Sex-specific effects of dehydroepiandrosterone (DHEA) on bone mineral density and body composition: A pooled analysis of four clinical trials.

OBJECTIVE: Studies of dehydroepiandrosterone (DHEA) therapy in older adults suggest sex-specific effects on bone mineral density (BMD) and body composition, but the ability of a single study to reach this conclusion was limited. We evaluated the effects of DHEA on sex hormones, BMD, fat mass and fat-free mass in older women and men enrolled in four similar clinical trials. DESIGN: Pooled analyses of data from four double-blinded, randomized controlled trials. PARTICIPANTS: Women (n = 295) and men (n = 290) aged 55 years or older who took DHEA or placebo tablet daily for 12 months. MEASUREMENTS: Twelve-month changes in BMD, fat mass, fat-free mass and serum DHEA sulphate (DHEAS), (17)estradiol, testosterone and insulin-like growth factor-1 (IGF-1). RESULTS: Women on DHEA had increases (mean ± SD; all P < 0.001 vs placebo) in DHEAS (231 ± 164 µg/dL), testosterone (18.6 ± 20.9 µg/dL), (17)estradiol (8.7 ± 11.0 pg/mL) and IGF-1 (25.1 ± 52.3 ng/mL), and men had increases in DHEAS (269.0 ± 177 µg/dL; P < 0.01), (17)estradiol (4.8 ± 12.2 pg/m; P < 0.01) and IGF-1 (6.3 ± 41.4 ng/mL; P < 0.05). Women on DHEA had increases in lumbar spine (1.0% ± 3.4%) and trochanter (0.5% ± 3.8%) BMD and maintained total hip BMD (0.0% ± 2.8%); men had no BMD benefit and a decrease in fat mass (-0.4 ± 2.6 kg; all P < 0.01 vs placebo). CONCLUSIONS: Dehydroepiandrosterone therapy may be an effective approach for preserving bone and muscle mass in women. Key questions are (a) the extent to which longer duration DHEA can attenuate the loss of bone and muscle in women, and (b) whether DHEA has a more favourable benefit-to-risk profile for women than oestrogen therapy.

Adipocytokine profiles in a putative novel postmenopausal polycystic ovary syndrome (PCOS) phenotype parallel those in premenopausal PCOS: the Rancho Bernardo Study.

The objective was to investigate whether the associations between leptin, adiponectin, andadiposity reported in classic polycystic ovary syndrome (PCOS) are also observed in elderly women with a novel putative postmenopausal PCOS phenotype. We studied 713 postmenopausal community-dwelling women. Diagnosis of the novel phenotype required the presence of ≥3 diagnostic features including: 1) a personal history of oligomenorrhea; 2) history of infertility or miscarriage; 3) current or past clinical or hormonal evidence of hyperandrogenism; 4) central obesity; 5) biochemical evidence of insulin resistance. Women in the control group had ≤2 of these components. Mean age (±SD) was 74±8 years for the study cohort. Sixty-six women (9.3%) had the putative PCOS phenotype. Serum leptin was higher (mean 25.70±15.67 vs 14.94+9.89 ng/mL, P<.01) and adiponectin lower (mean 11.72±4.80 vs 17.31±7.45 µg/mL, P<.01) in cases vs controls. Leptin was positively, and adiponectin inversely, associated with an increasing number of phenotype features (P<.01 for linearity). In age-adjusted regression analysis, adjustment for waist circumference eliminated the association between leptin and the PCOS phenotype, but not the association between adiponectin and the PCOS phenotype. In this novel postmenopausal PCOS phenotype, adipocytokine profiles and their associations with adiposity parallel those reported in younger women with classic PCOS. These results support our hypothesis that a putative phenotype analogous to PCOS can be identified in postmenopausal women using clinical and biochemical criteria. Use of this novel phenotype could provide a basis for studies of the delayed consequences of PCOS in older women.

Metabolic syndrome and 16-year cognitive decline in community-dwelling older adults.

