@article {1435, title = {Associations of postmenopausal estrogen use with cardiovascular disease and its risk factors in older women. The CHS Collaborative Research Group.}, journal = {Circulation}, volume = {88}, year = {1993}, month = {1993 Nov}, pages = {2163-71}, abstract = {

BACKGROUND: Postmenopausal estrogen replacement therapy has been associated with favorable levels of cardiovascular disease risk factors, but these associations and the relations between estrogen use and subclinical disease have not been examined in large samples of older women.

METHODS AND RESULTS: Present and past estrogen use was ascertained in 2955 women > or = 65 years old in the Cardiovascular Health Study, a study of risk factors for coronary heart disease and stroke in the elderly. Present estrogen use was reported by 12\% of these women and past use by an additional 26.5\%. Estrogen use (past or present) was strongly associated with lower low-density lipoprotein cholesterol, fibrinogen, glucose, insulin, obesity, and age and higher high-density lipoprotein cholesterol and socioeconomic status (all P < .0001). Estrogen users also had lower levels of subclinical disease as measured by carotid intimal-medial thickness, carotid stenosis grade, ECG left ventricular mass, and Doppler mitral peak flow velocities (each P < .02). Relations were similar in younger and older women (65 to 74 versus > or = 75 years) and smokers and nonsmokers and were unchanged after women with poor medication compliance were excluded. After adjustment for other factors, estrogen use was associated with decreased carotid wall thickness, although this association was of borderline significance after further adjustment for lipids.

CONCLUSIONS: Postmenopausal estrogen use in this sample of older women was associated with favorable cardiovascular disease risk factor profiles and with lower measures of subclinical disease. These findings suggest that postmenopausal estrogen use may be associated with lower risk of cardiovascular disease in women well into the eighth decade of life.

}, keywords = {Aged, Aging, Cardiovascular Diseases, Carotid Arteries, Carotid Stenosis, Electrocardiography, Estrogen Replacement Therapy, Female, Heart, Heart Ventricles, Humans, Patient Compliance, Risk Factors, Smoking, Ultrasonography}, issn = {0009-7322}, author = {Manolio, T A and Furberg, C D and Shemanski, L and Psaty, B M and O{\textquoteright}Leary, D H and Tracy, R P and Bush, T L} } @article {1465, title = {Current estrogen-progestin and estrogen replacement therapy in elderly women: association with carotid atherosclerosis. CHS Collaborative Research Group. Cardiovascular Health Study.}, journal = {Ann Epidemiol}, volume = {6}, year = {1996}, month = {1996 Jul}, pages = {314-23}, abstract = {

The cardioprotective effects of combined estrogen/progestin replacement therapy have been questioned. Therefore, we have compared carotid arterial wall thickening and the prevalence of carotid stenosis in elderly women (> or = 65 years old) currently using replacement estrogen/progestins (E + P) with arterial pathology and its prevalence in women using unopposed estrogens (E). This cross-sectional study used baseline data from all 2962 women participating in the Cardiovascular Health Study, a population-based study of coronary heart disease and stroke in elderly adults. Users of hormone replacement therapy (HRT) were categorized as never (n = 1726), past (n = 787), current E (n = 280), or current E + P (n = 73). Maximal intimal-medial thicknesses of the internal and common carotid arteries and stenosis of the internal carotid arteries were measured by ultrasonography. Current E + P users resembled current E users in most respects, although some lifestyle factors were more favorable among E + P users. Current E + P use and current E use (as compared with no use) were associated with smaller internal carotid wall thicknesses (-0.22 mm; P = 0.003; and -0.09 mm; P = 0.05, respectively) and smaller common carotid wall thicknesses (-0.05 mm; P = 0.03; and -0.02 mm; P = 0.1, respectively) and lower odds ratios (OR) for carotid stenosis (> or = 1\% vs. 0\%); OR = 0.61; 95\% confidence interval [CI]: 0.36 to 1.01; and OR = 0.91, 95\% CI: 0.67 to 1.24, respectively), after adjustment for current lifestyle and risk factors. When both groups of current HRT users were compared, there were no significant differences in carotid wall thicknesses or prevalence of carotid stenosis. For this sample of elderly women, both current E + P therapy and current E therapy were associated with decreased measures of carotid atherosclerosis. These measures did not differ significantly between the two groups of HRT users.

