Aging leads to vascular changes, including thickening and stiffening of large elastic arteries (aorta and carotid), increases in systolic blood pressure, and widening of pulse pressure, which predispose older adults to cardiovascular disease (CVD) (reviewed by Fleg and Strait ). Arterial stiffness is a strong predictor of future CVD events and mortality (16,35); therefore, it is an important therapeutic target for CVD prevention. Aerobic exercise training is often prescribed for reducing CVD risk, but exercise prescription for older adults remains generic, and there is still controversy regarding the optimal exercise regimen for attenuating arterial stiffening in aging.
High-intensity interval training (HIIT) and isocaloric moderate-intensity continuous training (MICT) on the treadmill have been reported to improve CVD risk factors, including aerobic fitness, endothelial function, and cardiac function, in patients with cardiometabolic diseases (18,24,32,38), but the effect of HIIT on these risk factors has been found to be greater compared with MICT. We are aware of only two studies that have compared the effect of HIIT and MICT on arterial stiffness (4,6). These studies demonstrated that HIIT is more effective in improving arterial stiffness than MICT in young and middle-age patients with hypertension (6) and young women at high familial risk for hypertension (4). However, the effect of HIIT versus MICT on arterial stiffness in older adults has not been investigated.
In older adults, balance and musculoskeletal problems often limit weight-bearing exercise. Because the world population is aging, the number of musculoskeletal disorders is expected to increase by 70% worldwide in the next 15 yr (23); therefore, alternative non–weight-bearing exercise modalities need to be established to allow implementation in a larger portion of the older population. All-extremity non–weight-bearing exercise is an appealing modality because it allows compensation for fatigue caused by unilateral or lower extremity musculoskeletal problems and activates a large amount of skeletal muscle mass. We have recently established that all-extremity HIIT and MICT are feasible and safe in older adults (9), but whether these non–weight-bearing alternatives improve arterial stiffness in aging is unknown. Therefore, the purpose of this randomized controlled trial was to compare the effect of all-extremity non–weight-bearing HIIT and MICT on arterial stiffness in previously sedentary older adults free of cardiovascular and other major clinical disease.
Men and women 55 and 79 yr of age were recruited in the study. More than 80% of those enrolled were 60 yr or older. Subjects did not smoke or use tobacco products and were free of overt cardiovascular and other major clinical disease (e.g., diabetes, liver disease, and renal disease) as assessed by rigorous screening: medical history, physical examination, blood tests (i.e., comprehensive metabolic and lipid panels and complete blood count with differential), and 12-lead electrocardiogram during rest and diagnostic graded exercise test. Before study enrollment, subjects were not on hormone replacement therapy (i.e., estrogen, progesterone, and testosterone) for at least 2 yr, and female subjects were postmenopausal (i.e., cessation of menses for ≥2 yr). Subjects on stable use of medication for controlling lipids and blood pressure were included in the intervention but were required not to alter their therapeutic regimen during study participation. Subjects were weight stable (i.e., <5% body weight change) for at least 6 months before enrollment and were asked to maintain their dietary habits constant during study participation. Subjects were sedentary for at least 12 months before enrollment, defined as no regular aerobic exercise training (i.e., they engaged in <30 min of aerobic exercise 2 or fewer times per week), based on self-reported habitual physical activity using the modifiable activity questionnaire. Subjects were instructed not to increase their leisure-time activity during study participation. Triaxial accelerometers (ActiGraph GT3X, software version 5.10.0; ActiGraph LLC, Pensacola, FL) were used to monitor physical activity for 4 d (three weekdays and one weekend day) before study enrollment. Activity monitoring was repeated at the end of the intervention to examine any potential changes in physical activity that could confound our results.
The study was approved by the Institutional Review Board of the University of Florida. The purpose, nature, and risks of the study were explained to the subjects and their written informed consent was obtained before participation.
