03150nas a2200493 4500008004100000022001400041245010400055210006900159260001300228300001200241490000700253520179600260653000902056653001502065653002302080653001502103653001502118653001102133653001502144653002202159653003102181653001602212653001102228653002002239653001802259653002502277653000902302653003002311653002402341653002402365653001802389653001502407100001702422700001702439700002102456700002102477700002902498700002302527700001802550700001802568700001802586700001702604856003502621 2004 eng d a1046-667300aInflammatory and prothrombotic markers and the progression of renal disease in elderly individuals.0 aInflammatory and prothrombotic markers and the progression of re c2004 Dec a3184-910 v153 a
Inflammatory and prothrombotic markers are elevated in individuals with mild to moderate renal disease. It was hypothesized that these markers may also be determinants of the progression of renal disease. The association of six markers-serum C-reactive protein (CRP), white blood cell (WBC) count, fibrinogen, factor VII, albumin, and hemoglobin-with subsequent elevations of creatinine and decline in estimated GFR in the Cardiovascular Health Study, a community-based cohort of elderly individuals, was analyzed. Linear regression was used to determine predictors of an annualized change in serum creatinine as the main outcome. Duration of follow-up was 7 yr for the original cohort and 4 yr for the more recently recruited black cohort. A total of 588 (12.7%) individuals had a decline in estimated GFR of at least 3 ml/min per yr per 1.73 m(2). Higher CRP (P < 0.001), WBC count (P < 0.001), fibrinogen (P < 0.001), and factor VII (P < 0.001) levels and lower albumin (P < 0.001) and hemoglobin levels (P < 0.001) were associated with a rise in creatinine, after adjusting for age. With additional adjustments for race, gender, baseline creatinine, systolic and diastolic BP, lipid levels, weight, and pack-years smoking, higher CRP, factor VII, fibrinogen, WBC count, and lower albumin and hemoglobin levels remained associated with a rise in creatinine. Similar results were found for decline in estimated GFR. The decline in GFR was greater with increasing number of inflammatory or prothrombotic markers that were above the median (below for hemoglobin and albumin). Inflammatory and prothrombotic markers are predictors for a change in kidney function in elderly individuals. Interventions that reduce inflammation might confer significant cardiovascular and renal benefits.
10aAged10aBiomarkers10aC-Reactive Protein10aCreatinine10aFactor VII10aFemale10aFibrinogen10aFollow-Up Studies10aGlomerular Filtration Rate10aHemoglobins10aHumans10aLeukocyte Count10aLinear Models10aLongitudinal Studies10aMale10aPredictive Value of Tests10aProspective Studies10aRenal Insufficiency10aSerum Albumin10aThrombosis1 aFried, Linda1 aSolomon, Cam1 aShlipak, Michael1 aSeliger, Stephen1 aStehman-Breen, Catherine1 aBleyer, Anthony, J1 aChaves, Paolo1 aFurberg, Curt1 aKuller, Lewis1 aNewman, Anne uhttps://chs-nhlbi.org/node/81303275nas a2200589 4500008004100000022001400041245004900055210004800104260001300152300001100165490000700176520170100183653001601884653000901900653002201909653001501931653002101946653002501967653001501992653002802007653001502035653001402050653002402064653001102088653002502099653001102124653001402135653003102149653003102180653000902211653001502220653003002235653001402265653002002279653003202299653003002331653001602361653002202377100002402399700002002423700001602443700001802459700002002477700002102497700003202518700001702550700001702567700002202584700002002606700002402626856003502650 2005 eng d a1046-667300aCystatin C and subclinical brain infarction.0 aCystatin C and subclinical brain infarction c2005 Dec a3721-70 v163 aSubclinical brain infarcts (SBI) are common in the elderly and are associated with covert neurologic and cognitive impairment. Although renal impairment is associated with accelerated cerebrovascular disease and an increased risk for clinically apparent brain infarct, few studies have examined the relationship between renal function and SBI, and these may have been limited by the inaccuracy of creatinine as a renal function marker. A cross-sectional study was performed among older adults in the Cardiovascular Health Study to examine associations between SBI and two serum markers of renal function: Serum creatinine (SCr) and cystatin C (CysC). Patients had cranial magnetic resonance imaging and renal markers measured in 1992 to 1993. Logistic regression was used to estimate