02852nas a2200409 4500008004100000022001400041245012300055210006900178260001300247300001100260490000700271520173400278653000902012653001802021653002802039653001902067653002202086653001702108653001102125653002202136653001102158653002402169653001202193653000902205653002402214653001702238653001702255653001802272100001502290700001802305700001802323700001702341700001902358700001502377700001502392856003502407 1999 eng d a0149-599200aAntidiabetic treatment trends in a cohort of elderly people with diabetes. The cardiovascular health study, 1989-1997.0 aAntidiabetic treatment trends in a cohort of elderly people with c1999 May a736-420 v223 a

OBJECTIVE: This study characterizes the pharmaceutical treatment of type 2 diabetes from 1989-1990 to 1996-1997 in an elderly cohort.

RESEARCH DESIGN AND METHODS: A total of 5,888 adults aged > or = 65 years were recruited and attended a baseline clinic visit in 1989-1990 (n = 5,201, original cohort) or 1992-1993 (n = 687. African-American [new] cohort) as participants of the Cardiovascular Health Study. Fasting serum glucose (FSG) was measured at baseline. Medication use was ascertained by drug inventory at all annual clinic visits. Diabetes was defined at baseline as insulin or oral hypoglycemic agent (OHA) use or as having an FSG > or = 7.0 mmol/l (126 mg/dl), the current consensus definition of diabetes.

RESULTS: A total of 387 (7%) original (FSG = 9.8 mmol/l [177 mg/dl]) and 115 (17%) new (FSG = 10.6 mmol/l [191 mg/dl]) cohort members had pharmacologically treated diabetes at baseline. Among those in the original and in the new cohorts who survived follow-up, respectively, OHA use decreased from 80 to 48% (P < 0.001) and from 67 to 50% (P < 0.003) and insulin use increased from 20 to 33% (P = 0.001) and from 33 to 37% (P = 0.603). There were 396 (8%) original (FSG = 8.8 mmol/l [159 mg/dl]) and 45 (7%) new (FSG = 10.0 mmol/l [181 mg/dl]) cohort members with diabetes untreated at baseline. Among them, respectively, OHA use reached 38 and 30% and insulin use reached 6 and 16% in 1996-1997.

CONCLUSIONS: Diabetes was common in this elderly cohort, and > 80% of treated patients with diabetes at baseline were not achieving fasting glucose goals of < or = 6.7 mmol/l (120 mg/dl). Many untreated at baseline remained untreated after 7 years of follow-up.

10aAged10aBlood Glucose10aCardiovascular Diseases10aCohort Studies10aDiabetes Mellitus10aDrug Therapy10aFemale10aFollow-Up Studies10aHumans10aHypoglycemic Agents10aInsulin10aMale10aProspective Studies10aRisk Factors10aTime Factors10aUnited States1 aSmith, N L1 aHeckbert, S R1 aBittner, V, A1 aSavage, P, J1 aBarzilay, J, I1 aDobs, A, S1 aPsaty, B M uhttps://chs-nhlbi.org/node/59103458nas a2200469 4500008004100000022001400041245016100055210006900216260001600285300001000301490000800311520210300319653001602422653000902438653001802447653002802465653002802493653002702521653002202548653001202570653001102582653002402593653001102617653002502628653000902653653002402662653001702686653003202703653002302735653001802758653003002776100001902806700002102825700001402846700001602860700001502876700001702891700001202908700001602920700001702936856003502953 1999 eng d a0140-673600aCardiovascular disease in older adults with glucose disorders: comparison of American Diabetes Association criteria for diabetes mellitus with WHO criteria.0 aCardiovascular disease in older adults with glucose disorders co c1999 Aug 21 a622-50 v3543 a

BACKGROUND: The new fasting American Diabetes Association (ADA) criteria for the diagnosis of diabetes mellitus rely mainly on fasting blood glucose concentrations and use a lower cut-off value for diagnosis than the WHO criteria. We aimed to assess the sensitivity of these criteria for the detection of cardiovascular disease, the main complication of diabetes mellitus in the elderly.

METHODS: We did a cross-sectional and prospective analysis of 4515 participants of the Cardiovascular Health Study, an 8 year longitudinal study designed to identify factors related to the onset and course of cardiovascular disease in adults aged at least 65 years. We calculated the prevalence and incidence of cardiovascular disease for the ADA and WHO criteria.

