestyle modification appears to work effectively to reduce central artery stiffness as well as the prevalence of MS components. While further understandings of the association between central artery stiffness and lifestyle modification are much desired, we now need to step forward and take action to reduce central artery stiffness and MS, leading to prevention of eventual CVD events.

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