}, keywords = {Aged, Arteriosclerosis, Carotid Arteries, Carotid Stenosis, Cohort Studies, Confidence Intervals, Cross-Sectional Studies, Databases, Factual, Drug Therapy, Combination, Estrogen Replacement Therapy, Estrogens, Female, Health Status Indicators, Humans, Odds Ratio, Progestins, Reproductive History, Ultrasonography, United States, Women{\textquoteright}s Health}, issn = {1047-2797}, author = {Jonas, H A and Kronmal, R A and Psaty, B M and Manolio, T A and Meilahn, E N and Tell, G S and Tracy, R P and Robbins, J A and Anton-Culver, H} } @article {616, title = {Estrogen replacement therapy and MRI-demonstrated cerebral infarcts, white matter changes, and brain atrophy in older women: the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {48}, year = {2000}, month = {2000 May}, pages = {467-72}, abstract = {

OBJECTIVE: We studied the relationship between the use of estrogen replacement therapy (ERT) and cerebral magnetic resonance imaging (MRI) abnormalities among older women.

DESIGN: A population-based prospective study (Cardiovascular Health Study).

SETTING: Four regions in the United States.

PARTICIPANTS: A total of 2133 (62.9\% of the eligible) women aged 65 to 95 years (mean age 74.8), on whom MRI was performed in 1992-1994.

MEASUREMENTS: Presence of global brain atrophy, white matter changes, small infarct-like lesion (ILL) (<3 mm), MRI infarcts (> or =3 mm, mostly small and asymptomatic), and cognitive function as measured by Mini-Mental State Exam (MMSE), and by ERT use (current/past/never), adjusted for a number of socioeconomic, lifestyle, and reproductive covariates.

RESULTS: Current use of ERT was reported by 15\% and past use by another 23\% of participants; 35\% of all women had MRI infarcts. The prevalence of MRI infarcts did not differ in current or past users from those who had never used ERT (nonusers). Bifrontal distance, the largest distance between frontal horns, and the size of ventricles were larger among current ERT users compared to past users or nonusers (P (trend) = .01), adjusted for all other covariates, but no dose-response relationship to current or past ERT use was found. Duration of estrogen use was not associated with any atrophy measure. Cortical atrophy measure, sulcal widening, or white matter disease did not differ significantly by ERT use or duration of use. Central measures of atrophy, bifrontal distance, and ventricular size were significantly associated with cognition as measured by MMSE.

CONCLUSIONS: Current ERT users had much more clinically significant central atrophy than nonusers, but the implications remained unclear.

}, keywords = {Aged, Aged, 80 and over, Atrophy, Brain, Brain Infarction, Estrogen Replacement Therapy, Female, Humans, Intelligence Tests, Life Style, Magnetic Resonance Imaging, Population Surveillance, Prevalence, Prospective Studies, Social Class, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2000.tb04990.x}, author = {Luoto, R and Manolio, T and Meilahn, E and Bhadelia, R and Furberg, C and Cooper, L and Kraut, M} } @article {617, title = {Estrogen use, APOE, and cognitive decline: evidence of gene-environment interaction.}, journal = {Neurology}, volume = {54}, year = {2000}, month = {2000 May 23}, pages = {1949-54}, abstract = {

OBJECTIVE: APOE-epsilon4 increases the risk of cognitive decline, while elderly women who take estrogen may have less risk of cognitive decline. The authors sought to determine whether estrogen use modifies the association between APOE-epsilon4 and cognitive decline.

METHOD: - As part of the Cardiovascular Health Study, 3,393 Medicare-eligible women (> or =65 years) were randomly selected and recruited from Sacramento County, CA; Washington County, MD; Forsyth County, NC; and Pittsburgh, PA. Cognitive testing was administered annually; the authors studied the 2,716 women with cognitive testing on > or =2 visits. They analyzed change in score on the Modified Mini-Mental State Examination (3MS) as a function of estrogen use, APOE genotype, and baseline common and internal carotid artery wall thickening.

