Central arterial compliance is associated with age- and habitual exercise-related differences in cardiovagal baroreflex sensitivity.

Background- Cardiovagal baroreflex sensitivity (BRS) declines with age but is favorably modulated by habitual aerobic exercise. We tested the hypothesis that compliance (transducing capacity) of an elastic artery in which baroreceptors are located is associated with these age-exercise interactions. Methods and Results- Nine young (28+/-1 years old) and 9 older (65+/-1) sedentary and 10 young (27+/-1) and 9 older (63+/-2) endurance-trained healthy men were studied. Cardiovagal BRS was assessed conventionally (R-R interval-systolic blood pressure [SBP] relation) by the Oxford technique. Because of age-associated increases in central arterial stiffness, cardiovagal BRS was expressed with both peripheral (Finapres) and central (applanation tonometry) SBP values. The change in carotid artery end-systolic lumen diameter (ultrasonography) per unit increase in SBP and the slope of the R-R interval-carotid artery diameter relation also were determined. Cardiovagal BRS declined with age in both sedentary ( approximately 65%) and endurance-trained ( approximately 40%) men but was higher in endurance-trained than sedentary older men regardless of the SBP values used (all P<0.05). Changes in carotid artery lumen diameter per unit increase in SBP mirrored these differences in cardiovagal BRS (all P<0.05). Thus, R-R interval prolongation per unit increase in carotid artery diameter was not different among the groups (P>0.70). Conclusions- These results demonstrate that age- and habitual exercise-related differences in cardiovagal BRS are associated with corresponding differences in carotid artery compliance among healthy men.

Aging, habitual exercise, and dynamic arterial compliance.

BACKGROUND: A reduction in compliance of the large-sized cardiothoracic (central) arteries is an independent risk factor for the development of cardiovascular disease with advancing age. METHODS AND RESULTS: We determined the role of habitual exercise on the age-related decrease in central arterial compliance by using both cross-sectional and interventional approaches. First, we studied 151 healthy men aged 18 to 77 years: 54 were sedentary, 45 were recreationally active, and 53 were endurance exercise-trained. Central arterial compliance (simultaneous B-mode ultrasound and arterial applanation tonometry on the common carotid artery) was lower (P:<0.05) in middle-aged and older men than in young men in all 3 groups. There were no significant differences between sedentary and recreationally active men at any age. However, arterial compliance in the endurance-trained middle-aged and older men was 20% to 35% higher than in the 2 less active groups (P:<0.01). As such, age-related differences in central arterial compliance were smaller in the endurance-trained men than in the sedentary and recreationally active men. Second, we studied 20 middle-aged and older (53+/-2 years) sedentary healthy men before and after a 3-month aerobic exercise intervention (primarily walking). Regular exercise increased central arterial compliance (P:<0.01) to levels similar to those of the middle-aged and older endurance-trained men. These effects were independent of changes in body mass, adiposity, arterial blood pressure, or maximal oxygen consumption. CONCLUSIONS: Regular aerobic-endurance exercise attenuates age-related reductions in central arterial compliance and restores levels in previously sedentary healthy middle-aged and older men. This may be one mechanism by which habitual exercise lowers the risk of cardiovascular disease in this population.

Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men.

BACKGROUND: In sedentary humans endothelium-dependent vasodilation is impaired with advancing age contributing to their increased cardiovascular risk, whereas endurance-trained adults demonstrate lower age-related risk. We determined the influence of regular aerobic exercise on the age-related decline in endothelium-dependent vasodilation. METHODS AND RESULTS: In a cross-sectional study, 68 healthy men 22 to 35 or 50 to 76 years of age who were either sedentary or endurance exercise-trained were studied. Forearm blood flow (FBF) responses to intra-arterial infusions of acetylcholine and sodium nitroprusside were measured by strain-gauge plethysmography. Among the sedentary men, the maximum FBF response to acetylcholine was 25% lower in the middle aged and older compared with the young group (P:<0.01). In contrast, there was no age-related difference in the vasodilatory response to acetylcholine among the endurance-trained men. FBF at the highest acetylcholine dose was almost identical in the middle aged and older (17.3+/-1.3 mL/100 mL tissue per minute) and young (17.7+/-1.4 mL/100 mL tissue per minute) endurance-trained groups. There were no differences in the FBF responses to sodium nitroprusside among the sedentary and endurance- trained groups. In an exercise intervention study, 13 previously sedentary middle aged and older healthy men completed a 3-month, home-based aerobic exercise intervention (primarily walking). After the exercise intervention, acetylcholine-mediated vasodilation increased approximately 30% (P:<0.01) to levels similar to those in young adults and middle aged and older endurance-trained men. CONCLUSIONS: Our results indicate that regular aerobic exercise can prevent the age-associated loss in endothelium-dependent vasodilation and restore levels in previously sedentary middle aged and older healthy men. This may represent an important mechanism by which regular aerobic exercise lowers the risk of cardiovascular disease in this population.