FINDINGS: There was a higher prevalence of cardiovascular disease among individuals with impaired glucose or newly diagnosed diabetes by both criteria than among those with normal glucose concentrations. However, because fewer individuals had abnormal glucose states by the fasting ADA criteria (22.3%) than by the WHO criteria (46.8%), the number of cases of cardiovascular disease attributable to abnormal glucose states was a third of that attributable by the WHO criteria (53 vs 159 cases per 10,000). For the two sets of criteria, the relative risk for incident cardiovascular disease (mean follow-up 5.9 years) was higher in individuals with impaired glucose and newly diagnosed diabetes than in those with normal glucose. Individuals classified as normal by the fasting ADA criteria had a higher absolute number of incident events (455 of 581 events) than those classified as normal by the WHO criteria (269 of 581 events). Fasting ADA criteria were therefore less sensitive than the WHO criteria for predicting cardiovascular disease among individuals with abnormal glucose (sensitivity, 28% vs 54%).

INTERPRETATION: The new fasting ADA criteria seem to be less predictive than the WHO criteria for the burden of cardiovascular disease associated with abnormal glucose in the elderly.

10aAge Factors10aAged10aBlood Glucose10aCardiovascular Diseases10aCross-Sectional Studies10aDiabetes Complications10aDiabetes Mellitus10aFasting10aFemale10aGlucose Intolerance10aHumans10aLongitudinal Studies10aMale10aProspective Studies10aRisk Factors10aSensitivity and Specificity10aSocieties, Medical10aUnited States10aWorld Health Organization1 aBarzilay, J, I1 aSpiekerman, C, F1 aWahl, P W1 aKuller, L H1 aCushman, M1 aFurberg, C D1 aDobs, A1 aPolak, J, F1 aSavage, P, J uhttps://chs-nhlbi.org/node/60003104nas a2200469 4500008004100000022001400041245014800055210006900203260001300272300001100285490000700296520173400303653000902037653002002046653002802066653003002094653001902124653002202143653003002165653003002195653002402225653001102249653002402260653001902284653001102303653000902314653003302323653001502356653001802371100001902389700002102408700001602429700001602445700001502461700002002476700001902496700001802515700001702533700001702550710003202567856003502599 2001 eng d a0149-599200aPrevalence of clinical and isolated subclinical cardiovascular disease in older adults with glucose disorders: the Cardiovascular Health Study.0 aPrevalence of clinical and isolated subclinical cardiovascular d c2001 Jul a1233-90 v243 a

OBJECTIVE: Clinical cardiovascular disease (CVD) is highly prevalent among people with diabetes. However, there is little information regarding the prevalence of subclinical CVD and its relation to clinical CVD in diabetes and in the glucose disorders that precede diabetes.

RESEARCH DESIGN AND METHODS: Participants in the Cardiovascular Health Study, aged > or = 65 years (n = 5,888), underwent vascular and metabolic testing. Individuals with known disease in the coronary, cerebral, or peripheral circulations were considered to have clinical disease. Those without any clinical disease in whom CVD was detected by ultrasonography, electrocardiography, or ankle arm index in any of the three vascular beds were considered to have isolated subclinical disease.

RESULTS: Approximately 30% of the cohort had clinical disease, and approximately 60% of the remainder had isolated subclinical disease. In those with normal glucose status, isolated subclinical disease made up most of the total CVD. With increasing glucose severity, the proportion of total CVD that was clinical disease increased; 75% of men and 66% of women with normal fasting glucose status had either clinical or subclinical CVD. Among those with known diabetes, the prevalence was approximately 88% (odds ratio [OR] 2.46 for men and 4.22 for women, P < 0.0001). There were intermediate prevalences and ORs for those with impaired fasting glucose status and newly diagnosed diabetes.

CONCLUSIONS: Isolated subclinical CVD is common among older adults. Glucose disorders are associated with an increased prevalence of total CVD and an increased proportion of clinical disease relative to subclinical disease.