the associations between renal function (estimated by 1/SCr and 1/CysC) and SBI, controlling for potential confounding factors. SBI were present in 789 (28.7%) of 2784 participants. A linear association with SBI was observed for 1/CysC (per 1-SD decrement; odds ratio [OR] 1.20; 95% confidence interval [CI] 1.09 to 1.32; P < 0.001) but not for 1/SCr (OR 1.08; 95% CI 0.98 to 1.19; P = 0.14), for which a quadratic U-shaped association was suggested (P = 0.004). In a model with both markers, 1/CysC was linearly associated with SBI (OR 1.26; P < 0.001), whereas 1/SCr was not (OR 1.06; P = 0.3). The prevalence of SBI was directly associated with quintile of CysC, whereas the association between SCr and SBI was U-shaped, with greater prevalence at high and low levels. Compared with creatinine, CysC, a novel marker of renal function, has a stronger and more direct association with SBI in the elderly.
10aAge Factors10aAged10aAged, 80 and over10aBiomarkers10aBrain Infarction10aConfidence Intervals10aCreatinine10aCross-Sectional Studies10aCystatin C10aCystatins10aDisease Progression10aFemale10aGeriatric Assessment10aHumans10aIncidence10aIschemic Attack, Transient10aMagnetic Resonance Imaging10aMale10aOdds Ratio10aPredictive Value of Tests10aPrognosis10aRisk Assessment10aSensitivity and Specificity10aSeverity of Illness Index10aSex Factors10aSurvival Analysis1 aSeliger, Stephen, L1 aLongstreth, W T1 aKatz, Ronit1 aManolio, Teri1 aFried, Linda, F1 aShlipak, Michael1 aStehman-Breen, Catherine, O1 aNewman, Anne1 aSarnak, Mark1 aGillen, Daniel, L1 aBleyer, Anthony1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/86203443nas a2200421 4500008004100000022001400041245012400055210006900179260001300248300001100261490000700272520226300279653002202542653000902564653001502573653002802588653001502616653001402631653002402645653001102669653003102680653001102711653002002722653001802742653002502760653000902785653001702794100002302811700001402834700001602848700001702864700003202881700001702913700001802930700001702948700002102965856003502986 2006 eng d a1046-667300aAfrican ancestry, socioeconomic status, and kidney function in elderly African Americans: a genetic admixture analysis.0 aAfrican ancestry socioeconomic status and kidney function in eld c2006 Dec a3491-60 v173 aKidney disease is a major public health problem in the United States that affects African Americans disproportionately. The relative contribution of environmental and genetic factors to the increased burden of kidney disease among African Americans is unknown. The associations of genetic African ancestry and socioeconomic status with kidney function were studied cross-sectionally and longitudinally among 736 community-dwelling African Americans who were aged >65 yr and participating in the Cardiovascular Health Study. Genetic African ancestry was determined by genotyping 24 biallelic ancestry-informative markers and combining this information statistically to generate an estimate of ancestry for each individual. Kidney function was evaluated by cystatin C and estimated GFR (eGFR) using the Modification of Diet in Renal Disease equation. Longitudinal changes in serum creatinine and eGFR were estimated using baseline and follow-up values. In cross-sectional analyses, there was no association between genetic African ancestry and either measure of kidney function (P = 0.36 for cystatin C and 0.68 for eGFR). African ancestry was not associated with change in serum creatinine > or =0.05 mg/dl per yr (odds ratio [OR] 0.94; 95% confidence interval [CI] 0.83 to 1.06) or with change in eGFR > or =3 ml/min per 1.73 m(2) per yr (OR 1.02; 95% CI 0.92 to 1.13). In contrast, self reported African-American race was strongly associated with increased risk for kidney disease progression compared with white individuals for change in creatinine (OR 1.77; 95% CI 1.33 to 2.36) and for change in eGFR (OR 3.21; 95% CI 2.54 to 4.06). Among self-identified African Americans, low income (< US dollars 8000/yr) was strongly associated with prevalent kidney dysfunction by cystatin C >1.29 g/dl (adjusted OR 2.7; 95% CI 1.0 to 7.5) or by eGFR <60 ml/min per 1.73 m(2) (adjusted OR 3.2; 95% CI 1.1 to 9.4) compared with those with incomes >US dollars 35,000/yr. Alleles that are known to be present more frequently in the African ancestral group were not associated with kidney dysfunction or kidney disease progression. Rather, kidney dysfunction in elderly African Americans seems more attributable to differences in environmental and social factors.
