Sarcopenic obesity and risk of cardiovascular disease and mortality: a population-based cohort study of older men.

OBJECTIVES: To examine associations between sarcopenia, obesity, and sarcopenic obesity and risk of cardiovascular disease (CVD) and all-cause mortality in older men. DESIGN: Prospective cohort study. SETTING: British Regional Heart Study. PARTICIPANTS: Men aged 60-79 years (n = 4,252). MEASUREMENTS: Baseline waist circumference (WC) and midarm muscle circumference (MAMC) measurements were used to classify participants into four groups: sarcopenic, obese, sarcopenic obese, or optimal WC and MAMC. The cohort was followed for a mean of 11.3 years for CVD and all-cause mortality. Cox regression analyses assessed associations between sarcopenic obesity groups and all-cause mortality, CVD mortality, CVD events, and coronary heart disease (CHD) events. RESULTS: There were 1,314 deaths, 518 CVD deaths, 852 CVD events, and 458 CHD events during follow-up. All-cause mortality risk was significantly greater in sarcopenic (HR = 1.41, 95% CI = 1.22-1.63) and obese (HR = 1.21, 95% CI = 1.03-1.42) men than in the optimal reference group, with the highest risk in sarcopenic obese (HR = 1.72, 95% CI = 1.35-2.18), after adjustment for lifestyle characteristics. Risk of CVD mortality was significantly greater in sarcopenic and obese but not sarcopenic obese men. No association was seen between sarcopenic obesity groups and CHD or CVD events. CONCLUSION: Sarcopenia and central adiposity were associated with greater cardiovascular mortality and all-cause mortality. Sarcopenic obese men had the highest risk of all-cause mortality but not CVD mortality. Efforts to promote healthy aging should focus on preventing obesity and maintaining muscle mass

Diet quality in older age: the influence of childhood and adult socio-economic circumstances.

Socio-economic gradients in diet quality are well established. However, the influence of material socio-economic conditions particularly in childhood, and the use of multiple disaggregated socio-economic measures on diet quality have been little studied in the elderly. In the present study, we examined childhood and adult socio-economic measures, and social relationships, as determinants of diet quality cross-sectionally in 4252 older British men (aged 60-79 years). A FFQ provided data on daily fruit and vegetable consumption and the Elderly Dietary Index (EDI), with higher scores indicating better diet quality. Adult and childhood socio-economic measures included occupation/father's occupation, education and household amenities, which combined to create composite scores. Social relationships included social contact, living arrangements and marital status. Both childhood and adult socio-economic factors were independently associated with diet quality. Compared with non-manual social class, men of childhood manual social class were less likely to consume fruit and vegetables daily (OR 0·80, 95 % CI 0·66, 0·97), as were men of adult manual social class (OR 0·65, 95 % CI 0·54, 0·79), and less likely to be in the top EDI quartile (OR 0·73, 95 % CI 0·61, 0·88), similar to men of adult manual social class (OR 0·66, 95 % CI 0·55, 0·79). Diet quality decreased with increasing adverse adult socio-economic scores; however, the association with adverse childhood socio-economic scores diminished with adult social class adjustment. A combined adverse childhood and adulthood socio-economic score was associated with poor diet quality. Diet quality was most favourable in married men and those not living alone, but was not associated with social contact. Diet quality in older men is influenced by childhood and adulthood socio-economic factors, marital status and living arrangements

Body composition, dietary patterns, cardiovascular disease and mortality in older age

Obesity and poor quality diet are major interrelated risk factors for cardiovascular disease (CVD) and mortality, which are well established in middle-aged populations. However, there is controversy on the effects of obesity on CVD and mortality in the elderly. Since body composition changes with age (visceral fat increases and muscle mass decreases) it may be important to also account for muscle mass in the elderly. However, few studies have examined the combined effects of adiposity and sarcopenia (low muscle mass) on CVD risk and mortality in the elderly. There is also a paucity of data on the associations between dietary patterns and CVD risk and mortality in older age. This thesis uses the British Regional Heart Study, a population based prospective cohort of men, to investigate the impact of body composition (obesity and sarcopenia) and dietary patterns on the risk of cardiovascular endpoints and all-cause mortality in older age (60-79 years). The main findings are that sarcopenic men (defined using mid-arm muscle circumference) and obese men (defined using waist circumference) had a significantly increased risk of CVD mortality and all-cause mortality. Men with both sarcopenia and obesity showed the highest all-cause mortality risk, and also an increased CVD mortality risk although non-significant. Adherence to an a priori defined dietary pattern (the Elderly Dietary Index, a modified Mediterranean-style diet) was associated with a lower risk of CVD mortality and all-cause mortality. Adherence to a ‘high fat/low fibre’ diet, identified by principal component analysis, was associated with an increased risk of all-cause mortality but not CVD mortality. Adherence to a ‘high sugar’ diet was associated with an increased risk of coronary heart disease (CHD) events and CVD events. Body composition and dietary patterns are therefore important risk factors for CVD and all-cause mortality which persist in older age