10aAged10aAngina Pectoris10aCardiovascular Diseases10aCerebrovascular Disorders10aCohort Studies10aDiabetes Mellitus10aDiabetes Mellitus, Type 110aDiabetes Mellitus, Type 210aElectrocardiography10aFemale10aGlucose Intolerance10aHeart Diseases10aHumans10aMale10aPeripheral Vascular Diseases10aPrevalence10aUnited States1 aBarzilay, J, I1 aSpiekerman, C, F1 aKuller, L H1 aBurke, G, L1 aBittner, V1 aGottdiener, J S1 aBrancati, F, L1 aOrchard, T, J1 aO'Leary, D H1 aSavage, P, J1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/65202810nas a2200397 4500008004100000022001400041245013300055210006900188260001300257300001100270490000700281520171100288653000901999653001502008653001802023653002302041653002802064653001902092653002202111653001102133653001102144653001702155653001702172653002502189653000902214653002102223653001702244100001902261700001502280700001802295700001502313700001602328700001802344700001502362856003502377 2001 eng d a0012-179700aThe relation of markers of inflammation to the development of glucose disorders in the elderly: the Cardiovascular Health Study.0 arelation of markers of inflammation to the development of glucos c2001 Oct a2384-90 v503 a

Several studies suggest that inflammation plays a role in the pathogenesis of some glucose disorders in adults. We tested this hypothesis in a longitudinal cohort study of older individuals who had normal fasting glucose (FG) values at baseline. We compared the baseline levels of six inflammatory markers in participants who had developed glucose disorders at follow-up with those of participants whose FG remained normal at follow-up. Participants were members of the Cardiovascular Health Study, a prospective study of risk factors for cardiovascular disease in adults > or =65 years. All 5,888 participants had baseline testing, including FG and markers of inflammation: white blood cell and platelet counts and albumin, fibrinogen, C-reactive protein (CRP), and factor VIIIc levels. At 3-4 years of follow-up, 4,481 (84.5%) of those who were alive had FG levels retested. Participants who developed diabetes (n = 45) had higher median levels of CRP at baseline than those who remained normoglycemic. On multivariate analysis, those with elevated CRP levels (75th percentile [2.86 mg/l] vs. 25th percentile [0.82 mg/l]) were 2.03 times (95% confidence intervals, 1.44-2.86) more likely to have diabetes on follow-up. Adjustment for confounders and other inflammatory markers did not appreciably change this finding. There was no relationship between the development of diabetes and other markers of inflammation. Inflammation, as measured by CRP levels, is associated with the development of diabetes in the elderly. Understanding the role of inflammation in the pathogenesis of glucose disorders in this age-group may lead to better classification and treatment of glucose disorders among them.

10aAged10aBiomarkers10aBlood Glucose10aC-Reactive Protein10aCardiovascular Diseases10aCohort Studies10aDiabetes Mellitus10aFemale10aHumans10aHypoglycemia10aInflammation10aLongitudinal Studies10aMale10aReference Values10aRisk Factors1 aBarzilay, J, I1 aAbraham, L1 aHeckbert, S R1 aCushman, M1 aKuller, L H1 aResnick, H, E1 aTracy, R P uhttps://chs-nhlbi.org/node/66102437nas a2200373 4500008004100000022001400041245011600055210006900171260001300240300001100253490000700264520142900271653000901700653001501709653002301724653002801747653001601775653001101791653001501802653001101817653001701828653001801845653002001863653000901883653001901892653001601911653001601927100001901943700001601962700001801978700001501996700001702011856003502028 2006 eng d a0307-056500aThe association of markers of inflammation with weight change in older adults: the Cardiovascular Health Study.0 aassociation of markers of inflammation with weight change in old c2006 Sep a1362-70 v303 a

OBJECTIVE: Elevated levels of inflammation factors often precede weight loss and may be causally related to it. Newer studies suggest that elevated levels of inflammation factors also precede weight gain. In this study, we examined whether inflammation factors are elevated in individuals, age >or=65 years, who lost or gained >5% weight over a 3 year follow-up period compared to those with stable weight.

SUBJECTS: In total, 3254 participants in the Cardiovascular Health Study whose weight was stable; 661 who gained >5% weight; and 842 who lost >5% weight.

MEASUREMENTS: C-reactive protein (CRP), fibrinogen, factor VIIIc, white blood cell (WBC) and platelet counts, and interleukin-6 (IL-6) levels.

RESULTS: As compared to participants whose weight was stable, those who lost >5% weight had higher baseline CRP concentration (1.05 (95% CI, 1.02, 1.08) per interquartile increase) and WBC count (1.10 (1.01, 1.19) per interquartile increase) on adjusted analyses. Those who gained >5% weight had higher baseline CRP (1.05 (1.01, 1.08)), fibrinogen (1.13 (1.01, 1.27)), and factor VIIIc (1.15 (1.03, 1.30)).