A total of 89 research volunteers provided written informed consent to participate in the study. Subjects who met the study inclusion criteria (n = 49) were randomized to HIIT (n = 17; 13 women), MICT (n = 18; 10 women), or nonexercise controls (CONT; n = 14; 10 women). Randomization was based on computer-generated random numbers and was stratified by initial peak oxygen consumption (L·min−1). Arterial stiffness measurements were performed in the morning, at the same time of day pre- and postintervention, by the same researchers strictly following standard operating procedures. Data were coded to ensure blinding during analysis.
HIIT and MICT were performed on an all-extremity non–weight-bearing air-braked ergometer (Airdyne AD4; Schwinn, Vancouver, WA), which incorporates pulling/pushing the handlebars with the upper extremities while cycling with lower extremities. Exercise sessions were conducted 4 d·wk−1 for 8 wk under supervision. MICT consisted of 47 min at 70% HRpeak and included a 10-min warm-up and 5-min cooldown at the same intensity. HIIT consisted of 40 min of 4 × 4 min at 90% HRpeak alternated by 3 × 3 min active recovery at 70% HRpeak and a 10-min warm-up and 5-min cooldown at 70% HRpeak. The intensity and duration of HIIT and MICT were based on the protocols published by Tjonna et al. (32), which were designed to result in isocaloric expenditure on the treadmill. In the current study, the caloric cost of the all-extremity HIIT and MICT protocols was confirmed to be equal by measuring oxygen consumption during HIIT and MICT using computer-assisted open-circuit spirometry.
HRpeak was determined during the maximal exercise test at preintervention. An HR telemetry system (Polar Team 2 Pro, version 1.4.3; Polar Electro Oy, Kempele, Finland) was used to monitor and record HR throughout each training session. Subjects were instructed to alter the speed of their arm and leg movement to achieve their target HR. The intervention was preceded by a period of familiarization/preconditioning because subjects were previously sedentary and unfamiliar with all-extremity exercise. The initial exercise duration/intensity was determined by the subject's motivation, fitness level, and capacity to perform all-extremity exercise. Initial intensity was based on a self-selected comfortable pace and in the majority of subjects ranged between 65% and 75% HRpeak, whereas the initial duration was at least 15 min (average = 24 ± 2 min). Duration and intensity were gradually increased every session as tolerated until subjects were able to complete 40 continuous minutes of exercise at 70% HRpeak. To reach this goal, 5 ± 1 sessions were required on average.
All resting cardiovascular measurements were performed in the morning, in a semidarkened temperature-controlled room, after a minimum of 20 min of supine quiet rest. In accordance to recently published guidelines (33), subjects abstained from alcohol, caffeine, medication use, and food intake (including fluids other than water) for at least 12 h before data collection.
Aortic pulse wave velocity
Aortic pulse wave velocity (PWV), commonly measured as carotid to femoral PWV (cfPWV), is considered to be the gold standard method of assessing arterial stiffness in humans. cfPWV was measured using the SphygmoCor MM3 system (AtCor Medical, New South Wales, Australia) as we have previously described (10) and according to recently published guidelines (33). Briefly, cfPWV was determined by recording pressure pulse waves at the carotid and femoral arteries using a high-fidelity micromanometer (Millar Instruments, Houston, TX) and calculating the distance between the recording sites divided by the time delay between the carotid and the femoral pulse waves. The distance was measured using a nonstretchable tape from the suprasternal notch to the carotid recording site and from the suprasternal notch to the femoral recording site; the former distance was subtracted from the latter and used in the calculation of cfPWV. The average of three high-quality measures, as defined by the manufacturer, was used for analysis. The reliability of cfPWV measures was previously examined in our laboratory in adults 21 to 79 yr of age (n = 22) using repeated measures obtained within 1 wk (unpublished data). Cronbach's alpha intraclass reliability coefficient was 0.974, P < 0.0001, and mean ± SE was 6.50 ± 0.30 versus 6.53 ± 0.30 m·s−1 for day 1 versus day 2, P = 0.8.
