Robert M. Boudreau

Elevated Aortic Pulse Wave Velocity, a Marker of Arterial Stiffness, Predicts Cardiovascular Events in Well-Functioning Older Adults

Background—Aging results in vascular stiffening and an increase in the velocity of the pressure wave as it travels down the aorta. Increased aortic pulse wave velocity (aPWV) has been associated with mortality in clinical but not general populations. The objective of this investigation was to determine whether aPWV is associated with total and cardiovascular (CV) mortality and CV events in a community-dwelling sample of older adults. Methods and Results—aPWV was measured at baseline in 2488 participants from the Health, Aging and Body Composition (Health ABC) study. Vital status, cause of death and coronary heart disease (CHD), stroke, and congestive heart failure were determined from medical records. Over 4.6 years, 265 deaths occurred, 111 as a result of cardiovascular causes. There were 341 CHD events, 94 stroke events, and 181 cases of congestive heart failure. Results are presented by quartiles because of a threshold effect between the first and second aPWV quartiles. Higher aPWV was associated with both total mortality (relative risk, 1.5, 1.6, and 1.7 for aPWV quartiles 2, 3, and 4 versus 1; P=0.019) and cardiovascular mortality (relative risk, 2.1, 3.0, and 2.3 for quartiles 2, 3, and 4 versus 1; P=0.004). aPWV quartile was also significantly associated with CHD (P=0.007) and stroke (P=0.001). These associations remained after adjustment for age, gender, race, systolic blood pressure, known CV disease, and other variables related to events. Conclusions—Among generally healthy, community-dwelling older adults, aPWV, a marker of arterial stiffness, is associated with higher CV mortality, CHD, and stroke.

Longitudinal study of muscle strength, quality, and adipose tissue infiltration

BACKGROUND Sarcopenia is thought to be accompanied by increased muscle fat infiltration. However, no longitudinal studies have examined concomitant changes in muscle mass, strength, or fat infiltration in older adults. OBJECTIVE We present longitudinal data on age-related changes in leg composition, strength, and muscle quality (MQ) in ambulatory, well-functioning men and women. We hypothesized that muscle cross-sectional area (CSA) and strength would decrease and muscular fat infiltration would increase over 5 y. DESIGN Midthigh muscle, subcutaneous fat (SF), and intermuscular fat (IMF) CSAs and isokinetic leg muscle torque (MT) and MQ (MT/quadriceps CSA) were examined over 5 y in the Health, Aging, and Body Composition study cohort (n = 1678). RESULTS Men experienced a 16.1% loss of MT, whereas women experienced a 13.4% loss. Adjusted annualized decreases in MT were 2-5 times greater than the loss of muscle CSA in those who lost weight and in those who remained weight-stable. Weight gain did not prevent the loss of MT, despite a small increase in muscle CSA. Only those who gained weight had an increase in SF (P < 0.001), whereas those who lost weight also lost SF (P < 0.001). There was an age-related increase in IMF in men and women (P < 0.001), and IMF increased in those who lost weight, gained weight, or remained weight-stable (all P < 0.001). CONCLUSIONS Loss of leg MT in older adults is greater than muscle CSA loss, which suggests a decrease in MQ. Additionally, aging is associated with an increase in IMF regardless of changes in weight or SF.

Excessive Loss of Skeletal Muscle Mass in Older Adults with Type 2 Diabetes

OBJECTIVE A loss of skeletal muscle mass is frequently observed in older adults. The aim of the study was to investigate the impact of type 2 diabetes on the changes in body composition, with particular interest in the skeletal muscle mass. RESEARCH DESIGN AND METHODS We examined total body composition with dual-energy X-ray absorptiometry annually for 6 years in 2,675 older adults. We also measured mid-thigh muscle cross-sectional area (CSA) with computed tomography in year 1 and year 6. At baseline, 75-g oral glucose challenge tests were performed. Diagnosed diabetes (n = 402, 15.0%) was identified by self-report or use of hypoglycemic agents. Undiagnosed diabetes (n = 226, 8.4%) was defined by fasting plasma glucose (≥7 mmol/l) or 2-h postchallenge plasma glucose (≥11.1 mmol/l). Longitudinal regression models were fit to examine the effect of diabetes on the changes in body composition variables. RESULTS Older adults with either diagnosed or undiagnosed type 2 diabetes showed excessive loss of appendicular lean mass and trunk fat mass compared with nondiabetic subjects. Thigh muscle CSA declined two times faster in older women with diabetes than their nondiabetic counterparts. These findings remained significant after adjusting for age, sex, race, clinic site, baseline BMI, weight change intention, and actual weight changes over time. CONCLUSIONS Type 2 diabetes is associated with excessive loss of skeletal muscle and trunk fat mass in community-dwelling older adults. Older women with type 2 diabetes are at especially high risk for loss of skeletal muscle mass.

