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The associations of subclinical atherosclerotic cardiovascular disease with hip fracture risk and bone mineral density in elderly adults.

ABSTRACT: In the absence of clinically recognized cardiovascular disease, increased carotid artery intimal medial thickness was associated with higher hip fracture risk in older adults, despite its association with higher bone mineral density (BMD). Low ankle brachial index and aortic wall thickness were not associated with fracture risk or BMD. INTRODUCTION:Clinically recognized cardiovascular disease (CVD) is associated with osteoporosis and hip fracture risk, but the relationship of subclinical atherosclerosis to bone health is not certain. METHODS:We followed 3385 participants from the Cardiovascular Health Study (mean age 74.7?±?5.3 years) with a median time to fracture of 12.1 years who underwent baseline carotid artery and aortic wall ultrasound scanning and ankle brachial blood pressure index (ABI) determinations. A subset underwent bone mineral density (BMD) testing. RESULTS:There were 494 hip fractures during follow-up. Among persons without clinical CVD, an average standard-deviation increase in a composite score of maximal common and internal carotid artery intimal medial thickness (cIMT) was associated with increased risk of hip fracture [(HR 1.18 [1.04, 1.35]), even though cIMT was positively associated with BMD. Neither aortic wall thickness nor ABI were associated with hip fracture risk or BMD. Among participants with clinical CVD, cIMT and aortic wall thickness, but not ABI, were associated with increased hip fracture risk. CONCLUSION:Subclinical cIMT is associated with an increased risk of hip fractures despite being associated with increased BMD. This finding suggests that vascular health, even in its early stages, is linked to bone health, by pathways other than BMD.

SUBMITTER: Barzilay JI

PROVIDER: S-EPMC6487649 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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The associations of subclinical atherosclerotic cardiovascular disease with hip fracture risk and bone mineral density in elderly adults.

Barzilay J I JI Buzkova P P Cauley J A JA Robbins J A JA Fink H A HA Mukamal K J KJ

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 20180821 10

In the absence of clinically recognized cardiovascular disease, increased carotid artery intimal medial thickness was associated with higher hip fracture risk in older adults, despite its association with higher bone mineral density (BMD). Low ankle brachial index and aortic wall thickness were not associated with fracture risk or BMD.<h4>Introduction</h4>Clinically recognized cardiovascular disease (CVD) is associated with osteoporosis and hip fracture risk, but the relationship of subclinical ...[more]

PMID: 30132027

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Project description:Screening for osteoporosis with bone mineral density (BMD) is recommended for older adults. It is unclear whether repeating a BMD screening test improves fracture risk assessment.To determine whether changes in BMD after 4 years provide additional information on fracture risk beyond baseline BMD and to quantify the change in fracture risk classification after a second BMD measure.Population-based cohort study involving 310 men and 492 women from the Framingham Osteoporosis Study with 2 measures of femoral neck BMD taken from 1987 through 1999.Risk of hip or major osteoporotic fracture through 2009 or 12 years following the second BMD measure.Mean age was 74.8 years. The mean (SD) BMD change was -0.6% per year (1.8%). Throughout a median follow-up of 9.6 years, 76 participants experienced an incident hip fracture and 113 participants experienced a major osteoporotic fracture. Annual percent BMD change per SD decrease was associated with risk of hip fracture (hazard ratio [HR], 1.43 [95% CI, 1.16 to 1.78]) and major osteoporotic fracture (HR, 1.21 [95% CI, 1.01 to 1.45]) after adjusting for baseline BMD. At 10 years' follow-up, 1 SD decrease in annual percent BMD change compared with the mean BMD change was associated with 3.9 excess hip fractures per 100 persons. In receiver operating characteristic (ROC) curve analyses, the addition of BMD change to a model with baseline BMD did not meaningfully improve performance. The area under the curve (AUC) was 0.71 (95% CI, 0.65 to 0.78) for the baseline BMD model compared with 0.68 (95% CI, 0.62 to 0.75) for the BMD percent change model. Moreover, the addition of BMD change to a model with baseline BMD did not meaningfully improve performance (AUC, 0.72 [95% CI, 0.66 to 0.79]). Using the net reclassification index, a second BMD measure increased the proportion of participants reclassified as high risk of hip fracture by 3.9% (95% CI, -2.2% to 9.9%), whereas it decreased the proportion classified as low risk by -2.2% (95% CI, -4.5% to 0.1%).In untreated men and women of mean age 75 years, a second BMD measure after 4 years did not meaningfully improve the prediction of hip or major osteoporotic fracture. Repeating a BMD measure within 4 years to improve fracture risk stratification may not be necessary in adults this age untreated for osteoporosis.

Project description:BackgroundThe associations between visceral adipose tissue (VAT) and bone mineral density (BMD) or fracture have been controversial and the causality of the associations remains to be assessed. This study aimed to explore the associations of VAT^ (predicted value of VAT mass) with BMD and fracture risk in men and women, and to examine their potential causation by two-sample Mendelian randomization (MR) analyses.MethodsUK Biobank is a large, population-based prospective cohort study that recruited more than 500,000 participants aged 40-69 in the United Kingdom from 2006 to 2010. In this study, we used a validated and reliable prediction model to estimate the VAT amount of the participants. On this basis, linear and nonlinear multivariable statistical models were used to explore the association of VAT^ with BMD and fracture risk in different groups of sex and BMI. In observational analyses, the multivariable linear regression model and Cox proportional-hazards model were used to assess VAT^ association with BMD and fracture risk, respectively. Inverse variance weighting was used as the main result of MR analysis.ResultsIn 190,836 men, an inverted U-shaped association was observed between VAT^ and heel BMD (P for nonlinearity < 0.001), with a turning point of VAT^ = 1.25 kg. Per kg increase in VAT^ was associated with a 0.13 standard deviation (SD) increase in heel BMD (P = 1.5 × 10-16) among men with lower amounts of VAT^, and associated with a 0.05 SD decrease in heel BMD (P = 1.3 × 10-15) among men with higher amounts of VAT^. In 193,592 women, per kg increase in VAT^ was monotonically associated with a 0.16 SD increase in heel BMD (P = 1.2 × 10-136, P for VAT^-sex interaction = 8.4 × 10-51). During a median follow-up of 8.2 years, VAT^ was associated with lower risks of hip fractures in the overall men and women (P for VAT^-sex interaction = 1.9 × 10-4 for total fractures; 1.5 × 10-4 for other fractures). There were significant interactions of VAT^ and BMI on heel BMD and fracture risks in men only (P for VAT^-BMI interaction = 5.9 × 10-31 for heel BMD; 2.7 × 10-4 for total fractures; 5.7 × 10-3 for hip fractures; 6.8 × 10-3 for other fractures). In two-sample MR analyses, evidence of causality was not observed between VAT^ and DXA-derived BMD or fractures.ConclusionsThese novel findings demonstrated gender-dependent associations of VAT^ with BMD and fracture risk, with the association in men being modified by adiposity. Evidence of causality was not observed, suggesting that the observational association of VAT^ with BMD and fracture risk could be the result of confounding.

Dataset Information

The associations of subclinical atherosclerotic cardiovascular disease with hip fracture risk and bone mineral density in elderly adults.

Publications

The associations of subclinical atherosclerotic cardiovascular disease with hip fracture risk and bone mineral density in elderly adults.

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