ApoE e2 and aging-related outcomes in 379,000 UK Biobank participants

This is the final version. Available on open access from Impact Journals via the DOI in this recordThe Apolipoprotein E (APOE) e4 allele is associated with reduced longevity and increased Coronary Artery Disease (CAD) and Alzheimer's disease, with e4e4 having markedly larger effect sizes than e3e4. The e2 longevity promoting variant is less studied. We conducted a phenome-wide association study of ApoE e2e3 and e2e2 with aging phenotypes, to assess their potential as targets for anti-aging interventions. Data were from 379,000 UK Biobank participants, aged 40 to 70 years. e2e3 (n=46,535) had mostly lower lipid-related biomarker levels including reduced total and LDL-cholesterol, and lower risks of CAD (Odds Ratio=0.87, 95% CI: 0.83 to 0.90, p=4.92×10-14) and hypertension (OR=0.94, 95% CI: 0.92 to 0.97, p=7.28×10-7) versus e3e3. However, lipid changes in e2e2 (n=2,398) were more extreme, including a marked increase in triglyceride levels (0.41 Standard Deviations, 95% CI: 0.37 to 0.45, p=5.42×10-92), with no associated changes in CAD risks. There were no associations with biomarkers of kidney function. The effects of both e2e2 and e2e3 were minimal on falls, muscle mass, grip strength or frailty. In conclusion, e2e3 has protective effects on some health outcomes, but the effects of e2e2 are not similar, complicating the potential usefulness of e2 as a target for anti-aging intervention.National Institute on Agin

Sarcopenic obesity and cardiometabolic health and mortality in older adults: a growing health concern in an ageing population

This is the final version. Available on open access from Springer via the DOI in this record. PURPOSE OF REVIEW: Sarcopenic obesity (SO) is a growing public health problem in older adults. Whether SO confers higher risk of cardiometabolic disease and mortality than obesity or sarcopenia alone is still a matter of debate. We focus on recent findings on SO and cardiometabolic health and mortality in older adults. RECENT FINDINGS: SO is associated with increased mortality compared to non-sarcopenic obesity, but similar mortality risk compared to sarcopenia without obesity. SO is associated with a higher risk of cardiovascular disease (CVD), diabetes, and physical disability than obesity or sarcopenia alone. SO, in the presence of diabetes, is associated with the highest risk of CVD and chronic kidney disease. A definition and diagnostic criteria for SO has recently been proposed (ESPEN and EASO). SO is associated with more adverse outcomes overall than sarcopenia or obesity alone. Future research is required to assess the impact of the new SO definition on health outcomes

Red cell distribution width and common disease onsets in 240,477 healthy volunteers followed for up to 9 years

This is the final version. Available on open access from Public Library of Science via the DOI in this recordData Availability: Ethical approval for UK Biobank study was obtained from the North West Multi-Centre Research Ethics Committee. All of the UK Biobank data used in this research is available to bona fide researchers following an application to the UK Biobank (http://www.ukbiobank.ac.uk/register-apply/). The UK Biobank data provided for our approved research project cannot be released by the authors to third parties, this is a legal obligation as part of our Material Transfer Agreement. The authors did not have any special access privileges that others would not have.Higher Red Blood Cell Distribution Width (RDW or anisocytosis) predicts incident coronary artery disease (CAD) plus all-cause and cardiovascular mortality, but its predictive value for other common diseases in healthy volunteers is less clear. We aimed to determine the shorter and longer term associations between RDW and incident common conditions in participants free of baseline disease, followed for 9 years. We undertook a prospective analysis of RDW% using 240,477 healthy UK Biobank study volunteers aged 40-70 years at baseline, with outcomes ascertained during follow-up (≤9 years). Participants were free of anemia, CAD, type-2 diabetes, stroke, hypertension, COPD, and any cancer (except non-melanoma skin cancer) at baseline. Survival models (with competing Hazards) tested associations with outcomes from hospital admission records and death certificates. High RDW (≥15% variation, n = 6,050) compared to low (<12.5% n = 20,844) was strongly associated with mortality (HR 3.10: 95% CI 2.57 to 3.74), adjusted for age, sex, smoking status, education level, mean cell volume and hemoglobin concentration. Higher RDW was also associated with incident CAD (sub-HR 1.67: 1.40 to 1.99), heart failure, peripheral vascular disease, atrial fibrillation, stroke, and cancer (sHR 1.37: 1.21 to 1.55; colorectal cancer sHR 1.92: 1.36 to 2.72), especially leukemia (sHR 2.85: 1.63 to 4.97). Associations showed dose-response relationships, and RDW had long-term predictive value (≥4.5 years after assessment) for the majority of outcomes, which were similar in younger and older persons. In conclusion, higher RDW predicted onsets of a wide range of common conditions as well as mortality in a large healthy volunteer cohort. RDW is not just a short term predictor, as high levels were predictive 4.5 to 9 years after baseline in healthy volunteers. The wide range of outcomes reflects known RDW genetic influences, including diverse disease risks. RDW may be a useful clinical marker for inclusion in wellness assessments.This work is supported by internal funding from the University of Exeter Medical School (L.C.P. and D.M.), a UK Medical Research Council (grant number MR/M023095/1) award (D.M. and J.L.A.), internal funding from the University of Connecticut Health Center (G.A.K.), and the Intramural Research Program of the National Institute on Aging, U.S. National Institutes of Health (L.F.)

