Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity

Dietary fat and cholesterol and risk of cardiovascular disease in older adults: The Health ABC Study

Background and aims: Although dietary fats and cholesterol have previously been associated with risk of cardiovascular disease (CVD) in middle-aged populations, less is known among older adults. The purpose of this study was to determine the association between dietary fats, cholesterol, and eggs and CVD risk among community-dwelling adults aged 70-79 in the Health, Aging and Body Composition Study. Methods and results: Diet was assessed using an interviewer-administered 108-item food frequency questionnaire (n= 1941). CVD events were defined as a confirmed myocardial infarction, coronary death, or stroke. Relative rates of CVD over 9 years of follow-up were estimated using Cox proportional hazards models. During follow-up, there were 203 incident cases of CVD. There were no significant associations between dietary fats and CVD risk. Dietary cholesterol (HR (95% CI): 1.47 (0.93, 2.32) for the upper vs. lower tertile; P for trend, 0.10) and egg consumption (HR (95% CI): 1.68 (1.12, 2.51) for 3+/week vs <1/week; P for trend, 0.01) were associated with increased CVD risk. However, in sub-group analyses, dietary cholesterol and egg consumption were associated with increased CVD risk only among older adults with type 2 diabetes (HR (95% CI): 3.66 (1.09, 12.29) and 5.02 (1.63, 15.52), respectively, for the upper vs. lower tertile/group). Conclusions: Dietary cholesterol and egg consumption were associated with increased CVD risk among older, community-dwelling adults with type 2 diabetes. Further research on the biological mechanism(s) for the increased CVD risk with higher dietary cholesterol and frequent egg consumption among older adults with diabetes is warranted. © 2009 Elsevier B.V

A higher protein intake is not associated with 5-year change in mid-thigh muscle cross-sectional area by computed tomography in older adults: the health, aging, and body composition (Health ABC) study

Rationale: A higher protein intake is suggested to preserve muscle mass during aging, and may therefore reduce the risk for sarcopenia. We explored whether the amount, type (animal/vegetable) and essential amino acid (EAA) composition of protein intake were associated with 5-year change in mid-thigh muscle cross-sectional area (CSA) in older adults. Methods: Protein intake was assessed at year 2 by a Block food frequency questionnaire in 2,597 participants of the Health ABC study, aged 70–79 y. At year 1 and year 6 mid-thigh muscle CSA (cm2) was measured by computed tomography. Multiple linear regression analysis was used to examine the association between energy adjusted protein residuals (total, animal and vegetable protein) and muscle CSA at year 6, adjusted for muscle CSA at year 1 and potential confounders including prevalent health conditions, physical activity and 5-year change in fat mass. EAA intake was expressed as percentage of total protein intake. Results: Mean protein intake was 0.90 (SD 0.36) g/kg/d and mean 5-year change in muscle CSA was −9.8 (17.0) cm2 (n = 1,561). No association was observed between energy adjusted total (β = −0.00 cm2 ; SE = 0.03; P = 0.98), animal (β = −0.00 cm2; SE = 0.03; P = 0.92), and plant (β = +0.07 cm2; SE = 0.07; P = 0.291) protein intake and muscle CSA at year 6, adjusted for baseline mid-thigh muscle area and potential confounders. No associations were observed for the EAAs. Conclusion: A higher total, animal or vegetable protein intake was not associated with 5 year change in mid-thigh cross sectional area in older adults. This conclusion contradicts some, but not all previous research, therefore optimal protein intake for older adults is currently not known

Transition to Sarcopenia and Determinants of Transitions in Older Adults: A Population-Based Study

Background. Diagnostic criteria for sarcopenia from appendicular lean mass (ALM), strength, and performance have been proposed, but little is known regarding the progression of sarcopenia. We examined the time course of sarcopenia and determinants of transitioning toward and away from sarcopenia. Methods. ALM, gait speed, and grip strength were assessed seven times over 9 years in 2,928 initially well-functioning adults aged 70-79. Low ALM was defined as less than 7.95 kg/

Low subcutaneous thigh fat is a risk factor for unfavourable glucose and lipid levels, independently of high abdominal fat: the Health ABC study

Aims: We investigated whether low subcutaneous thigh fat is an independent risk factor for unfavourable glucose and lipid levels, and whether these associations differ between sexes, and between white and black adults. Our secondary aim was to investigate which body composition characteristics (lean tissue, fat tissue) are reflected by anthropometric measures (waist and thigh circumference). Methods: Anthropometric measurements and computed tomography of the abdomen and of the thigh were performed for all participants of the Health, Aging and Body Composition Study, who were aged 70-79 years. Fasting glucose, triglycerides and HDL-cholesterol, and 2-h postload glucose were determined. Results: After excluding those already diagnosed with diabetes or dyslipidaemia, we analysed data from 2,106 participants. After adjustment for abdominal subcutaneous and visceral fat, and intermuscular thigh fat, larger thigh subcutaneous fat area was statistically significantly associated with lower ln-transformed triglycerides [standardised beta (95% CI) -0.12 (-0.20 to -0.04) in men and -0.13 (-0.21 to -0.05) in women] and higher ln-HDL-cholesterol [0.10 (0.02 to 0.19) and 0.09 (0.01 to 0.18), respectively]. The associations with lower glucose levels were strong in men [-0.11 (-0.20 to -0.02) for fasting and -0.14 (-0.23 to -0.05) for postload glucose], but not statistically significant in women [-0.02 (-0.10 to 0.07) and -0.04 (-0.13 to 0.05), respectively]. There were no differences in the associations between white and black persons. Waist circumference was more strongly associated with abdominal subcutaneous fat, and this association became stronger with increasing BMI, whereas the association with visceral fat became weaker. Thigh circumference was equally dependent on thigh fat and thigh muscle in men, whereas in women the fat component was the main contributor. Conclusion: Larger subcutaneous thigh fat is independently associated with more favourable glucose (in men) and lipid levels (in both sexes) after accounting for abdominal fat depots, which are associated with unfavourable glucose and lipid levels. Anthropometric measures reflect different fat depots at different levels of BMI at the abdomen, and reflect both fat and lean tissue at the thigh. These results emphasise the importance of accurate measures of regional body composition when investigating potential health risks. © Springer-Verlag 2005

Added value of physical performance measures in predicting adverse health-related events: results from the Health, Aging And Body Composition Study.

