03233nas a2200445 4500008004100000022001400041245014200055210006900197260001300266300001200279490000700291520198100298653000902279653001002288653002102298653001202319653001002331653001902341653002402360653001602384653001502400653001102415653001902426653001102445653002002456653002502476653003102501653000902532653002902541653001502570653002402585653003202609653001802641100001802659700002002677700002002697700001502717700002002732856003502752 2001 eng d a1524-462800aAlcohol consumption and subclinical findings on magnetic resonance imaging of the brain in older adults: the cardiovascular health study.0 aAlcohol consumption and subclinical findings on magnetic resonan c2001 Sep a1939-460 v323 a

BACKGROUND AND PURPOSE: Subclinical findings on MRI of the brain are associated with poorer cognitive and neurological function among older adults. We sought to determine how alcohol consumption is related to these findings.

METHODS: As part of the Cardiovascular Health Study, 3660 adults aged 65 years and older underwent MRI of the brain from 1992 to 1994. We excluded 284 participants with a confirmed history of cerebrovascular disease. We assessed self-reported intake of beer, wine, and liquor at the annual clinic visit closest to the date of the MRI and grouped participants into 6 categories: abstainers, former drinkers, <1 drink weekly, 1 to <7 drinks weekly, 7 to <15 drinks weekly, and >/=15 drinks weekly. Neuroradiologists assessed white matter grade, infarcts, ventricular size, and sulcal size in a standardized and blinded manner. We used multivariate regression to control for sociodemographic and clinical characteristics.

RESULTS: We found a U-shaped relationship between alcohol consumption and white matter abnormalities. Compared with abstainers, individuals consuming 1 to <7 drinks had an OR of 0.68, and those consuming >/=15 drinks weekly had an OR of 0.95 (p for quadratic term=0.01). Heavier alcohol consumption was associated with a lower prevalence of infarcts (OR for >/=15 drinks weekly relative to abstainers 0.59; P for trend=0.004), but larger ventricular size (OR for >/=15 drinks weekly relative to abstainers 1.32; P for trend=0.006) and sulcal size (OR for >/=15 drinks weekly relative to abstainers 1.53; P for trend=0.007).

CONCLUSIONS: Moderate alcohol consumption is associated with a lower prevalence of white matter abnormalities and infarcts, thought to be of vascular origin, but with a dose-dependent higher prevalence of brain atrophy on MRI among older adults. The extent to which these competing associations influence overall brain function will require further study.

10aAged10aAging10aAlcohol Drinking10aAtrophy10aBrain10aBrain Diseases10aCerebral Infarction10aComorbidity10aDemography10aFemale10aHealth Surveys10aHumans10aLogistic Models10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aNerve Fibers, Myelinated10aOdds Ratio10aProspective Studies10aSensitivity and Specificity10aUnited States1 aMukamal, K, J1 aLongstreth, W T1 aMittleman, M, A1 aCrum, R, M1 aSiscovick, D, S uhttps://chs-nhlbi.org/node/66002833nas a2200409 4500008004100000022001400041245010900055210006900164260001300233300001200246490000700258520172900265653002701994653000902021653002102030653002402051653002202075653001702097653001102114653001502125653001302140653000802153653001802161653001102179653002502190653000902215653002002224653001702244653002102261653001802282100001802300700001802318700001702336700001502353700002002368856003502388 2007 eng d a0937-941X00aAlcohol consumption, bone density, and hip fracture among older adults: the cardiovascular health study.0 aAlcohol consumption bone density and hip fracture among older ad c2007 May a593-6020 v183 a

INTRODUCTION: Previous studies have found inconsistent relationships of alcohol consumption with risk of hip fracture, and the importance of bone mineral density and risk of falls in mediating such a relationship has not been determined.

METHODS: As part of the Cardiovascular Health Study, a population-based cohort study of adults aged 65 years and older from four U.S. communities, 5,865 participants reported their use of beer, wine, and liquor yearly. We identified cases of hip fracture unrelated to malignancy or motor vehicle accidents using hospitalization discharge diagnoses. A subgroup of 1,567 participants in two communities underwent dual-energy x-ray absorptiometry scans to assess bone mineral density.

RESULTS: A total of 412 cases of hip fracture occurred during an average of 12 years of follow-up. There was a significant U-shaped relationship between alcohol intake and risk of hip fracture (p quadratic 0.02). Compared with long-term abstainers, the adjusted hazard ratios for hip fracture were 0.78 (95% confidence interval [CI], 0.61-1.00) among consumers of up to 14 drinks per week and 1.18 (95% CI, 0.77-1.81) among consumers of 14 or more drinks per week. Alcohol intake was associated with bone mineral density of the total hip and femoral neck in a stepwise manner, with approximately 5% (95% CI, 1%-9%) higher bone density among consumers of 14 or more drinks per week than among abstainers. These relationships were all similar among men and women.

CONCLUSIONS: Among older adults, moderate alcohol consumption has a U-shaped relationship with risk of hip fracture, but a graded positive relationship with bone mineral density at the hip.

