Estimated aortic stiffness is independently associated with cardiac baroreflex sensitivity in humans: role of ageing and habitual endurance exercise.

We hypothesised that differences in cardiac baroreflex sensitivity (BRS) would be independently associated with aortic stiffness and augmentation index (AI), clinical biomarkers of cardiovascular disease risk, among young sedentary and middle-aged/older sedentary and endurance-trained adults. A total of 36 healthy middle-aged/older (age 55-76 years, n=22 sedentary and n=14 endurance-trained) and 5 young sedentary (age 18-31 years) adults were included in a cross-sectional study. A subset of the middle-aged/older sedentary adults (n=12) completed an 8-week-aerobic exercise intervention. Invasive brachial artery blood pressure waveforms were used to compute spontaneous cardiac BRS (via sequence technique), estimated aortic pulse wave velocity (PWV) and AI (AI, via brachial-aortic transfer function and wave separation analysis). In the cross-sectional study, cardiac BRS was 71% lower in older compared with young sedentary adults (P<0.05), but only 40% lower in older adults who performed habitual endurance exercise (P=0.03). In a regression model that included age, sex, resting heart rate, mean arterial pressure (MAP), body mass index and maximal exercise oxygen uptake, estimated aortic PWV (ß±s.e.=-5.76±2.01, P=0.01) was the strongest predictor of BRS (model R(2)=0.59, P<0.001). The 8-week-exercise intervention improved BRS by 38% (P=0.04) and this change in BRS was associated with improved aortic PWV (r=-0.65, P=0.044, adjusted for changes in MAP). Age- and endurance-exercise-related differences in cardiac BRS are independently associated with corresponding alterations in aortic PWV among healthy adults, consistent with a mechanistic link between variations in the sensitivity of the baroreflex and aortic stiffness with age and exercise.

The SRC substrate Tks5, podosomes (invadopodia), and cancer cell invasion.

Some years ago, we employed a screen of phage cDNA expression libraries to identify novel substrates of the protein tyrosine kinase Src. One of these, Tks5 (previously known as Fish), is a large scaffolding protein with an amino-terminal PX domain and five SH3 domains. In normal fibroblasts, Tks5 is cytoplasmic, but the protein is found in podosomes when the cells are transformed with Src. Using short interfering RNA technology, we have shown that Tks5 is required for podosome formation. Furthermore, cells with reduced Tks5 expression are poorly invasive through Matrigel. Tks5 is expressed and localized to podosomes in invasive human cancer cell lines and in tumor tissue, particularly breast cancers and melanomas. In these cells too, Tks5 is required for invasion. Our future work will focus on the identification of the binding partners of Tks5 that are responsible for podosome formation and invasion, and on determining the role of Tks5 in animal models of metastasis.

Influence of adiposity on tonic sympathetic support of resting metabolism in healthy adults.

BACKGROUND: beta-Adrenergic receptor sympathetic nervous system (beta-AR SNS) support of resting metabolic rate (RMR) is attenuated with older age, female sex, and a sedentary lifestyle. Total and abdominal adiposity and/or body fat pattern modulate some SNS-mediated physiological functions. OBJECTIVE: To determine if total and abdominal adiposity and/or body fat distribution are independently related to SNS support of RMR. DESIGN: Cross-sectional comparison of beta-AR SNS support of RMR. SUBJECTS: A total of 54 healthy male and female subjects aged 18-75 y. MEASUREMENTS: RMR (ventilated hood, indirect calorimetry) before (baseline) and during complete beta-AR blockade; body composition by dual energy X-ray absorptiometry. RESULTS: Forward stepwise multiple regression analysis using sex, exercise status, age group, %body fat, total adiposity, abdominal adiposity, and the ratio of abdominal adiposity to hip adiposity as variables revealed sex to be the strongest predictor, explaining 21% of the variability in beta-AR SNS support of RMR (P=0.0006). Age group explained an additional 4% and exercise status a further 4% (both P=0.10). %Body fat, total adiposity, abdominal adiposity, and the ratio of abdominal adiposity to hip adiposity did not enter the equation. CONCLUSION: Total and abdominal adiposity and body fat pattern are not independent physiological determinants of beta-AR SNS support of RMR among healthy men and women. Moreover, further support is provided for our previous finding of attenuated beta-AR SNS support of RMR with age, female sex, and sedentary lifestyle.

