Changes in V̇O2max and Carotid IMT
Changes in V̇O2max from adolescence to age 36 (Table 3) and from young adulthood to age 36 (Table 4) were not significantly associated with carotid IMT. To investigate whether the relationship between changes in V̇O2max and carotid IMT was or was not linear in the range of changes observed herein, we stratified changes in V̇O2max (from young adulthood to age 36) into three categories of equal size: “decrease,” “stable,” and “increase.” These categories were then included in the regression models as dummy variables, with the category “decrease” as reference, to investigate whether carotid IMT differed between these categories. We hypothesized that carotid IMT would be lower in the category “increase” as compared with the others. However, in crude analyses and also after adjustment for covariates, no differences were found among the three categories (Fig. 1).
Changes in V̇O2max and Arterial Stiffness
From adolescence to age 36 (
Changes in V̇O2max were directly and significantly associated with carotid distension (P = 0.015). This led to a positive and significant association between changes in V̇O2max and carotid distensibility (P = 0.020) and compliance (P = 0.037). However, after adjustment for potential confounders, the associations with distension and distensibility decreased and were no longer significant, whereas those with carotid compliance remained significant (P = 0.039). Changes in V̇O2max levels were inversely but not significantly associated with the carotid elastic modulus. In both crude and adjusted analyses, changes in V̇O2max were significantly associated with compliance (P < 0.001 and P = 0.005, respectively) but not distensibility (P = 0.085 and P = 0.870, respectively) of the femoral artery. This was a consequence of the net effect of positive associations with femoral diameter and distension, and negative associations with local pulse pressure. Changes in V̇O2max were directly and independently associated with brachial artery diameter (P = 0.003 for adjusted analyses) in men only (P = 0.009 for interaction with gender) but not with brachial distension, pulse pressure, and stiffness coefficients.
From young adulthood to age 36 (
Changes in V̇O2max were positively and significantly associated with compliance (P = 0.046), but not distensibility, of the carotid artery. After adjustment for potential confounders, this association was no longer significant. One must notice, however, that the estimates of the associations between changes in V̇O2max from young adulthood to age 36 and carotid distension, distensibility, and compliance were stronger than in the period of change between adolescence and age 36; the lack of significance may be explained by the relatively reduced number of subjects (i.e., less power) considered in these analyses (N = 118 vs 154). Changes in V̇O2max were not significantly associated with carotid elastic modulus. In both crude and adjusted analyses, changes in V̇O2max were positively associated with the diameter of the brachial artery (P = 0.037 and P = 0.039, respectively) in men only (P = 0.050 for interaction with gender), and with the distension of both the brachial (P = 0.012 and P = 0.008) and the femoral (P = 0.002 and P = 0.009) arteries. This resulted in a positive and significant association with distensibility of the femoral artery (P = 0.021 in adjusted analyses) and compliance of both arteries (in adjusted analyses P = 0.013 and P = 0.007, brachial and femoral arteries, respectively).
Impact of Changes in PA on Changes in V̇O2max and Large Artery Properties
We hypothesized that positive changes in V̇O2max reflect a more active lifestyle. To support this, and in the context of the present study, we first related changes in V̇O2max with concomitant changes in PA levels. The Pearson’s correlation coefficients were, for men and women, respectively, 0.22 and 0.23 (from adolescence to age 36) and 0.30 and 0.26 (from young adulthood to age 36) (P < 0.05 for all). These associations are further illustrated in Figure 2. We then investigated the relationships between changes in PA and large artery properties, and the potential mediating role of changes in V̇O2max on these relationships (Tables 5 and 6). Overall, and in both periods of change, the relationships between changes in PA and large artery properties mimic those between changes in V̇O2max and the same arterial properties (adjusted model). Moreover, the inclusion of changes in V̇O2max in the regression models resulted in a decrease of the regression coefficients in almost all the relationships investigated. This confirms our hypothesis that the impact of changes in PA on large artery properties would be, at least partially, mediated by changes in V̇O2max. However, changes in PA levels were still independently associated with arterial properties such as the distensibility of the brachial artery (in women only) (P = 0.034 and P = 0.055 from adolescence to age 36 and from young adulthood to age 36, respectively), and with the compliance of the brachial (P = 0.028) and the femoral arteries (P = 0.013), in the period of changes from young adulthood to age 36.