Carotid artery compliance and structure
Carotid artery compliance, an established measure of arterial stiffness, was assessed by recording images of the common carotid artery using high-resolution ultrasonography (Aplio XV; Toshiba Medical Systems, Otawara, Japan) and simultaneous contralateral carotid pressure using applanation tonometry (TCB-500; Millar Instruments), as we have previously described (10). Briefly, the carotid pressure waveforms were obtained with a pencil-type tonometry transducer, and the signal was calibrated by the brachial diastolic and mean arterial pressure using the SphygmoCor MM3 software (AtCor Medical). The common carotid artery was imaged with the ultrasound transducer placed at a 90° angle to the vessel so that the near and far walls were clearly visualized. Common carotid artery diameters and intima-media thickness (IMT) were measured approximately 2 cm proximal to the carotid bulb using a commercially available wall tracking software (Vascular Analysis Tools 5.8.2; Medical Imaging Applications, Coralville, IA). Carotid arterial compliance (C), a measure of arterial buffering capacity (20), was calculated as follows:
where D1 and D0 are the maximal and minimal carotid diameters, and P1 and P0 are the highest and lowest carotid pressures. IMT was measured at the far wall following established guidelines (28). IMT and lumen diameter for normalizing wall thickness were measured at end diastole.
Central and peripheral blood pressures
Aortic pressure was determined noninvasively using the SphygmoCor MM3 device (AtCor Medical) as we have previously described (10). Briefly, radial artery pressure waveforms were recorded using a high-fidelity micromanometer (Millar Instruments) and were calibrated using the brachial diastolic and mean arterial pressure. Aortic pressure waveforms were generated from the radial waveforms by the SphygmoCor software (AtCor Medical) by applying proprietary digital signal processing and a mathematical transfer function. Only high quality recordings, as defined by the manufacturer, were used for analysis. Peripheral blood pressure was measured over the brachial artery using an automated oscillometric device (Dinamap; GE, Boston, MA). Aortic and brachial pulse pressures were calculated as the difference between the corresponding systolic and diastolic pressures.
Maximal exercise test
The maximal exercise test was performed on the treadmill because walking is a familiar exercise modality for sedentary older individuals and treadmill test results are a significant mortality predictor in older adults (30). The graded exercise protocol consisted of a 6-min warm-up at a walking speed corresponding to 70%–80% of the age-predicted maximal HR followed by grade increases of 2.5% every 2 min until volitional exhaustion (3,9,11). To allow determination of improvements in time to exhaustion (i.e., maximal exercise test duration) in response to the intervention, postintervention testing for each participant was performed by replicating their preintervention protocol. Oxygen consumption was measured using computer-assisted open-circuit spirometry. Peak oxygen consumption (V˙O2peak) is reported because not all subjects attained at least three of the following criteria for establishing maximal oxygen consumption: 1) a plateau in oxygen consumption (<100 mL) with increasing exercise intensity, 2) a maximal respiratory exchange ratio of at least 1.15, 3) achievement (±10 bpm) of age-predicted HRmax (220 − age), and 4) a rating of perceived exertion of at least 18 on Borg's scale. HRpeak was defined as the highest HR recorded during the maximal exercise test.
Height, weight, body mass index, and waist circumference
Body weight was measured to the nearest 0.1 kg with an electronic scale (Tanita, Arlington Heights, IL) and height was measured three times to the nearest mm with a stadiometer while subjects were barefoot and dressed in light clothing. Body mass index was determined as weight divided by height squared (kg·m−2). Waist circumference, a surrogate measure of abdominal adiposity, was measured at the iliac crest using a nonstretchable tape and the average of three measures was used in the analysis.
Fasting blood samples were analyzed by a clinical laboratory via spectrophotometry using standard procedures.
