02957nas a2200373 4500008004100000022001400041245013400055210006900189260001300258300000900271490000800280520182700288653000902115653002502124653002802149653002802177653003002205653001102235653001402246653003202260653001702292100002502309700001902334700001602353700002402369700002502393700002002418700002402438700001902462700002202481700002402503700002002527856003602547 2014 eng d a1879-148400aFibroblast growth factor 23, the ankle-brachial index, and incident peripheral artery disease in the Cardiovascular Health Study.0 aFibroblast growth factor 23 the anklebrachial index and incident c2014 Mar a91-60 v2333 a

BACKGROUND: Fibroblast growth factor 23 (FGF23) has emerged as a novel risk factor for mortality and cardiovascular events. Its association with the ankle-brachial index (ABI) and clinical peripheral artery disease (PAD) is less known.

METHODS: Using data (N = 3143) from the Cardiovascular Health Study (CHS), a cohort of community dwelling adults >65 years of age, we analyzed the cross-sectional association of FGF23 with ABI and its association with incident clinical PAD events during 9.8 years of follow up using multinomial logistic regression and Cox proportional hazards models respectively.

RESULTS: The prevalence of cardiovascular disease (CVD) and traditional risk factors like diabetes, coronary artery disease, and heart failure increased across higher quartiles of FGF23. Compared to those with ABI of 1.1-1.4, FGF23 per doubling at baseline was associated with prevalent PAD (ABI < 0.9) although this association was attenuated after adjusting for CVD risk factors, and kidney function (OR 0.91, 95% CI 0.76-1.08). FGF23 was not associated with high ABI (>1.4) (OR 1.06, 95% CI 0.75-1.51). Higher FGF23 was associated with incidence of PAD events in unadjusted, demographic adjusted, and CVD risk factor adjusted models (HR 2.26, 95% CI 1.28-3.98; highest versus lowest quartile). The addition of estimated glomerular filtration and urine albumin to creatinine ratio to the model however, attenuated these findings (HR 1.46, 95% CI, 0.79-2.70).

CONCLUSIONS: In community dwelling older adults, FGF23 was not associated with baseline low or high ABI or incident PAD events after adjusting for confounding variables. These results suggest that FGF23 may primarily be associated with adverse cardiovascular outcomes through non atherosclerotic mechanisms.

10aAged10aAnkle Brachial Index10aCardiovascular Diseases10aCross-Sectional Studies10aFibroblast Growth Factors10aHumans10aIncidence10aPeripheral Arterial Disease10aRisk Factors1 aGarimella, Pranav, S1 aIx, Joachim, H1 aKatz, Ronit1 aChonchol, Michel, B1 aKestenbaum, Bryan, R1 ade Boer, Ian, H1 aSiscovick, David, S1 aShastri, Shani1 aHiramoto, Jade, S1 aShlipak, Michael, G1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/623903001nas a2200397 4500008004100000022001400041245012100055210006900176260001300245300001300258490000700271520187200278653001002150653000902160653002202169653002802191653001702219653002802236653001102264653002202275653002002297653001102317653001402328653000902342653002302351100002002374700002102394700002502415700002402440700002002464700002002484700002402504700002002528700001902548856003602567 2015 eng d a1523-468100aAssociation of Fetuin-A With Incident Fractures in Community-Dwelling Older Adults: The Cardiovascular Health Study.0 aAssociation of FetuinA With Incident Fractures in CommunityDwell c2015 Aug a1394-4020 v303 a

