Jeanette G. Wright

Accelerated Longitudinal Decline of Aerobic Capacity in Healthy Older Adults

Background—The ability of older persons to function independently is dependent largely on the maintenance of sufficient aerobic capacity and strength to perform daily activities. Although peak aerobic capacity is widely recognized to decline with age, its rate of decline has been estimated primarily from cross-sectional studies that may provide misleading, overly optimistic estimates of aging changes. Methods and Results—To determine longitudinal rate of change in aerobic capacity and the influence of age, gender, and physical activity on these changes, we performed serial measurements of peak treadmill oxygen consumption (peak &OV0312;o2) in 375 women and 435 men ages 21 to 87 years from the Baltimore Longitudinal Study of Aging, a community-dwelling cohort free of clinical heart disease, over a median follow-up period of 7.9 years. A linear mixed-effects regression model was used to calculate the predicted longitudinal 10-year rate of change in peak &OV0312;o2, expressed in milliliters per minute, for each age decade from the 20s through the 70s after adjustment for self-reported leisure-time physical activity. A longitudinal decline in peak &OV0312;o2 was observed in each of the 6 age decades in both sexes; however, the rate of decline accelerated from 3% to 6% per 10 years in the 20s and 30s to >20% per 10 years in the 70s and beyond. The rate of decline for each decade was larger in men than in women from the 40s onward. Similar longitudinal rates of decline prevailed when peak &OV0312;o2 was indexed per kilogram of body weight or per kilogram of fat-free mass and in all quartiles of self-reported leisure-time physical activity. When the components of peak &OV0312;o2 were examined, the rate of longitudinal decline of the oxygen pulse (ie, the O2 utilization per heart beat) mirrored that of peak &OV0312;o2, whereas the longitudinal rate of heart rate decline averaged only 4% to 6% per 10 years, and accelerated only minimally with age. Conclusions—The longitudinal rate of decline in peak &OV0312;o2 in healthy adults is not constant across the age span in healthy persons, as assumed by cross-sectional studies, but accelerates markedly with each successive age decade, especially in men, regardless of physical activity habits. The accelerated rate of decline of peak aerobic capacity has substantial implications with regard to functional independence and quality of life, not only in healthy older persons, but particularly when disease-related deficits are superimposed.

Pulse Wave Velocity Is an Independent Predictor of the Longitudinal Increase in Systolic Blood Pressure and of Incident Hypertension in the Baltimore Longitudinal Study of Aging

OBJECTIVES This study sought to evaluate whether pulse wave velocity (PWV), a noninvasive index of arterial stiffness, is a predictor of the longitudinal changes in systolic blood pressure (SBP) and of incident hypertension. BACKGROUND Although arterial stiffness is believed to underlie, in part, the age-associated changes in SBP, particularly at older ages, few longitudinal studies in humans have examined the relationship between arterial stiffness and blood pressure. METHODS Pulse wave velocity was measured at baseline in 449 normotensive or untreated hypertensive volunteers (age 53 +/- 17 years). Repeated measurements of blood pressure were performed during an average follow-up of 4.9 +/- 2.5 years. RESULTS After adjusting for covariates including age, body mass index, and mean arterial pressure, linear mixed effects regression models showed that PWV was an independent determinant of the longitudinal increase in SBP (p = 0.003 for the interaction term with time). In a subset of 306 subjects who were normotensive at baseline, hypertension developed in 105 (34%) during a median follow-up of 4.3 years (range 2 to 12 years). By stepwise Cox proportional hazards models, PWV was an independent predictor of incident hypertension (hazard ratio 1.10 per 1 m/s increase in PWV, 95% confidence interval 1.00 to 1.30, p = 0.03) in individuals with a follow-up duration greater than the median. CONCLUSIONS Pulse wave velocity is an independent predictor of the longitudinal increase in SBP and of incident hypertension. This suggests that PWV could help identify normotensive individuals who should be targeted for the implementation of interventions aimed at preventing or delaying the progression of subclinical arterial stiffening and the onset of hypertension.

Longitudinal Trajectories of Arterial Stiffness and the Role of Blood Pressure: The Baltimore Longitudinal Study of Aging

Carotid-femoral pulse wave velocity (PWV), a marker of arterial stiffness, is an established independent cardiovascular risk factor. Little information is available on the pattern and determinants of the longitudinal change in PWV with aging. Such information is crucial to elucidating mechanisms underlying arterial stiffness and the design of interventions to retard it. Between 1988 and 2013, we collected 2 to 9 serial measures of PWV in 354 men and 423 women of the Baltimore Longitudinal Study of Aging, who were 21 to 94 years of age and free of clinically significant cardiovascular disease. Rates of PWV increase accelerated with advancing age in men more than women, leading to sex differences in PWV after the age of 50 years. In both sexes, not only systolic blood pressure (SBP) ≥140 mm Hg but also SBP of 120 to 139 mm Hg was associated with steeper rates of PWV increase compared with SBP<120 mm Hg. Furthermore, there was a dose-dependent effect of SBP in men with marked acceleration in PWV rate of increase with age at SBP ≥140 mm Hg compared with SBP of 120 to 139 mm Hg. Except for waist circumference in women, no other traditional cardiovascular risk factors predicted longitudinal PWV increase. In conclusion, the steeper longitudinal increase of PWV in men than women led to the sex difference that expanded with advancing age. Age and SBP are the main longitudinal determinants of PWV, and the effect of SBP on PWV trajectories exists even in the prehypertensive range.

