Serum urate levels and the risk of hip fractures: data from the Cardiovascular Health Study.

PURPOSE: Uric acid inhibits vitamin D activation experimentally and higher serum urate levels are associated with higher parathyroid hormone levels in humans suggesting a link between uric acid and bone health. We hypothesized that hyperuricemia may increase the risk of fractures in older adults. METHODS: 1963 men and 2729 women ≥65 years of age who participated in the Cardiovascular Health Study and had baseline serum urate levels were included in the study. The primary outcome was incident hip fracture, assessed prospectively through June, 2008 by inpatient and outpatient records. The analysis was stratified by sex a priori. RESULTS: There was a U-shaped relationship between serum urate levels and hip fractures in men. Men in the lowest and the highest urate quartiles (<4.88 and ≥6.88 mg/dL respectively) had a significantly higher rate of fractures in unadjusted analysis. However, upon multivariate adjustment, only the HR for hip fracture in highest quartile versus the reference remained significant (HR 1.9; 95% C.I. 1.1, 3.1; p value 0.02). High serum urate levels were not associated with hip fractures in women. CONCLUSION: In this large prospective cohort of community-dwelling older adults, increased serum urate levels were associated with an increased risk of hip fractures in men. Further studies are needed to confirm these findings and to understand the mechanisms that underlie them.

Markers of mineral metabolism are not associated with aortic pulse wave velocity in community-living elderly persons: the Health Aging and Body Composition study.

BACKGROUND: Disorders in mineral metabolism are associated with risk for cardiovascular disease (CVD) events in patients with kidney disease as well as in the general population. This risk is thought to be mediated, in part, through the mechanism of stiffening of the arteries. METHODS: The objective of this study was to evaluate the relationships between serum calcium, phosphorus, intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D levels and arterial pulse wave velocity (aPWV) among 2,229 community-dwelling elderly persons participating in the Health Aging and Body Composition (Health ABC) study. RESULTS: The mean age of the participants was 72 years; 52% were woman, 39% were black, and 17% had chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)). In parallel unadjusted analyses, the following associations were observed: 2.86% greater aPWV per 12 ng/ml (s.d.) lower 25-hydroxyvitamin D (95% confidence interval -4.38%, -1.31%), 3.04% greater aPWV per 28 pg/ml (s.d.) higher iPTH (95% confidence interval 1.42-4.68%), and 2.37% lower aPWV per 0.5 mg/dl (s.d.) higher phosphorus (95% confidence interval -3.90% to - 0.81%). Except for phosphorus, these associations were attenuated and rendered no longer statistically significant after adjustment for demographic risk factors, clinical site, season, medications and other CVD risk factors. The results were similar in men and women and were not dependent on the presence of CKD. CONCLUSIONS: Among well-functioning community-dwelling elderly persons, only serum phosphorus was associated with aPWV; and this association was in the opposite direction of the one hypothesized. Factors other than vascular stiffening may mediate the relationship between disordered mineral metabolism and CVD events in community-living elders.

Association of cystatin C with adverse outcomes.

PURPOSE OF REVIEW: To discuss recent studies which have evaluated determinants of cystatin C and to focus on the relationship of cystatin C with mortality, cardiovascular disease (CVD), and noncardiovascular outcomes. RECENT FINDINGS: In the Chronic Kidney Disease Epidemiology Study cystatin C was associated with demographic characteristics independent of measured glomerular filtration rate (GFR), although this was to a smaller extent than creatinine. In patients with established chronic kidney disease (CKD), cystatin C was strongly and inversely correlated with measured GFR, suggesting that although cystatin C may have other determinants, it is primarily a measure of kidney function. Several cohort studies, particularly in older adults, have now demonstrated that cystatin C is linearly associated with mortality, CVD and non-CVD outcomes, whereas creatinine is primarily associated with risk in individuals with more advanced kidney disease. A recent study has also shown that changes in kidney function as ascertained by cystatin C, even within the relatively normal range, are associated with subsequent CVD and all-cause mortality among older adults. SUMMARY: Cystatin C appears to capture an association of mild kidney disease with increased risk of mortality, CVD and non-CVD outcomes. Future studies should evaluate whether cystatin C can improve medical decision-making and lead to favorable patient outcomes.

Cystatin C associates with arterial stiffness in older adults.

Large arteries commonly become stiff in kidney failure, but few studies have investigated arterial stiffness in earlier stages of kidney disease. We evaluated the association between kidney function and aortic pulse wave velocity (aPWV) and its potential modification by race, diabetes, or coronary heart disease in older adults. We measured aPWV in 2468 participants in the Health Aging and Body Composition (Health ABC) study; mean age was 73.7 yr, 40% were black, and 24% had diabetes. After categorizing kidney function into three groups on the basis of cystatin C level, multivariable analysis revealed that the medium and high cystatin C groups associated with a 5.3% (95% confidence interval 0.8 to 10.0%) and 8.0% (95% confidence interval 2.2 to 14.1%) higher aPWV than the low cystatin C group; however, chronic kidney disease, as defined by estimated GFR <60 ml/min per 1.73 m(2), did not significantly associate with aPWV. We did not identify interactions between cystatin C and race, diabetes, or coronary heart disease. In conclusion, stiffness of large arteries, a major risk factor for cardiovascular disease, may partially mediate the association between cystatin C and cardiovascular risk in older adults.

Uric acid and long-term outcomes in CKD.

BACKGROUND: Hyperuricemia is prevalent in patients with chronic kidney disease (CKD); however, data are limited about the relationship of uric acid levels with long-term outcomes in this patient population. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial (N = 840) conducted from 1989 to 1993 to examine the effects of strict blood pressure control and dietary protein restriction on progression of stages 3 to 4 CKD. This analysis included 838 patients. PREDICTOR: Uric acid level. OUTCOMES & MEASUREMENTS: The study evaluated the association of baseline uric acid levels with all-cause mortality, cardiovascular disease (CVD) mortality, and kidney failure. RESULTS: Mean age was 52 +/- 12 (SD) years, glomerular filtration rate was 33 +/- 12 mL/min/1.73 m(2), and uric acid level was 7.63 +/- 1.66 mg/dL. During a median follow-up of 10 years, 208 (25%) participants died of any cause, 127 (15%) died of CVD, and 553 (66%) reached kidney failure. In multivariate models, the highest tertile of uric acid was associated with increased risk of all-cause mortality (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.07 to 2.32), a trend toward CVD mortality (HR, 1.47; 95% CI, 0.90 to 2.39), and no association with kidney failure (HR, 1.20; 95% CI, 0.95 to 1.51) compared with the lowest tertile. In continuous analyses, a 1-mg/dL greater uric acid level was associated with 17% increased risk of all-cause mortality (HR, 1.17; 95% CI, 1.05 to 1.30) and 16% increased risk of CVD mortality (HR, 1.16; 95% CI, 1.01 to 1.33), but was not associated with kidney failure (HR, 1.02; 95% CI, 0.97 to 1.07). LIMITATIONS: Primary analyses were based on a single measurement of uric acid. Results are generalizable primarily to relatively young white patients with predominantly nondiabetic CKD. CONCLUSIONS: In patients with stages 3 to 4 CKD, hyperuricemia appears to be an independent risk factor for all-cause and CVD mortality, but not kidney failure.