Reductions in basal limb blood flow and vascular conductance with human ageing: role for augmented alpha-adrenergic vasoconstriction.

1. Basal whole-limb blood flow and vascular conductance decrease with age in men. We determined whether these age-associated changes in limb haemodynamics are mediated by tonically augmented sympathetic alpha-adrenergic vasoconstriction. 2. Seven young (28 +/- 2 years; mean +/- S.E.M.) and eight older (64 +/- 2 years) healthy, normotensive adult men were studied. Baseline femoral artery blood flow (Doppler ultrasound) and calculated vascular conductance were 29 and 31 % lower, respectively, and vascular resistance was 53 % higher in the older men (all P < 0.001). 3. Local (intra-femoral artery) alpha-adrenergic receptor blockade with phentolamine evoked greater increases in femoral blood flow (105 +/- 11 vs. 60 +/- 6 %) and vascular conductance (125 +/- 13 vs. 66 +/- 7 %), and reductions in vascular resistance (55 +/- 2 vs. 39 +/- 3 %) in the experimental limb of the older compared with the young men (all P < 0.001). As a result, alpha-adrenergic receptor blockade eliminated the significance of the age-associated differences in absolute levels of femoral blood flow (500 +/- 51 vs. 551 +/- 35 ml min(-1)), vascular conductance (6.02 +/- 0.73 vs. 6.33 +/- 0.26 U), and vascular resistance (0.17 +/- 0.03 vs. 0.16 +/- 0.01 U; P = 0.4-0.8, n.s.). Femoral haemodynamics in the control limb were unaffected by phentolamine administration in the contralateral (experimental) limb. Complete alpha-adrenergic receptor blockade was demonstrated by the absence of vasoconstriction in the experimental limb in response to the cold pressor test. Local propranolol was administered to control for any beta-adrenergic effects of phentolamine. Propranolol did not affect haemodynamics in the experimental or control limbs. 4. Our results indicate that the age-related reductions in basal limb blood flow and vascular conductance are mediated largely by chronically elevated sympathetic alpha-adrenergic vasoconstriction. This may have important physiological and pathophysiological implications for the ageing human.

Altered autonomic support of arterial blood pressure with age in healthy men.

BACKGROUND: Primary aging is associated with changes in the autonomic nervous system (ANS), but the functional significance of these changes for systemic circulatory control of arterial blood pressure (BP) is unknown. We tested the hypothesis that ANS support of BP is altered in healthy older humans. METHODS AND RESULTS: A total of 23 young (aged 24+/-1 years; systolic/diastolic BP, 126+/-2/66+/-1 mm Hg) and 16 older (aged 65+/-1 years; systolic/diastolic BP, 125+/-3/62+/-2 mm Hg) healthy men were studied before and during ganglionic blockade (intravenous trimethaphan). The reduction in mean BP (radial artery catheter) with trimethaphan was almost twice as great in the older men (-33+/-2 versus -19+/-2 mm Hg; -40% versus -22% of baseline; P<0.01) due to a lack of increase in heart rate (3+/-2 versus 25+/-2 bpm; P<0.001) and cardiac output (-0.42+/-0.19 versus 1.01+/-0.26 L/min; P<0.001); the decreases in systemic vascular resistance were not different. The absence of tachycardia in the older men was associated with reduced baseline heart rate variability (HRV, P<0.05); the change in heart rate with trimethaphan correlated with the standard deviation of the R-R intervals (HRV(SD R-R interval); r=0.57, P<0.001). Among individual subjects (pooled groups), the reductions in mean BP with trimethaphan were most strongly related to measures of sympathetic activity (r=0.58 to 0.67, P<0.005), change in mean BP with intravenous phenylephrine (r=0.57, P<0.001), and HRV(SD R-R interval) (r=-0.40, P<0.01). CONCLUSIONS: ANS support of BP is altered with age in healthy men due to less cardiac vagal inhibition of heart rate and cardiac output. Basal sympathetic activity and alpha-adrenergic vascular sensitivity are also key physiological correlates of ANS support of BP in healthy men.