Statistical analyses were performed using SPSS version 23, and power calculations were performed using G*Power version 3.0.1. Statistical significance for all analyses was set at P < 0.05. Because of the novelty of our intervention, there were no previous data on which to base formal a priori calculations for effect size and sample size for our primary outcomes of cfPWV and carotid artery compliance. Post hoc power calculations indicate that for α = 0.05, our study had >80% power to demonstrate a significant effect of the intervention on cfPWV for effect sizes ≤0.08 and on carotid artery compliance for effect sizes ≤0.22. Data normality and outliers were evaluated using the Explore procedure in SPSS. To compare baseline group differences, one-way ANOVA was used. To examine the effect of the intervention, a 3 × 2 repeated-measures ANOVA was used to test the group (CONT, MICT, and HIIT) by time (pre- vs postintervention) interaction. Significant group–time interactions were followed by post hoc pairwise multiple comparisons adjusted using the Bonferroni correction. Data are reported as mean ± SEM.
Of the 49 subjects who were randomized, 9 (18%) did not complete the intervention for the following reasons: in HIIT due to family issues (n = 1) and schedule conflict (n = 2); in MICT due to family issues (n = 1), schedule conflict (n = 1), or lack of motivation (n = 2); and in CONT due to inability to contact for follow-up measures (n = 2). Two subjects were excluded from the analysis: one subject in MICT due to illness unrelated to the intervention and one subject in CONT due to noncompliance. All-extremity exercise training was well tolerated, and there were no adverse events. Exercise training compliance was similar for MICT and HIIT (90% ± 4% vs 90% ± 2%, respectively; P = 0.9). The caloric expenditure per exercise session was also similar for MICT and HIIT (241 ± 15 vs 226 ± 15 kcal, respectively; P = 0.5).
Arterial stiffness, carotid artery structure, and blood pressure
There were no significant baseline differences in subject characteristics (P ≥ 0.1; Table 1) or measures of arterial stiffness, carotid artery structure, and blood pressure (P ≥ 0.1; Tables 2 and 3). In response to the intervention, arterial stiffness improved in MICT as indicated by decreases in cfPWV (P = 0.04 vs preintervention; Table 2) and increases in common carotid artery compliance (P = 0.001 vs preintervention; Table 2 and Fig. 1). However, common carotid artery compliance and cfPWV did not change in HIIT (P = 0.3 and P = 0.99, respectively) and CONT (P = 0.8 and P = 0.06). Common carotid artery diameter and IMT were unaffected by the intervention (P ≥ 0.7 for group–time interaction; Table 2). Aortic and brachial pressures and HR did not change with the intervention (P = 0.5 for group–time interaction; Table 3).
Physical activity and other subject characteristics
Physical activity measured by accelerometry was not different pre- versus postintervention, indicating that our results are not confounded by changes in physical activity beyond the prescribed exercise sessions (P ≥ 0.4 for group–time interaction; Table 1). Time to exhaustion during the maximal exercise test improved in both HIIT and MICT by 2.2 ± 0.4 and 1.0 ± 0.4 min, respectively (P < 0.0001 and P = 0.02 vs preintervention) but remained unchanged in CONT (P = 0.5 vs preintervention; P = 0.008 for group–time interaction). V˙O2peak improved in HIIT by 2.8 ± 0.5 mL·kg−1·min−1 (P < 0.0001 vs preintervention; Table 1) but did not change in MICT (P = 0.7) and CONT (P = 0.9). Body weight, body mass index, waist circumference, and blood lipids remained unchanged (P ≥ 0.1 for group–time interaction; Table 1).
This is the first study to compare the effect of HIIT and MICT on arterial stiffness (i.e., aortic PWV and common carotid artery compliance) in older adults. Our main finding was that all-extremity MICT, but not HIIT, improved aortic PWV (i.e., cfPWV), and common carotid artery compliance in previously sedentary older adults who were free of overt cardiovascular and other major clinical disease. Improvements in arterial stiffness occurred over a relatively brief period of exercise training (8 wk) and were not confounded by changes in aortic and brachial blood pressure, HR, body mass index, abdominal adiposity, blood lipids, or aerobic fitness.
