02646nas a2200433 4500008004100000022001400041245009700055210006900152260001300221300001100234490000700245520147400252653000901726653002201735653002001757653001901777653003301796653001101829653001901840653001801859653001101877653002601888653000901914653002401923653000901947653001601956653001801972653001401990100001702004700002102021700002002042700002102062700002002083700001802103700002002121700001802141700001702159856003602176 2015 eng d a1532-860000aSerum urate levels and the risk of hip fractures: data from the Cardiovascular Health Study.0 aSerum urate levels and the risk of hip fractures data from the C c2015 Mar a438-460 v643 a

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.

10aAged10aAged, 80 and over10aBody Mass Index10aCohort Studies10aEstrogen Replacement Therapy10aFemale10aHealth Surveys10aHip Fractures10aHumans10aKaplan-Meier Estimate10aMale10aProspective Studies10aRisk10aSex Factors10aUnited States10aUric Acid1 aMehta, Tapan1 aBůzková, Petra1 aSarnak, Mark, J1 aChonchol, Michel1 aCauley, Jane, A1 aWallace, Erin1 aFink, Howard, A1 aRobbins, John1 aJalal, Diana uhttps://chs-nhlbi.org/node/662402478nas a2200241 4500008004100000022001400041245012400055210007000179260001600249300000700265490000700272520174300279100001702022700002102039700002002060700001802080700002102098700002402119700002102143700001902164700001702183856003602200 2017 eng d a1471-236900aHigher plasma transforming growth factor (TGF)-β is associated with kidney disease in older community dwelling adults.0 aHigher plasma transforming growth factor TGFβ is associated with c2017 Mar 21 a980 v183 a

BACKGROUND: TGF-β is induced in the vasculature with aging suggesting that high plasma TGF-β levels may be a risk factor for chronic kidney disease (CKD) in older adults.

METHODS: We conducted a cross-sectional analysis of the association between plasma TGF-β levels and CKD including data for 1722 older adults who had participated in the 1996/97 visit of the Cardiovascular Health Study (CHS). Prevalent CKD was defined as eGFR < 60 mL/min/1.73 m(2) or urinary albumin/creatinine ratio (ACR) ≥30 mg/g. We also evaluated whether baseline TGF-β levels predicted change in eGFR, cardiovascular (CV) events, or mortality in longitudinal analysis.

RESULTS: Plasma TGF-β levels were significantly and independently associated with lower eGFR in cross-sectional analysis. Doubling of TGF-β was significantly associated with lower eGFR (β estimate after adjusting for CV risk factors = -1.18, 95% CI -2.03, -0.32). We observed no association with albuminuria. There was no association between baseline TGF-β and change in eGFR, but each doubling of TGF-β at baseline was associated with increased risk of a composite outcome of CV events and mortality, adjusted HR 1.10 (95% C.I. 1.02- 1.20, p = 0.006).

CONCLUSION: In this large cohort of community-dwelling older individuals, high plasma TGF-β levels are modestly, but independently associated with lower eGFR but not with albuminuria in cross-sectional analysis. In addition, TGF-β levels are associated with increased risk of CV events and mortality. Further research is needed to determine the direction of association between plasma TGF-β and the risk of CKD and CKD-associated morbidities in older adults.

1 aMehta, Tapan1 aBůzková, Petra1 aKizer, Jorge, R1 aDjoussé, Luc1 aChonchol, Michel1 aMukamal, Kenneth, J1 aShlipak, Michael1 aIx, Joachim, H1 aJalal, Diana uhttps://chs-nhlbi.org/node/735102586nas a2200289 4500008004100000022001400041245011400055210006900169260001600238520170000254100002601954700002101980700002402001700002302025700002002048700002002068700002002088700001802108700002202126700001902148700002002167700001302187700001902200700001702219700002402236856003602260 2017 eng d a1523-468100aSoluble Inflammatory Markers and Risk of Incident Fractures in Older Adults: The Cardiovascular Health Study.0 aSoluble Inflammatory Markers and Risk of Incident Fractures in O c2017 Oct 043 a

