Advanced glycation end products and their circulating receptors predict cardiovascular disease mortality in older community-dwelling women.

AIMS: To characterize the relationship between advanced glycation end products (AGEs) and circulating receptors for AGEs (RAGE) with cardiovascular disease mortality. METHODS: The relationships between serum AGEs, total RAGE (sRAGE), and endogenous secretory RAGE (esRAGE), and mortality were characterized in 559 community-dwelling women, double dagger 65 years, in Baltimore, Maryland. RESULTS: During 4.5 years of follow-up, 123 (22%) women died, of whom 54 died with cardiovascular disease. The measure of serum AGEs was carboxymethyl-lysine (CML), a dominant AGE. Serum CML predicted cardiovascular disease mortality (Hazards Ratio [HR] for highest vs lower three quartiles, 1.94, 95% Confidence Interval [CI] 1.08-3.48, p=0.026), after adjusting for age, race, body mass index, and renal insufficiency. Serum sRAGE (ng/mL) and esRAGE (ng/mL) predicted cardiovascular disease mortality (HR per 1 Standard Deviation [SD] 1.27, 95% CI 0.98-1.65, p=0.07; HR 1.28, 95% CI 1.02-1.63, p=0.03), after adjusting for the same covariates. Among non-diabetic women, serum CML, sRAGE, and esRAGE, respectively, predicted cardiovascular disease mortality (HR for highest vs lower three quartiles, 2.29, 95% CI 1.21-4.34, p=0.01; HR per 1 SD, 1.24, 95% CI 0.92-1.65, p=0.16; HR per 1 SD 1.45, 95% CI 1.08-1.93, p=0.01), after adjusting for the same covariates. CONCLUSIONS: High circulating AGEs and RAGE predict cardiovascular disease mortality among older community-dwelling women. AGEs are a potential target for interventions, as serum AGEs can be lowered by change in dietary pattern and pharmacological treatment.

Elevated serum advanced glycation end products and poor grip strength in older community-dwelling women.

BACKGROUND: Advanced glycation end products (AGEs) have been implicated in the pathogenesis of diabetes, heart disease, and kidney failure and may potentially affect skeletal muscle. Whether AGEs are associated with poor muscle strength is unknown. METHODS: Serum carboxymethyl-lysine (CML), a dominant AGE, circulating soluble form of receptor for advanced glycation end products (sRAGE), and endogenous secretory receptor for advanced glycation end product (esRAGE) and grip strength were measured in 559 moderately to severely disabled women, age 65 and older, in the Women's Health and Aging Study I in Baltimore, Md. RESULTS: Mean (standard deviation) grip strength among women in the highest quartile of serum CML compared with women in the lower three quartiles was 18.6 and 20.0 kg, respectively (p = .002), adjusting for age, race, body mass index, cognitive dysfunction, depression, and diabetes. Serum sRAGE and esRAGE were not significantly associated with grip strength. CONCLUSIONS: Women with high serum AGEs have greater muscle weakness. Further studies are needed to determine whether AGEs, a potentially modifiable risk factor, are associated with physical performance and disability in older adults.

Advanced glycation end products and their circulating receptors and level of kidney function in older community-dwelling women.

BACKGROUND: Advanced glycation end products (AGEs) and the receptor for AGE (RAGE) are implicated in the pathogenesis of kidney disease; however, their relation with level of kidney function has not been well characterized. STUDY DESIGN: Cross-sectional and prospective. SETTING & PARTICIPANTS: 548 moderately to severely disabled community-dwelling women in the Women's Health and Aging Study I in Baltimore, MD. PREDICTOR: Serum carboxymethyl-lysine (CML), a dominant AGE; total soluble RAGE (sRAGE); and endogenous secretory RAGE (esRAGE). OUTCOMES & MEASUREMENTS: Glomerular filtration rate (GFR), prevalent and incident decreased GFR (GFR < 60 mL/min/1.73 m(2)). Serum CML, sRAGE, and esRAGE. RESULTS: Of 548 women, 283 (51.6%) had decreased GFR at baseline. Serum CML level was associated with decreased GFR (OR [all expressed per 1 SD], 1.98; 95% CI, 1.41 to 2.76; P < 0.001) in a multivariate logistic regression model adjusting for age, race, hemoglobin A(1c) level, and chronic diseases. Serum sRAGE and esRAGE levels (both in nanograms per milliliter) were associated with decreased GFR (OR, 1.42; 95% CI, 1.12 to 1.79; P = 0.003; OR, 1.42; 95% CI, 1.14 to 1.77; P = 0.001, respectively) in separate multivariate logistic regression models adjusting for potential confounders. Of 230 women without decreased GFR at baseline, 32 (13.9%) developed decreased GFR by the follow-up visit 12 months later. Serum CML (in micrograms per milliliter), sRAGE, and esRAGE levels at baseline were associated with the prevalence of decreased GFR 12 months later (OR, 1.80; 95% CI, 1.19 to 2.71; P = 0.005; OR, 1.32; 95% CI, 1.01 to 1.74; P = 0.05; and OR, 1.33; 95% CI, 1.01 to 1.77; P = 0.05, respectively) in separate multivariate logistic regression models adjusting for potential confounders. LIMITATIONS: Small number of incident cases, limited follow-up, creatinine values not standardized. CONCLUSIONS: AGE and circulating RAGE levels are independently associated with decreased GFR and seem to predict decreased GFR. AGEs are amenable to interventions because serum AGE levels can be decreased by change in dietary pattern and pharmacological treatment.

Circulating oxidized low-density lipoproteins are associated with overweight, obesity, and low serum carotenoids in older community-dwelling women.

OBJECTIVE: The objective of this study was to determine whether total serum carotenoids, alpha-tocopherol, selenium, and obesity were independently associated with oxidized low-density lipoproteins (ox-LDLs) in moderately to severely disabled older women living in the community. METHODS: Serum ox-LDLs, carotenoids, alpha-tocopherol, and selenium were measured in a population-based sample of 543 moderately to severely disabled women > or = 65 y in the Women's Health and Aging Study I in Baltimore, Maryland. RESULTS: Total serum carotenoids, smoking, overweight (body mass index 25-29.9 kg/m(2)), and obesity (body mass index > or = 30 mg/kg(2)) were significantly associated with the ox-LDL/LDL cholesterol ratio after adjusting for age, C-reactive protein, and chronic diseases. alpha-Tocopherol and selenium were not significantly associated with the ox-LDL/LDL cholesterol ratio. CONCLUSION: Older women who are overweight or obese or who have low total serum carotenoids are more likely to have higher lipoprotein oxidation. Weight reduction in overweight/obese women and increased intake of carotenoid-rich foods may potentially reduce lipoprotein oxidation.

Low serum selenium concentrations are associated with poor grip strength among older women living in the community.

Aging is associated with a loss of muscle strength, and, in turn, loss of muscle strength has been associated with increased risk of frailty, disability and mortality. The factors that contribute to loss of muscle strength with aging have not been well characterized. Selenium is important in normal muscle function because of its role in selenoenzymes that protect muscle against oxidative damage. We hypothesized that low serum selenium concentrations were associated with poor grip strength. We examined the association between serum selenium and hand grip strength among 676 moderately to severely disabled community-dwelling women in the Women's Health and Aging Study I in Baltimore, Maryland. After adjusting for age, race, body mass index, Mini-Mental Status Examination score, current smoking, hypertension, congestive heart failure and depression, serum selenium was associated with grip strength (P=0.04). This study supports the idea that selenium is important to muscle strength in older women.