Fetuin-A, a serum protein that regulates calcium mineralization, has been associated with bone mineral density (BMD) in several cross-sectional human studies, suggesting a possible beneficial effect on clinically important measures of bone health. Fetuin-A and incidence of subsequent fracture was assessed in 4714 men and women ≥65 years of age. Proportional hazards models were used to estimate risk of incident hip (hospital discharge ICD-9 codes) and composite fracture (hip, pelvis, humerus, or proximal forearm; hospital discharge ICD-9 codes and Medicare claims data). A total of 576 participants had an incident hip fracture (median follow-up 11.2 years) and 768 had an incident composite fracture (median follow-up 6.9 years). In unadjusted analyses, there was no association between fetuin-A (per SD increase) and risk of hip fracture (hazard ratio [HR], 0.96; 95% CI, 0.88 to 1.05) or composite fracture (HR, 0.99; 95% CI, 0.92 to 1.06). Results were not significantly changed after adjustment for potential confounding variables. Analyses modeling fetuin-A in quartiles or within a subset with available BMD measures also showed no statistically significant association with risk of hip or composite fracture. Though fetuin-A was positively associated with areal BMD in partially adjusted models (total hip: β, 0.013 g/cm(2) ; 95% CI, 0.005 to 0.021; femoral neck: β, 0.011 g/cm(2) ; 95% CI, 0.004 to 0.018; and lumbar spine: β, 0.007 g/cm(2) ; 95% CI, 0.001 to 0.028), these associations were no longer significant after further adjustment for BMI and in final multivariate models. In this large sample of community-dwelling older adults, a small positive association between fetuin-A and areal BMD appeared attributable to confounding variables and we found no evidence of an association between fetuin-A and risk of clinical fracture.

10aAdult10aAged10aAged, 80 and over10aalpha-2-HS-Glycoprotein10aBone Density10aCross-Sectional Studies10aFemale10aFollow-Up Studies10aFractures, Bone10aHumans10aIncidence10aMale10aModels, Biological1 aFink, Howard, A1 aBůzková, Petra1 aGarimella, Pranav, S1 aMukamal, Kenneth, J1 aCauley, Jane, A1 aKizer, Jorge, R1 aBarzilay, Joshua, I1 aJalal, Diana, I1 aIx, Joachim, H uhttps://chs-nhlbi.org/node/666602888nas a2200481 4500008004100000022001400041245008700055210006900142260001300211300001200224490000700236520154100243653000901784653002201793653001601815653001501831653002801846653002501874653001501899653002401914653001101938653003101949653001801980653001101998653001402009653002802023653000902051653003202060653001502092100002502107700001902132700001602151700001902167700002402186700002202210700002502232700002402257700002202281700002402303700002302327700002002350856003602370 2015 eng d a1523-175500aUrinary uromodulin, kidney function, and cardiovascular disease in elderly adults.0 aUrinary uromodulin kidney function and cardiovascular disease in c2015 Nov a1126-340 v883 a

Urinary uromodulin (uUMOD) is the most common secreted tubular protein in healthy adults. However, the relationship between uUMOD and clinical outcomes is still unclear. Here we measured uUMOD in 192 participants of the Cardiovascular Health Study with over a 30% decline in estimated glomerular filtration rate (eGFR) over 9 years, 54 with incident end-stage renal disease (ESRD), and in a random subcohort of 958 participants. The association of uUMOD with eGFR decline was evaluated using logistic regression and with incident ESRD, cardiovascular disease, heart failure, and mortality using Cox proportional regression. Mean age was 78 years and median uUMOD was 25.8 μg/ml. In a case-control study evaluating eGFR decline (192 cases and 231 controls), each 1-s.d. higher uUMOD was associated with a 23% lower odds of eGFR decline (odds ratio 0.77 (95% CI 0.62-0.96)) and a 10% lower risk of mortality (hazard ratio 0.90 (95% CI 0.83-0.98)) after adjusting for demographics, eGFR, albumin/creatinine ratio, and other risk factors. There was no risk association of uUMOD with ESRD, cardiovascular disease, or heart failure after multivariable adjustment. Thus, low uUMOD levels may identify persons at risk of progressive kidney disease and mortality above and beyond established markers of kidney disease, namely eGFR and the albumin/creatinine ratio. Future studies need to confirm these results and evaluate whether uUMOD is a marker of tubular health and/or whether it plays a causal role in preserving kidney function.