PURPOSE: To determine whether metabolic syndrome is associated with accelerated cognitive decline in community-dwelling older adults. METHODS: A longitudinal study of 993 adults (mean 66.8 ± 8.7 years) from the Rancho Bernardo Study. Metabolic syndrome components, defined by 2001 NCEP-ATP III criteria, were measured in 1984-1987. Cognitive function was first assessed in 1988-1992. Cognitive assessments were repeated approximately every 4 years, for a maximum 16-year follow-up. Mixed-effects models examined longitudinal rate of cognitive decline by metabolic syndrome status, controlling for factors plausibly associated with cognitive function (diabetes, inflammation). RESULTS: Metabolic syndrome was more common in men than women (14% vs. 9%, p = .01). In women, metabolic syndrome was associated with greater executive function and long-term memory decline. These associations did not differ by inflammatory biomarker levels. Diabetes did not alter the association of metabolic syndrome with long-term recall but modified the association with executive function: metabolic syndrome was associated with accelerated executive function decline in diabetic women only. Metabolic syndrome was not related to rate of decline on any cognitive measure in men. CONCLUSIONS: Metabolic syndrome was a risk factor for accelerated cognitive decline, but only in women. Prevention of metabolic syndrome may aid in maintenance of cognitive function with age.

Sex differences in the association of Framingham Cardiac Risk Score with cognitive decline in community-dwelling elders without clinical heart disease.

OBJECTIVE: To investigate a possible link between cardiovascular risk factors and age-related cognitive decline, the association of the 1998 Framingham Cardiac Risk Score (FCRS) with the trajectory of cognitive function test (CFT) performance over an 18 year period was examined in adults 50 years and older without clinical heart disease at baseline. METHODS: Participants were 985 men and women who had assessments of cognitive function at 3- to 4-year intervals. The association of FCRS category with CFT score trajectory was examined using mixed-effects models stratified by sex and controlling for age, educational level, and number of successive cognitive assessments. RESULTS: At baseline, median FCRS corresponded to a 14% risk of a coronary heart disease event within 10 years for men and an 8% risk for women; 31% of men and 6% of women were at high (>20%) risk. In longitudinal analyses, women with FCRS risk higher than 7% had a higher rate of decline on tests of verbal fluency (p values < .05) and long-term recall (p values < .01) compared with low-risk women; modest, but significant (p values < .05), differences in the trajectory of Mini-Mental State Examination and Trail-Making Test B scores were also apparent. FCRS category was not related to the rate of decline in CFT performance in men. CONCLUSIONS: For older women, very low levels of risk of coronary heart disease were associated with preservation of cognitive function for 10 years, suggesting that the maintenance of cardiovascular health may slow cognitive decline. The minimal association in men, who were at higher baseline risk, may be due to the selective attrition of men with greater cognitive decline.

Sex and age differences in the association of obesity and smoking with hypertension and type 2 diabetes in Southern California American Indians, 2002-2006.

OBJECTIVE: Assess age and sex differences in the association of obesity and smoking with diabetes and hypertension and report the prevalence of these cardiovascular disease (CVD) risk factors in Southern California American Indian/Alaska Native (AlAN) adults. DESIGN: Cross-sectional study. SETTING: Visit data from 2002-2006 were extracted from one Southern California AlAN health clinic system. PARTICIPANTS: 10,351 AIAN adults visiting the health clinic system. MAIN OUTCOME MEASURES: Odds ratios were examined to assess the association of obesity and smoking with diabetes and hypertension and prevalence rates for obesity, smoking, diabetes, and hypertension were reported. RESULTS: Obesity (women: 53%, men: 55%), smoking (women: 16%, men: 18%), diabetes (women: 14%, men: 16%), and hypertension (women: 32%, men: 37%) were very prevalent. For women aged -35 years, increasing obesity was significantly associated with diabetes. For men aged -25 years, morbid obesity and smoking were significantly associated with diabetes for many age groups. Increasing overweight/obesity and smoking were associated with hypertension among adults aged 18-65 years. CONCLUSIONS: Southern California AIANs had higher obesity, diabetes, and hypertension prevalence than the general Southern California population, and higher obesity prevalence compared to other AIANs. Highly prevalent risk factors create a great burden, as CVD is the leading cause of death among AIAN adults. AIANs are diverse and need interventions tailored to cultural customs and health problems most prevalent in each tribal community.