Inflammatory markers and incident fracture risk in older men and women: the Health Aging and Body Composition Study.

The inflammation of aging hypothesis purports that aging is the accumulation of damage, which results, in part, from chronic activation of inflammation process. We tested this hypothesis in relationship to fractures in 2985 men and women enrolled in the Health ABC study. Results showed that subjects with the greatest number of inflammatory markers have the highest risk of fracture.

Executive Function, Memory, and Gait Speed Decline in Well-Functioning Older Adults

BACKGROUND In community-dwelling older adults, global cognitive function predicts longitudinal gait speed decline. Few prospective studies have evaluated whether specific executive cognitive deficits in aging may account for gait slowing over time. METHODS Multiple cognitive tasks were administered at baseline in 909 participants in the Health, Aging, and Body Composition Study Cognitive Vitality Substudy (mean age 75.2 ± 2.8 years, 50.6% women, 48.4% black). Usual gait speed (m/s) over 20 minutes was assessed at baseline and over a 5-year follow-up. RESULTS Poorer performance in each cognitive task was cross-sectionally associated with slower gait independent of demographic and health characteristics. In longitudinal analyses, each 1 SD poorer performance in global function, verbal memory, and executive function was associated with 0.003-0.004 m/s greater gait speed decline per year (p =.03-.05) after adjustment for baseline gait speed, demographic, and health characteristics. CONCLUSIONS In this well-functioning cohort, several cognitive tasks were associated with gait speed cross-sectionally and predicted longitudinal gait speed decline. These data are consistent with a shared pathology underlying cognitive and motor declines but do not suggest that specific executive cognitive deficits account for slowing of usual gait in aging.

Slower gait, slower information processing and smaller prefrontal area in older adults

BACKGROUND Slower gait in older adults is related to smaller volume of the prefrontal area (PFAv). The pathways underlying this association have not yet been explored. Understanding slowing gait could help improve function in older age. We examine whether the association between smaller PFAv and slower gait is explained by lower performance on numerous neuropsychological tests. HYPOTHESIS We hypothesise that slower information processing explains this association, while tests of language or memory will not. METHODS Data on brain imaging, neuropsychological tests (information processing speed, visuospatial attention, memory, language, mood) and time to walk 15 feet were obtained in 214 adults (73.3 years, 62% women) free from stroke and dementia. Covariates included central (white matter hyperintensities, vision) and peripheral contributors of gait (vibration sense, muscle strength, arthritis, body mass index), demographics (age, race, gender, education), as well as markers of prevalent vascular diseases (cardiovascular disease, diabetes and ankle arm index). RESULTS In linear regression models, smaller PFAv was associated with slower time to walk independent of covariates. This association was no longer significant after adding information processing speed to the model. None of the other neuropsychological tests significantly attenuated this association. CONCLUSIONS We conclude that smaller PFAv may contribute to slower gait through slower information processing. Future longitudinal studies are warranted to examine the casual relationship between focal brain atrophy with slowing in information processing and gait.

Gait Speed Predicts Decline in Attention and Psychomotor Speed in Older Adults: The Health Aging and Body Composition Study

Background/Aims: Gait speed is cross-sectionally associated with attention and psychomotor speed in older community dwellers. It is unclear if gait speed predicts decline in these cognitive domains over time. Methods: Usual gait speed (m/s) over 6 m was measured at baseline in 2,776 Health, Aging and Body Composition Study participants (mean age ± SD 73.5 ± 2.8 years, 53% women, 37% blacks). The Digit Symbol Substitution Test (DSST) was administered at baseline and after 5 years to assess attention and psychomotor speed. We used multivariate logistic regression models to calculate the risk of DSST 5-year decline [>1 SD from mean change (9 points)] across quartiles of gait speed, adjusting for demographics, weight, physical activity, comorbidities, depression and Modified Mini-Mental State Examination. Results: After 5 years, 389 (17.1%) participants declined in DSST. Compared to those in the highest quartile of gait speed (>1.35 m/s), participants in the lowest quartile (<1.05 m/s) were more likely to decline in DSST independently of the considered covariates (OR 1.74, 95% CI 1.21–2.51, adjusted p for trend across quartiles = 0.006). Conclusions: In this cohort of older community dwellers, gait speed independently predicted a decline in DSST after 5 years.