Age-predicted maximal heart rate revisited.

OBJECTIVES: We sought to determine a generalized equation for predicting maximal heart rate (HRmax) in healthy adults. BACKGROUND: The age-predicted HRmax equation (i.e., 220 - age) is commonly used as a basis for prescribing exercise programs, as a criterion for achieving maximal exertion and as a clinical guide during diagnostic exercise testing. Despite its importance and widespread use, the validity of the HRmax equation has never been established in a sample that included a sufficient number of older adults. METHODS: First, a meta-analytic approach was used to collect group mean HRmax values from 351 studies involving 492 groups and 18,712 subjects. Subsequently, the new equation was cross-validated in a well-controlled, laboratory-based study in which HRmax was measured in 514 healthy subjects. RESULTS: In the meta-analysis, HRmax was strongly related to age (r = -0.90), using the equation of 208 - 0.7 x age. The regression equation obtained in the laboratory-based study (209 - 0.7 x age) was virtually identical to that obtained from the meta-analysis. The regression line was not different between men and women, nor was it influenced by wide variations in habitual physical activity levels. CONCLUSIONS: 1) A regression equation to predict HRmax is 208 - 0.7 x age in healthy adults. 2) HRmax is predicted, to a large extent, by age alone and is independent of gender and habitual physical activity status. Our findings suggest that the currently used equation underestimates HRmax in older adults. This would have the effect of underestimating the true level of physical stress imposed during exercise testing and the appropriate intensity of prescribed exercise programs.

Blood pressure reductions with exercise and sodium restriction in postmenopausal women with elevated systolic pressure: role of arterial stiffness.

OBJECTIVES: This study determined the relative efficacy of aerobic exercise (daily walking) and moderate dietary sodium restriction (sodium intake <100 mmol/day) for reducing systolic blood pressure (SBP) and pulse pressure (PP) in postmenopausal women with elevated initial levels, and the potential role of reductions in large artery stiffness in these changes. BACKGROUND: Lifestyle behaviors are recommended for lowering blood pressure (BP) in adults with elevated baseline levels, but there is little information as to the relative efficacy of different interventions or the mechanisms underlying their potential beneficial effects. METHODS: After baseline measurements and random assignment, 35 nonmedicated healthy postmenopausal women with SBP between 130 and 159 mm Hg completed three months of either aerobic (walking) exercise (n = 18; 62 +/- 9 years, mean +/- SD) or moderate dietary sodium restriction (SR) (n = 17; 65 +/- 10 years, mean +/- SD). RESULTS: Body mass and composition, plasma volume, and fasting concentrations of metabolic coronary risk factors did not differ between the groups at baseline or change with intervention. Systolic BP and PP at rest decreased with both exercise and SR (p < 0.05); however, the reductions were three- to fourfold greater with SR (p < 0.05). Sodium restriction, but not exercise, also reduced 24-h SBP and PP (p < 0.05). Aortic pulse wave velocity (PWV) and carotid augmentation index were reduced only with SR (p < 0.05). Changes in SBP and PP at rest and over 24 h correlated with the corresponding changes in aortic PWV (r = 0.53 to 0.61, p < 0.01). CONCLUSIONS: Moderate SR lowers SBP and PP in postmenopausal women with elevated baseline levels more than does daily walking. The greater blood pressure reductions with SR may be mediated in part by a decrease in the stiffness of the large elastic arteries.

Carotid artery wall hypertrophy with age is related to local systolic blood pressure in healthy men.

Carotid artery intima-media thickness (IMT) increases with advancing age in humans. The underlying mechanism of this increase is unknown, but data from animal studies suggest that a chronic increase in local distending pressure can act as a stimulus. To test this hypothesis, we studied a total of 129 healthy normotensive, nonobese, nonsmoking men aged 18 to 77 years. Brachial systolic blood pressure (SBP) was unchanged, but carotid SBP increased progressively with age (P<0.05). Carotid IMT and the ratio of carotid IMT to lumen (ultrasonography) increased progressively with age (P<0.05). Carotid IMT was approximately 50% greater in the older compared with the young men. Carotid SBP was positively related to carotid IMT (r=0.55, P<0.001). After carotid SBP was taken into account (ANCOVA), the age-related difference in carotid IMT was no longer statistically significant (P=0.22). We conclude that carotid IMT increases with age in healthy men in the absence of elevations in peripheral SBP. Carotid SBP increases progressively with advancing age in this population and is significantly related to the corresponding carotid wall hypertrophy. These results support the hypothesis that chronic increases in local distending pressure may be an important mechanism in the wall thickening that occurs with human aging in central elastic arteries.