Vitamin d, parathyroid hormone, and cardiovascular mortality in older adults: the Rancho Bernardo study.

BACKGROUND: recent systematic reviews have cast doubt on the association between vitamin D and cardiovascular disease. No prior studies have investigated the association between 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH](2)D), or intact parathyroid hormone and cardiovascular mortality in a temperate climate. METHODS: a total of 1073 community-dwelling older adults were evaluated in 1997-1999; serum levels of 25(OH)D (mean 42 ng/mL), 1,25(OH)(2)D (median 29 pg/mL), and intact parathyroid hormone (median 46 pg/mL) were measured; mean estimated glomerular filtration rate was 74 mL/min/1.73 m(2). Participants were followed up to 10.4 (mean 6.4) years with 111 cardiovascular deaths. RESULTS: in unadjusted Cox proportional hazards models, higher levels of 1,25(OH)(2)D were protective against cardiovascular mortality, whereas higher levels of intact parathyroid hormone predicted increased risk of cardiovascular death. After adjusting for age alone or multiple covariates, there was no significant association between 25(OH)D, 1,25(OH)(2)D, or intact parathyroid hormone and cardiovascular mortality; results did not differ by an estimated glomerular filtration rate ≥ 60 mL/min/1.73 m(2) or<60 mL/min/1.73 m(2). CONCLUSION: in this prospective study of Caucasian, middle-income, community-dwelling older adults living in sunny southern California, serum levels of 25(OH)D, 1,25(OH)(2)D, and intact parathyroid hormone were not independently associated with cardiovascular mortality.

High-density lipoprotein subclasses are a potential intermediary between alcohol intake and reduced risk of cardiovascular disease: the Rancho Bernardo Study.

We conducted a cross-sectional study of NMR-derived HDL subclasses and alcohol intake among 2171 community-dwelling older adults with a large proportion of daily or near-daily alcohol consumers (44 %). We aimed to assess whether, in addition to increasing total HDL, alcohol may induce a beneficial shift in HDL particle size distribution. Participants were categorised based on reported alcohol intake (g per week) and on frequency (none, < 3 times/week, 3-4 times/week, ≥ 5 times/week). The association between alcohol intake and lipoprotein fractions was examined using sex-specific linear regression models adjusted for age, BMI, diabetes, current smoking, exercise and hormone therapy in women. There was a stepwise gradient with the highest weekly alcohol consumption associated with the highest total HDL size and greatest number of medium and large HDL particles, as well as higher total HDL concentrations (all P < 0.001); total small HDL did not differ. Alcohol-HDL size associations were similar in both sexes and did not differ by use of hormone replacement therapy in women. In conclusion, regular alcohol consumers had a higher number and percentage of large HDL particles than non-drinkers. These results suggest that one way that alcohol may decrease CVD is through potentially favourable changes in lipoprotein subclass composition.

Does leptin predict incident hypertension in older adults?

OBJECTIVE: Leptin is associated with blood pressure (BP) in experimental and cross-sectional studies, but only one previous prospective study of middle-aged men has reported the association between leptin and incident hypertension. We examined the association of leptin levels with incident hypertension in a population-based study of older men and women. DESIGN: Longitudinal cohort study. POPULATION: Participants were 602 community-dwelling older adults with normal baseline BP levels who attended a research clinic visit between 1984 and 1987 and again 4.4 years later (mean age was 66.2 +/- 11.4; 60.6% were men; mean body mass index (BMI) 24.9 +/- 3.4 kg/m(2)). MEASUREMENTS: Hypertension was defined as systolic BP > or =140 mmHg and/or diastolic BP > or =90 mmHg and/or antihypertensive drug treatment. Leptin was measured by radioimmunoassay. RESULTS: After an average 4.4-year follow-up (minimum 2-maximum 7 years), 106 (17.6%) new cases of hypertension were identified. At baseline, participants who developed hypertension were older and had higher systolic BP and higher total cholesterol compared to participants who remained normotensive. Baseline serum leptin levels were higher in participants who developed hypertension compared to persistent normotensives [median (25th-75th range)] [8.8(5-16) vs 7(4-11) ng/ml, P = 0.002]. In logistic regression models, leptin (log-transformed) predicted incident hypertension before and after adjustments for baseline age, BMI, systolic BP, total cholesterol, medications, and previous cardiovascular disease (OR 1.75 95% CI 1.17-2.61, P = 0.006). This association persisted after exclusion of 45 obese participants. CONCLUSION: Higher leptin levels were independently associated with increased odds of incident hypertension in older adults.