Arterial stiffness, carotid artery structure, and blood pressure
A change in the aortic PWV of 1 m·s−1 is associated with ~14% change in CVD risk (35). In our study, aortic PWV improved by 0.5 m·s−1 after 8 wk of all-extremity MICT, and this change was independent of changes in HR or blood pressure. We are aware of only one aerobic exercise intervention focusing on aortic PWV in older adults, but this study resulted in no improvements in PWV after 1 yr of moderate-intensity cycling (21). Our conflicting findings could be due to differences in the exercise modalities (lower extremity exercise in the previous study vs all-extremity exercise in current study) and in the younger age of our subjects (average age 70 vs 64 yr in our study). In agreement with our data, aortic PWV improved after moderate-intensity walking/jogging in middle-age men (7) and moderate-intensity cycling in middle-age women (39).
In our study, carotid artery compliance improved by about 30% after all-extremity MICT in sedentary older adults. Our results are in accordance with previous reports on the effect of moderate-intensity brisk walking on arterial compliance in sedentary middle-age men (7) and older men and women (19,27,29,31). It is not surprising that carotid artery diameter, IMT, and IMT normalized to lumen diameter were not affected by our intervention. Our data are consistent with other short-term studies in middle-age and older men and postmenopausal women, which did not result in significant structural changes in carotid artery (19,29,31). Substantially longer interventions may be required to result in carotid artery IMT modification.
In previous studies, arterial stiffness improved after 12 to 16 wk of moderate-intensity lower body exercise in middle-aged and older adults (7,19,31,39), whereas, in our study, improvements in arterial stiffness occurred over a relatively shorter training duration (8 wk). This could be due to the larger amount of active skeletal muscle mass involved in all-extremity exercise, but this remains to be determined by directly comparing all-extremity versus lower-extremity exercise in the same cohort.
Central aortic pressures are increasingly recognized as being more important contributors to the pathogenesis of CVD than peripheral pressures (34). In our intervention, aortic and brachial blood pressure did not significantly change, which is in agreement with previous short-term aerobic exercise interventions in middle-age and older adults (1,7,22,31). Our data suggest that improvements in aortic PWV can occur independent of blood pressure lowering effects of exercise. MICT resulted in improvements in time to exhaustion but not aerobic fitness in our study, which is consistent with previous reports in middle-age and older adults (22,31). On the basis of this finding, it appears that improvements in aerobic fitness are not a prerequisite for improvements in arterial stiffness (aortic PWV and carotid artery compliance). Our results are also not confounded by weight loss or changes in total and abdominal adiposity or blood lipids. Collectively, our data suggest that the exercise-induced improvements in arterial stiffness are likely due to direct vascular effects as opposed to being secondary adaptations to improvements in traditional CVD risk factors.
As expected, aerobic fitness improved more in response to HIIT than MICT in our study, which is consistent with previous reports (8,9,18,24,26,32,38). Improvements in aerobic fitness are associated with reductions in CVD risk (12,15), but cfPWV and carotid artery compliance did not improve with HIIT in our study. To the best of our knowledge, there are no published data on the effect of HIIT on arterial stiffness in older adults. However, in young and middle-age patients with hypertension and young women at high familial risk for hypertension, HIIT but not MICT resulted in significantly improved cfPWV (4,6). Our discrepant results may be due to differences in our exercise interventions. The exercise intensity, duration, and frequency; the intervention length; and the exercise ergometer (lower extremity weight-bearing exercise on treadmill versus all-extremity non–weight-bearing exercise on cycle ergometer) were different in our studies. Differences in the subjects' age and health status may also have contributed to our conflicting results.