We found that: 1) longitudinal changes in V̇O2max and PA levels from adolescence to age 36 were not associated with carotid IMT and Young’s elastic modulus; 2) changes in V̇O2max,, but not PA, were inversely associated with carotid stiffness, a relationship in part dependent on, and possibly mediated by changes in other risk factors; 3) changes in V̇O2max and PA were inversely and independently associated with brachial and femoral stiffness; and 4) the associations between changes in PA and large artery stiffness were partially explained by concomitant changes in V̇O2max.
Changes in cardiorespiratory fitness and daily PA and carotid IMT.
In a previous study within the AGAHLS, V̇O2max during adolescence and at age 36 were inversely and independently associated with carotid IMT at age 36 in men (11). In the present study, changes in V̇O2max and PA levels (either from adolescence to age 36 or from young adulthood to age 36) were not associated with smaller carotid IMT values. Shorter-term improvement of V̇O2max through physical exercise (3 months) also did not reduce carotid IMT (31). However, the same investigators had previously reported a decrease in wall thickness of the femoral artery with increased levels of V̇O2max after a physical exercise program with the same duration (9). Taken together, these and our findings suggest that a reduction of the wall thickness with increased V̇O2max levels in healthy and risk-free subjects may be site specific, i.e., evident in muscular (such as the femoral) but not elastic (such as the carotid) arteries (21). This could be partially explained by the greater number of smooth muscle cells and plasticity of the muscular as compared with elastic arteries and/or by different exercise-induced adaptations in local pulsatile blood pressure and flow velocity that would generate different shear and tensile stress forces within the arterial tree (19,21). In this line, a short-term exercise-induced decrease in IMT thus reflects a medial adaptive response rather than a decrease in atherosclerosis (a disorder of the intimal layer). Whether such a decrease in medial thickness reduces cardiovascular risk is unknown.
Despite the lack of evidence of the beneficial effects of improving V̇O2max on carotid IMT in healthy subjects, physical exercise has been a successful tool in multifactorial programs for coronary atherosclerosis reduction in patients with coronary artery disease (12). We should emphasize that we studied only 36-yr-old healthy men and women without evidence of atherosclerotic disease. It is possible that increased PA and/or V̇O2max levels have a beneficial effect on carotid IMT in older subjects and/or subjects with clinically elevated levels of IMT or cardiovascular risk factors.
Changes in cardiorespiratory fitness and daily PA and arterial diameter.
An increase in levels of V̇O2max and PA was directly and strongly associated with greater diameters of the brachial artery in men and the femoral artery in both men and women, but not with the diameter of the carotid artery. In athletes, as compared with sedentary peers, the diameter of the femoral (but not the carotid) artery is greater (9,26). We show that changes in cardiorespiratory fitness throughout the first decades of life are related to the size of muscular arteries in adults that have not undergone any special physical training intervention to modify their physical fitness other than the repeated measure of V̇O2max. It is likely that this adaptation is related to an increased blood flow (and therefore, shear stress) in arteries supplying exercising musculature (9,14,26). Such a mechanism may also explain the lack of an association between changes in V̇O2max and PA and the diameter of the carotid artery. Why gender modulates these (as well as distension) adaptations differently according to the site in the muscular arterial tree is not clear but may involve hormonal factors and differences in risk profile, habitual patterns of PA, and arterial properties (22).
Changes in cardiorespiratory fitness and daily PA and arterial stiffness.
Changes in V̇O2max from adolescence to age 36 were independently associated with compliance (i.e., buffering capacity) of the elastic carotid and the muscular femoral arteries but not distensibility (i.e., elastic properties) of these arteries. However, in a shorter period (i.e., from young adulthood to age 36), where stronger estimates of association were found for almost all the studied variables (Table 4 vs Table 3), changes in V̇O2max were not only independently associated with compliance but also with the distensibility of both the brachial and the femoral arteries. This suggests that these arteries underwent adaptations toward a more elastic wall constitution, due to the relatively stronger association of changes in V̇O2max with distension than with diameter. Results of analyses of changes in PA levels were, in general, quite similar to those of analyses of changes in V̇O2max. The lack of association between changes in PA and stiffness of the carotid artery agrees with the ARIC study (28), in which only vigorous activities (in that study >5 METs), i.e., the type of activities that might result in changes in V̇O2max levels, were positively but weakly associated with distensibility of this artery. Nevertheless, the associations between changes in V̇O2max and arterial stiffness properties of the carotid artery were not independent of changes in covariates, as the regression coefficients changed considerably after adjustments. In additional analyses, mean blood pressure and changes in HDL cholesterol and body weight were the main “confounders” in the associations with carotid distension, distensibility, and compliance. Mean blood pressure is a true confounder in the associations investigated herein because these stiffness estimates are dependent on distending pressure, an aspect that we wished to adjust for. However, HDL cholesterol and body weight are variables that can be also in the pathway between V̇O2max and arterial stiffness, suggesting that the beneficial effects of V̇O2max on the carotid artery are mediated by changes in other risk factors. The adjusted estimates presented here may thus underestimate the true associations between changes in V̇O2max and carotid stiffness properties. Overall our study, as do others (8,30), supports the concept that improving V̇O2max and PA levels reduces arterial stiffness and might attenuate the age-related reduction in arterial stiffness. However, a fact of major importance for public health recommendations that has emerged from recent studies (20,27) is that this beneficial effects may be achieved with aerobic exercise but not resistance training.