Obesity and other cardiovascular disease risk factors and their association with osteoarthritis in Southern California American Indians, 2002-2006.

OBJECTIVE: Assess age and sex differences in the association of obesity and other CVD risk factors with osteoarthritis (OA) in Southern California American Indian/Alaska Native (AIAN) adults. DESIGN: Cross-sectional study. SETTING: Southern California. PARTICIPANTS: 6,299 AIAN adults aged 35+ years from health clinic system. MAIN OUTCOME MEASURES: Osteoarthritis prevalence. RESULTS: Age-adjusted OA prevalence was 16.5% in women and 11.5% in men. OA prevalence increased with age and was higher in women. Very and morbid levels of obesity were associated with higher OA prevalence in some age groups. Hypertension was strongly associated with increased OA and current smoking tended to be associated with increased OA. For men, we found no association between diabetes and OA; however, diabetes was associated with more OA for women aged 35-54 years. CONCLUSIONS: Southern California AIANs may have lower OA prevalence than the US population as a whole. Comparisons of OA prevalence with other AIAN communities were not possible due to lack of other similar published results. Further studies are needed to determine the impact of OA within this understudied minority population.

A prospective study of abdominal obesity and coronary artery calcium progression in older adults.

OBJECTIVE: Little is known about obesity measurements and coronary artery calcium (CAC) progression in older adults. We examined the sex-specific association between measures of body size and fat distribution with CAC progression. SUBJECTS AND METHODS: Participants were 156 men and 182 women (mean age 67 yr) without known heart disease who had electron-beam computed tomography for CAC at baseline and again 4.5 yr later. Obesity assessments were weight, height, body mass index, waist and hip circumference, waist to hip ratio, waist to height ratio, sc and visceral adipose tissue (SAT, VAT), and SAT to VAT ratio based on abdominal electron-beam computed tomography. CAC progression was defined as categorical (square root increased on total CAC volume score > or = 2.5 mm(3)) and continuous variables. RESULTS: During the follow-up, 55% of men and 38.5% of women had CAC progression. Increased waist to hip ratio (> or = 0.9 for men, > or = 0.85 for women) and waist to height ratio (> or = 0.55 for men, > or = 0.54 for women) were positively and independently associated with CAC progression [median (interquartile range)] [60.8 (145) vs. 10.8 (56) mm(3), P = 0.002 and 50 (153) vs. 22(84) mm(3), P = 0.03, respectively]. In women but not men, an increased waist circumference (> 88 cm) independently predicted CAC progression (odds ratio 3.0 95% confidence interval 1.03-8.0, P = 0.04), whereas VAT to SAT ratio predicted CAC progression in men but not women (odds ratio 2.8 95% confidence interval 1.01-7.8, P = 0.04). CONCLUSION: In this study of older adults without known heart disease, abdominal obesity was an independent predictor of CAC progression. These results point to the importance of using clinical measurements of abdominal obesity to identify individuals at increased risk for atherosclerosis.

Treated hypothyroidism, cognitive function, and depressed mood in old age: the Rancho Bernardo Study.