Age- and limb-related differences in the vasoconstrictor response to limb dependency are not mediated by a sympathetic mechanism in humans.

AIMS: We tested the hypotheses that vasoconstrictor responses to limb dependency are: (i) greater in the leg than the arm, (ii) impaired with age and (iii) not sympathetically mediated. METHODS: Vascular responses to limb dependency (i.e. lowering the limb from heart level to 30 cm below heart level) were determined in 17 young and 17 older adults. Indices of blood flow were obtained in the brachial and popliteal arteries (Doppler ultrasound) as well as in the cutaneous circulation (forearm and calf using laser-Doppler flowmetry). Vasoconstriction was quantified by calculating the indices of vascular resistance as height corrected mean arterial pressure/limb blood velocity or skin flux. A second group of subjects repeated the limb dependency trials after acute systemic sympathetic blockade. RESULTS: Limb dependency increased vascular resistance index in the brachial artery (∆59 ± 8%; P<0.05) and popliteal artery (∆99 ± 10%; P<0.05 for change in heart level and brachial vs. popliteal) of young and older adults (∆60 + 9% brachial and ∆61 ± 7% popliteal arteries; P<0.05 for change in heart level and response in popliteal young vs. older adults). In contrast, cutaneous vasoconstrictor responses to limb dependency were similar in the forearm (∆218 ± 29% and ∆200 ± 29% for young and older adults, respectively) and calf (∆257 ± 32% and ∆236 ± 29%; all P<0.05 from heart level) of young and older adults. Vasoconstrictor responses to limb dependency were not affected by sympathetic blockade in young or older adults. CONCLUSION: These findings indicate that age-, limb-, and tissue-related differences may exist in the vasoconstrictor response to limb dependency in healthy humans, which are not sympathetically mediated.

The aging cardiovascular system: changes in autonomic function at rest and in response to exercise.

Tonic vagal modulation of cardiac period (R-R interval) decreases with advancing age, but is greater in middle-aged and older adults who habitually perform aerobic exercise compared with their sedentary peers. Cardiovagal baroreflex sensitivity also declines markedly with age in sedentary adults but only 50% as much in regularly exercising adults. In previously sedentary middle-aged and older adults, a 3-month program of moderate aerobic exercise increases cardiovagal baroreflex sensitivity by 25%. Tonic (basal) sympathetic nervous system (SNS) activity increases with advancing age in both sedentary and habitually exercising adults. Despite this, SNS beta-adrenergic support of energy metabolism (resting metabolic rate--RMR) declines with age in sedentary individuals. However, SNS beta-adrenergic support of RMR is maintained with age in endurance exercise-trained adults and therefore is much greater in middle-aged and older individuals who exercise regularly compared with their sedentary peers. Thus, regular aerobic (endurance) exercise modulates selective age-associated impairments in autonomic nervous system-physiological function.

Smaller age-associated reductions in leg venous compliance in endurance exercise-trained men.

We determined the independent and interactive influences of aging and habitual endurance exercise on calf venous compliance in humans. We tested the hypotheses that calf venous compliance is 1) reduced with age in sedentary and endurance-trained men, and 2) elevated in young and older endurance-trained compared with age-matched sedentary men. We studied 8 young (28 +/- 1 yr) and 8 older (65 +/- 1) sedentary, and 8 young (27 +/- 1) and 8 older (63 +/- 2) endurance-trained men. Calf venous compliance was measured in supine subjects by inflating a venous collecting cuff, placed above the knee, to 60 mmHg for 8 min and then decreasing cuff pressure at 1 mmHg/s to 0 mmHg. Calf venous compliance was determined using the first derivative of the pressure-volume relation during cuff pressure reduction (compliance = beta(1) + 2. beta(2). cuff pressure). Calf venous compliance was reduced with age in sedentary (approximately 40%) and endurance-trained men (approximately 20%) (both P < 0.01). Furthermore, calf venous compliance was approximately 70-120% greater in endurance-trained compared with age-matched sedentary men and approximately 30% greater in older endurance-trained compared with young sedentary men (both P < 0.01). These data indicate that calf venous compliance is reduced with age in sedentary and endurance-trained men, but compliance is better preserved in endurance-trained men.

Age-associated changes in cardiovagal baroreflex sensitivity are related to central arterial compliance.