10aAged10aAged, 80 and over10aAlbuminuria10aBiomarkers10aCardiovascular Diseases10aCase-Control Studies10aCreatinine10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHeart Failure10aHumans10aIncidence10aKidney Failure, Chronic10aMale10aProportional Hazards Models10aUromodulin1 aGarimella, Pranav, S1 aBiggs, Mary, L1 aKatz, Ronit1 aIx, Joachim, H1 aBennett, Michael, R1 aDevarajan, Prasad1 aKestenbaum, Bryan, R1 aSiscovick, David, S1 aJensen, Majken, K1 aShlipak, Michael, G1 aChaves, Paulo, H M1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/677003025nas a2200469 4500008004100000022001400041245008200055210006900137260001300206300001300219490000700232520171300239653000901952653002801961653002501989653002402014653001102038653001802049653001102067653002802078653000902106653002202115653001602137653002402153653003302177100001902210700001902229700002102248700001802269700002102287700001902308700001602327700002302343700001802366700002002384700002602404700002502430700002002455700002402475700002002499856003602519 2015 eng d a1533-345000aUrine Collagen Fragments and CKD Progression-The Cardiovascular Health Study.0 aUrine Collagen Fragments and CKD ProgressionThe Cardiovascular H c2015 Oct a2494-5030 v263 a

Tubulointerstitial fibrosis is common with ageing and strongly prognostic for ESRD but is poorly captured by eGFR or urine albumin to creatinine ratio (ACR). Higher urine levels of procollagen type III N-terminal propeptide (PIIINP) mark the severity of tubulointerstitial fibrosis in biopsy studies, but the association of urine PIIINP with CKD progression is unknown. Among community-living persons aged ≥65 years, we measured PIIINP in spot urine specimens from the 1996 to 1997 Cardiovascular Health Study visit among individuals with CKD progression (30% decline in eGFR over 9 years, n=192) or incident ESRD (n=54) during follow-up, and in 958 randomly selected participants. We evaluated associations of urine PIIINP with CKD progression and incident ESRD. Associations of urine PIIINP with cardiovascular disease, heart failure, and death were evaluated as secondary end points. At baseline, mean age (±SD) was 78±5 years, mean eGFR was 63±18 ml/min per 1.73 m(2), and median urine PIIINP was 2.6 (interquartile range, 1.4-4.2) μg/L. In a case-control study (192 participants, 231 controls), each doubling of urine PIIINP associated with 22% higher odds of CKD progression (adjusted odds ratio, 1.22; 95% confidence interval, 1.00 to 1.49). Higher urine PIIINP level was also associated with incident ESRD, but results were not significant in fully adjusted models. In a prospective study among the 958 randomly selected participants, higher urine PIIINP was significantly associated with death, but not with incident cardiovascular disease or heart failure. These data suggest higher urine PIIINP levels associate with CKD progression independently of eGFR and ACR in older individuals.

10aAged10aCardiovascular Diseases10aCase-Control Studies10aDisease Progression10aFemale10aHeart Failure10aHumans10aKidney Failure, Chronic10aMale10aPeptide Fragments10aProcollagen10aProspective Studies10aRenal Insufficiency, Chronic1 aIx, Joachim, H1 aBiggs, Mary, L1 aMukamal, Kenneth1 aDjoussé, Luc1 aSiscovick, David1 aTracy, Russell1 aKatz, Ronit1 aDelaney, Joseph, A1 aChaves, Paulo1 aRifkin, Dena, E1 aHughes-Austin, Jan, M1 aGarimella, Pranav, S1 aSarnak, Mark, J1 aShlipak, Michael, G1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/666002938nas a2200205 4500008004100000022001400041245009500055210006900150260001600219520228600235100002502521700002002546700001902566700002102585700002402606700002202630700002402652700002002676856003602696 2016 eng d a1523-683800aUrinary Uromodulin and Risk of Urinary Tract Infections: The Cardiovascular Health Study.0 aUrinary Uromodulin and Risk of Urinary Tract Infections The Card c2016 Oct 283 a

BACKGROUND: Laboratory studies suggest that urinary uromodulin, the most common protein in the urine of healthy adults, may protect against urinary tract infection (UTI). Epidemiologic studies evaluating this relationship in humans are lacking.