Several in vitro and animal studies have showed that inflammatory markers play a role in bone remodeling and pathogenesis of osteoporosis. Additionally, some human longitudinal studies showed suggestive associations between elevated inflammatory markers and increased risk of nontraumatic fractures. We examined several inflammatory markers and multiple fracture types in a single study of older individuals with extensive follow-up. We assessed the association of four inflammatory markers with the risk of incident hip fractures among 5265 participants of the Cardiovascular Health Study (CHS) and a composite endpoint of incident fractures of the hip, pelvis, humerus, or proximal forearm in 4477 participants. Among CHS participants followed between 1992 and 2009, we observed 480 incident hip fractures during a median follow-up of 11 years. In the composite fracture analysis cohort of 4477 participants, we observed 711 fractures during a median follow-up of 7 years. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for hip fracture associated with doubling of IL-6 were HR 1.15 (95% CI, 1.02 to 1.30) overall and HR 1.17 (95% CI, 1.01 to 1.35) in women. We also observed a positive association between each unit increase in white blood cell (WBC) count and risk of hip fracture: HR 1.04 (95% CI, 1.01 to 1.06) overall and HR 1.06 (95% CI, 0.95 to 1.20) in women. We observed no significant associations between any of the four inflammatory markers and a composite fracture endpoint. Our findings suggest that chronic inflammatory and immune processes may be related to higher rates of incident hip fractures. © 2017 American Society for Bone and Mineral Research.

1 aStojanović, Danijela1 aBůzková, Petra1 aMukamal, Kenneth, J1 aHeckbert, Susan, R1 aPsaty, Bruce, M1 aFink, Howard, A1 aCauley, Jane, A1 aWallace, Erin1 aCurtis, Lesley, H1 aHirsch, Calvin1 aBudoff, Matthew1 aLi, Dong1 aYoung, Rebekah1 aJalal, Diana1 aDelaney, Joseph, Ac uhttps://chs-nhlbi.org/node/759202924nas a2200337 4500008004100000022001400041245008300055210006900138260001600207300000700223490000700230520199400237653000902231653001202240653001802252653001102270653002702281653002202308100002402330700002102354700002002375700002002395700001902415700001702434700002102451700001902472700001802491700001702509700002402526856003602550 2023 eng d a1862-351400aThe associations of markers of endothelial dysfunction with hip fracture risk.0 aassociations of markers of endothelial dysfunction with hip frac c2023 Mar 02 a390 v183 a

UNLABELLED: Endothelial dysfunction underlies the development of atherosclerotic vascular disease, which in turn is associated with osteoporotic fractures. Here, we examined the association of two markers of endothelial dysfunction with incident hip fracture risk in older adults but found no statistically significant associations between them.

PURPOSE/INTRODUCTION: Endothelial dysfunction underlies the development of atherosclerotic vascular disease. Vascular disease, in turn, is associated with the risk of osteoporotic fractures, such as hip fractures. Here, we examine whether two measures of endothelial dysfunction are related to hip fracture risk.

METHODS: Participants for this study were 2792 individuals (mean age 78.6 years) who had flow-mediated dilation (FMD) measured after ischemia in the forearm and 2255 adults (mean age 73.3 years) with measured soluble intercellular adhesion molecule (siCAM) levels, a constitutive endothelial cell membrane protein associated with the initiation of atherosclerosis. Mean follow-up was 9.7 and 11.7 years, respectively. There were 375 and 265 incident hip fractures, respectively, in each group.

RESULTS: In Cox proportional hazards models, there was no significant association between FMD response and incident hip fracture (HR per 1% higher FMD was 0.98 [0.93, 1.04]; p = 0.44). In exploratory analyses, when data were examined dichotomously, participants in the lowest 80% of FMD (≤ 4.5%) had an adjusted 1.29 (0.98, 1.68; p = 0.067) higher hazard of hip fracture compared to participants in the upper 20% of FMD change. There were no significant associations between siCAM and incident hip fracture whether examined as a continuous or dichotomized variable.

CONCLUSIONS: Among older adults, two measures of endothelial dysfunction were not significantly associated with hip fracture risk. There was a trend for higher fracture risk with lower FMD.

10aAged10aForearm10aHip Fractures10aHumans10aOsteoporotic Fractures10aVascular Diseases1 aBarzilay, Joshua, I1 aBůzková, Petra1 aFink, Howard, A1 aCauley, Jane, A1 aCarbone, Laura1 aElam, Rachel1 aRobbins, John, A1 aStein, Phyllis1 aSheets, Kerry1 aJalal, Diana1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/9316