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Biomedical subjects

Stephen B Kritchevsky

Publications and source records attributed to Stephen B Kritchevsky.

At least 19 recordsLinked to original sources
PubMed2006

Impact of inflammation on the relationship among alcohol consumption, mortality, and cardiac events: the health, aging, and body composition study.

BACKGROUND: Uncertainty remains about the overall survival benefit of alcohol consumption and the mechanisms underlying the cardioprotective effect of light to moderate alcohol intake. Recent evidence suggests an anti-inflammatory effect of light to moderate alcohol consumption. We investigated the relationship of alcohol intake with all-cause mortality and cardiac events and evaluated whether this relationship is mediated or modified by inflammatory markers. METHODS: The analysis included 2487 subjects, aged 70 to 79 years, without baseline coronary heart disease (CHD) or heart failure (HF), participating in the Health, Aging, and Body Composition study. All-cause mortality and incident cardiac events (CHD and HF) were detected during a mean follow-up of 5.6 years. Alcohol consumption and serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP) were assessed at baseline. RESULTS: A total of 397 participants died, and 383 experienced an incident cardiac event. Compared with never or occasional drinkers, subjects drinking 1 to 7 drinks per week had lower age-, sex-, and race-adjusted incidences of death (27.4 vs 20.1 per 1000 person-years, respectively) and cardiac events (28.9 vs 20.8 per 1000 person-years). After adjustment for confounders, compared with never or occasional drinkers, light to moderate drinkers (1-7 drinks per week) showed a decreased risk of death (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.56-1.00) and cardiac events (HR, 0.72; CI, 0.54-0.97). Adjustment for potential mediators, and particularly inflammatory marker levels, did not affect the strength of this association. CONCLUSION: Light to moderate alcohol consumption was associated with significantly lower rates of cardiac events and longer survival, independent of its anti-inflammatory effect.

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PubMed2006

Renal function and heart failure risk in older black and white individuals: the Health, Aging, and Body Composition Study.

BACKGROUND: Chronic kidney disease is a risk factor for heart failure, an association that may be particularly important in blacks who are disproportionately affected by both processes. Our objective was to determine whether the association of chronic kidney disease with incident heart failure differs between blacks and whites. METHODS: The study population comprised participants in the Health, Aging, and Body Composition Study without a diagnosis of heart failure (1124 black and 1676 white community-dwelling older persons). The main predictors were quintiles of cystatin C and creatinine concentrations and estimated glomerular filtration rate. The main outcome measure was incident heart failure. RESULTS: Over a mean 5.7 years, 200 participants developed heart failure. High concentrations of cystatin C and low estimated glomerular filtration rate were each associated with heart failure, but the magnitude was greater for blacks than for whites (cystatin C concentration: adjusted hazard ratio for quintile 5 [> or =1.18 mg/dL] vs quintile 1 [<0.84 mg/dL] was 3.0 [95% confidence interval 1.4-6.5] in blacks and 1.4 [95% confidence interval, 0.8-2.5] in whites; estimated glomerular filtration rate: adjusted hazard ratio for quintile 5 (<59.2 mL/min) vs quintile 1 (>86.7 mL/min) was 2.7 [95% confidence interval, 1.4-4.9] in blacks and 1.8 [95% confidence interval, 0.9-3.6] in whites). For cystatin C, this association was observed at more modest decrements in kidney function among blacks as well. The population attributable risk of heart failure was 47% for blacks with moderate or high concentrations of cystatin C (> or =0.94 mg/dL) (56% prevalence) but only 5% among whites (64% prevalence). CONCLUSION: The association of kidney dysfunction with heart failure appears stronger in blacks than for whites, particularly when cystatin C is used to measure kidney function.

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PubMed2006

Association of long-distance corridor walk performance with mortality, cardiovascular disease, mobility limitation, and disability.