RESULTS: A total of 297 (11\%) women were current estrogen users and 336 (12\%) were past estrogen users. Over the 6-year average follow-up, baseline current users declined 1.5 points on the 3MS whereas never users declined 2.7 points (p = 0.023). Compared with epsilon4-negative women, epsilon4-positive women had a greater adjusted hazard ratio of cognitive impairment (3MS < 80), hazard risk [HR] = 1.47; 95\% CI, 1.13 to 1.90. There was an interaction between estrogen use and epsilon4 presence (p = 0.037). Among epsilon4-negative women, current estrogen use reduced the risk of adjusted cognitive impairment compared with never users by almost half (HR = 0.59; 95\% CI, 0.36 to 0.99), whereas, it did not reduce the risk among epsilon4-positive women (current use, HR = 1.33; 95\% CI, 0.74 to 2.42). Compared with never use, current estrogen use was associated with less internal and common carotid wall thickening in epsilon4-negative women but not in epsilon4-positive women (p for interaction < 0.05 for both). Differences remained after adjusting for age, education, race, and stroke.

CONCLUSIONS: Estrogen use was associated with less cognitive decline among epsilon4-negative women but not epsilon4-positive women. Potential mechanisms, including carotid atherosclerosis, by which epsilon4 may interact with estrogen and cognition warrant further investigation.

}, keywords = {Aged, Alzheimer Disease, Apolipoprotein E4, Apolipoproteins E, Carotid Stenosis, Estrogen Replacement Therapy, Female, Genotype, Humans, Mental Status Schedule, Neuropsychological Tests, Risk Factors}, issn = {0028-3878}, doi = {10.1212/wnl.54.10.1949}, author = {Yaffe, K and Haan, M and Byers, A and Tangen, C and Kuller, L} } @article {670, title = {Estrogen replacement and brachial artery flow-mediated vasodilation in older women.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {21}, year = {2001}, month = {2001 Dec}, pages = {1955-61}, abstract = {

It remains unclear whether estrogen therapy (with or without progestin) improves endothelial function in older postmenopausal women with or at risk for coronary heart disease. To address this issue, we analyzed brachial artery flow-mediated vasodilation in the Cardiovascular Health Study, a longitudinal study of cardiovascular risk factors in subjects over 65 years of age. At the tenth annual Cardiovascular Health Study examination, 1662 women returned for follow-up. Eighteen percent (n=291) were current users of estrogen replacement, most of whom (75.9\%, n=221) took unopposed estrogen. Brachial artery ultrasound examinations measuring vasodilation in response to a flow stimulus (hyperemia) were performed on 1636 women. There were no statistical differences in brachial flow-mediated vasodilator responses between users and nonusers, even after adjustment for potential confounders. Absence of an effect was most notable in women over 80 years old and in those with established cardiovascular disease. However, among women without clinical or subclinical cardiovascular disease or its risk factors, there was a significant association between hormone replacement therapy use and flow-mediated vasodilator responses (P=0.01). Among older postmenopausal women, favorable vascular effects of estrogen may be limited to those who have not yet developed atherosclerotic vascular disease. These data emphasize the importance of ongoing efforts to determine the role of hormone replacement therapy for primary prevention of cardiovascular disease.

}, keywords = {Aged, Aged, 80 and over, Analysis of Variance, Brachial Artery, Cardiovascular Diseases, Drug Therapy, Combination, Estrogen Replacement Therapy, Estrogens, Female, Humans, Longitudinal Studies, Progestins, Risk Factors, Ultrasonography, Vasodilation}, issn = {1524-4636}, doi = {10.1161/hq1201.100241}, author = {Herrington, D M and Espeland, M A and Crouse, J R and Robertson, J and Riley, W A and McBurnie, M A and Burke, G L} } @article {631, title = {Hormone replacement therapy is associated with higher FEV1 in elderly women.}, journal = {Am J Respir Crit Care Med}, volume = {163}, year = {2001}, month = {2001 Feb}, pages = {423-8}, abstract = {