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.

Tonic sympathetic support of metabolic rate is attenuated with age, sedentary lifestyle, and female sex in healthy adults.

We recently demonstrated in young adult humans that the sympathetic nervous system contributes to the control of resting metabolic rate via tonic beta-adrenergic receptor stimulation. In the present follow-up study we determined the respective effects of age, habitual exercise status, and sex on this regulatory mechanism. Resting metabolic rate (ventilated hood, indirect calorimetry) was determined in 55 healthy sedentary or endurance exercise-trained adults, aged 18-35 or 60-75 yr (29 men and 26 women), before (baseline) and during the infusion of either a nonselective beta-adrenergic receptor antagonist (propranolol) or saline (control). Relative to baseline values, during beta-adrenergic receptor antagonism resting metabolic rate adjusted for fat-free mass was reduced to a lesser extent in older (mean +/- SE, -130 +/- 46 kJ/d) compared with young (-297 +/- 46) adults, sedentary (-151 +/- 50) compared with endurance exercise-trained (-268 +/- 46) adults, and women (-105 +/- 33) compared with men (-318 +/- 50; all P < 0.01). Reductions in resting metabolic rate during beta-adrenergic receptor antagonism were positively related to higher baseline resting metabolic rate and plasma catecholamine concentrations and negatively related to adiposity (all P < 0.05). Resting metabolic rate was unchanged in response to saline control in all groups. These results provide experimental support for the hypothesis that aging, sedentary living, and female sex are associated with attenuated sympathetic nervous system support of resting metabolic rate in healthy adult humans.

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-related decline in RMR in physically active men: relation to exercise volume and energy intake.

We tested the hypothesis that resting metabolic rate (RMR) declines with age in physically active men (endurance exercise > or =3 times/wk) and that this decline is related to weekly exercise volume (h/wk) and/or daily energy intake. Accordingly, we studied 137 healthy adult men who had been weight stable for > or =6 mo: 32 young [26 +/- 1 (SE) yr] and 34 older (62 +/- 1 yr) sedentary males (internal controls); and 39 young (27 +/- 1 yr) and 32 older (63 +/- 2 yr) physically active males (regular endurance exercise). RMR was measured by indirect calorimetry (ventilated hood system) after an overnight fast and approximately 24 h after exercise. Because RMR is related to fat-free mass (FFM; r = 0.76, P < 0.001, current study), FFM was covaried to adjust RMR (RMR(adj)). RMR(adj) was lower with age in both the sedentary (72.0 +/- 2.0 vs. 64.0 +/- 1.3 kcal/h, P < 0.01) and the physically active (76.6 +/- 1.1 vs. 67.9 +/- 1.2 kcal/h, P < 0.01) males. In the physically active men, RMR(adj) was related to both exercise volume (no. of h/wk, regardless of intensity; r = 0.56, P < 0.001) and estimated energy intake (r = 0.58, P < 0.001). Consistent with these relations, RMR(adj) was not significantly different in subgroups of young and older physically active men matched either for exercise volume (h/wk; n = 11 each) or estimated energy intake (kcal/day; n = 6 each). These results indicate that 1) RMR, per unit FFM, declines with age in highly physically active men; and 2) this decline is related to age-associated reductions in exercise volume and energy intake and does not occur in men who maintain exercise volume and/or energy intake at a level similar to that of young physically active men.

Maximal aerobic capacity across age in healthy Hispanic and Caucasian women.