Serum 25-hydroxyvitamin D and clinical fracture risk in a multiethnic cohort of women: The women's health initiative (WHI)

Low 25‐hydroxyvitamin D [25(OH)D] levels have been linked to hip fracture in white women. To study the association of 25(OH)D with risk of fracture in multiethnic women, we performed a nested case‐control study within the prospective Womens Health Initiative (WHI) Observational Study. Incident fractures were identified in 381 black, 192 Hispanic, 113 Asian, and 46 Native American women over an average of 8.6 years. A random sample of 400 white women who fractured was chosen. One control individual was selected per case and matched on age, race/ethnicity, and blood draw date. 25(OH)D, parathyroid hormone, and vitamin D–binding protein (DBP) were measured in fasting baseline serum. Conditional logistic regression models were used to calculate the odds ratio (OR) and 95% CI. In multivariable models, higher 25(OH)D levels compared with levels less than 20 ng/mL were associated with a lower risk of fracture in white women (20 to <30 ng/mL: OR = 0.82, 95% CI 0.58–1.16; ≤30.0 ng/mL: OR = 0.56, 95% CI 0.35–0.90; p trend = 0.02). In contrast, higher 25(OH)D (≥20 ng/mL) compared with levels less than 20 ng/mL were associated with a higher risk of fracture in black women (OR = 1.45, 95% CI 1.06–1.98; p trend = 0.043). Higher 25(OH)D (≥30.0 ng/mL) was associated with higher fracture risk in Asian women after adjusting for DBP (OR = 2.78, 95% CI 0.99–7.80; p trend = 0.04). There was no association between 25(OH)D and fracture in Hispanic or Native American women. Our results suggest divergent associations between 25(OH)D and fracture by race/ethnicity. The optimal level of 25(OH)D for skeletal health may differ in white and black women.

Coronary Artery Calcium, Carotid Artery Wall Thickness and Cardiovascular Disease Outcomes in Adults 70 to 99 Years Old

Few population studies have evaluated the associations of both coronary artery calcium (CAC) and carotid ultrasound with cardiovascular events, especially in adults >70 years of age. At the Pittsburgh Field Center of the Cardiovascular Health Study, 559 men and women, mean age 80.2 (SD 4.1) years had CAC score assessed by electron beam computerized tomographic scan and common and internal carotid artery intimal medial wall thickness (CCA-IMT and ICA-IMT) by carotid ultrasound between 1998 and 2000 and were followed for total and incident cardiovascular disease events through June 2003. Crude rates and hazard ratios for total and incident events were examined with and without adjustment for cardiovascular risk factors. After 5 years, there were 127 cardiovascular disease events, 48 myocardial infarctions or cardiovascular disease deaths, and 28 strokes or stroke deaths. Total and incident cardiovascular disease event rates were higher in each quartile of CAC and CCA-IMT, but not of ICA-IMT. For total cardiovascular disease, the adjusted hazard ratio for the fourth versus first quartile of CAC was 2.1 (95% confidence interval 1.2 to 3.9) and for CCA-IMT was 2.3 (95% confidence interval 1.3 to 4.1). The CCA-IMT was more strongly related to stroke risk than was CAC, although CAC was also an important predictor of stroke. No significant gender differences were found, although relative risks appeared to be stronger in women, especially for stroke. In conclusion, in adults >70 years of age, CAC and CCA-IMT had similar hazard ratios for total cardiovascular disease and coronary heart disease. The CCA-IMT was more strongly related to stroke than CAC, but CAC was also a predictor of stroke.

Number and Dosage of Central Nervous System Medications on Recurrent Falls in Community Elders: The Health, Aging and Body Composition Study

BACKGROUND Few studies have examined the risk of multiple or high doses of combined central nervous system (CNS) medication use for recurrent falls in the elderly. The study objective was to evaluate whether multiple- or high-dose CNS medication use in older adults was associated with a higher risk of recurrent (>or=2) falls. METHODS This longitudinal cohort study included 3,055 participants from the Health, Aging and Body Composition study who were well functioning at baseline. CNS medication use (benzodiazepine and opioid receptor agonists, antipsychotics, antidepressants) was determined annually (except Year 4) during in-person interviews. The number and summated standard daily doses (SDDs; low, medium, and high) of CNS medications were computed. Falls 1 year later were ascertained annually for 5 years. RESULTS For a period of 5 years, as many as 24.1% of CNS medication users took 2+ agents annually, whereas as no more than 18.9% of CNS medication users took high doses annually (3+ SDDs). Yearly, as many as 9.7% of participants reported recurrent falls. Multivariable Generalized Estimating Equation analyses showed that multiple CNS medication users compared with never users had an increased risk of sustaining 2+ falls (adjusted odds ratio [OR] 1.95; 95% confidence interval [CI] 1.35-2.81). Those taking high (3+) CNS SDDs also exhibited an increased risk of 2+ falls (adjusted OR 2.89; 95% CI 1.96-4.25). CONCLUSIONS Higher total daily doses of CNS medications were associated with recurrent falls. Further studies are needed to determine the impact of reducing the number of CNS medications and/or dosage on recurrent falls.