CONTEXT: Aerobic fitness, an important predictor of cardiovascular disease and mortality, is difficult to assess by maximal exercise testing in older adults. Extended walking tests have been examined as outcome predictors in medically ill populations but not in community-dwelling older adults. OBJECTIVE: To determine whether an extended walking test predicts poor outcomes in older adults. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study enrolling 3075 community-dwelling adults aged 70 to 79 years living in Pittsburgh, Pa, or Memphis, Tenn. Of those participating in the Health, Aging, and Body Composition Study, 1584 (52%) were women and 1281 (42%) were black. Participants enrolled from March 1997 to April 1998. Ability to complete the long-distance corridor walk and total performance time was assessed at the baseline examination. MAIN OUTCOME MEASURES: Total mortality, incident cardiovascular disease, incident mobility limitation, and mobility disability were ascertained after a mean (SD) of 4.9 (0.9) years. RESULTS: Among patients eligible to exercise, 351 died, 308 had episodes of incident cardiovascular disease, 1116 had occurrences of mobility limitation, and 509 had occurrences of mobility disability. Inability to complete walking 400 m tended to be associated with a higher risk of mortality and incident cardiovascular disease and, after accounting for potential confounders, was associated with incident mobility limitation (212.6 vs 79.1 events/1000 person-years; adjusted hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.58-2.18; P<.001) and mobility disability (85.2 vs 28.8 events/1000 person-years; adjusted HR, 1.95; 95% CI, 1.56-2.44; P<.001). Of those who completed 400 m, each additional minute of performance time was associated with an adjusted HR of 1.29 (95% CI, 1.12-1.48) for mortality, 1.20 (95% CI, 1.01-1.42) for incident cardiovascular disease, 1.52 (95% CI, 1.41-1.63) for mobility limitation, and 1.52 (95% CI, 1.37-1.70) for disability after adjustment for demographics, health behaviors, clinical and subclinical disease, and cardiovascular disease risk factors. Findings were consistent in both men and women and blacks and whites. Among participants who completed the test and after adjusting for potential confounders, those in the poorest quartile of functional capacity (walk time >362 seconds) had a higher risk of death than those in the best quartile (walk time <290 seconds; adjusted HR, 3.23; 95% CI, 2.11-4.94; P<.001). CONCLUSIONS: Older adults in the community who reported no difficulty walking had a wide range of performance on this extended walking test. Ability to do the test and performance were important prognostic factors for total mortality, cardiovascular disease, mobility limitation, and mobility disability in persons in their eighth decade.

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PubMed2006

Myeloperoxidase polymorphism and cognitive decline in older adults in the Health, Aging, and Body Composition Study.

Myeloperoxidase, an antimicrobial enzyme, produces oxidative free radicals. Rarely found in normal brain tissue, myeloperoxidase has been detected in microglia associated with Alzheimer's disease plaques. The authors examined a G-463A polymorphism in the promoter region of the myeloperoxidase gene (MPO) to determine the relation of MPO variants to cognitive decline over 4 years in a cohort of adults, aged 70-79 years at baseline (1997-1998), recruited from Memphis, Tennessee, and Pittsburgh, Pennsylvania, into the Health, Aging, and Body Composition Study. In this sample, 8% of the participants had the AA, 36.9% the AG, and 55.2% the GG genotype of MPO. The frequency of AA and AG genotypes was higher in Blacks than Whites (11.2% vs. 5.9%, and 44.1% vs. 32.9%, respectively). Multivariate logistic regression analyses showed that, for participants with the MPO AA genotype, cognitive decline was 1.58 (95% confidence interval: 1.07, 2.35) times more likely than for participants with the AG genotype and 1.96 (95% confidence interval: 1.33, 2.88) times more likely than for those with the GG genotype. Interactions between MPO and race, sex, or the apolipoprotein gene were not significant. In this sample, MPO AA, associated with decreased production of myeloperoxidase, was found to be a risk factor for cognitive decline.

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PubMed2006

Metabolic syndrome and the risk of cardiovascular disease in older adults.