Estrogen and progesterone use have been associated with improved pulmonary function in premenopausal women. However, little research has examined the relationship between hormone replacement therapy (HRT) and pulmonary function in postmenopausal women. We examined the relationship of HRT with spirometry in 2,353 women aged 65 yr and older participating in the Cardiovascular Health Study in 1993/1994. Current use of HRT was hypothesized to be associated with higher FEV1, higher FVC, and less pulmonary obstruction (FEV1/FVC < 65\%). FEV1 was higher among current HRT users compared to noncurrent users in the following groups: overall (1.82 L versus 1.66 L, p < 0.0001), among women without asthma (1.85 L versus 1.69 L, p < 0.0001), among former smokers (1.76 L versus 1.60 L, p = 0.013), and among never smokers (1.90 L versus 1.72 L, p < 0.0001). Overall, HRT use was associated with a lower prevalence of pulmonary obstruction (OR 0.75 [95\% CI 0.55, 0.99]). After controlling for potential confounders, HRT use was significantly associated with higher FEV(1) (p = 0.031) and with a lower prevalence of obstruction (OR 0.67 [95\% CI 0.48, 0.95]). We conclude that postmenopausal women who use HRT have higher levels of FEV1 and less obstruction, which could not be explained by their lower rates of smoking and other health factors associated with HRT use.

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, Estrogen Replacement Therapy, Female, Forced Expiratory Volume, Humans, Longitudinal Studies, Spirometry, Vital Capacity}, issn = {1073-449X}, doi = {10.1164/ajrccm.163.2.2003040}, author = {Carlson, C L and Cushman, M and Enright, P L and Cauley, J A and Newman, A B} } @article {659, title = {Post-menopausal hormone therapy and concentrations of protein C and antithrombin in elderly women.}, journal = {Br J Haematol}, volume = {114}, year = {2001}, month = {2001 Jul}, pages = {162-8}, abstract = {

The effects of post-menopausal hormone therapy (HRT) on blood coagulation in elderly women are not well defined. We studied associations of HRT use with levels of natural anticoagulant proteins in a cross-sectional study of 3393 women > or = 65 years of age participating in the Cardiovascular Health Study. Protein C antigen and antithrombin were measured in all users (n = 230 unopposed oestrogen; 60 oestrogen/progestin) and a comparison group of 196 age- and race-matched non-users. Compared with non-users, oestrogen use was associated with higher protein C (4.80 vs. 4.30 microg/ml, P < 0.01). Results were similar for oestrogen/progestin (P > 0.05). In both user groups, antithrombin was lower than in non-users (109\% for each vs. 115\% in non-users, P < 0.001). Adjustment for factors related to prescription of HRT and to anticoagulant protein levels had little impact on the results. For antithrombin, associations with HRT were larger for thinner Caucasian women and black women. Venous thrombosis from HRT may be mediated partly by alterations in antithrombin, but not protein C concentrations. This study extends previous observations to older women, the group at highest risk of venous thromboembolism. Studies of HRT-induced alterations in anticoagulant function in relation to the occurrence of thrombosis with HRT are required.

}, keywords = {Aged, Antithrombins, Black People, Body Mass Index, Cross-Sectional Studies, Estrogen Replacement Therapy, Female, Humans, Logistic Models, Postmenopause, Progestins, Protein C, Risk Factors, Venous Thrombosis, White People}, issn = {0007-1048}, doi = {10.1046/j.1365-2141.2001.02911.x}, author = {Cushman, M and Psaty, B M and Meilahn, E N and Dobs, A S and Kuller, L H} } @article {721, title = {Hormone replacement therapy and sleep-disordered breathing.}, journal = {Am J Respir Crit Care Med}, volume = {167}, year = {2003}, month = {2003 May 01}, pages = {1186-92}, abstract = {

Disordered breathing during sleep is more common among postmenopausal women than among their premenopausal counterparts, possibly because of declining levels of estrogen and progesterone. We examined the relationship between the use of replacement hormones and sleep-disordered breathing in a sample of 2,852 noninstitutionalized women, 50 years of age or older, who participated in the Sleep Heart Health Study. The frequency of apneas and hypopneas per hour of sleep (apnea-hypopnea index) was determined by unattended, single-night polysomnography at the participant{\textquoteright}s home. The prevalence of sleep-disordered breathing (apnea-hypopnea index of 15 or more) among hormone users (61 of 907) was approximately half the prevalence among nonusers (286 of 1,945). Multivariable adjustment for known determinants of the disorder, including age, body mass index, and neck circumference, has attenuated the association, but only moderately (adjusted odds ratio, 0.55; 95\% confidence interval, 0.41 to 0.75). The inverse association between hormone use and sleep-disordered breathing was evident in various subgroups and was particularly strong among women 50 to 59 years old (adjusted odds ratio, 0.36; 95\% confidence interval, 0.21 to 0.60). If the observed associations are causal, hormone replacement therapy could have a role in preventing or alleviating sleep-disordered breathing.