Cardiovagal baroreflex sensitivity (BRS) declines with advancing age in humans, but the underlying mechanism has not been established. Using two different approaches, we determined the relation between age-associated decline in cardiovagal BRS and the compliance of an artery in which arterial baroreceptors are located. First, we measured carotid artery compliance (via the simultaneous application of ultrasonography and arterial applanation tonometry) and cardiovagal BRS (phase IV of the Valsalva maneuver) in 47 healthy sedentary men that varied widely in age (19--76 yr). Cardiovagal BRS declined progressively with age (r = -0.69; P < or = 0.001) and was positively related to carotid artery compliance (r = 0.71; P < or = 0.001). Stepwise multiple-regression analysis revealed that carotid artery compliance was the strongest independent physiological correlate of cardiovagal BRS and that it explained 51% of the total variance. Second, we studied 13 middle-aged and older previously sedentary men (age 56 +/- 2 yr) before and after 13 wk of aerobic exercise intervention. Regular exercise increased both cardiovagal BRS and carotid artery compliance (P < 0.05) and the two events were strongly and positively related (r = 0.72; P < 0.01). We conclude that reduced carotid artery compliance may play an important mechanistic role in age-associated decrease in cardiovagal BRS in healthy sedentary humans.

Regular aerobic exercise modulates age-associated declines in cardiovagal baroreflex sensitivity in healthy men.

1. Cardiovagal baroreflex sensitivity (BRS), the arterial baroreflex-mediated change in the R-R interval per unit change in systolic blood pressure, decreases with advancing age in sedentary adult humans. We determined the effects of regular aerobic exercise on the age-related decline in cardiovagal BRS. 2. In the cross-sectional study, 133 healthy men 18-79 years of age who were either sedentary, performing moderate aerobic exercise, or endurance exercise trained were studied. Among the sedentary men, cardiovagal BRS (phase IV of Valsalva's manoeuvre) was progressively lower (P < 0.05) in the middle-aged ( approximately 33 %) and older ( approximately 60 %) groups compared with the young group. In contrast, cardiovagal BRS was similar in the young and middle-aged men in the moderate exercise and endurance-trained groups. Cardiovagal BRS was lower (P < 0.05) in the older exercising men, but the magnitude of decline across age ( approximately 30 %) was only half as great as that in sedentary men. Cardiovagal BRS was 40-75 % greater (P < 0.05) in middle-aged and older men who exercised regularly compared with their sedentary peers. 3. In the intervention study, a 3 month aerobic exercise intervention (primarily walking) increased cardiovagal BRS by an average of 25 % (P < 0.05) in 13 previously sedentary middle-aged and older (56 +/- 1 years) healthy men. 4. Our results demonstrate for the first time that regular aerobic exercise: (1) attenuates the age-associated decline in cardiovagal BRS; and (2) partially restores the loss of cardiovagal BRS in previously sedentary middle-aged and older healthy men.

Regular endurance exercise induces expansive arterial remodelling in the trained limbs of healthy men.

1. In experimental animals chronic elevations in arterial blood flow increase the lumen diameter and reduce the intima-media thickness (IMT) of the arterial segment involved. We determined whether intermittent elevations in active muscle blood flow associated with regular aerobic leg exercise induced such expansive arterial remodelling in the common femoral artery of humans. 2. In the cross-sectional study 53 sedentary (47 +/- 2 years) and 55 endurance exercise-trained (47 +/- 2 years) men were studied. Common femoral artery lumen diameter (B-mode ultrasound) was 7 % greater (9.62 +/- 0.12 vs. 9.03 +/- 0.13 mm), and femoral IMT (0.46 +/- 0.02 vs. 0.55 +/- 0.02 mm) and IMT/lumen ratio were 16-21 % smaller in the endurance-trained men (all P < 0.001). Basal femoral artery blood flow (duplex ultrasound) was not different, shear stress tended to be lower (P = 0.08), and mean femoral tangential wall stress was 30 % higher in the endurance-trained men (P < 0.001). 3. In the intervention study 22 men (51 +/- 2 years) were studied before and after 3 months of regular aerobic leg exercise (primarily walking). After training, the femoral diameter increased by 9 % (8.82 +/- 0.18 vs. 9.60 +/- 0.20 mm), and IMT (0.65 +/- 0.05 vs. 0.56 +/- 0.05 mm) and the IMT/lumen ratio were approximately 15-20 % smaller (all P < 0.001). Basal femoral blood flow and shear stress were not different after training, whereas the mean femoral tangential wall stress increased by 31 %. The changes in arterial structure were not related to changes in risk factors for atherosclerosis. 4. Our results are consistent with the concept that regular aerobic leg exercise induces expansive arterial remodelling in the femoral artery of healthy men. This adaptive process is produced by even a moderate training stimulus, is not obviously dependent on corresponding improvements in risk factors for atherosclerosis, and is robust, occurring in healthy men of different ages.