OBJECTIVE: Overt hypothyroidism is associated with cognitive impairment, which can be reversed if treated early and appropriately. We compared cognitive function (CF) of euthyroid older adults with those who had long-term treated hypothyroidism. METHODS: Between 1999 and 2003, the CF of 885 euthyroid and 149 hypothyroid-treated older adults (primary hypothyroidism after surgery or autoimmune thyroid disease) was assessed using three standardized CF tests: the modified mini-mental state examination, Trails B, and verbal fluency. Depressed mood was assessed using the Beck Depression Inventory (BDI). Only participants with thyroid stimulating hormone (TSH) in the normal range were included. RESULTS: The treated hypothyroid group had been treated with l-thyroxine for an average of 20 years. Those with treated hypothyroidism were older than the euthyroid group (76.1+/-9.6 vs 73.6+/-10.2 years, P=0.005) and were much more often women (81.6 vs 54.8%, P<0.001). TSH levels were similar between groups (median interquartile range=1.57 (1.19) vs 1.54 (1.59) mIU/l, P=0.81). Compared to euthyroid, the treated hypothyroidism group had more frequent antidepressant medication use (19.5 vs 8.5%, P<0.001) but similar BDI scores. Performance on the three CF tests did not differ by thyroid hormone treatment. Results were not changed after adjustment for age, sex, antidepressant medication use, exercise, and total cholesterol. CONCLUSION: Long-term treated hypothyroidism is not associated with impaired CF or depressed mood in old age. The lack of association with CF is reassuring with regard to long-term use of thyroid hormone therapy.

Vitamin D status and cardiometabolic risk factors in the United States adolescent population.

OBJECTIVE: Evidence on the association of vitamin D with cardiovascular risk factors in youth is very limited. We examined whether low serum vitamin D levels (25-hydroxyvitamin D [25(OH)D]) are associated with cardiovascular risk factors in US adolescents aged 12 to 19 years. METHODS: We conducted a cross-sectional analysis of 3577 fasting, nonpregnant adolescents without diagnosed diabetes who participated in the 2001-2004 National Health and Nutrition Examination Survey. Cardiovascular risk factors were measured using standard methods and defined according to age-modified Adult Treatment Panel III definitions. RESULTS: Mean 25(OH)D was 24.8 ng/mL; it was lowest in black (15.5 ng/mL), intermediate in Mexican American (21.5 ng/mL), and highest in white (28.0 ng/mL) adolescents (P < .001 for each pairwise comparison). Low 25(OH)D levels were strongly associated with overweight status and abdominal obesity (P for trend < .001 for both). After adjustment for age, gender, race/ethnicity, BMI, socioeconomic status, and physical activity, 25(OH)D levels were inversely associated with systolic blood pressure (P = .02) and plasma glucose concentrations (P = .01). The adjusted odds ratio (95% confidence interval) for those in the lowest (<15 ng/mL) compared with the highest quartile (>26 ng/mL) of 25(OH)D for hypertension was 2.36 (1.33-4.19); for fasting hyperglycemia it was 2.54 (1.01-6.40); for low high-density lipoprotein cholesterol it was 1.54 (0.99-2.39); for hypertriglyceridemia it was 1.00 (0.49-2.04); and for metabolic syndrome it was 3.88 (1.57-9.58). CONCLUSIONS: Low serum vitamin D in US adolescents is strongly associated with hypertension, hyperglycemia, and metabolic syndrome, independent of adiposity.

Insulinlike growth factor-1, insulinlike growth factor binding protein-1, and cognitive function in older men and women.