10aAfrican Americans10aAged10aCreatinine10aCross-Sectional Studies10aCystatin C10aCystatins10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Diseases10aLinear Models10aLongitudinal Studies10aMale10aSocial Class1 aPeralta, Carmen, A1 aZiv, Elad1 aKatz, Ronit1 aReiner, Alex1 aBurchard, Esteban González1 aFried, Linda1 aKwok, Pui-Yan1 aPsaty, Bruce1 aShlipak, Michael uhttps://chs-nhlbi.org/node/92703867nas a2200745 4500008004100000022001400041245012900055210006900184260001300253300001100266490000600277520177500283653002802058653002102086653001102107653001702118653003402135653000902169653001102178653000902189653001702198653001402215100001602229700001902245700001902264700002102283700002202304700002002326700002302346700001902369700002402388700002202412700001902434700001902453700002002472700001902492700002102511700002002532700001202552700002002564700002102584700002302605700001202628700001902640700002002659700002102679700002002700700002202720700003002742700002102772700002302793700001902816700002602835700002002861700002802881700002102909700002002930700002002950700002402970700002402994700002803018700002103046700001803067856003603085 2010 eng d a1942-326800aMultiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors.0 aMultiple genetic loci influence serum urate levels and their rel c2010 Dec a523-300 v33 aBACKGROUND: Elevated serum urate levels can lead to gout and are associated with cardiovascular risk factors. We performed a genome-wide association study to search for genetic susceptibility loci for serum urate and gout and investigated the causal nature of the associations of serum urate with gout and selected cardiovascular risk factors and coronary heart disease (CHD).
METHODS AND RESULTS: Meta-analyses of genome-wide association studies (GWAS) were performed in 5 population-based cohorts of the Cohorts for Heart and Aging Research in Genome Epidemiology consortium for serum urate and gout in 28 283 white participants. The effect of the most significant single-nucleotide polymorphism at all genome-wide significant loci on serum urate was added to create a genetic urate score. Findings were replicated in the Women's Genome Health Study (n=22 054). Single-nucleotide polymorphisms at 8 genetic loci achieved genome-wide significance with serum urate levels (P=4×10(-8) to 2×10(-242) in SLC22A11, GCKR, R3HDM2-INHBC region, RREB1, PDZK1, SLC2A9, ABCG2, and SLC17A1). Only 2 loci (SLC2A9, ABCG2) showed genome-wide significant association with gout. The genetic urate score was strongly associated with serum urate and gout (odds ratio, 12.4 per 100 μmol/L; P=3×10(-39)) but not with blood pressure, glucose, estimated glomerular filtration rate, chronic kidney disease, or CHD. The lack of association between the genetic score and the latter phenotypes also was observed in the Women's Genome Health Study.
CONCLUSIONS: The genetic urate score analysis suggested a causal relationship between serum urate and gout but did not provide evidence for one between serum urate and cardiovascular risk factors and CHD.