OBJECTIVES: The purpose of this study was to assess whether metabolic syndrome (MetSyn) predicts a higher risk for cardiovascular events in older adults. BACKGROUND: The importance of MetSyn as a risk factor has not previously focused on older adults and deserves further study. METHODS: We studied the impact of MetSyn (38% prevalence) on outcomes in 3,035 participants in the Health, Aging, and Body Composition (Health ABC) study (51% women, 42% black, ages 70 to 79 years). RESULTS: During a 6-year follow-up, there were 434 deaths overall, 472 coronary events (CE), 213 myocardial infarctions (MI), and 231 heart failure (HF) hospital stays; 59% of the subjects had at least one hospital stay. Coronary events, MI, HF, and overall hospital stays occurred significantly more in subjects with MetSyn (19.9% vs. 12.9% for CE, 9.1% vs. 5.7% for MI, 10.0% vs. 6.1% for HF, and 63.1% vs. 56.1% for overall hospital stay; all p < 0.001). No significant differences in overall mortality was seen; however, there was a trend toward higher cardiovascular mortality (5.1% vs. 3.8%, p = 0.067) and coronary mortality (4.5% vs. 3.2%, p = 0.051) in patients with MetSyn. After adjusting for baseline characteristics, patients with MetSyn were at a significantly higher risk for CE (hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.28 to 1.91), MI (HR 1.51, 95% CI 1.12 to 2.05), and HF hospital stay (HR 1.49, 95% CI 1.10 to 2.00). Women and whites with MetSyn had a higher coronary mortality rate. The CE rate was higher among subjects with diabetes and with MetSyn; those with both had the highest risk. CONCLUSIONS: Overall, subjects over 70 years are at high risk for cardiovascular events; MetSyn in this group is associated with a significantly greater risk.

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PubMed2006

Comparing bloodstream infection rates: the effect of indicator specifications in the evaluation of processes and indicators in infection control (EPIC) study.

OBJECTIVE: Bloodstream infection (BSI) rates are used as comparative clinical performance indicators; however, variations in definitions and data-collection approaches make it difficult to compare and interpret rates. To determine the extent to which variation in indicator specifications affected infection rates and hospital performance rankings, we compared absolute rates and relative rankings of hospitals across 5 BSI indicators. DESIGN: Multicenter observational study. BSI rate specifications varied by data source (clinical data, administrative data, or both), scope (hospital wide or intensive care unit specific), and inclusion/exclusion criteria. As appropriate, hospital-specific infection rates and rankings were calculated by processing data from each site according to 2-5 different specifications. SETTING: A total of 28 hospitals participating in the EPIC study. PARTICIPANTS: Hospitals submitted deidentified information about all patients with BSIs from January through September 1999. RESULTS: Median BSI rates for 2 indicators based on intensive care unit surveillance data ranged from 2.23 to 2.91 BSIs per 1000 central-line days. In contrast, median rates for indicators based on administrative data varied from 0.046 to 7.03 BSIs per 100 patients. Hospital-specific rates and rankings varied substantially as different specifications were applied; the rates of 8 of 10 hospitals were both greater than and less than the mean. Correlations of hospital rankings among indicator pairs were generally low (rs=0-0.45), except when both indicators were based on intensive care unit surveillance (rs = 0.83). CONCLUSIONS: Although BSI rates seem to be a logical indicator of clinical performance, the use of various indicator specifications can produce remarkably different judgments of absolute and relative performance for a given hospital. Recent national initiatives continue to mix methods for specifying BSI rates; this practice is likely to limit the usefulness of such information for comparing and improving performance.

Cross Infection↗
PubMed2006

Physical exercise and comorbidity. Results from the Fitness and Arthritis in Seniors Trial (FAST).

BACKGROUND AND AIMS: Physical exercise is associated with a lower risk of disability. The impact of comorbidity on the benefits from physical exercise has not been clearly investigated. Elders with comorbidity may benefit from physical exercise to preserve physical function. METHODS: Data are from 435 participants with knee osteoarthritis aged > or = 60 years enrolled in the Fitness and Arthritis in Seniors Trial (FAST), who were randomly assigned to 18-month health educational (HE), weight training (WT), or aerobic exercise (AE) interventions. Comorbidity was defined as the presence of osteoarthritis and > or = 2 clinical conditions. Percent changes in the 6-minute walk test, self-reported disability and knee pain from baseline to 3-, 9-, and 18-month follow-up visits were analyzed according to comorbidity, using analysis of variance. Significances were adjusted using the Bonferroni method. RESULTS: Mean age of the sample was 68.7 years. In participants with comorbidity (n=197), those in the AE intervention showed significant improvement in walking speed, compared to WT and HE groups, since the beginning of follow-up. Subjects with comorbidity in AE and WT groups showed improvement of the disability score at the 3-month follow-up visit compared to those in the HE group. This improvement was maintained at the end of the follow-up by the only AE group compared to the HE one (p=0.06). In participants with comorbidity, the pain score was improved by the AE intervention. CONCLUSIONS: AE and WT interventions improve physical function in individuals with comorbidity. AE improves physical function and knee pain independently of the presence of comorbidity.