CONCLUSIONS: Inflammation factors are associated with weight gain and weight loss in older individuals. These findings suggest that subclinical inflammation, or unknown factors associated with subclinical inflammation, contribute to weight change.

10aAged10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aFactor VIII10aFemale10aFibrinogen10aHumans10aInflammation10aInterleukin-610aLeukocyte Count10aMale10aPlatelet Count10aWeight Gain10aWeight Loss1 aBarzilay, J, I1 aForsberg, C1 aHeckbert, S R1 aCushman, M1 aNewman, A, B uhttps://chs-nhlbi.org/node/89202730nas a2200361 4500008004100000022001400041245016200055210006900217260001300286300001100299490000700310520169000317653000902007653002202016653002502038653001802063653001202081653001102093653002402104653001502128653001102143653000902154653002302163653001702186100001602203700001902219700002202238700001702260700002002277700001802297700001802315856003502333 2007 eng d a0742-307100aThe relationship of heart rate and heart rate variability to non-diabetic fasting glucose levels and the metabolic syndrome: the Cardiovascular Health Study.0 arelationship of heart rate and heart rate variability to nondiab c2007 Aug a855-630 v243 a

BACKGROUND: Increased heart rate (HR) and diminished heart rate variability (HRV) are signs of early cardiovascular autonomic neuropathy. We tested the hypotheses that increased HR and diminished HRV are present in people: (i) with increased fasting glucose (FG) levels not in the range of diabetes mellitus (DM), and (ii) in people with the metabolic syndrome (MetS) independent of elevated FG levels.

METHODS: HR and HRV were determined in 1267 adults (mean age 72 years) who had Holter monitoring and FG measures: 536 had normal FG levels (NORM, FG 4.5-5.5 mmol/l), 363 had mildly impaired FG (IFG-1, FG 5.6-6.0 mmol/l), 182 had significantly impaired FG (IFG-2, FG 6.1-6.9 mmol/l) and 178 had DM (FG > 6.9 mmol/l or use of glucose-lowering agents/insulin). HR and HRV in NORM/IFG-1 was further compared by the number of components of the MetS and compared by the presence or absence of MetS in IFG-2/DM.

RESULTS: HRV indices were more impaired in IFG-2 and DM than in NORM or IFG-1. There were few differences in HRV indices between NORM and IFG-1 or between IFG-2 and DM. In NORM/IFG-1 participants, having > or = 2 components of the MetS was associated with a greater decrease in HRV compared with having no or one components. In IFG-2/DM participants, MetS was associated with decreased HRV compared with no MetS.

CONCLUSIONS: Increased HR and diminished HRV occur in the non-diabetic FG range. Diminished HRV is associated with the MetS, independent of FG levels. Both these results suggest that factors associated with increasing non-diabetic FG levels and the MetS play a role in the onset of cardiac autonomic impairment.

10aAged10aAged, 80 and over10aArrhythmias, Cardiac10aBlood Glucose10aFasting10aFemale10aGlucose Intolerance10aHeart Rate10aHumans10aMale10aMetabolic Syndrome10aRisk Factors1 aStein, P, K1 aBarzilay, J, I1 aDomitrovich, P, P1 aChaves, P, M1 aGottdiener, J S1 aHeckbert, S R1 aKronmal, R, A uhttps://chs-nhlbi.org/node/95203088nas a2200421 4500008004100000022001400041245010300055210006900158260001300227300001400240490000700254520196800261653000902229653002202238653001602260653001702276653001102293653002202304653001802326653001402344653001102358653001402369653002602383653000902409653002702418653001702445653001602462653001802478100001902496700001802515700001202533700001802545700001502563700001902578700001502597700001802612856003602630 2013 eng d a1433-296500aAlbuminuria is associated with hip fracture risk in older adults: the cardiovascular health study.0 aAlbuminuria is associated with hip fracture risk in older adults c2013 Dec a2993-30000 v243 a

UNLABELLED: The microcirculation plays an important role in bone health. Here, we examine whether albuminuria, a marker of renal microvascular disease, is associated with the risk of hip fracture in older adults (age, 78 years). We find a small independent association in women but not in men.

INTRODUCTION: The microvascular circulation plays an important role in bone physiology. Two studies of middle-aged adults have found that albuminuria (>30 mg albumin/g creatinine), a disorder of the renal microvasculature, is associated with fracture risk. Here, we examine whether albuminuria is related to hip fracture risk and reduced hip bone mineral density (BMD) in older adults with a mean age of 78 years.