We tested the hypothesis that the age-related decline in maximal aerobic capacity, as measured by maximal oxygen uptake (VO(2 max)), is greater in Hispanic than in Caucasian women. We studied 146 healthy sedentary women aged 20-75 yr: 53 Hispanic (primarily of Mexican descent) and 93 Caucasian (non-Hispanic white). The groups did not differ in mean age, body mass, percent body fat, estimated physical activity-related energy expenditure, or education-based socioeconomic status (SES). During maximal exercise, respiratory exchange ratio, rating of perceived exertion, and percent predicted maximal heart rate were similar across age and ethnicity, suggesting equivalent maximum voluntary efforts in all subjects. VO(2 max) (ml x kg(-1) x min(-1)) was inversely related to age (P < 0.01) in Caucasian (r =-0.68) and Hispanic (r = -0.61) women. The absolute rate of decline in VO(2 max) with age was the same in the two groups (-0.31 ml x kg(-1) x min(-1) x yr(-1)). The relative rate of decline (% from age 25 yr) also was similar in the Caucasian (-9.0%) and Hispanic (-9.2%) women. When subjects of all ages were pooled, mean levels of VO(2 max) were similar in the two groups (approximately 28 ml x kg(-1) x min(-1)). These results, the first to our knowledge in Hispanics, indicate that mean levels of VO(2 max), as well as the rate of decline in VO(2 max) with age, are similar in healthy sedentary Hispanic and Caucasian women of similar SES. Thus it does not appear that Hispanic ethnicity per se modulates maximal aerobic capacity in this population.

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.

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.

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.

Direct evidence for tonic sympathetic support of resting metabolic rate in healthy adult humans.

The sympathetic nervous system (SNS) plays an important role in the regulation of energy expenditure. However, whether tonic SNS activity contributes to resting metabolic rate (RMR) in healthy adult humans is controversial, with the majority of studies showing no effect. We hypothesized that an intravenous propranolol infusion designed to achieve complete beta-adrenergic blockade would result in a significant acute decrease in RMR in healthy adults. RMR (ventilated hood, indirect calorimetry) was measured in 29 healthy adults (15 males, 14 females) before and during complete beta-adrenergic blockade documented by plasma propranolol concentrations > or =100 ng/ml, lack of heart rate response to isoproterenol, and a plateau in RMR with increased doses of propranolol. Propranolol infusion evoked an acute decrease in RMR (-71 +/- 11 kcal/day; -5 +/- 0.7%, P < 0.0001), whereas RMR was unchanged from baseline levels during a saline control infusion (P > 0.05). The response to propranolol differed from the response to saline control (P < 0.01). The absolute and percent decreases in RMR with propranolol were modestly related to baseline plasma concentration of norepinephrine (r = 0.38, P = 0.05; r = 0.44, P = 0.02, respectively). These findings provide direct evidence for the concept of tonic sympathetic beta-adrenergic support of RMR in healthy nonobese adults.

Age-related decreases in basal limb blood flow in humans: time course, determinants and habitual exercise effects.

Basal whole-limb blood flow is lower in older than in young healthy sedentary men due to a lower limb vascular conductance. In Study 1, we determined whether age-associated reductions in basal whole-leg (femoral artery) blood flow and vascular conductance are modulated by habitual physical activity by studying 89 healthy men aged 20-35 or 55-75 years (26 sedentary, 31 physically active and 32 endurance exercise trained). Femoral blood flow (duplex Doppler) and vascular conductance were approximately 20-30 % lower (P < 0.01) in the older men in all three physical activity groups. In Study 2, to determine the temporal pattern and relation to local metabolism and lean tissue mass of the age-associated reductions in femoral blood flow, we studied 142 healthy men aged 18-79 years. Femoral blood flow (r = -0.40) and vascular conductance (r = -0.51) were linearly and inversely related to age (both P < 0.001). Leg fat-free mass (r = -0.48) and estimated leg oxygen consumption (r = -0.49) declined with advancing age (both P < 0.001), and were strongly and positively related (r = 0.75; P < 0.001). The age-associated decline in femoral blood flow correlated with the corresponding reductions in leg fat-free mass and estimated leg oxygen consumption (both r = 0.47; P < 0.001). We concluded that: (1) basal whole-limb blood flow and vascular conductance decrease progressively with advancing age in healthy men; (2) reductions in both limb fat-free mass and oxygen consumption are related to the decline in whole-limb blood flow with age; and (3) habitual aerobic exercise does not appear to modulate the age-related reductions in basal limb blood flow and vascular conductance.

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.

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.