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PubMed2006

Plasminogen activator inhibitor type 1 gene polymorphisms and haplotypes are associated with plasma plasminogen activator inhibitor type 1 levels but not with myocardial infarction or stroke.

BACKGROUND: The 4G allele in the promoter region of the plasminogen activator inhibitor type 1 (PAI-1) gene is associated with higher plasma PAI-1 levels and activity, but its association with cardiovascular diseases is unclear. We investigated the association of polymorphisms and common haplotypes of the PAI-1 gene with plasma PAI-1 levels, as well as the risk of myocardial infarction and stroke. METHODS AND RESULTS: This study is a prospective analysis of 2995 community-based participants (41% blacks and 51% women) aged 70 to 79 years old in the Health, Aging, and Body Composition Study. From 1997/1998 to 2001, 177 myocardial infarction events and 101 stroke events were identified. In addition to the 4G/5G polymorphism, 2 potential functional variants and other 4 haplotype-tagging variants were genotyped. In general linear models, the 4G allele was associated with higher PAI-1 levels after adjusting for age, sex, race, and site (26, 29, and 32 ng/mL for 5G/5G, 4G/5G, and 4G/4G, respectively; P for trend < .0001), but none of the other 6 polymorphisms was associated with PAI-1 levels. Haplotype analysis produced similar results. However, in Cox proportional hazard models, neither the polymorphisms nor the common haplotypes of the PAI-1 gene was associated with the risk of either myocardial infarction or stroke. CONCLUSIONS: The 4G allele is associated with higher PAI-1 levels, but this study does not support an association of the PAI gene polymorphisms with the risk of either myocardial infarction or stroke.

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PubMed2006

Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort.

BACKGROUND: Although muscle strength and mass are highly correlated, the relationship between direct measures of low muscle mass (sarcopenia) and strength in association with mortality has not been examined. METHODS: Total mortality rates were examined in the Health, Aging and Body Composition (Health ABC) Study in 2292 participants (aged 70-79 years, 51.6% women, and 38.8% black). Knee extension strength was measured with isokinetic dynamometry, grip strength with isometric dynamometry. Thigh muscle area was measured by computed tomography (CT) scan, and leg and arm lean soft tissue mass were determined by dual energy x-ray absorptiometry (DXA). Both strength and muscle size were assessed as in gender-specific Cox proportional hazards models, with age, race, comorbidities, smoking status, level of physical activity, fat area by CT or fat mass by DXA, height, and markers of inflammation, including interleukin-6, C-reactive protein, and tumor necrosis factor-alpha considered as potential confounders. RESULTS: There were 286 deaths over an average of 4.9 (standard deviation = 0.9) years of follow-up. Both quadriceps and grip strength were strongly related to mortality. For quadriceps strength (per standard deviation of 38 Nm), the crude hazard ratio for men was 1.51 (95% confidence interval, 1.28-1.79) and 1.65 (95% confidence interval, 1.19-2.30) for women. Muscle size, determined by either CT area or DXA regional lean mass, was not strongly related to mortality. In the models of quadriceps strength and mortality, adjustment for muscle area or regional lean mass only slightly attenuated the associations. Further adjustment for other factors also had minimal effect on the association of quadriceps strength with mortality. Associations of grip strength with mortality were similar. CONCLUSION: Low muscle mass did not explain the strong association of strength with mortality, demonstrating that muscle strength as a marker of muscle quality is more important than quantity in estimating mortality risk. Grip strength provided risk estimates similar to those of quadriceps strength.

Age Factors↗
PubMed2006

Effects of a physical activity intervention on measures of physical performance: Results of the lifestyle interventions and independence for Elders Pilot (LIFE-P) study.

BACKGROUND: The Short Physical Performance Battery (SPPB), which includes walking, balance, and chair stands tests, independently predicts mobility disability and activities of daily living disability. To date, however, there is no definitive evidence from randomized controlled trials that SPPB scores can be improved. Our objective was to assess the effect of a comprehensive physical activity (PA) intervention on the SPPB and other physical performance measures. METHODS: A total of 424 sedentary persons at risk for disability (ages 70-89 years) were randomized to a moderate-intensity PA intervention or a successful aging (SA) health education intervention and were followed for an average of 1.2 years. RESULTS: The mean baseline SPPB score on a scale of 0-12, with 12 corresponding to highest performance, was 7.5. At 6 and 12 months, the PA versus SA group adjusted SPPB (+/- standard error) scores were 8.7 +/- 0.1 versus 8.0 +/- 0.1, and 8.5 +/- 0.1 versus 7.9 +/- 0.2, respectively (p < .001). The 400-meter walking speed was also significantly improved in the PA group. The PA group had a lower incidence of major mobility disability defined as incapacity to complete a 400-meter walk (hazard ratio = 0.71, 95% confidence interval = 0.44-1.20). CONCLUSIONS: A structured PA intervention improved the SPPB score and other measures of physical performance. An intervention that improves the SPPB performance may also offer benefit on more distal health outcomes, such as mobility disability.

