03114nas a2200433 4500008004100000022001400041245009600055210006900151260001300220300001100233490000700244520194700251653000902198653002202207653002002229653001502249653001902264653002802283653003502311653002102346653002202367653001102389653001102400653000902411653002602420653002402446653001702470653001102487100001802498700001602516700001602532700001302548700001402561700002002575700001702595700001502612700001702627856003602644 2013 eng d a1432-042800aPrediction and classification of cardiovascular disease risk in older adults with diabetes.0 aPrediction and classification of cardiovascular disease risk in  c2013 Feb a275-830 v563 a

AIMS/HYPOTHESIS: We sought to derive and validate a cardiovascular disease (CVD) prediction algorithm for older adults with diabetes, and evaluate the incremental benefit of adding novel circulating biomarkers and measures of subclinical atherosclerosis.

METHODS: As part of the Cardiovascular Health Study (CHS), a population-based cohort of adults aged ≥65 years, we examined the 10 year risk of myocardial infarction, stroke and cardiovascular death in 782 older adults with diabetes, in whom 265 events occurred. We validated predictive models in 843 adults with diabetes, who were followed for 7 years in a second cohort, the Multi-Ethnic Study of Atherosclerosis (MESA); here 71 events occurred.

RESULTS: The best fitting standard model included age, smoking, systolic blood pressure, total and HDL-cholesterol, creatinine and the use of glucose-lowering agents; however, this model had a C statistic of 0.64 and poorly classified risk in men. Novel biomarkers did not improve discrimination or classification. The addition of ankle-brachial index, electrocardiographic left ventricular hypertrophy and internal carotid intima-media thickness modestly improved discrimination (C statistic 0.68; p = 0.002) and classification (net reclassification improvement [NRI] 0.12; p = 0.01), mainly in those remaining free of CVD. Results were qualitatively similar in the MESA, with a change in C statistic from 0.65 to 0.68 and an NRI of 0.09 upon inclusion of subclinical disease measures.

CONCLUSIONS/INTERPRETATION: Standard clinical risk factors and novel biomarkers poorly discriminate and classify CVD risk in older adults with diabetes. The inclusion of subclinical atherosclerotic measures modestly improves these features, but to develop more robust risk prediction, a better understanding of the pathophysiology and determinants of CVD in this patient group is needed.

10aAged10aAged, 80 and over10aAtherosclerosis10aBiomarkers10aBlood Pressure10aCardiovascular Diseases10aCarotid Intima-Media Thickness10aCholesterol, HDL10aDiabetes Mellitus10aFemale10aHumans10aMale10aMyocardial Infarction10aRegression Analysis10aRisk Factors10aStroke1 aMukamal, K, J1 aKizer, J, R1 aDjoussé, L1 aIx, J, H1 aZieman, S1 aSiscovick, D, S1 aSibley, C, T1 aTracy, R P1 aArnold, A, M uhttps://chs-nhlbi.org/node/585902719nas a2200241 4500008004100000022001400041245007500055210006900130260001300199300001100212490000700223520205900230100001902289700001802308700001602326700001602342700001302358700001502371700002002386700001702406700001802423856003602441 2016 eng d a1433-296500aFibrosis markers, hip fracture risk, and bone density in older adults.0 aFibrosis markers hip fracture risk and bone density in older adu c2016 Feb a815-200 v273 a

UNLABELLED: We examined whether blood levels of two markers of fibrosis (transforming growth factor beta one (TGF-β1) and procollagen type III N-terminal propeptide (PIIINP)) are related to hip fracture risk and to bone mineral density (BMD). TGF-β1 levels were associated with lower hip fracture risk in women and with lower BMD in men. PIIINP levels were not associated with either outcome.

INTRODUCTION: TGF-β1 serves several roles in bone formation and resorption. A consequence of TGF-β1 activation is the production of PIIINP, a marker of collagen III deposition. Here, we explore whether these two biomarkers are related to incident hip fracture and bone mineral density (BMD) and whether their associations are modified by systemic inflammation, as measured by C-reactive protein (CRP) levels.