STUDY DESIGN: Prospective longitudinal cohort study.

SETTING & PARTICIPANTS: 953 participants enrolled in the Cardiovascular Health Study.

PREDICTOR: Uromodulin assayed using enzyme-linked immunosorbent assay in spot urine samples.

OUTCOMES: Composite of outpatient UTI events or UTI-related hospitalizations and each of them individually identified using International Classification of Diseases, Ninth Revision (ICD-9) codes using negative binomial regression with robust standard errors adjusted for age, race, sex, body mass index, diabetes, estimated glomerular filtration rate, and urinary albumin and urinary creatinine excretion.

RESULTS: Median uromodulin level was 25.9 (IQR, 17.3-38.9) μg/mL, mean age of participants was 78 years, 61% were women, and 15% were black. There were 331 outpatient UTI events and 87 UTI-related hospitalizations among 186 participants during a median 9.9 years of follow-up. Persons in the highest quartile (>38.93μg/mL) of uromodulin concentration had a significantly lower risk for the composite outcome (incidence rate ratio [IRR], 0.47; 95% CI, 0.29-0.79) compared with those in the lowest quartile (≤17.26μg/mL). This association remained significant for outpatient UTI events (highest vs lowest quartile even after excluding those with prior UTI: IRR, 0.42; 95% CI, 0.23-0.77). The direction of association with UTI hospitalization was similar, but not statistically significant (IRR, 0.78; 95% CI, 0.39-1.58).

LIMITATIONS: Use of ICD-9 codes to identify outcomes and lack of generalizability to younger populations.

CONCLUSIONS: High urinary uromodulin levels are associated with lower risk for UTI in older community-dwelling adults independent of traditional UTI risk factors. This finding supports prior laboratory data indicating a protective role of uromodulin against UTI. Further research is needed to understand if this may lead to new treatments to prevent or treat UTI.

1 aGarimella, Pranav, S1 aBartz, Traci, M1 aIx, Joachim, H1 aChonchol, Michel1 aShlipak, Michael, G1 aDevarajan, Prasad1 aBennett, Michael, R1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/736902608nas a2200241 4500008004100000022001400041245009900055210006900154260001300223300001400236490000700250520187800257100002202135700002002157700002202177700002002199700002202219700002402241700002502265700001902290700002102309856003602330 2017 eng d a1533-345000aFibroblast Growth Factor 23 and the Risk of Infection-Related Hospitalization in Older Adults.0 aFibroblast Growth Factor 23 and the Risk of InfectionRelated Hos c2017 Apr a1239-12460 v283 a

Within monocytes, 1,25-dihydroxyvitamin D [1,25(OH)2D] is important for production of cathelicidins, which in turn, are critical for antibacterial action. Fibroblast growth factor 23 (FGF23) decreases 1,25(OH)2D production and thus, could increase infection risk. We examined this possibility in 3141 community-dwelling adults ages ≥65 years old at baseline in the Cardiovascular Health Study using Cox proportional hazards models to examine the association between FGF23 concentrations and first infection-related hospitalizations and determine whether associations differed by the presence of CKD (eGFR<60 ml/min per 1.73 m(2) [n=832] or urine albumin-to-creatinine ratio >30 mg/g [n=577]). Mean±SD age of participants was 78±5 years old, 60% of participants were women, and the median plasma FGF23 concentration was 70 (interquartile range, 53-99) relative units per milliliter. In fully adjusted models, higher FGF23 concentrations associated with higher risk of first infection-related hospitalization (hazard ratio [HR], 1.11; 95% confidence interval [95% CI], 1.03 to 1.20 per doubling of FGF23) during a median follow-up of 8.6 years. In participants with or without CKD (defined by eGFR), FGF23 concentration associated with first infection-related hospitalization with HRs of 1.24 (95% CI, 1.08 to 1.42) and 1.06 (95% CI, 0.97 to 1.17) per doubling of FGF23, respectively (P=0.13 for interaction). Associations did not differ between groups when stratified by urine albumin-to-creatinine ratio. In sensitivity analyses, the addition of serum calcium, phosphorus, 25-hydroxyvitamin D, intact parathyroid hormone, and 24,25-dihydroxyvitamin D did not meaningfully change the estimates. In conclusion, in community-dwelling older adults, higher plasma FGF23 concentrations independently associated with the risk of first infection-related hospitalization.