Cardiorespiratory fitness and a physical active lifestyle have a favorable impact on cardiovascular health, either via the reduction of other risk factors (e.g., hypertension, dyslipidemia, Type 2 diabetes, obesity) or via direct effects on the cardiovascular system (29). In our study, we confirm that the salutary associations of cardiorespiratory fitness with the properties of the elastic carotid artery are most likely mediated by the preservation of a more favorable body composition and HDL levels throughout age in the fitter individuals. We also show that an increase in cardiorespiratory fitness and daily PA levels are inversely and independently associated with arterial stiffness, especially in the muscular vasculature. An explanation for these direct effects of training-induced improvements of cardiorespiratory fitness, either acutely or chronically, is an adaptation to shear stress forces (14,29). During exercise, blood flow increases, leading to higher intraluminal shear forces, which stimulate the endothelium to release relaxing factors, mainly believed to be nitric oxide (NO), resulting in arterial vasodilation. In response to chronic increases in blood flow, arterial remodeling occurs (larger vessel diameter) in order to restore basal shear stress, a phenomenon that was shown to be endothelium dependent (3). Other mechanisms might be involved, such as a decrease in vascular smooth muscle tone due not only to an improved local and basal production of NO but also to an exercise-induced reduction in sympathetic tone and/or renin-angiotensin system activity (15). Moreover, emerging evidence suggests that PA and cardiorespiratory fitness may have anti-inflammatory (1) and antithrombotic (29) effects that, in turn, affect vascular structure and function.
Role of PA and implications for public health.
The results found in this study suggest that improving V̇O2max may be an important tool for the prevention of cardiovascular disease and that improvement of V̇O2max levels can be achieved by engaging a more physically active lifestyle. Although V̇O2max has a genetic component, it is primarily determined by PA. This has been also previously reported in the same population of the present study (17). Moreover, PA, as compared with other lifestyles (nutrient intake, smoking, and alcohol consumption), is a strong correlate of cardiovascular risk factors (e.g., body fatness) (32), a pathway via which one may also expect healthy effects on arterial properties. Nevertheless, changes in PA levels were also inversely associated with arterial stiffness (especially in the muscular arteries) independently of changes in V̇O2max. Again, this suggests that other mechanisms than a change in V̇O2max are involved. In addition, it also suggests that any change in PA, even not reflected in changes in V̇O2max (that usually occur with moderate-heavy intensities) may be sufficient for a salutary impact on arterial stiffness. In this line, the low-intensity activities (i.e., 4–7 METs) had the highest frequency and duration, and have contributed the most (about 2/3) for the total PA score calculated at age 36 in the AGAHLS (data not shown). This is important information for public health policies directed to the general population, in the sense that increases in these kinds of activities may be easier to achieve. Therefore, from a public health point of view, our results support the promotion of a more physical active lifestyle, either starting during adolescence or later during young adult life, as a tool for primary prevention of cardiovascular disease.
The first author of this paper was supported by a research grant from the Foundation for Science and Technology–Portuguese Ministry of Science and Technology (grant PRAXIS XXI/BD/19760/99). The AGALHS has, since 1974, been supported by major grants from the Foundation for Educational Research, the Dutch Prevention Fund, the Netherlands Heart Foundation, the Dutch Ministry of Public Health, Well Being and Sport, the Dairy Foundation on Nutrition and Health, the Netherlands Olympic Committee/Netherlands Sports Federation, Heineken BV, and the Scientific Board on Smoking and Health.
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Keywords:©2003The American College of Sports Medicine
PHYSICAL ACTIVITY; ADOLESCENCE; YOUNG ADULTHOOD; INTIMA-MEDIA THICKNESS