METHODS: Participants were from the Cardiovascular Health Study (mean age 78 years; mean follow-up 8.3 years). We included 1681 persons with measured levels of TGF-β1 (149 hip fractures) and 3226 persons with measured levels of PIIINP (310 hip fractures).

RESULTS: Among women, higher TGF-β1 levels were associated with lower hip fracture risk (HR, per doubling, 0.78 [95 % CI 0.61, 0.91]). Among men, TGF-β1 levels were associated with hip fracture risk in a non-linear manner, but among those with elevated CRP levels, doubling was associated with increased risk of fracture (HR 2.22 [1.20, 4.08]) (p = 0.02, interaction between low and high CRP and TGF-β1 on fracture risk). TGF-β1 levels had no significant association with total hip or total body BMD in women but were significantly associated with lower BMD in men. There were no associations of PIIINP levels with hip fracture risk or BMD in men or women.

CONCLUSIONS: TGF-β1 levels appear to be associated with bone-related phenotypes in a sex-specific manner. The reasons for these differences between men and women regarding TGF-β1 levels and hip fracture risk and bone density require further investigation.

1 aBarzilay, J, I1 aBůžková, P1 aKizer, J, R1 aDjoussé, L1 aIx, J, H1 aFink, H, A1 aSiscovick, D, S1 aCauley, J, A1 aMukamal, K, J uhttps://chs-nhlbi.org/node/680602781nas a2200253 4500008004100000022001400041245012400055210006900179260001600248520203400264100001502298700001002313700001702323700002402340700001802364700001302382700002002395700001502415700001802430700001602448700001102464700001602475856003602491 2019 eng d a1433-296500aBiochemical markers of bone turnover and risk of incident hip fracture in older women: the Cardiovascular Health Study.0 aBiochemical markers of bone turnover and risk of incident hip fr c2019 Jun 213 a

The relationships of osteocalcin (OC) and C-telopeptide of type I collagen (CTX) with long-term incidence of hip fracture were examined in 1680 post-menopausal women from a population-based study. CTX, but not OC, levels were associated with incident hip fracture in these participants, a relationship characterized by an inverted U-shape.

INTRODUCTION: We sought to investigate the relationships of OC, a marker of bone formation, and CTX, a marker of bone resorption, with long-term incidence of hip fracture in older women.

METHODS: We included 1680 women from the population-based Cardiovascular Health Study (mean [SD] age 74.5 [5.0] years). The longitudinal association of both markers with incidence of hip fracture was examined using multivariable Cox models.

RESULTS: During a median follow-up of 12.3 years, 288 incident hip fractures occurred. Linear spline analysis did not demonstrate an association between OC levels and incident hip fracture. By contrast, increasing levels of CTX up to the middle-upper range were associated with a significantly greater risk of hip fracture (HR = 1.52 per SD increment, 95% CI = 1.10-2.09), while further increases were associated with a marginally non-significant lower risk (HR = 0.80 per SD increment, 95% CI = 0.63-1.01), after full adjustment for potential confounders. In analyses of quartiles, CTX exhibited a similar inverted U-shaped relationship with incident fracture after adjustment, with a significant association observed only for the comparison of quartile 3 to quartile 1 (HR = 1.63, 95% CI = 1.10-2.43). In a subset with available measures, both OC and CTX were inversely associated with bone mineral density of the hip.

CONCLUSION: CTX, but not OC, levels were associated with incident hip fracture in post-menopausal women, a relationship characterized by an inverted U-shape. These findings highlight the complex relationship of bone turnover markers with hip fracture risk.

1 aMassera, D1 aXu, S1 aWalker, M, D1 aValderrábano, R, J1 aMukamal, K, J1 aIx, J, H1 aSiscovick, D, S1 aTracy, R P1 aRobbins, J, A1 aBiggs, M, L1 aXue, X1 aKizer, J, R uhttps://chs-nhlbi.org/node/8106