1 aNowak, Kristen, L1 aBartz, Traci, M1 aDalrymple, Lorien1 ade Boer, Ian, H1 aKestenbaum, Bryan1 aShlipak, Michael, G1 aGarimella, Pranav, S1 aIx, Joachim, H1 aChonchol, Michel uhttps://chs-nhlbi.org/node/735402495nas a2200265 4500008004100000022001400041245011100055210006900166260001300235300001200248490000800260520168800268100002201956700001601978700002001994700002502014700002102039700002402060700002002084700002502104700002002129700002502149700001902174856003602193 2018 eng d a1873-276300aThe 24,25 to 25-hydroxyvitamin D ratio and fracture risk in older adults: The cardiovascular health study.0 a2425 to 25hydroxyvitamin D ratio and fracture risk in older adul c2018 Feb a124-1300 v1073 a

25-hydroxyvitamin D [25(OH)D] may not optimally indicate vitamin D receptor activity. Higher concentrations of its catabolic product 24,25-dihydroxyvitmin D [24,25(OH)2D] and a higher ratio of 24,25(OH)2D to 25(OH)D (the vitamin D metabolite ratio [VMR]) may provide additional information on receptor activity. We compared the strength of associations of these markers with serum PTH concentrations, hip bone mineral density (BMD), and risk of incident hip fracture in community-living older participants in the Cardiovascular Health Study. Among 890 participants, the mean age was 78years, 60% were women, and the mean 25(OH)D was 28±11ng/ml. In cross-sectional analysis, the strength of association of each vitamin D measure with PTH was similar; a 1% higher 25(OH)D, 24,25(OH)2D, and VMR were associated with 0.32%, 0.25%, and 0.26% lower PTH, respectively (p<0.05 for all). Among 358 participants with available BMD data, we found no associations of 25(OH)D or VMR with BMD, whereas higher 24,25(OH)2D was modestly associated with greater hip BMD (1% higher 24,25(OH)2D associated with 0.04% [95% CI 0.01-0.08%] higher BMD). Risk of incident hip fracture risk was evaluated using a case-cohort design. There were 289 hip fractures during a mean follow up time of 8.4years. Both higher 24,25(OH)2D and VMR were associated with lower risk of hip fracture (HR per SD higher, 0.73 [0.61, 0.87] and 0.74 [0.61, 0.88], respectively) whereas 25(OH)D was not associated with hip fracture (HR 0.93 [0.79, 1.10]). We conclude that evaluating vitamin D status by incorporating assessment of 24,25(OH)D and the VMR provides information on bone health above and beyond 25(OH)D alone.

1 aGinsberg, Charles1 aKatz, Ronit1 ade Boer, Ian, H1 aKestenbaum, Bryan, R1 aChonchol, Michel1 aShlipak, Michael, G1 aSarnak, Mark, J1 aHoofnagle, Andrew, N1 aRifkin, Dena, E1 aGarimella, Pranav, S1 aIx, Joachim, H uhttps://chs-nhlbi.org/node/756102544nas a2200229 4500008004100000022001400041245011800055210006900173260001600242520180400258100002002062700002102082700001902103700002202122700002402144700002302168700002402191700001802215700002002233700002502253856003602278 2019 eng d a1440-179700aAssociation of serum and urinary uromodulin and their correlates in older adults-The Cardiovascular Health Study.0 aAssociation of serum and urinary uromodulin and their correlates c2019 Dec 173 a