Activities of Daily Living↗
PubMed2006

Association of inflammatory markers with socioeconomic status.

BACKGROUND: This study examines the association between socioeconomic status (SES) and inflammatory markers in well-functioning older adults and seeks to determine whether any association remains after adjusting for biomedical and behavioral factors typically related to elevated serum levels of inflammatory markers. METHODS: Data were obtained from 3044 men and women, aged 70-79 from Pittsburgh, Pennsylvania and Memphis, Tennessee participating in the Health, Aging and Body Composition study. Three indicators of SES were used: education, income, and ownership of financial assets. Serum levels of interleukin-6, C-reactive protein, and tumor necrosis factor-alpha were measured. RESULTS: Low SES was associated with significantly elevated levels of interleukin-6, C-reactive protein, and tumor necrosis factor-alpha compared to high SES. Behavioral factors (including smoking, drinking, obesity) explained a substantial part of the inverse association between SES and inflammatory markers. Adjustment for prevalent diseases (including heart diseases, lung disease, and diabetes) associated with inflammation explained less of the association. CONCLUSIONS: This study suggests that interventions to improve health behaviors, even in old age and especially in low SES groups, may be useful in reducing risks associated with inflammation.

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PubMed2006

Abdominal obesity is an independent risk factor for chronic heart failure in older people.

OBJECTIVES: To examine whether total and abdominal adiposity are risk factors for the development of chronic heart failure (CHF) in older men and women. DESIGN: Prospective, longitudinal cohort: The Health, Aging and Body Composition study. SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania, metropolitan areas. PARTICIPANTS: Three thousand seventy-five well-functioning community-dwelling older adults aged 70 to 79. MEASUREMENTS: Body composition using dual energy X-ray absorptiometry, visceral adipose tissue area using computed tomography, adjudicated CHF. RESULTS: Of the remaining (640 participants excluded from original group of 3,075) 2,435 participants (1,081 men, 1,354 women) without coronary heart disease or CHF at baseline, there were 166 confirmed diagnoses of CHF during the median+/-standard deviation (SD) follow-up of 6.1+/-1.4 years. After adjustment for age, race, sex, site, education, smoking, and chronic obstructive pulmonary disorder, all adiposity variables (body mass index (BMI), adipose tissue mass, percentage body fat, waist-to-thigh ratio, waist circumference, and visceral and subcutaneous abdominal adipose tissue) were significant predictors of the development of CHF. In a model that included waist circumference and BMI, waist circumference was associated with incident CHF (hazard ratio (HR)=1.27, 95% confidence interval (CI)=1.04-1.54 per SD increase, P=.02), but BMI was not (HR=1.08, 95% CI=0.86-1.35). When waist circumference and percentage fat were included together, both variables were significant predictors of CHF (waist: HR=1.17, 95% CI=1.00-1.36 per SD increase, P=.05; percentage fat: HR=1.47, 95% CI=1.16-1.87 per SD increase, P=.002). Stepwise adjustment for inflammation, hypertension, insulin resistance, and diabetes mellitus did not decrease the relative risk of a greater waist circumference for the development of CHF (all HR=1.27-1.32, 95% CI=1.02-1.61 per SD increase). CONCLUSION: Abdominal body fat distribution may be a stronger risk factor for CHF than overall obesity.

Absorptiometry, Photon↗
PubMed2006

Dog ownership, walking behavior, and maintained mobility in late life.

