F2-isoprostanes and adiposity in older adults.

We examined whether a systemic marker of oxidative stress, F(2)-isoprostanes (F(2)-IPs), was associated with total and regional adiposity, adipocytokines, and change in adiposity. Using data from 726 participants enrolled in the Health, Aging, and Body Composition (Health ABC) study, F(2)-IPs and adipocytokines were measured from baseline plasma samples. Total adiposity was measured by whole-body dual-energy X-ray absorptiometry and regional adiposity by abdominal and thigh computed tomography scans at baseline and 5-year follow-up. ANOVA models were estimated to examine associations between F(2)-IP tertiles and baseline adiposity and changes in body composition. Median F(2)-IPs was 54.3 pg/ml; women had significantly higher levels than men (61.5 vs. 48.9 pg/ml, P < 0.001). F(2)-IPs were associated with higher levels of adiponectin, leptin, and tumor necrosis factor-α (TNF-α). Positive associations were found between F(2)-IPs and all measures of total and regional adiposity among women. In linear regression models, adipocytokines mediated associations among women. Over 5 years of follow-up, women in the highest vs. lowest F(2)-IP tertile exhibited significant loss of weight (lowest tertile: -1.1 kg, highest tertile: -2.7 kg, P < 0.05). In conclusion, F(2)-IPs were associated with measures of total and regional adiposity in women alone and these associations were partially explained by adipocytokines. F(2)-IPs predicted loss of total adiposity over time among women.

Assessment of eptifibatide clearance by hemodialysis using an in vitro system.

BACKGROUND/AIMS: Eptifibatide is a parenteral glycoprotein IIb-IIIa inhibitor that prevents platelet aggregation. Although contraindicated in dialysis patients due to limited safety and dialysis data, eptifibatide is prescribed in this population and is associated with bleeding complications. This study was done to determine dialysis clearance (CL(D)) of eptifibatide using an in vitro system. METHODS: Three common dialyzers were tested. In vitro dialysis was performed at a dialysate flow rate of 500 ml/min, 'blood' flow rate (Q(B)) of 200 and 400 ml/min, and the minimal ultrafiltration rate. Eptifibatide CL(D) and fraction removed were calculated for each condition. RESULTS: CL(D) ranged from 122 to 225 ml/min and was not significantly different among the dialyzers tested. CL(D) was flow dependent with higher clearances observed at higher Q(B). The estimated fraction of eptifibatide removed was 73-83%. CONCLUSIONS: These data suggest that hemodialysis is an effective method to decrease the effects of eptifibatide in patients with impaired kidney function.

Kidney dysfunction and fatal cardiovascular disease--an association independent of atherosclerotic events: results from the Health, Aging, and Body Composition (Health ABC) study.

BACKGROUND: Impaired kidney function has been associated with increased risk for death, myocardial infarction, stroke, and heart failure in high-risk populations. We evaluated whether impaired kidney function predicted risk of fatal cardiovascular disease independent of prevalent and incident cardiovascular events. METHODS: The Health, Aging, and Body Composition study is a cohort of well-functioning, elderly participants aged 70 to 79 years at entry. We measured serum cystatin C and creatinine from baseline plasma samples of 3044 participants and followed them over 6 years, examining the associations among kidney function, cardiovascular death, and incident cardiovascular events. Cystatin C was categorized as low (< 0.84 mg/L), medium (0.84-1.18 mg/L), or high (> or = 1.19 mg/L); serum creatinine (cutoff value of > or = 1.3 in women and > or = 1.5 in men) and estimated glomerular filtration rate (eGFR; greater and less than 60 mL/min per 1.73 m2) were dichotomized. RESULTS: During follow-up, 242 cardiovascular deaths occurred, of which 69 were in participants without prior cardiovascular events; 294 incident cardiovascular events occurred including 135 myocardial infarctions and 163 strokes. Higher cystatin C concentrations were significantly associated with cardiovascular death (adjusted hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.05-2.76 for the medium cystatin C group; and HR 2.24, 95% CI 1.30-3.86 for the high cystatin C group, relative to the low cystatin C group). The point estimate was of greater magnitude in the analysis that excluded prevalent cardiovascular disease (adjusted HR 2.68, 95% CI 0.94-7.70 for the medium cystatin C group; and HR 4.91, 95% CI, 1.55-15.54 for the high cystatin C group). Elevated creatinine levels (adjusted HR 1.54, 95% CI 1.02-2.33, and HR 2.28, 95% CI 1.10-4.73 among participants without a history of cardiovascular disease) were also associated with cardiovascular death. No significant association was found between low eGFR and cardiovascular death. In addition, cystatin C, low eGFR, or elevated creatinine levels were not associated with other cardiovascular events. CONCLUSION: Impaired kidney function is a strong predictor of cardiovascular death, particularly among participants without prior history of cardiovascular disease.

Chronic kidney disease and functional limitation in older people: health, aging and body composition study.

OBJECTIVES: To assess whether chronic kidney disease (CKD) is independently associated with incident physical-function limitation. DESIGN: Prospective cohort study. SETTING: Two sites: Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Two thousand one hundred thirty-five men and women aged 70 to 79 without functional limitation at baseline from the Health, Aging and Body Composition Study. MEASUREMENTS: Functional limitation was defined as difficulty in walking one-quarter of a mile or climbing 10 steps on two consecutive reports 6 months apart (in the same function). Kidney function was measured using serum cystatin C. Estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease formula (<60 versus > or =60 mL/min per 1.73 m(2)), was a secondary predictor. Muscle strength, lean body mass according to dual energy x-ray absorptiometry, comorbidity, medication use, and inflammatory markers were evaluated as covariates. RESULTS: Persons in the highest (> or =1.13 mg/L) quartile of cystatin C experienced a significantly higher risk of developing functional limitation than those in the lowest (<0.86 mg/L) quartile (hazard ratio (HR)=1.70, 95% confidence interval (CI)=1.40-2.07). The association between the fourth cystatin C quartile and functional limitation remained after adjustment for demographics, lean body mass, comorbidity, muscle strength, and gait speed (HR=1.41, 95% CI=1.13-1.75), although the association was attenuated after adjustment for markers of inflammation (HR=1.15, 95% CI=0.90-1.46). Similar results were found for eGFR less than 60 mL/min per 1.73 m(2), although the association with functional limitation remained after adjustment for inflammatory markers (HR=1.30, 95% CI=1.08-1.56). CONCLUSION: CKD is associated with the development of functional impairment independent of comorbidity, body composition, and tests of strength and physical performance. The mechanism may be related to a heightened inflammatory state in CKD.

Fluconazole-carbamazepine interaction.

The patient we describe had elevated carbamazepine serum concentrations during concomitant fluconazole administration (400 mg/day), including serial concentrations both before and after antifungal therapy. Since fluconazole is a known inhibitor of the cytochrome P450 enzyme system, this suggests an inhibition of carbamazepine metabolism.