Uromodulin is released into serum (sUMOD) and urine (uUMOD) exclusively by renal tubular cells. Both sUMOD and uUMOD are correlated with estimated glomerular filtration rate (eGFR), and associated with mortality and cardiovascular disease (CVD). However, no study to our knowledge has measured both sUMOD and uUMOD in the same population, thus the relationship of sUMOD with uUMOD with one another, and their respective correlates have not been evaluated simultaneously. We evaluated the correlations of sUMOD, uUMOD with eGFR in a random sub-cohort (n = 933) of the Cardiovascular Health Study and their associations with demographic and laboratory parameters and CVD risk factors using multi-variable linear regression analysis. The mean age of the cohort was 78 years, 40% were male and 15% were Black. The mean sUMOD level was 127 ng/mL, uUMOD was 30 500 ng/mL and eGFR was 63 mL/min/1.73 m . Correlation between sUMOD and uUMOD, adjusted for eGFR was moderate (r = 0.27 [95% confidence interval = 0.21-0.33]). The correlation of eGFR with sUMOD (r = 0.44 [0.39-0.49]) was stronger than with uUMOD (r = 0.21 [0.15-0.27]). In multi-variable analysis adjusting sUMOD for uUMOD and vice versa, sUMOD was independently associated with eGFR (β = 1.3 [1.1-1.6]), log2 C-reactive protein (β = -4.2 [-6.8 to -1.6]) and male sex (β = -13.6 [-22.7 to -4.5]). In contrast, male sex was associated with higher uUMOD (β = 3700 [400-7000]), while diabetes (β = -6400 [-10 600 to -2100]) and hypertension (-4300 [-7500 to -1100]) were associated with lower uUMOD levels. We conclude that sUMOD is more strongly associated with eGFR compared with uUMOD. Correlates of sUMOD and uUMOD differ substantially, suggesting that apical and basolateral secretion may be differentially regulated.

1 aSteubl, Dominik1 aBůzková, Petra1 aIx, Joachim, H1 aDevarajan, Prasad1 aBennett, Michael, R1 aChaves, Paolo, H M1 aShlipak, Michael, G1 aBansal, Nisha1 aSarnak, Mark, J1 aGarimella, Pranav, S uhttps://chs-nhlbi.org/node/827902803nas a2200229 4500008004100000022001400041245012600055210006900181260001600250520205500266100002002321700002102341700002502362700001902387700002202406700002402428700002302452700002402475700001802499700002002517856003602537 2019 eng d a1460-238500aAssociation of serum uromodulin with mortality and cardiovascular disease in the elderly-the Cardiovascular Health Study.0 aAssociation of serum uromodulin with mortality and cardiovascula c2019 Mar 213 a

BACKGROUND: Uromodulin (UMOD) is released by renal tubular cells into the serum (sUMOD) and urine. Lower urine UMOD has been linked to mortality and cardiovascular disease but much less is known about sUMOD. We evaluated the association of sUMOD with these outcomes in community-dwelling older adults.

METHODS: We measured sUMOD in a random subcohort of 933 participants enrolled in the Cardiovascular Health Study. The associations of sUMOD with all-cause mortality, incident heart failure (HF) and incident cardiovascular disease (CVD; myocardial infarction, stroke and mortality due to coronary disease or stroke) were evaluated using multivariable Cox regression, adjusting for study participants' demographics, estimated glomerular filtration rate (eGFR), albuminuria and CVD risk factors. Generalized additive models with splines were used to address the functional form of sUMOD with outcomes. Due to nonlinear associations of sUMOD with all outcomes, 2.5% of the values on either end of the sUMOD distribution were excluded from the analyses, limiting the range of sUMOD to 34.3-267.1 ng/mL.