Central adiposity and the overweight risk paradox in aging: follow-up of 130,473 UK Biobank participants

This is the final version of the article. Available from American Society for Nutrition via the DOI in this record.Background: For older groups, being overweight [body mass index (BMI; in kg/m(2)): 25 to <30] is reportedly associated with a lower or similar risk of mortality than being normal weight (BMI: 18.5 to <25). However, this "risk paradox" is partly explained by smoking and disease-associated weight loss. This paradox may also arise from BMI failing to measure fat redistribution to a centralized position in later life.Objective: This study aimed to estimate associations between combined measurements of BMI and waist-to-hip ratio (WHR) with mortality and incident coronary artery disease (CAD).Design: This study followed 130,473 UK Biobank participants aged 60-69 y (baseline 2006-2010) for ≤8.3 y (n = 2974 deaths). Current smokers and individuals with recent or disease-associated (e.g., from dementia, heart failure, or cancer) weight loss were excluded, yielding a "healthier agers" group. Survival models were adjusted for age, sex, alcohol intake, smoking history, and educational attainment. Population and sex-specific lower and higher WHR tertiles were <0.91 and ≥0.96 for men and <0.79 and ≥0.85 for women, respectively.Results: Ignoring WHR, the risk of mortality for overweight subjects was similar to that for normal-weight subjects (HR: 1.09; 95% CI: 0.99, 1.19; P = 0.066). However, among normal-weight subjects, mortality increased for those with a higher WHR (HR: 1.33; 95% CI: 1.08, 1.65) compared with a lower WHR. Being overweight with a higher WHR was associated with substantial excess mortality (HR: 1.41; 95% CI: 1.25, 1.61) and greatly increased CAD incidence (sub-HR: 1.64; 95% CI: 1.39, 1.93) compared with being normal weight with a lower WHR. There was no interaction between physical activity and BMI plus WHR groups with respect to mortality.Conclusions: For healthier agers (i.e., nonsmokers without disease-associated weight loss), having central adiposity and a BMI corresponding to normal weight or overweight is associated with substantial excess mortality. The claimed BMI-defined overweight risk paradox may result in part from failing to account for central adiposity, rather than reflecting a protective physiologic effect of higher body-fat content in later life.AB reported grants from the UK National Institute for Health Research (NIHR) School for Public Health Research (Ageing Well Programme) during the conduct of the study and was an employee of Pfizer Italia until November 2012.Supported by UK Medical Research Council award MR/M023095/1 to DM, the National Institute for Health Research School for Public Health Research Ageing Well Programme (partnership), and the Intramural Research Program of the NIH National Institute on Aging

Central adiposity and the overweight risk paradox in aging: follow-up of 130,473 UK Biobank participants