Mechanisms of exercise-induced improvements in arterial stiffness
Advancing age is associated with arterial stiffening because of alterations in vascular structure and vascular smooth muscle function, which affects vascular tone (recently reviewed in Santos-Parker et al. ). Age-related structural changes include increases in elastin fragmentation and collagen deposition and cross-linking of these proteins by advanced glycation end products leading to additional stiffening (25). Age-related decreases in nitric oxide bioavailability, increases in vasoconstrictor activity (endothelin), decreases in carotid baroreflex sensitivity, and increases in sympathetic nerve activity lead to increased vascular tone, which contributes to arterial stiffening (25). These functional and structural changes have been linked to age-related oxidative stress and inflammation (13,14,36,37).
The mechanisms by which all-extremity MICT improves cfPWV and carotid artery compliance are not clear. Currently, there is inadequate information regarding the mechanisms responsible for the effects of aerobic exercise on arterial stiffness in humans. This is largely due to the limited experimental tools that can be used to provide mechanistic insight (25) and the inability to obtain arterial wall samples from large elastic arteries (e.g., aorta and carotid artery) in healthy humans at pre- and postintervention. Moreover, there is lack of consistent strong associations between measures of arterial stiffness and circulating blood factors, including markers of oxidative stress and inflammation.
Given the relatively short duration of our intervention, we speculate that improvements in arterial stiffness in our study are not likely to be due to changes in arterial wall composition of elastin and collagen because adaptations are thought to require a long period of time. It is reasonable to hypothesize that the mechanisms by which MICT improved arterial stiffness in our study may possibly include any of the following adaptations: decreases in oxidative stress and inflammation, increases in nitric oxide bioavailability, decreases in vasoconstrictor activity, increases in cardiovagal baroreflex sensitivity, or decreases in sympathetic nervous system activity. Any of these potential changes could lead to vascular smooth muscle relaxation and reductions in vascular tone and stiffness, but the exact mechanisms remain to be elucidated.
It is not clear why arterial stiffness improved in response to all-extremity MICT but not HIIT. We have demonstrated that caloric expenditure and exercise compliance did not differ between the two forms of exercise; however, other differences may have possibly led to the disparate effects on arterial stiffness. First, the pattern or magnitude of increase in arterial wall shear stress may have been different during HIIT and MICT, resulting in divergent local and systemic adaptations: HIIT consisted of intermitted high-intensity exercise interspersed with periods of active recovery, whereas MICT consisted of continuous moderate-intensity exercise. Second, the duration of MICT per session was longer to match the higher caloric expenditure of HIIT, which likely influenced the duration of augmented arterial shear stress. Third, each bout of HIIT may have resulted in greater acute increases in blood pressure or sympathetic nervous system activity compared with MICT, which may have counteracted any potential improvements in arterial stiffness. In support of this concept, intensive resistance exercise, which is known to intermittently increase blood pressure, has previously been shown to have unfavorable effects on arterial compliance (17).
Study strengths and limitations
Our study has several strengths: 1) novelty of our exercise intervention and findings, 2) randomized controlled design, 3) HR monitoring/recording during supervised exercise, 4) use of standardized testing procedures and blinding, 5) rigorous screening and exclusion of subjects with major clinical disease or subjects who were not previously sedentary or weight stable, and 6) changes in cfPWV and carotid artery compliance were not confounded by changes in HR, blood pressure, or other CVD risk factors. Our study also has some potential limitations. We can only speculate on the mechanisms responsible for the exercise-induced improvements in cfPWV and carotid artery compliance. Additional studies are needed to directly investigate the underlying mechanisms. It is also important to reproduce our results in larger cohorts which allow adequately powered sex-specific analysis. However, according to a recent meta-analysis, there is no indication of sex differences in the effect of exercise on arterial stiffness (2).
This is the first study to demonstrate that 8 wk of all-extremity non–weight-bearing MICT improved arterial stiffness in previously sedentary older adults free of major clinical disease. However, all-extremity non–weight-bearing HIIT did not result in changes in arterial stiffness. Our findings are not confounded by changes in other CVD risk factors such as reductions in aortic and brachial blood pressure, body mass index, and abdominal adiposity or improvements in aerobic fitness and blood lipids. Our results have important implications for optimizing exercise recommendations for CVD prevention in aging, especially for older individuals who might be unable to engage in weight-bearing exercise.