Independent Prognostic Significance of Ischemic ST-Segment Response Limited to Recovery From Treadmill Exercise in Asymptomatic Subjects

BACKGROUND Although exercise-induced ST depression is an independent predictor of future coronary events in asymptomatic populations, the predictive value of ST depression beginning after exercise cessation is unknown. METHODS AND RESULTS We analyzed the treadmill exercise tests of 825 healthy volunteers who were 22 to 89 years of age from the Baltimore Longitudinal Study of Aging. All subjects were free from coronary heart disease by history, physical examination, and resting ECG. From 825 participants, 611 (group 0) had no ischemic ST-segment changes during or after treadmill exercise, while 214 subjects developed > or = 1-mm flat or downsloping ST depression: 151 (group 1) had ST changes starting during exercise, and 63 (group 2) had changes limited to recovery. Groups 1 and 2 were similar in age, sex, smoking status, hypertension prevalence, fasting plasma glucose, and serum cholesterol (CHOL). However, both groups were older and had higher CHOL and prevalence of hypertension than group 0. Treadmill exercise duration, peak oxygen consumption, and maximal heart rate were similar between groups 1 and 2 but were lower than in group 0 (each P < 0.05). During a mean follow-up time of 9 years, 55 subjects developed coronary events (angina pectoris, myocardial infarction, or coronary death): 21 of 611 (3.4%) in group 0, 22 of 151 (14.6%) in group 1, and 12 of 63 (19%) in group 2 (P = 0.001). By survival analysis, the risk of coronary events was similar in groups 1 and 2 but significantly higher than in group 0 (P < 0.0001). Multiple logistic regression showed that age (odds ratio [OR] = 1.07 per year, P = 0.00001), CHOL (OR = 1.02 per 1 mg, P = 0.0001), and presence of ST-segment depression (OR = 2.59, P = 0.007 and OR = 2.38, P = 0.04 for groups 1 and 2, respectively) were independent predictors of events. CONCLUSIONS Thus, ischemic ST-segment changes developing during recovery from treadmill exercise in apparently healthy individuals have adverse prognostic significance similar to those appearing during exercise.

Nitric oxide inhibition as a mechanism for blood pressure increase during salt loading in normotensive postmenopausal women.

Objectives Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO), which plays an important role in natriuresis. We determined whether changes in endothelium-dependent vasodilation (EDD) and plasma ADMA predict changes in blood pressure (BP) after salt loading in normotensive postmenopausal women (PMW). Methods In 15 normotensive PMW (age 50–60 years), not receiving estrogen, ambulatory 24-h BP, plasma lipids, and ADMA were measured after 4 days of a low-salt diet (70 mEq/day) and following 7 days of high-salt intake (260 mEq/day). Brachial artery diameter at rest, during reactive hyperemia, i.e. EDD, and after sublingual nitroglycerin, i.e. non-EDD, were measured by ultrasound. The 24-h urinary NO metabolite (NOx) was measured by Griess reaction. Plasma ADMA was measured by high-pressure liquid chromatography. Results During low-salt, 24-h BP levels averaged 121 ± 11 and 69 ± 7 mmHg for systolic BP (SBP) and diastolic BP (DBP), respectively. After salt loading, average 24-h BP increases were: 7.6 mmHg for SBP, 2.2 mmHg for DBP, and 5.5 mmHg for pulse pressure (PP). Increases of 24-h SBP and 24-h PP after salt loading correlated directly with changes in ADMA (partial R2 = 0.16 for 24-h SBP and 0.17 for 24-h PP, P < 0.05 for both) and inversely with changes in EDD (partial R2 = 0.13, P = 0.09 for 24 h SBP and partial R2 = 0.15, P = 0.07 for 24-h PP), after adjustment for age and cholesterol. Conclusions Inhibition of NO bioavailability by ADMA and a subsequent reduction in EDD contribute to the increase in BP during high-salt intake in normotensive PMW not receiving estrogen.