METHODS: From the Cardiovascular Health Study (41 % male), 3,110 adults with albuminuria testing were followed up for incident hip fracture for up to 9.5 years. BMD was performed in a subset of 1,208 participants.

RESULTS: There were 313 hip fractures during follow-up (7.7 % of men; 11.7 % of women). The incidence rate for men, with and without albuminuria, was 1.43 and 0.93/100 person-years of follow-up (p = 0.02); for women, 1.84 and 1.33 (p = 0.04). After adjustment for osteoporosis-related factors, frailty and falling, a doubling of albuminuria was significantly associated with hip fracture risk in women (hazard ratio, 1.12, 95 % CI, 1.001-1.25), but not in men. In the subcohort with BMD measurement, increased urine albumin levels were significantly associated with decreased total hip BMD in men (-0.009 g calcium/cm(2) (-0.017, -0.001); p = 0.04), but not in women.

CONCLUSIONS: In older women, albuminuria is associated with a small, but statistically significant, increased risk of hip fracture independent of other explanatory factors. No such risk appears to be present in men, although their total hip BMD is lower in association with albuminuria.

10aAged10aAged, 80 and over10aAlbuminuria10aBone Density10aFemale10aFollow-Up Studies10aHip Fractures10aHip Joint10aHumans10aIncidence10aKaplan-Meier Estimate10aMale10aOsteoporotic Fractures10aRisk Factors10aSex Factors10aUnited States1 aBarzilay, J, I1 aBůžková, P1 aChen, Z1 ade Boer, I, H1 aCarbone, L1 aRassouli, N, N1 aFink, H, A1 aRobbins, J, A uhttps://chs-nhlbi.org/node/605902719nas 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/680602598nas a2200241 4500008004100000022001400041245003600055210003500091260001300126300001200139490000700151520201600158100001402174700001802188700001502206700001802221700001702239700001102256700001902267700001602286700001802302856003602320 2016 eng d a1433-296500aSoluble CD14 and fracture risk.0 aSoluble CD14 and fracture risk c2016 May a1755-630 v273 a

UNLABELLED: Soluble CD14 (sCD14) is an inflammatory marker associated with osteoclasts. Using Cox proportional hazards models, we found a positive association between plasma levels of sCD14 and risk of incident fracture among participants in the Cardiovascular Health Study. sCD14 may be useful in identifying those at risk for fracture.

INTRODUCTION: Soluble CD14, a proinflammatory cytokine, is primarily derived from macrophages/monocytes that can differentiate into osteoclasts. The purpose of this study was to examine the relationship between sCD14 levels and osteoporotic fractures.

METHODS: In the Cardiovascular Health Study, 5462 men and women had sCD14 levels measured at baseline. Incident hip fractures (median follow-up time 12.5 years) and incident composite fractures (defined as the first hip, pelvis, humerus, or distal radius fracture, median follow-up 8.6 years) were identified from hospital discharge summaries and/or Medicare claims data. Cox proportional hazards models were used to model the association between sCD14 levels and time to incident hip or composite fracture, overall and as a function of race and gender.

RESULTS: In unadjusted models, there was a positive association between sCD14 levels (per 1 standard deviation increase, i.e., 361.6 ng/mL) and incident hip (HR, 1.26; 95 % CI, 1.17, 1.36) and composite (HR, 1.20; 95 % CI, 1.12, 1.28) fractures. When models were fully adjusted for demographics, lifestyle factors, and medication use, these associations were no longer significant. However, in whites, the association of sCD14 levels with hip fractures remained significant in fully adjusted models (HR, 1.11; 95 % CI, 1.01-1.23). Associations of sCD14 levels with hip and composite fracture did not differ between men and women.

CONCLUSIONS: In this large cohort of community-dwelling older adults, higher sCD14 levels were associated with an increased risk of incident hip fractures in whites.

1 aBethel, M1 aBůžková, P1 aFink, H, A1 aRobbins, J, A1 aCauley, J, A1 aLee, J1 aBarzilay, J, I1 aJalal, D, I1 aCarbone, L, D uhttps://chs-nhlbi.org/node/692602627nas a2200229 4500008004100000022001400041245012200055210006900177260001300246300001400259490000700273520194000280100001902220700001802239700001502257700001702272700001802289700002002307700001602327700001802343856003602361 2016 ENG d a1433-296500aSystemic markers of microvascular disease and bone mineral density in older adults : The cardiovascular health study.0 aSystemic markers of microvascular disease and bone mineral densi c2016 Nov a3217-32250 v273 a

Here we report that abnormal brain white matter and, to a lesser extent, albuminuria are associated with reduced bone mineral density in the hip, spine, and total body in men and women. These findings may explain the increased hip fracture risk reported in some studies in association with microvascular disorders.