This work was supported by the National Institutes of Health (NIA AG 050203 to D. D. C.).
The authors thank Karen Mackay, Andre Revell, Austin Nolz, Kevin Priddy, Blake Dalley, Lily Malone, Jessica Howard, Estefania Vasconez, and Lindsay Wainman for assistance with conducting this intervention. The authors also express their gratitude to the study participants for their time and efforts.
The authors declare no conflict of interest.
The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation.
The results of the present investigation do not constitute endorsement by the American College of Sports Medicine.
1. Akazawa N, Ra SG, Sugawara J, Maeda S. Influence of aerobic exercise training on post-exercise responses of aortic pulse pressure and augmentation pressure in postmenopausal women. Front Physiol
2. Ashor AW, Lara J, Siervo M, Celis-Morales C, Mathers JC. Effects of exercise modalities on arterial stiffness and wave reflection: a systematic review and meta-analysis of randomized controlled trials. PLoS One
3. Christou DD, Gentile CL, DeSouza CA, Seals DR, Gates PE. Fatness is a better predictor of cardiovascular disease risk factor profile than aerobic fitness in healthy men. Circulation
4. Ciolac EG, Bocchi EA, Bortolotto LA, Carvalho VO, Greve JM, Guimarães GV. Effects of high-intensity aerobic interval training vs. moderate exercise on hemodynamic, metabolic and neuro-humoral abnormalities of young normotensive women at high familial risk for hypertension. Hypertens Res
5. Fleg JL, Strait J. Age-associated changes in cardiovascular structure and function: a fertile milieu for future disease. Heart Fail Rev
6. Guimaraes GV, Ciolac EG, Carvalho VO, D'Avila VM, Bortolotto LA, Bocchi EA. Effects of continuous vs. interval exercise training on blood pressure and arterial stiffness in treated hypertension. Hypertens Res
7. Hayashi K, Sugawara J, Komine H, Maeda S, Yokoi T. Effects of aerobic exercise training on the stiffness of central and peripheral arteries in middle-aged sedentary men. Jpn J Physiol
8. Helgerud J, Hoydal K, Wang E, et al. Aerobic high-intensity intervals improve V˙O2max
more than moderate training. Med Sci Sports Exerc
9. Hwang CL, Yoo JK, Kim HK, et al. Novel all-extremity high-intensity interval training improves aerobic fitness, cardiac function and insulin resistance in healthy older adults. Exp Gerontol
10. Hwang MH, Yoo JK, Kim HK, et al. Validity and reliability of aortic pulse wave velocity and augmentation index determined by the new cuff-based SphygmoCor Xcel. J Hum Hypertens
11. Hwang MH, Yoo JK, Luttrell M, et al. Mineralocorticoid receptors modulate vascular endothelial function in human obesity. Clin Sci (Lond)
12. Katzmarzyk PT, Gagnon J, Leon AS, et al. Fitness, fatness, and estimated coronary heart disease risk: the HERITAGE Family Study. Med Sci Sports Exerc
13. Lakatta EG, Levy D. Arterial and cardiac aging
: major shareholders in cardiovascular disease enterprises: Part I. Aging
arteries: a “set up” for vascular disease. Circulation
14. Lakatta EG, Levy D. Arterial and cardiac aging
: major shareholders in cardiovascular disease enterprises: Part II. The aging
heart in health: links to heart disease. Circulation
15. Lee DC, Sui X, Artero EG, et al. Long-term effects of changes in cardiorespiratory fitness and body mass index on all-cause and cardiovascular disease mortality in men: the Aerobics Center Longitudinal Study. Circulation
16. Meaume S, Benetos A, Henry OF, Rudnichi A, Safar ME. Aortic pulse wave velocity predicts cardiovascular mortality in subjects >70 years of age. Arterioscler Thromb Vasc Biol