This is the final version of the article. Available from American Society for Nutrition via the DOI in this record.Background: For older groups, being overweight [body mass index (BMI; in kg/m(2)): 25 to <30] is reportedly associated with a lower or similar risk of mortality than being normal weight (BMI: 18.5 to <25). However, this "risk paradox" is partly explained by smoking and disease-associated weight loss. This paradox may also arise from BMI failing to measure fat redistribution to a centralized position in later life.Objective: This study aimed to estimate associations between combined measurements of BMI and waist-to-hip ratio (WHR) with mortality and incident coronary artery disease (CAD).Design: This study followed 130,473 UK Biobank participants aged 60-69 y (baseline 2006-2010) for ≤8.3 y (n = 2974 deaths). Current smokers and individuals with recent or disease-associated (e.g., from dementia, heart failure, or cancer) weight loss were excluded, yielding a "healthier agers" group. Survival models were adjusted for age, sex, alcohol intake, smoking history, and educational attainment. Population and sex-specific lower and higher WHR tertiles were <0.91 and ≥0.96 for men and <0.79 and ≥0.85 for women, respectively.Results: Ignoring WHR, the risk of mortality for overweight subjects was similar to that for normal-weight subjects (HR: 1.09; 95% CI: 0.99, 1.19; P = 0.066). However, among normal-weight subjects, mortality increased for those with a higher WHR (HR: 1.33; 95% CI: 1.08, 1.65) compared with a lower WHR. Being overweight with a higher WHR was associated with substantial excess mortality (HR: 1.41; 95% CI: 1.25, 1.61) and greatly increased CAD incidence (sub-HR: 1.64; 95% CI: 1.39, 1.93) compared with being normal weight with a lower WHR. There was no interaction between physical activity and BMI plus WHR groups with respect to mortality.Conclusions: For healthier agers (i.e., nonsmokers without disease-associated weight loss), having central adiposity and a BMI corresponding to normal weight or overweight is associated with substantial excess mortality. The claimed BMI-defined overweight risk paradox may result in part from failing to account for central adiposity, rather than reflecting a protective physiologic effect of higher body-fat content in later life.AB reported grants from the UK National Institute for Health Research (NIHR) School for Public Health Research (Ageing Well Programme) during the conduct of the study and was an employee of Pfizer Italia until November 2012.Supported by UK Medical Research Council award MR/M023095/1 to DM, the National Institute for Health Research School for Public Health Research Ageing Well Programme (partnership), and the Intramural Research Program of the NIH National Institute on Aging

Healthier diet quality and dietary patterns are associated with lower risk of mobility limitation in older men

Purpose To investigate associations between diet quality, dietary patterns and mobility limitation 15 years later in a population-based sample of older British men. Methods We used longitudinal data from 1234 men from the British Regional Heart Study, mean age 66 years at baseline. Mobility limitation was defined as difficulty going up- or downstairs or walking 400 yards as a result of a long-term health problem. Dietary intake was measured using a food frequency questionnaire data from which the Healthy Diet Indicator (HDI), the Elderly Dietary Index (EDI), and three a posteriori dietary patterns were derived. The a posteriori dietary patterns were identified using principal components analysis: (1) high fat/low fibre, (2) prudent and (3) high sugar. Results Men with greater adherence to the EDI or HDI were less likely to have mobility limitation at follow-up, top vs bottom category odds ratio for the EDI OR 0.50, 95% CI 0.34, 0.75, and for the HDI OR 0.55, 95% CI 0.35, 0.85, after adjusting for age, social class, region of residence, smoking, alcohol consumption and energy intake. Men with a higher score for the high-fat/low-fibre pattern at baseline were more likely to have mobility limitation at follow-up, top vs bottom quartile odds ratio OR 3.28 95% CI 2.05, 5.24. These associations were little changed by adjusting for BMI and physical activity. Conclusion Our study provides evidence that healthier eating patterns could contribute to prevention or delay of mobility limitation in older British men

Low Vitamin D Levels and Risk of Incident Delirium in 351,000 Older UK Biobank Participants

This is the final version. Available on open access from Wiley via the DOI in this recordBACKGROUND/OBJECTIVES Delirium is common in older adults, especially following hospitalization. Because low vitamin D levels may be associated with increased delirium risk, we aimed to determine the prognostic value of blood vitamin D levels, extending our previous genetic analyses of this relationship. DESIGN Prospective cohort analysis. SETTING Community‐based cohort study of adults from 22 cities across the United Kingdom (the UK Biobank). PARTICIPANTS Adults aged 60 and older by the end of follow‐up in the linked hospital inpatient admissions data, up to 14 years after baseline (n = 351,320). MEASUREMENTS At baseline, serum vitamin D (25‐OH‐D) levels were measured. We used time‐to‐event models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between vitamin D deficiency and incident hospital‐diagnosed delirium, adjusted for age, sex, assessment month, assessment center, and ethnicity. We performed Mendelian randomization genetic analysis in European participants to further investigate vitamin D and delirium risk. RESULTS A total of 3,634 (1.03%) participants had at least one incident hospital‐diagnosed delirium episode. Vitamin D deficiency (50 nmol/L). Increased risk was not limited to the deficient group: insufficient levels (25–50 nmol/L) were also at increased risk (HR = 1.38; 95% CI = 1.28–1.49; P = 4*10−18). The association was independent of calcium levels, hospital‐diagnosed fractures, dementia, and other relevant cofactors. In genetic analysis, participants carrying more vitamin D–increasing variants had a reduced likelihood of incident delirium diagnosis (HR = .80 per standard deviation increase in genetically instrumented vitamin D: .73–.87; P = 2*10−7). CONCLUSION Progressively lower vitamin D levels predicted increased risks of incident hospital‐diagnosed delirium, and genetic evidence supports a shared causal pathway. Because low vitamin D levels are simple to detect and inexpensive and safe to correct, an intervention trial to confirm these results is urgently needed.Alzheimer’s SocietyMedical Research Council (MRC)National Institute on Agin