Role of Nondiagnostic Exercise-Induced ST-Segment Abnormalities in Predicting Future Coronary Events in Asymptomatic Volunteers

Background—Whether exercise-induced ST-segment depression <1 mm is an independent predictor of future coronary events (CEs) in asymptomatic subjects is unknown. Methods and Results—We performed maximal treadmill exercise tests on 1083 volunteers from the Baltimore Longitudinal Study of Aging who were free from clinical coronary heart disease. Exercise ST-segment changes were stratified by Minnesota code criteria: 11:1 (n=213), flat or downsloping ST depression ≥1 mm; 11:2 (n=66), flat or downsloping ST depression ≥0.5 mm and <1 mm; 11:4 (n=124), ST-J depression ≥1 mm with slowly rising ST segments; and 11:5 (n=69), minor ST depression (<0.5 mm) before exercise that worsened to flat or downsloping ST depression ≥1 mm during or after exercise. Risk of CE was compared with subjects with normal exercise ECG (n=611). Over a mean follow-up of 7.9 years, 76 subjects developed CEs (angina pectoris, myocardial infarction, or coronary death). On univariate analysis, age (relative risk [RR]=1.07/year, P <0.0001), male sex (RR=1.98, P =0.009), plasma cholesterol (RR=1.02/mg per dL, P <0.0001), hypertension (RR=2.23, P =0.002), duration of exercise (RR=0.71/min, P =0.0001), and systolic blood pressure at peak effort (RR=1.02/mm Hg, P =0.002) were associated with CE. By Cox proportional hazards analysis, age (RR=1.06/year, P <0.0001), male sex (RR=2.76, P =0.0002), plasma cholesterol (RR=1.02 per 1 mg/dL, P <0.0001), duration of exercise (RR=0.87/min, P =0.004), and ST-segment changes coded as either 11:1 (RR=2.70, P =0.0005) or 11:5 (RR=2.73, P =0.04) were independent predictors of CE. Conclusions—Both a classic ischemic ST-segment exercise response and intensification of minor preexercise ST-segment depression to levels ≥1 mm independently predicted future CE in this asymptomatic population. Neither slowly rising ST depression nor horizontal ST depression <1 mm was prognostic.

Cardiorespiratory Fitness and Accelerated Cognitive Decline With Aging

BACKGROUND Growing evidence suggests that self-reported physical activity accounts for variability in cognitive function among older adults, and aerobic intervention may improve cognitive function in this population. However, much less is known about the longitudinal association between direct measures of cardiorespiratory fitness and cognitive function across the life span. The present study examined the prospective association between symptom-limited maximal oxygen consumption (VO2max) and longitudinal performance on a comprehensive neuropsychological battery. METHODS Up to 1,400 participants aged 19-94 years underwent initial VO2max assessment and completed subsequent tests of memory, attention, perceptuomotor speed, language, and executive function, in addition to cognitive screening measures, on up to six occasions (mean, M = 2; standard deviation, SD = 1) for up to 18 years (M = 7, SD = 3). Mixed-effects regression models were adjusted for demographic, biomedical, and behavioral confounders. RESULTS Analyses revealed significant longitudinal associations between baseline VO2max and trajectory of performance on multiple measures of verbal and visual memory, as well as on a cognitive screening test (all ps < .05). Individuals with lower VO2max demonstrated accelerated trajectories of cognitive decline over time. CONCLUSIONS Baseline cardiorespiratory fitness is related to longitudinal neuropsychological performance, and memory appears to be a particularly vulnerable domain. Evidence that aerobic fitness is associated with accelerated cognitive decline emphasizes the possible importance of behavioral interventions to optimize cognitive aging over time.

The Relationship Between Aerobic Exercise Capacity and Circulating IGF-1 Levels In Healthy Men and Women

OBJECTIVES: To determine whether aerobic capacity is associated independently with insulin‐like growth factor‐I (IGF‐1) levels in healthy community‐dwelling men and women.

Early repolarization: an electrocardiographic predictor of enhanced aerobic fitness.

The presence or absence of early repolarization on the electrocardiogram at rest was correlated with aerobic exercise capacity in healthy volunteers from the Baltimore Longitudinal Study of Aging. Patients with early repolarization had both longer treadmill exercise duration and higher peak oxygen consumption than age-and gender-matched control subjects.

Effect of estrogen replacement therapy on the ST-segment response to postural and hyperventilation stimuli☆

Abstract It is widely recognized that exercise-induced ST-segment abnormalities often occur in women with normal coronary arteries. False-positive exercise responses from 14 to 67% have been reported. 1 The high frequency of ST-segment abnormalities at rest and in response to exercise in premenopausal women may be explained by their elevated plasma estrogen levels. Although direct testing of this hypothesis is difficult, the effect of estrogen on the ST-segment response to hyperventilation and postural shifts may provide insight into this question. These frequently used preexercise maneuvers are believed to provoke ST-segment shifts independent of myocardial ischemia. We designed this study to compare the frequency of abnormal ST-segment responses to sitting, hyperventilation and standing in postmenopausal women receiving estrogen replacement therapy versus those not receiving it.