17. Miyachi M, Kawano H, Sugawara J, et al. Unfavorable effects of resistance training on central arterial compliance: a randomized intervention study. Circulation
18. Molmen-Hansen HE, Stolen T, Tjonna AE, et al. Aerobic interval training reduces blood pressure and improves myocardial function in hypertensive patients. Eur J Prev Cardiol
19. Moreau KL, Donato AJ, Seals DR, DeSouza CA, Tanaka H. Regular exercise, hormone replacement therapy and the age-related decline in carotid arterial compliance in healthy women. Cardiovasc Res
20. O'Rourke MF, Staessen JA, Vlachopoulos C, Duprez D, Plante GE. Clinical applications of arterial stiffness; definitions and reference values. Am J Hypertens
21. Oudegeest-Sander MH, Olde Rikkert MG, Smits P, et al. The effect of an advanced glycation end-product crosslink breaker and exercise training on vascular function in older individuals: a randomized factorial design trial. Exp Gerontol
22. Pierce GL, Eskurza I, Walker AE, Fay TN, Seals DR. Sex-specific effects of habitual aerobic exercise on brachial artery flow-mediated dilation in middle-aged and older adults. Clin Sci (Lond)
23. Prince MJ, Wu F, Guo Y, et al. The burden of disease in older people and implications for health policy and practice. Lancet
24. Rognmo O, Hetland E, Helgerud J, Hoff J, Slordahl SA. High intensity aerobic interval exercise is superior to moderate intensity exercise for increasing aerobic capacity in patients with coronary artery disease. Eur J Cardiovasc Prev Rehabil
25. Santos-Parker JR, LaRocca TJ, Seals DR. Aerobic exercise and other healthy lifestyle factors that influence vascular aging
. Adv Physiol Educ
26. Schjerve IE, Tyldum GA, Tjønna AE, et al. Both aerobic endurance and strength training programmes improve cardiovascular health in obese adults. Clin Sci (Lond)
27. Seals DR. Edward F. Adolph Distinguished Lecture: the remarkable anti-aging
effects of aerobic exercise on systemic arteries. J Appl Physiol (1985)
28. Stein JH, Korcarz CE, Hurst RT, et al. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine. J Am Soc Echocardiogr
29. Sugawara J, Inoue H, Hayashi K, Yokoi T, Kono I. Effect of low-intensity aerobic exercise training on arterial compliance in postmenopausal women. Hypertens Res
30. Sui X, LaMonte MJ, Laditka JN, et al. Cardiorespiratory fitness and adiposity as mortality predictors in older adults. JAMA
31. Tanaka H, Dinenno FA, Monahan KD, Clevenger CM, DeSouza CA, Seals DR. Aging
, habitual exercise, and dynamic arterial compliance. Circulation
32. Tjonna AE, Lee SJ, Rognmo O, et al. Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome: a pilot study. Circulation
33. Townsend RR, Wilkinson IB, Schiffrin EL, et al. Recommendations for Improving and standardizing vascular research on arterial stiffness: a scientific statement from the American Heart Association. Hypertension
34. Vlachopoulos C, Aznaouridis K, O'Rourke MF, Safar ME, Baou K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. Eur Heart J
35. Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol
36. Vlachopoulos C, Dima I, Aznaouridis K, et al. Acute systemic inflammation increases arterial stiffness and decreases wave reflections in healthy individuals. Circulation
37. Wang M, Zhang J, Jiang LQ, et al. Proinflammatory profile within the grossly normal aged human aortic wall. Hypertension
38. Wisloff U, Stoylen A, Loennechen JP, et al. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients—a randomized study. Circulation
39. Yoshizawa M, Maeda S, Miyaki A, et al. Effect of 12 weeks moderate-intensity resistance training on arterial stiffness: a randomised controlled trial in women aged 32–59 years. Br J Sports Med
. 2009;43(8): 615–8.