10aAbsorptiometry, Photon10aAged10aAlcohol Drinking10aAlcoholic Beverages10aApolipoproteins E10aBone Density10aFemale10aFemur Neck10aGenotype10aHip10aHip Fractures10aHumans10aLongitudinal Studies10aMale10aRisk Assessment10aRisk Factors10aSex Distribution10aUnited States1 aMukamal, K, J1 aRobbins, J, A1 aCauley, J, A1 aKern, L, M1 aSiscovick, D, S uhttps://chs-nhlbi.org/node/94402511nas a2200229 4500008004100000022001400041245011600055210006900171260001600240520182000256100001802076700001802094700001702112700001602129700002002145700001602165700001602181700001602197700001702213700001502230856003602245 2016 eng d a1590-372900aThe association of lean and fat mass with all-cause mortality in older adults: The Cardiovascular Health Study.0 aassociation of lean and fat mass with allcause mortality in olde c2016 Jun 283 a

BACKGROUND AND AIMS: Understanding contributions of lean and fat tissue to cardiovascular and non-cardiovascular mortality may help clarify areas of prevention in older adults. We aimed to define distributions of lean and fat tissue in older adults and their contributions to cause-specific mortality.

METHODS AND RESULTS: A total of 1335 participants of the Cardiovascular Health Study (CHS) who underwent dual-energy x-ray absorptiometry (DEXA) scans were included. We used principal components analysis (PCA) to define two independent sources of variation in DEXA-derived body composition, corresponding to principal components composed of lean ("lean PC") and fat ("fat PC") tissue. We used Cox proportional hazards regression using these PCs to investigate the relationship between body composition with cardiovascular and non-cardiovascular mortality. Mean age was 76.2 ± 4.8 years (56% women) with mean body mass index 27.1 ± 4.4 kg/m(2). A greater lean PC was associated with lower all-cause (HR = 0.91, 95% CI 0.84-0.98, P = 0.01) and cardiovascular mortality (HR = 0.84, 95% CI 0.74-0.95, P = 0.005). The lowest quartile of the fat PC (least adiposity) was associated with a greater hazard of all-cause mortality (HR = 1.24, 95% CI 1.04-1.48, P = 0.02) relative to fat PCs between the 25th-75th percentile, but the highest quartile did not have a significantly greater hazard (P = 0.70).

CONCLUSION: Greater lean tissue mass is associated with improved cardiovascular and overall mortality in the elderly. The lowest levels of fat tissue mass are linked with adverse prognosis, but the highest levels show no significant mortality protection. Prevention efforts in the elderly frail may be best targeted toward improvements in lean muscle mass.

1 aSpahillari, A1 aMukamal, K, J1 aDeFilippi, C1 aKizer, J, R1 aGottdiener, J S1 aDjoussé, L1 aLyles, M, F1 aBartz, T, M1 aMurthy, V, L1 aShah, R, V uhttps://chs-nhlbi.org/node/713402502nas a2200241 4500008004100000245014200041210006900183260001200252300000900264490000700273520173500280653002502015653001702040653000902057653003202066100001702098700002102115700001702136700002002153700002002173700001802193856004902211 2018 eng d00aThe associations of subclinical atherosclerotic cardiovascular disease with hip fracture risk and bone mineral density in elderly adults.0 aassociations of subclinical atherosclerotic cardiovascular disea c08/2018 a22300 v293 aIn 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.10aBone mineral density10aHip fracture10aRisk10aSubclinical atherosclerosis1 aBarzilay, JI1 aBůzková, Petra1 aCauley, J, A1 aRobbins, J., A.1 aFink, Howard, A1 aMukamal, K, J uhttps://www.ncbi.nlm.nih.gov/pubmed/3013202703021nas a2200145 4500008004100000022001400041245011400055210006900169260001600238520253000254100001802784700001902802700001802821856003602839 2019 eng d a1433-296500aAssessing risk factors of non-fatal outcomes amid a competing risk of mortality: the example of hip fracture.0 aAssessing risk factors of nonfatal outcomes amid a competing ris c2019 Jun 293 a

The Fine-Gray method is often used instead of Cox regression to account for competing risks of death in time-to-event analyses for non-fatal outcomes. A series of examples using well-known risk factors of hip fracture in an older cohort with substantial competing mortality demonstrates that the Fine-Gray approach can yield estimates that implausibly contradict long-established associations, while Cox regression preserves them. Cox regression is generally preferred for risk factor-outcome associations even in the presence of competing risk of death.

INTRODUCTION: Factors like age, sex, and race are associated not only with risk of hip fracture but also with mortality. Substantial misunderstanding remains regarding the appropriate statistical approach to account for the competing risk of mortality.

METHODS: In the Cardiovascular Health Study, an ongoing cohort study of 5888 older adults, we followed participants for incident hip fracture from their 1992-1993 visit through June 2014. We contrasted the conventional cause-specific Cox analysis, which censors individuals at the time of death, with the Fine-Gray (FG) approach, which extends participant follow-up even after death, to estimate the association of well-established demographic and clinical factors with incident hip fracture.

RESULTS: For age, current smoking and sex, Cox and FG methods yielded directionally concordant but quantitatively different strengths of association. For example, the Cox hazard ratio (HR) for a 5-year increment in age was 1.74 (95% CI, 1.61-1.87), while the corresponding FG HR was 1.16 (1.09-1.24). In contrast, the FG approach estimated a stronger association of hip fracture with sex. The two approaches yielded nearly identical results for race. For diabetes and kidney function, the estimates were discordant in direction, and the FG HRs suggested effects that were in the opposite direction of well-understood and widely accepted associations.

CONCLUSIONS: Cause-specific Cox models provide appropriate estimates of hazard for non-fatal outcomes like hip fracture even in the presence of competing risk of mortality. The Cox approach estimates hazard in the population of individuals who have not yet had an incident hip fracture and remain alive, which is typically the group of clinical interest. The Fine-Gray method estimates hazard in a hypothetical population that can yield misleading inferences about risk factors in populations of clinical interest.

1 aBůžková, P1 aBarzilay, J, I1 aMukamal, K, J uhttps://chs-nhlbi.org/node/8098