Inflammation predicts accelerated brachial arterial wall changes in patients with recent-onset rheumatoid arthritis

Introduction Patients with recent-onset rheumatoid arthritis (RA) have impaired brachial artery endothelial function compared with controls matched for age, sex and cardiovascular risk factors. The present study examined endothelium-dependent (flow-mediated dilatation (FMD)) and independent (glyceryl trinitrate (GTN)-mediated dilatation (GMD)) structural responses in early RA patients, and determined progress over one year

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

Omega-6 and omega-3 fatty acids predict accelerated decline of peripheral nerve function in older persons

Pre-clinical studies suggest that both omega-6 and omega-3 fatty acids have beneficial effects on peripheral nerve function. Rats feed a diet rich in polyunsaturated fatty acids (PUFAs) showed modification of phospholipid fatty acid composition in nerve membranes and improvement of sciatic nerve conduction velocity (NCV). We tested the hypothesis that baseline plasma omega-6 and omega-3 fatty acids levels predict accelerated decline of peripheral nerve function. Changes between baseline and the 3-year follow-up in peripheral nerve function was assessed by standard surface ENG of the right peroneal nerve in 384 male and 443 female participants of the InCHIANTI study (age range: 24-97 years). Plasma concentrations of selected fatty acids assessed at baseline by gas chromatography. Independent of confounders, plasma omega-6 fatty acids and linoleic acid were significantly correlated with peroneal NCV at enrollment. Lower plasma PUFA, omega-6 fatty acids, linoleic acid, ratio omega-6/omega-3, arachidonic acid and docosahexanoic acid levels were significantly predicted a steeper decline in nerve function parameters over the 3-year follow-up. Low plasma omega-6 and omega-3 fatty acids levels were associated with accelerated decline of peripheral nerve function with aging. © 2007 EFNS

Outcomes of Treated Hypertension at Age 80 and Older: Cohort Analysis of 79,376 Individuals

This is the final version of the article. Available from Wiley via the DOI in this record.OBJECTIVES: To estimate outcomes according to attained blood pressure (BP) in the oldest adults treated for hypertension in routine family practice. DESIGN: Cohort analysis of primary care inpatient and death certificate data for individuals with hypertension. SETTING: Primary care practices in England (Clinical Practice Research Datalink). PARTICIPANTS: Individuals aged 80 and older taking antihypertensive medication and free of dementia, cancer, coronary heart disease, stroke, heart failure, and end-stage renal failure at baseline. MEASUREMENTS: Outcomes were mortality, cardiovascular events, and fragility fractures. Systolic BP (SBP) was grouped in 10-mmHg increments from less than 125 to 185 mmHg or more (reference 145–154 mmHg). RESULTS: Myocardial infarction hazards increased linearly with increasing SBP, and stroke hazards increased for SBP of 145 mmHg or greater, although lowest mortality was in individuals with SBP of 135 to 154 mmHg. Mortality of the 13.1% of patients with SBP less than 135 mmHg was higher than that of the reference group (Cox hazard ratio=1.25, 95% confidence interval=1.19–1.31; equating to one extra death per 12.6 participants). This difference in mortality was consistent over short- and long-term follow-up; adjusting for diastolic BP did not change the risk. Incident heart failure rates were higher in those with SBP less than 125 mmHg than in the reference group. CONCLUSION: In routine primary care, SBP less than 135 mmHg was associated with greater mortality in the oldest adults with hypertension and free of selected potentially confounding comorbidities. Although important confounders were accounted for, observational studies cannot exclude residual confounding. More work is needed to establish whether unplanned SBPs less than 135 mmHg in older adults with hypertension may be a useful clinical sign of poor prognosis, perhaps requiring clinical review of overall care.This work was supported in part by the National Institute for Health Research (NIHR) School for Public Health Research Ageing Well programme

Differential Effects of High-Carbohydrate and High-Fat Diet Composition on Metabolic Control and Insulin Resistance in Normal Rats