RESULTS: The mean age was 78 ± 5 years, 40% were male, sUMOD level was 127 ± 64 ng/mL, eGFR was 63 mL/min/1.73 m2 and 42% had CKD defined as eGFR <60 mL/min/1.73 m2. Patients in the lower sUMOD quartiles had lower eGFR and higher albuminuria (P < 0.01, respectively). During a median follow-up of 9.9 years, 805 patients died, 283 developed HF and 274 developed CVD. In multivariable analysis, higher sUMOD was significantly associated with a lower hazard for mortality {hazard ratio [HR] 0.89 [95% confidence interval (CI) 0.80-0.99] per 1 standard deviation (SD) higher sUMOD}, CVD [HR 0.80 (95% CI 0.67-0.96)] and the composite endpoint [HR 0.88 (95% CI 0.78-0.99)]; the association with HF was not statistically significant [HR 0.84 (95% CI 0.70-1.01)].

CONCLUSION: Higher sUMOD is independently associated with a lower risk for mortality and CVD in older adults.

1 aSteubl, Dominik1 aBůzková, Petra1 aGarimella, Pranav, S1 aIx, Joachim, H1 aDevarajan, Prasad1 aBennett, Michael, R1 aChaves, Paulo, H M1 aShlipak, Michael, G1 aBansal, Nisha1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/800702736nas a2200265 4500008004100000022001400041245010700055210006900162260001600231520191100247100002402158700002102182700002402203700001902227700001802246700002502264700001902289700002002308700002402328700001802352700001902370700002102389700002402410856003602434 2021 eng d a1532-541500aUrine creatinine concentration and clinical outcomes in older adults: The Cardiovascular Health Study.0 aUrine creatinine concentration and clinical outcomes in older ad c2021 Aug 073 a

PURPOSE: Loss of muscle mass and strength are associated with long-term adverse health outcomes in older adults. Urine creatinine concentrations (Ucr; mg/dl) are a measure of muscle tissue mass and turnover. This study assessed the associations of a spot Ucr level with muscle mass and with risk of hospitalization, mortality, and diabetes mellitus in older adults.

METHODS: We examined 3424 participants from the Cardiovascular Health Study who provided spot urine samples in 1996-1997 and who were followed through June 2015. All participants underwent baseline measurement of grip strength. In a sub-cohort, 1331 participants underwent dual energy X-ray absorptiometry (DEXA) scans, from which lean muscle mass was derived. Participants were followed for a median of 10 years for hospitalizations and mortality, and 9 years for diabetes mellitus.

RESULTS: In linear regression analysis, a one standard deviation higher Ucr concentration (64.6 mg/dl) was associated with greater grip strength (kg force) β = 0.44 [0.16, 0.72]; p = 0.002) and higher lean muscle mass (kg) (β = 0.43 [0.08, 0.78]; p = 0.02). In Cox regression analyses, each standard deviation greater Ucr concentration was associated with lower rates of hospitalizations (0.94 [95% confidence interval, 0.90, 0.98]; p < 0.001) and lower mortality risk (0.92 [0.88, 0.97]; p < 0.001), while a one standard deviation increase in muscle mass derived from DEXA had no such significant association. Ucr levels were not associated with incident diabetes mellitus risk (0.97 [0.85, 1.11]; p = 0.65).

CONCLUSION: A higher spot Ucr concentration was favorably associated with muscle mass and strength and with health outcomes in older community-living adults. The ease of obtaining a spot Ucr makes it an attractive analyte to use for gauging the health of older adults.

1 aBarzilay, Joshua, I1 aBůzková, Petra1 aShlipak, Michael, G1 aLyles, Mary, F1 aBansal, Nisha1 aGarimella, Pranav, S1 aIx, Joachim, H1 aKizer, Jorge, R1 aStrotmeyer, Elsa, S1 aDjoussé, Luc1 aBiggs, Mary, L1 aSiscovick, David1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/8825