OBJECTIVES: To assess the association between insulinlike growth factor (IGF)-1 and IGF binding protein (IGFBP)-1 with three cognitive function tests in a healthy elderly population. DESIGN: Cross-sectional analyses from the Rancho Bernardo Cohort Study. SETTING: Southern California community of Rancho Bernardo. PARTICIPANTS: Men (n=636) and women (n=899) from the Rancho Bernardo study (median age 74) were assessed between 1988 and 1992 for cognitive function using the Mini-Mental State Examination (MMSE), Verbal Fluency (VF) test, and Trail-Making Test Part B (Trails B). Blood samples were obtained at the same time for IGF-1 and IGFBP-1 levels. The association between biomarkers and cognitive function tests was assessed by dichotomizing tests at the clinically relevant cutoff using logistic regression and according to tertiles and continuous IGF-1 and IGFBP-1 levels using multivariate linear regression analyses. RESULTS: The mean MMSE, VF and Trails B scores indicated better cognitive function with higher IGF-1 tertile. Multivariate analyses showed that VF and MMSE were each significantly associated with IGF-1 in a dose-response manner for men (P for trend=.001), but no cognitive function tests were related to IGF-1 in women. For men, the highest IGFBP-1 tertile was inversely and significantly different from the lowest tertile for the MMSE test only (P for trend=.02). CONCLUSION: IGF-1 was independently and positively related to MMSE and VF in men, and IGFBP-1 was inversely associated with MMSE in men. Sex differences in the association should be further investigated.

Serum vitamin D, parathyroid hormone levels, and carotid atherosclerosis.

Evidence suggests low vitamin D and elevated parathyroid hormone (PTH) concentrations may increase risk for cardiovascular disease. However, little is known about the association between vitamin D or PTH and subclinical atherosclerosis. This cross-sectional study included 654 community-dwelling older adults aged 55-96 years (mean age, 75.5 years) without a history of coronary heart disease, revascularization, or stroke enrolled in the Rancho Bernardo Study who completed a clinic examination in 1997-1999 and provided a blood sample for determination of serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and PTH concentrations. Carotid artery intima-media wall thickness (IMT) was measured as an indicator of atherosclerosis at two sites with B-mode ultrasound. After adjusting for age, sex, smoking, alcohol intake, waist-to-hip ratio, exercise, season of blood draw, diabetes, and hypertension, geometric mean internal carotid IMT (p(trend) 0.022), but not common carotid IMT (p(trend) 0.834) decreased in a dose-dependent fashion with increasing concentration of 25(OH)D. There was no association of 1,25(OH)(2)D or PTH with either measure of carotid IMT. In subgroup analyses, 1,25(OH)(2)D was inversely associated with internal carotid IMT among those with hypertension (p for interaction 0.036). These findings from a population-based cohort of older adults suggest a potential role for vitamin D in the development of subclinical atherosclerosis. Additional research is needed to determine whether vitamin D may influence the progression of atherosclerosis, including the effects of supplementation on the atherosclerotic process.

Vasomotor symptoms and mortality: the Rancho Bernardo Study.

OBJECTIVE: The purpose of this study was to examine the associations of vasomotor symptoms with risk of all-cause, cardiovascular disease (CVD), and coronary heart disease (CHD) mortality in community-dwelling older women, with a mean age of 69 years. METHODS: This prospective population-based study included 867 postmenopausal women who provided lifestyle and menopause-related history at the 1984 to 1987 visit of the Rancho Bernardo Study and answered a 1989 mailed questionnaire on menopause and vasomotor symptoms. Ninety-eight percent were followed for vital status through July 2004. RESULTS: Overall, 73% reported hot flashes, of whom 39% also reported night sweats. During the 11.5-year average follow-up, there were 405 deaths, of which 194 were attributed to CVD and 71 to CHD. Hot flashes alone were not associated with all-cause mortality, but women who, in addition to hot flashes, also had night sweats had an almost 30% (hazard ratio [HR], 0.72; 95% CI, 0.55-0.94) lower all-cause mortality risk compared with women without this symptom, independent of body mass index, past or current use of estrogen or progestin, physical exercise, and smoking habit. There was a similar lower risk of CVD and CHD mortality in women with night sweats when adjusted for past or current use of estrogen or progestin (HR, 0.62; 95% CI, 0.42-0.92 and HR, 0.51; 95% CI, 0.26-0.99, respectively). These associations were independent of hormone use but were no longer significant after adjusting for body mass index, physical exercise, and smoking. CONCLUSIONS: Reported night sweats at menopause are associated with reduced risk of death over the following 20 years, independent of multiple risk factors including past or current use of postmenopausal estrogen therapy.