The macronutrient component of diets is critical for metabolic control and insulin action. The aim of this study was to compare the effects of high fat diets (HFDs) vs. high carbohydrate diets (HCDs) on metabolic control and insulin resistance in Wistar rats. Thirty animals divided into five groups (n = 6) were fed: (1) Control diet (CD); (2) High-saturated fat diet (HSFD); (3) High-unsaturated fat diet (HUFD); (4) High-digestible starch diet, (HDSD); and (5) High-resistant starch diet (HRSD) during eight weeks. HFDs and HCDs reduced weight gain in comparison with CD, however no statistical significance was reached. Calorie intake was similar in both HFDs and CD, but rats receiving HCDs showed higher calorie consumption than other groups, (p < 0.01). HRSD showed the lowest levels of serum and hepatic lipids. The HUFD induced the lowest fasting glycemia levels and HOMA-IR values. The HDSD group exhibited the highest insulin resistance and hepatic cholesterol content. In conclusion, HUFD exhibited the most beneficial effects on glycemic control meanwhile HRSD induced the highest reduction on lipid content and did not modify insulin sensitivity. In both groups, HFDs and HCDs, the diet constituents were more important factors than caloric intake for metabolic disturbance and insulin resistance

Obesity in Older People With and Without Conditions Associated With Weight Loss: Follow-up of 955,000 Primary Care Patients.

BACKGROUND: Moderate obesity in later life may improve survival, prompting calls to revise obesity control policies. However, this obesity paradox may be due to confounding from smoking, diseases causing weight-loss, plus varying follow-up periods. We aimed to estimate body mass index (BMI) associations with mortality, incident type 2 diabetes, and coronary heart disease in older people with and without the above confounders. METHODS: Cohort analysis in Clinical Practice Research Datalink primary care, hospital and death certificate electronic medical records in England for ages 60 to more than 85 years. Models were adjusted for age, gender, alcohol use, smoking, calendar year, and socioeconomic status. RESULTS: Overall, BMI 30-34.9 (obesity class 1) was associated with lower overall death rates in all age groups. However, after excluding the specific confounders and follow-up less than 4 years, BMI mortality risk curves at age 65-69 were U-shaped, with raised risks at lower BMIs, a nadir between 23 and 26.9 and steeply rising risks above. In older age groups, mortality nadirs were at modestly higher BMIs (all <30) and risk slopes at higher BMIs were less marked, becoming nonsignificant at age 85 and older. Incidence of diabetes was raised for obesity-1 at all ages and for coronary heart disease to age 84. CONCLUSIONS: Obesity is associated with shorter survival plus higher incidence of coronary heart disease and type 2 diabetes in older populations after accounting for the studied confounders, at least to age 84. These results cast doubt on calls to revise obesity control policies based on the claimed risk paradox at older ages

Poor Trail Making Test Performance Is Directly Associated with Altered Dual Task Prioritization in the Elderly – Baseline Results from the TREND Study

BACKGROUND: Deterioration of executive functions in the elderly has been associated with impairments in walking performance. This may be caused by limited cognitive flexibility and working memory, but could also be caused by altered prioritization of simultaneously performed tasks. To disentangle these options we investigated the associations between Trail Making Test performance--which specifically measures cognitive flexibility and working memory--and dual task costs, a measure of prioritization. METHODOLOGY AND PRINCIPAL FINDINGS: Out of the TREND study (Tuebinger evaluation of Risk factors for Early detection of Neurodegenerative Disorders), 686 neurodegeneratively healthy, non-demented elderly aged 50 to 80 years were classified according to their Trail Making Test performance (delta TMT; TMT-B minus TMT-A). The subjects performed 20 m walks with habitual and maximum speed. Dual tasking performance was tested with walking at maximum speed, in combination with checking boxes on a clipboard, and subtracting serial 7 s at maximum speeds. As expected, the poor TMT group performed worse when subtracting serial 7 s under single and dual task conditions, and they walked more slowly when simultaneously subtracting serial 7 s, compared to the good TMT performers. In the walking when subtracting serial 7 s condition but not in the other 3 conditions, dual task costs were higher in the poor TMT performers (median 20%; range -6 to 58%) compared to the good performers (17%; -16 to 43%; p<0.001). To the contrary, the proportion of the poor TMT performance group that made calculation errors under the dual tasking situation was lower than under the single task situation, but higher in the good TMT performance group (poor performers, -1.6%; good performers, +3%; p = 0.035). CONCLUSION: Under most challenging conditions, the elderly with poor TMT performance prioritize the cognitive task at the expense of walking velocity. This indicates that poor cognitive flexibility and working memory are directly associated with altered prioritization

Risk of Severe Non AIDS Events Is Increased among Patients Unable to Increase their CD4+ T-Cell Counts >200+/μl Despite Effective HAART

Immunological non-response (INR) despite virological suppression is associated with AIDS-defining events/death (ADE). Little is known about its association with serious non-AIDS-defining events (nADE)