OBJECTIVES: To examine dog walking among dog owners and the relationship between walking behavior of dog owners and non-dog owners and maintained gait speed over 3 years. DESIGN: Cross-sectional and longitudinal analyses of a prospective cohort study. SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS: Two thousand five hundred thirty-three community-dwelling adults aged 71 to 82 at 36 months of the Health, Aging and Body Composition Study. MEASUREMENTS: Dog ownership, reported walking behavior, change in walking behavior, and usual and rapid gait speed over 3 years. RESULTS: Of 394 dog owners, only 36% walked their dogs at least three times per week. Cross-sectionally, dog walkers were more likely to achieve 150 minutes of walking per week and had faster usual and rapid walking speeds (1.20 vs 1.14 m/s and 1.62 vs 1.52 m/s, respectively; P < .01 for both) than non-dog owners who did not walk at least three times per week and similar speeds as non-dog owners who walked at least 150 minutes per week (P > .50). Three years later, subjects who had been dog walkers at baseline were approximately twice as likely as any other group to achieve recommended walking levels, independent of covariates. Dog walkers experienced similar declines in usual and rapid walking speed as non-dog owners who walked at least three times per week but maintained their initial mobility advantage. CONCLUSION: Although dog ownership appears to facilitate walking behavior, only a minority of older dog owners walk their dogs. The mobility advantage of dog ownership was seen only in dog walkers and was similar to that associated with any walking. Given suboptimal walking activity in older adults, examining the degree to which dog ownership promotes walking activity in persons who do little walking on their own appears worth pursuing.

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PubMed2006

Diabetes, hyperglycemia, and inflammation in older individuals: the health, aging and body composition study.

OBJECTIVE: The objective of this study was to assess the association of inflammation with hyperglycemia (impaired fasting glucose [IFG]/impaired glucose tolerance [IGT]) and diabetes in older individuals. RESEARCH DESIGN AND METHODS: Baseline data from the Health, Aging and Body Composition study included 3,075 well-functioning black and white participants, aged 70-79 years. RESULTS: Of the participants, 24% had diabetes and 29% had IFG/IGT at baseline. C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels (P < 0.001) were significantly higher among diabetic participants and those with IFG/IGT. Odds of elevated IL-6 and TNF-alpha (>75th percentile) were, respectively, 1.95 (95% CI 1.56-2.44) and 1.88 (1.51-2.35) for diabetic participants and 1.51 (1.21-1.87) and 1.14 (0.92-1.42) for those with IFG/IGT after adjustment for age, sex, race, smoking, alcohol intake, education, and study site. Odds ratios for elevated CRP were 2.90 (2.13-3.95) and 1.45 (1.03-2.04) for diabetic women and men and 1.33 (1.07-1.69) for those with IFG/IGT regardless of sex. After adjustment for obesity, fat distribution, and inflammation-related conditions, IL-6 remained significantly related to both diabetes and IFG/IGT. CRP in women and TNF-alpha in both sexes were significantly related to diabetes, respectively, whereas risk estimates for IFG/IGT were decreased by adjustment for adiposity. Among diabetic participants, higher levels of HbA(1c) were associated with higher levels of all three markers of inflammation, but only CRP remained significant after full adjustment. CONCLUSIONS: Our findings show that dysglycemia is associated with inflammation, and this relationship, although consistent in diabetic individuals, also extends to those with IFG/IGT.

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PubMed2006

Diabetes, inflammation, and functional decline in older adults: findings from the Health, Aging and Body Composition (ABC) study.

OBJECTIVE: Age, diabetes, and elevated inflammatory markers independently increase the risk of functional decline. We examined the effect of C-reactive protein (CRP) and interleukin-6 (IL-6) on the incident mobility limitation in older adults with and without diabetes. RESEARCH DESIGN AND METHODS: We analyzed data from a cohort of 2,895 well-functioning adults aged 70-79 years, followed for development of persistent functional limitation over 3.5 years. Participants were assessed for the presence of diabetes according to fasting glucose and/or hypoglycemic medication use and were divided into three equal groups (tertiles) according to level of CRP or IL-6. Persistent functional limitation was defined as difficulty climbing 10 steps or walking one-quarter mile on two consecutive semiannual assessments. RESULTS: At baseline, 702 participants (24%) had diabetes. CRP values were (median +/- SD) 2.8 +/- 4.4 versus 3.7 +/- 5.4 for those with normal glucose and diabetes, respectively (P < 0.001). The unadjusted incidence of functional limitation associated with increased levels of CRP and IL-6 was greater among participants with diabetes. After adjusting for clinical and demographic covariates, persistent functional limitation for the highest tertile was greater compared with that for the lowest tertile of CRP or IL-6 for those with and without diabetes. CRP hazard ratios (HRs) were 1.7 (95% CI 1.2-2.3) versus 1.4 (1.1-1.6), respectively. IL-6 HRs were 1.8 (1.3-2.5) versus 1.6 (1.4-2.0), respectively. CONCLUSIONS: In initially high-functioning older adults, those with diabetes and higher inflammatory burden had an increased risk of functional decline. Interventions at early stages to reduce inflammation may preserve function in these individuals.