}, keywords = {Age Distribution, Aged, Body Mass Index, Causality, Cohort Studies, Confidence Intervals, Estrogen Replacement Therapy, Female, Humans, Logistic Models, Middle Aged, Multivariate Analysis, Odds Ratio, Polysomnography, Postmenopause, Prevalence, Sensitivity and Specificity, Severity of Illness Index, Sleep Apnea Syndromes, Sleep Stages, United States}, issn = {1073-449X}, doi = {10.1164/rccm.200210-1238OC}, author = {Shahar, Eyal and Redline, Susan and Young, Terry and Boland, Lori L and Baldwin, Carol M and Nieto, F Javier and O{\textquoteright}Connor, George T and Rapoport, David M and Robbins, John A} } @article {740, title = {Hormone replacement therapy and the risk of incident congestive heart failure: the Cardiovascular Health Study.}, journal = {J Womens Health (Larchmt)}, volume = {12}, year = {2003}, month = {2003 May}, pages = {341-50}, abstract = {

BACKGROUND: The development of congestive heart failure (CHF) in older persons is related to a variety of mechanisms. Hormone replacement therapy (HRT) affects several of the pathways that may be important in the development of CHF. We hypothesized that HRT would be associated with a decreased risk of incident CHF.

METHODS: Using Cox proportional-hazards regression, we assessed the risk of incident CHF (n = 304) associated with time-dependent past and current use of HRT compared to never use. The Cardiovascular Health Study is a prospective cohort study of community-dwelling adults aged 65 years and older. This analysis included female participants without a history of CHF at baseline (n = 3223).

RESULTS: At baseline, 62\% were never users, 26\% were past users, and 12\% were current users of HRT. Compared with never users, the multivariable relative risk (RR) of CHF was 1.01 (95\% confidence interval [95\% CI] 0.76,1.34) for past users and 1.34 (0.93,1.94) for current users. Results were similar among most treatment and clinical subgroups, except that the association of current HRT with CHF appeared to depend on body mass index (BMI) or osteoporosis status. The RR was 0.82 (0.43,1.60) for normal weight women, 1.65 (0.95,2.88) for overweight women, and 2.22 (1.06,4.67) for obese women (p = 0.01 for interaction). Similarly, the RR was 0.15 (0.04,0.65) for women with osteoporosis and 1.82 (1.25,2.65) for women without osteoporosis (p = 0.001 for interaction).

CONCLUSIONS: Overall, HRT was not associated with the risk of incident CHF, although BMI and osteoporosis appeared to modify the association of HRT with CHF. The risk of CHF was lower in patients with lower BMI or osteoporosis.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Cohort Studies, Estrogen Replacement Therapy, Female, Heart Failure, Humans, Incidence, Life Style, Middle Aged, Multivariate Analysis, Obesity, Osteoporosis, Postmenopausal, Proportional Hazards Models, Prospective Studies, Risk, Risk Factors, United States, Women{\textquoteright}s Health}, issn = {1540-9996}, doi = {10.1089/154099903765448853}, author = {Rea, Thomas D and Psaty, Bruce M and Heckbert, Susan R and Cushman, Mary and Meilahn, Elaine and Olson, Jean L and Lemaitre, Rozenn N and Smith, Nicholas L and Sotoodehnia, Nona and Chaves, Paulo H M} } @article {928, title = {Determinants of serum total and free testosterone levels in women over the age of 65 years.}, journal = {J Clin Endocrinol Metab}, volume = {92}, year = {2007}, month = {2007 Feb}, pages = {509-16}, abstract = {

CONTEXT: Little is known about testosterone (T) levels and their determinants in women of late postmenopausal age.

OBJECTIVE: We describe levels of total and free T and selected factors that influence these levels in a random sample of older women.

DESIGN: Levels of serum total T and free T by microdialysis were measured using ultrasensitive assays in 347 community-dwelling women aged 65-98 yr enrolled in the Cardiovascular Health Study. Cross-sectional analyses were performed to define factors associated with total and free T levels.