Sex differences in the association between adiponectin and BMD, bone loss, and fractures: the Rancho Bernardo study.

We evaluated sex differences in the prospective association between adiponectin with BMD, bone loss, and fractures. Adiponectin, an adipose-derived protein with insulin-sensitizing properties, is also expressed in bone-forming cells. Conflicting results and sex differences in the adiponectin-BMD association have been reported in cross-sectional studies. Serum adiponectin was measured in fasting blood samples obtained in 1984-1987 in 447 postmenopausal women (mean age: 76 yr) and 484 men (mean age: 75 yr). Four years later, BMD was measured at the midshaft radius by single photon absorptiometry and at the femoral neck, total hip, and lumbar spine by DXA. In 1992-1996, axial BMD was remeasured in 261 women and 264 men. Multivariable analysis adjusted for age, weight, calcium intake, type 2 diabetes, alcohol intake, and exercise. Among women, adiponectin was inversely associated with BMD at the femoral neck (beta = -0.002, p = 0.007), total hip (beta = -0.002, p = 0.009), lumbar spine (beta = -0.003, p = 0.008), and midshaft radius (beta = -0.002, p = 0.01) after 4.4 yr and at the femoral neck and total hip 8.6 yr later. Among men, adiponectin was inversely associated with BMD at the femoral neck, (beta = -0.002, p = 0.03), total hip (beta = -0.004, p < 0.001), and midshaft radius (beta = -0.003, p < 0.001) after 4.4 yr and at the hip 8.6 yr later. Adiponectin was not associated with 4-yr bone loss in either sex but was associated with vertebral fractures (adjusted OR: 1.13; 95% CI: 1.08-1.23; p = 0.009) among men only. Adiponectin was inversely associated with BMD; however, sex differences were observed by anatomical site and with regards to vertebral fractures.

Serum uric acid levels improve prediction of incident type 2 diabetes in individuals with impaired fasting glucose: the Rancho Bernardo Study.

OBJECTIVE: To determine whether serum uric acid predicts incident type 2 diabetes by glucose tolerance status in older community-dwelling adults. RESEARCH DESIGN AND METHODS: Participants without diabetes at baseline were evaluated for incident type 2 diabetes 13 years later. Baseline glucose tolerance status was defined as normoglycemia, impaired fasting glucose, and impaired postchallenge glucose tolerance. RESULTS: A total of 566 participants were included (mean age 63.3 +/- 8.6 years; 41% men). Regression models adjusted for age, sex, BMI, diuretic use, and estimated glomerular filtration rate showed that for each 1 mg/dl increment in uric acid levels, incident type 2 diabetes risk increased by approximately 60%. When analyses were stratified by glucose status, uric acid levels independently predicted incident type 2 diabetes among participants who had impaired fasting glucose (odds ratio 1.75, 95% CI 1.1-2.9, P = 0.02). CONCLUSIONS: Uric acid may be a useful predictor of type 2 diabetes in older adults with impaired fasting glucose.

Regular alcohol consumption is associated with increasing quality of life and mood in older men and women: the Rancho Bernardo Study.

OBJECTIVE: This study examines the sex-specific association between alcohol intake and health-related quality of life in middle class community-dwelling older adults. METHODS: Information on alcohol intake and measures of quality of life were obtained from 1594 participants (n=633 men, n=961 women) aged 50-97 years during a research clinic visit in 1992-1996, and from their responses to a phone interview and mailed questionnaires. Quality of life measures included the Medical Outcome Study Short Form 36 (SF-36), Quality of Well-Being (QWB) Scale, Life Satisfaction Index-Z (LSI-Z), and Satisfaction with Life Survey (SWLS). Depressed mood was assessed using the Beck Depression Inventory (BDI). Men and women were stratified into four groups of reported alcohol intake: non-drinker, occasional drinker (alcohol <3 times/week), light regular drinker (alcohol intake >/=3 times/week, but <170g/week), and moderate regular drinker (alcohol intake >/=3 times/week and >/=170g/week). RESULTS: Average age of both sexes was 72+/-10 years. Only 11% of the men and 17% of the women were non-drinkers; 54% of men and 40% of women reported drinking alcohol >/=3 times per week; 18% of men and 7.5% of women were heavier regular drinkers. In multivariable regression analyses, increasing frequency of alcohol use was positively associated with better quality of life in men and in women. Associations were not explained by age, physical activity, smoking, depressed mood, or common chronic diseases including diabetes, hypertension and cardiovascular disease. CONCLUSIONS: Regular alcohol consumption is associated with increased quality of life in older men and women.