INTRODUCTION: Markers of microvascular disease have been individually associated with increased risk of osteoporotic fractures in some studies. Here, we examine whether these markers are associated with reduced bone mineral density (BMD) individually and together.

METHODS: BMD testing using dual x-ray absorptiometry of the hip, lumbar spine, and total body was performed in 1473 participants from the Cardiovascular Health Study (mean age ~ 78 years): 1215 were assessed for urinary albumin-creatinine ratio, 944 for abnormal white matter disease (AWMD) by brain MRI, and 541 for retinal vascular disease with fundus photographs. Linear regression models were used to evaluate the cross-sectional association of each marker with BMD accounting for potentially confounding factors.

RESULTS: AWMD was associated with lower hip, spine, and total body BMD in women (β -3.08 to -4.53; p < 0.01 for all) and lower hip and total body BMD in men (β -2.90 to -4.24; p = 0.01-0.03). Albuminuria was associated with lower hip (β -3.37; p = .05) and total body (β -3.21; p = .02) BMD in men, but not in women. The associations of AWMD and albuminuria with BMD persisted with mutual adjustment and appeared to be additive to each other. Retinal vascular disease was not associated with BMD in men or women.

CONCLUSION: AWMD and, to a lesser extent, albuminuria were independently associated with lower BMD, suggesting that microvascular disease may play a role in the pathogenesis of reduced BMD. These findings need to be confirmed by longitudinal studies.

1 aBarzilay, J, I1 aBůžková, P1 aFink, H, A1 aCauley, J, A1 aRobbins, J, A1 aGarimella, P, S1 aJalal, D, I1 aMukamal, K, J uhttps://chs-nhlbi.org/node/711903021nas 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/809802353nas a2200217 4500008004100000022001400041245009900055210006900154260001600223520171400239100001901953700001801972700001601990700001002006700001302016700001402029700001502043700002302058700001802081856003602099 2021 eng d a1433-296500aSerum non-esterified fatty acid levels and hip fracture risk: The Cardiovascular Health Study.0 aSerum nonesterified fatty acid levels and hip fracture risk The  c2021 Mar 023 a

Among elderly participants from the Cardiovascular Health Study, we found that non-esterified trans fatty acid levels had a significant prospective association with hip fracture risk. Other non-esterified fatty acid classes were not associated with hip fracture risk.

INTRODUCTION: Serum non-esterified fatty acids (NEFAs) are bioactive metabolic intermediates that can be taken up by bone tissue. Their associations with hip fracture risk have not been previously examined.

METHODS: Thirty-five individual NEFAs in five classes (saturated [SFA], mono-un-saturated [MUFA], poly-unsaturated n-6 and n-3 [PUFA], and trans-FA) were measured in Cardiovascular Health Study participants (n = 2139, mean age 77.8 years) without known diabetes. The multivariable associations of NEFA levels with hip fracture risk were evaluated in Cox hazards models.

RESULTS: We documented 303 incident hip fractures during 11.1 years of follow-up. Among the five NEFA classes, total trans FA levels were positively associated with higher hip fracture risk (HR 1.17 [95% CI, 1.04, 1.31; p = 0.01] per one standard deviation higher level). The SFA lignoceric acid (24:0) was positively associated with higher risk (HR 1.09 [1.04, 1.1]; p < 0.001), while behenic (22:0) and docosatetraenoic (22:4 n6) acids were associated with lower risk (HR 0.76 [0.61, 0.94]; p = 0.01; 0.84 [0.70, 1.00]; p = 0.05, respectively).

CONCLUSION: Total plasma trans NEFA levels are related to hip fracture risk, suggesting an unrecognized benefit of their systematic removal from food. Novel associations of individual NEFAs with hip fracture risk require confirmation in other cohort studies.

1 aBarzilay, J, I1 aBůžková, P1 aDjoussé, L1 aIx, J1 aKizer, J1 aCauley, J1 aMatthan, N1 aLichtenstein, A, H1 aMukamal, K, J uhttps://chs-nhlbi.org/node/8702