OBJECTIVES: To determine how three different physical performance measures (PPMs) combine for added utility in predicting adverse health events in elders. DESIGN: Prospective cohort study. SETTING: Health, Aging and Body Composition Study. PARTICIPANTS: Three thousand twenty-four well-functioning older persons (mean age 73.6). MEASUREMENTS: Timed gait, repeated chair stands, and balance (semi- and full-tandem, and single leg stands each held for 30 seconds) tests were administered at baseline. Usual gait speed was categorized to distinguish high- and low-risk participants using the previously established 1-m/s cutpoint. The same population-percentile (21.3%) was used to identify cutpoints for the repeated chair stands (17.1 seconds) and balance (53.0 seconds) tests. Cox proportional hazard analyses were performed to evaluate the added value of PPMs in predicting mortality, hospitalization, and (severe) mobility limitation events over 6.9 years of follow-up. RESULTS: Risk estimates for developing adverse health-related events were similarly large for each of the three high-risk groups considered separately. Having more PPM scores at the high-risk level was associated with a greater risk of developing adverse health-related events. When all three PPMs were considered, having only one poor performance was sufficient to indicate a highly significantly higher risk of (severe) lower extremity and mortality events. CONCLUSION: Although gait speed is considered to be the most important predictor of adverse health events, these findings demonstrate that poor performance on other tests of lower extremity function are equally prognostic. This suggests that chair stand and standing balance performance may be adequate substitutes when gait speed is unavailable. © 2009, Copyright the Authors

Late-life depressed mood and weight change contribute to the risk of each other

Objective: Weight change may be considered an effect of depression. In turn, depression may follow weight change. Deteriorations in health may mediate these associations. The objective was to examine reciprocal associations between depressed mood and weight change, and the potentially mediating role of deteriorations in health (interim hospitalizations and incident mobility imitation) in these associations. Methods: Data were from 2406 black and white men and women, aged 70-79 from Pittsburgh, Pennsylvania and Memphis, Tennessee participating in the Health, Aging and Body composition (Health ABC) study. Depressed mood at baseline (T1) and 3-year follow-up (T4) was measured with the CES-D scale. Three weight change groups (T1-T4) were created: loss (≥5% loss), stable (within ±5% loss or gain), and weight gain (≥5% gain). Results: At T1 and T4, respectively 4.4% and 9.5% of the analysis sample had depressed mood. T1 depressed mood was associated with weight gain over the 3-year period (OR:1.91; 95%CI:1.13-3.22). Weight loss over the 3-year period was associated with T4 depressed mood (OR:1.51; 95%CI:1.05-2.16). Accounting for deteriorations in health in the reciprocal associations between weight change and depressed mood reduced effect sizes between 16-27%. Conclusions: In this study, depressed mood predicted weight gain over three years, while weight loss over three years predicted depressed mood. These associations were partly mediated through deteriorations in health. Implications for clinical practice and prevention include increased awareness that depressed mood can cause weight change, but can also be preceded by deteriorations in health and weight change. © 2010 American Association for Geriatric Psychiatry

Lifestyle Factors and Incident Mobility Limitation in Obese and Non-obese Older Adults.

Objective: This study examines the association between incident mobility limitation and 4 lifestyle factors: smoking, alcohol intake, physical activity, and diet in well-functioning obese (n = 667) and non-obese (n = 2027) older adults. Research Methods and Procedures: Data were from men and women, 70 to 79 years of age from Pittsburgh, PA and Memphis, TN, participating in the Health, Aging and Body Composition (Health ABC) study. In addition to individual lifestyle practices, a high-risk lifestyle score (0 to 4) was calculated indicating the total number of unhealthy lifestyle practices per person. Mobility limitation was defined as reported difficulty walking 1/4 mile or climbing 10 steps during two consecutive semiannual assessments over 6.5 years. Results: In non-obese older persons, significant risk factors for incident mobility limitation after adjustment for socio-demographics and health-related variables were current and former smoking [hazard ratio (HR) = 1.51; 95% confidence interval (CI), 1.20 to 1.89; HR = 1.40; 95% CI, 1.12 to 1.74), former alcohol intake (HR = 1.30; 95% CI, 1.05 to 1.60), low and medium physical activity (HR = 1.78; 95% CI, 1.45 to 2.18; HR = 1.29, 95% CI, 1.07 to 1.54), and eating an unhealthy diet (HR = 1.57; 95% CI, 1.17 to 2.10). In the obese, only low physical activity was associated with a significantly increased risk of mobility limitation (HR = 1.44; 95% CI, 1.08 to 1.92). Having two or more unhealthy lifestyle factors was a strong predictor of mobility limitation in the non-obese only (HR = 1.98; 95% CI, 1.61 to 2.43). Overall, obese persons had a significantly higher risk of mobility limitation compared with non-obese persons, independent of lifestyle factors (HR = 1.73; 95% CI, 1.52 to 1.96). Conclusions: These results underscore the importance of a healthy lifestyle for maintaining function among non-obese older adults. However, a healthy lifestyle cannot overcome the effect of obesity in obese older adults; this stresses the importance of preventing obesity to protect against mobility loss in older persons. Copyright © 2007 NAASO