RESULTS: In adjusted models: 1) total T levels declined with age until 80, whereas free T levels did not vary by age; 2) women with bilateral oophorectomy had 23\% lower total T and 16\% lower free T levels than those with at least one intact ovary; 3) oral estrogen users had total and free T levels that were 47\% lower than never users; 4) obese women had 47\% higher total T and 20\% higher free T levels, and overweight women had 24\% higher total T and 14\% higher free T levels, than normal weight women; and 5) free T levels were 51\% higher in black women. Corticosteroid users had 75\% lower total T and 43\% lower free T levels than nonusers.

CONCLUSIONS: Bilateral oophorectomy, estrogen use, corticosteroid use, and low body mass index are independent risk factors for lower T levels in women aged 65 yr and over. Although highly prevalent in women of this age, the physiological significance of low T levels in late postmenopausal women requires further investigation.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Aging, Body Mass Index, Cross-Sectional Studies, Estrogen Replacement Therapy, Female, Humans, Hypogonadism, Multivariate Analysis, Nonlinear Dynamics, Obesity, Ovariectomy, Ovary, Postmenopause, Predictive Value of Tests, Prevalence, Risk Factors, Testosterone}, issn = {0021-972X}, doi = {10.1210/jc.2006-1399}, author = {Cappola, Anne R and Ratcliffe, Sarah J and Bhasin, Shalender and Blackman, Marc R and Cauley, Jane and Robbins, John and Zmuda, Joseph M and Harris, Tamara and Fried, Linda P} } @article {1175, title = {Reproductive history, hormone replacement, and incidence of venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology.}, journal = {Br J Haematol}, volume = {149}, year = {2010}, month = {2010 May}, pages = {606-12}, abstract = {

Numerous studies have established that hormone replacement therapy increases the risk of venous thromboembolism (VTE), but an association of endogenous oestrogen exposure with the incidence of VTE is not fully established. Using a prospective design combining the Atherosclerosis Risk in Communities and the Cardiovascular Health Study cohort, we studied the 12-year risk of VTE in relation to hormone replacement therapy use, age at menopause, parity number, and type of menopause in 8236 post-menopausal women. There were no significant associations of age at menopause, parity number, or type of menopause with incidence of VTE. Women currently using hormone replacement had a 1.6-times higher multivariate-adjusted rate ratio (RR) of VTE compared with those without hormone use in the time-dependent model (RR=1.60, 95\% confidence interval [CI], 1.06-2.36; Population attributable fraction=6.7\%, 95\%CI, 1.0-10.3). When we excluded women with 1-year or more duration of hormone therapy at baseline, the association was stronger (RR=2.02, 95\%CI, 1.31-3.12). The multivariate-adjusted RRs of VTE for current users tended to be higher in those with idiopathic VTE (RR=2.40, 95\%CI, 1.40-4.12) than those with secondary VTE (RR=1.08, 95\%CI, 0.63-1.85). Hormone replacement therapy is associated with increased risk of VTE, but reproductive history markers of endogenous oestrogen exposure were not associated with VTE.

}, keywords = {Age Factors, Aged, Epidemiologic Methods, Estrogen Replacement Therapy, Female, Humans, Male, Middle Aged, Parity, Pregnancy, Reproductive History, United States, Venous Thromboembolism}, issn = {1365-2141}, doi = {10.1111/j.1365-2141.2010.08128.x}, author = {Ohira, Tetsuya and Folsom, Aaron R and Cushman, Mary and White, Richard H and Hannan, Peter J and Rosamond, Wayne D and Heckbert, Susan R} } @article {6624, title = {Serum urate levels and the risk of hip fractures: data from the Cardiovascular Health Study.}, journal = {Metabolism}, volume = {64}, year = {2015}, month = {2015 Mar}, pages = {438-46}, abstract = {

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.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Cohort Studies, Estrogen Replacement Therapy, Female, Health Surveys, Hip Fractures, Humans, Kaplan-Meier Estimate, Male, Prospective Studies, Risk, Sex Factors, United States, Uric Acid}, issn = {1532-8600}, doi = {10.1016/j.metabol.2014.11.006}, author = {Mehta, Tapan and B{\r u}zkov{\'a}, Petra and Sarnak, Mark J and Chonchol, Michel and Cauley, Jane A and Wallace, Erin and Fink, Howard A and Robbins, John and Jalal, Diana} }