Blood pressure and fasting plasma glucose rather than metabolic syndrome predict coronary artery calcium progression: the Rancho Bernardo Study.

OBJECTIVE: To examine the association of the metabolic syndrome, defined by World Health Organization (WHO) and Adult Treatment Panel III (ATP-III) criteria, and its components with coronary artery calcium (CAC) progression. RESEARCH DESIGN AND METHODS: Participants were 338 older community-dwelling men and women without known heart disease who had measurements of heart disease risk factors and CAC at two clinic visits within an average interval of 4.5 years. Progression was defined as an increase in total CAC volume score > or =2.5 mm(3). RESULTS: At baseline, mean age was 67.6 years; metabolic syndrome was present in 15.1% by WHO criteria and in 11.8% by ATP-III criteria, and 5.3% met both criteria. Participants with WHO-defined metabolic syndrome had a greater change in total CAC volume score than those without (P = 0.001). There was no significant difference in CAC volume change by ATP-III-defined metabolic syndrome status (P = 0.69). Overall, 46.4% of participants were CAC progressors. In logistic regression analyses adjusted for age, sex, smoking status, and LDL cholesterol, neither WHO-nor ATP-III-defined metabolic syndrome predicted CAC progression. Among metabolic syndrome components, only hypertension was independently associated with CAC progression (odds ratio 2.11 [95% CI 1.33-3.3], P = 0.002). Fasting blood glucose (>100 mg/dl) was an independent predictor of CAC progression, but only for the 118 participants younger than age 65 years (2.3 [1.01-5.5], P = 0.04). CONCLUSIONS: In older adults without known heart disease, blood pressure levels and fasting plasma glucose were better independent determinants of CAC progression than metabolic syndrome itself.

Differences in vitamin D status as a possible contributor to the racial disparity in peripheral arterial disease.

BACKGROUND: Racial differences in cardiovascular risk factors do not fully explain the higher prevalence of lower-extremity peripheral arterial disease (PAD) in black adults. OBJECTIVE: We sought to determine whether any of this excess risk may be explained by vitamin D status, which has been widely documented to be lower in blacks than in whites. DESIGN: This population-based cross-sectional study included 2987 white and 866 black persons aged >or=40 y from the 2001-2004 National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial pressure index of <0.90 in either leg. RESULTS: Mean (+/-SEM) 25-hydroxyvitamin D [25(OH)D] concentrations were significantly lower in black than in white adults (39.2 +/- 1.0 and 63.7 +/- 1.1 nmol/L, respectively; P < 0.001). Adjusted odds ratios for PAD decreased in a dose-dependent fashion with increasing quartiles of 25(OH)D in white adults [1.00 (referent), 0.86, 0.67, and 0.53; P for trend < 0.001]. In black adults, the association was nonlinear; models with cubic splines suggested evidence of greater odds for PAD and a trend for lower odds for PAD at the lowest and highest concentrations of 25(OH)D, respectively. After adjustment for racial differences in socioeconomic status and for traditional and novel risk factors, odds for PAD in black compared with white adults were reduced from 2.11 (95% CI: 1.55, 2.87) to 1.67 (1.11, 2.51). After additional adjustment for 25(OH)D, the odds were further reduced to 1.33 (0.84, 2.10). CONCLUSIONS: Racial differences in vitamin D status may explain nearly one-third of the excess risk of PAD in black compared with white adults. Additional research is needed to confirm these findings.