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PubMed2005

Cystatin C and mortality risk in the elderly: the health, aging, and body composition study.

Kidney dysfunction is known to decrease life expectancy in the elderly. Cystatin C is a novel biomarker of kidney function that may have prognostic utility in older adults. The association of cystatin C with mortality was evaluated in a biracial cohort of black and white ambulatory elderly and compared with that of serum creatinine concentrations. The Health, Aging and Body Composition study is a cohort of well-functioning elderly that was designed to evaluate longitudinal changes in weight, body composition, and function. A total of 3075 participants who were aged 70 to 79 yr and had no disability were recruited at sites in Memphis, TN, and Pittsburgh, PA, between April 1997 and June 1998 with a follow-up of 6 yr. At entry, the mean cystatin C was 1.05 mg/L and the mean creatinine was 1.06 mg/dl. After 6 yr of follow-up, 557 participants had died. The mortality rates in each ascending cystatin C quintile were 1.7, 2.7, 2.9, 3.1, and 5.4%/yr. After adjustment for demographic risk factors, comorbid health conditions, and inflammatory biomarkers (C-reactive protein, IL-6. and TNF-alpha), each quintile of cystatin C was significantly associated with increased mortality risk compared with the lowest: Hazard ratios (HR; 95% confidence intervals) quintile 1, -1.0 (referent); quintile 2, -1.74 (1.21 to 2.50); quintile 3, -1.51 (1.05 to 2.18); quintile 4, -1.49 (1.04 to 2.13); and quintile 5, -2.18 (1.53 to 3.10). These associations did not differ by gender or race. Results were consistent for cardiovascular and other-cause mortality, but not cancer mortality. Creatinine quintiles were not associated with mortality after multivariate adjustment (HR: 1.0 [referent], 1.00 [0.72 to 1.39], 0.95 [0.68 to 1.32], 1.11 [0.79 to 1.57], 1.16 [0.86 to 1.58]). Cystatin C is a strong, independent risk factor for mortality in the elderly. Future studies should investigate whether cystatin C has a role in clinical medicine.

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PubMed2005

Lipoprotein peroxidation and mobility limitation: results from the Health, Aging, and Body Composition Study.

BACKGROUND: Oxidative damage plays an important role in leading to major health-related events. The aim of this study was to assess the predictive value of a lipoprotein peroxidation marker, oxidized low-density lipoprotein (oxLDL) for incident mobility limitation (ML). METHODS: Data are from 2985 well-functioning elders enrolled in the Health ABC study (median follow-up, 4.1 years). All oxLDL levels were measured at the baseline assessment. The oxLDL/LDL cholesterol (LDL-C) ratio (log value) was used as a measure of lipoprotein peroxidation. Mobility limitation was defined by 2 consecutive semiannual reports of any difficulty either walking 1/4 mile or climbing up 10 steps without resting. Severe ML was defined by 2 consecutive reports of great difficulty or inability to do the same tasks. Cox proportional hazards models were performed to assess hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The mean (SD) age of the sample was 74.2 (2.9) years. After adjustment for potential confounders (sociodemographic factors, smoking, physical activity, body mass index, clinical conditions, biological markers, and medications), the relationship between the oxLDL/LDL-C ratio and disability events was statistically significant (per log-unit difference in the oxLDL/LDL-C ratio) (for ML: HR, 1.22; 95% CI, 1.06-1.41; for severe ML: HR, 1.43; 95% CI, 1.15-1.79). Consistent results were found when interleukin 6 level was included as a covariate in the adjusted models (ML: HR, 1.13; 95% CI, 0.98-1.31; severe ML: HR, 1.31; 95% CI, 1.05-1.64). No significant sex, race, interleukin 6 level, or clinical conditions interaction was found with the oxLDL/LDL-C ratio and mobility disability. CONCLUSIONS: Lipoprotein peroxidation predicts the onset of ML in older persons. The oxLDL predictive value for ML is partly explained by interleukin 6 levels.

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