10aCardiovascular Diseases10aCoronary Disease10aFemale10aGenetic Loci10aGenome-Wide Association Study10aGout10aHumans10aMale10aRisk Factors10aUric Acid1 aYang, Qiong1 aKöttgen, Anna1 aDehghan, Abbas1 aSmith, Albert, V1 aGlazer, Nicole, L1 aChen, Ming-Huei1 aChasman, Daniel, I1 aAspelund, Thor1 aEiriksdottir, Gudny1 aHarris, Tamara, B1 aLauner, Lenore1 aNalls, Michael1 aHernandez, Dena1 aArking, Dan, E1 aBoerwinkle, Eric1 aGrove, Megan, L1 aLi, Man1 aKao, W, H Linda1 aChonchol, Michel1 aHaritunians, Talin1 aLi, Guo1 aLumley, Thomas1 aPsaty, Bruce, M1 aShlipak, Michael1 aHwang, Shih-Jen1 aLarson, Martin, G1 aO'Donnell, Christopher, J1 aUpadhyay, Ashish1 aDuijn, Cornelia, M1 aHofman, Albert1 aRivadeneira, Fernando1 aStricker, Bruno1 aUitterlinden, André, G1 aParé, Guillaume1 aParker, Alex, N1 aRidker, Paul, M1 aSiscovick, David, S1 aGudnason, Vilmundur1 aWitteman, Jacqueline, C1 aFox, Caroline, S1 aCoresh, Josef uhttps://chs-nhlbi.org/node/123502802nas a2200469 4500008004100000022001400041245009700055210006900152260000900221300001000230490000700240520155000247653000901797653002801806653001501834653001501849653002401864653001101888653001501899653003101914653001101945653001101956653002001967653000901987653001601996653002202012653001702034653002202051100002302073700001602096700002102112700001602133700001602149700001702165700002502182700001602207700002202223700001602245700001702261700001802278856003602296 2011 eng d a1421-967000aKidney function decline in the elderly: impact of lipoprotein-associated phospholipase A(2).0 aKidney function decline in the elderly impact of lipoproteinasso c2011 a512-80 v343 aBACKGROUND: Whether lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) levels are associated with kidney function decline has not been well studied.
METHODS: We investigated associations of Lp-PLA(2) antigen and activity with kidney function decline and rapid decline over 5.7 years in the Cardiovascular Health Study (n = 4,359). We estimated kidney function by cystatin C (eGFRcys) in repeated measures, and defined rapid decline as ≥3 ml/min/1.73 m(2) per year. We stratified by baseline preserved GFR (≥60 ml/min/1.73 m(2)).
RESULTS: Mean age was 72 ± 5 years. Average eGFRcys decline was -1.79 ml/min/1.73 m(2) (SD = 2.60) per year. Among persons with preserved GFR, compared to the lowest quartile of Lp-PLA(2) antigen, eGFRcys decline was faster among persons in the second, β -0.31 (95% CI -0.52, -0.10), third -0.19 (-0.41, 0.02) and fourth quartiles -0.26 (-0.48, -0.04) after full adjustment. Persons in the highest quartile of Lp-PLA(2) antigen had increased odds of rapid decline 1.34 (1.03, 1.75), compared to the lowest. There was no significant association between levels of Lp-PLA(2) activity and eGFRcys decline or rapid decline. Associations were not statistically significant among persons with low eGFR (<60 ml/min/1.73 m(2)) at baseline.
CONCLUSION: Higher levels of Lp-PLA(2) antigen but not activity were significantly associated with faster rates of kidney function decline. These findings may suggest a novel vascular pathway for kidney disease progression.
10aAged10aCardiovascular Diseases10aCreatinine10aCystatin C10aDisease Progression10aFemale10aGeriatrics10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aMale10aMiddle Aged10aPhospholipases A210aRisk Factors10aTreatment Outcome1 aPeralta, Carmen, A1 aKatz, Ronit1 aShlipak, Michael1 aDubin, Ruth1 aDeBoer, Ian1 aJenny, Nancy1 aFitzpatrick, Annette1 aKoro, Carol1 aKestenbaum, Bryan1 aIx, Joachim1 aSarnak, Mark1 aCushman, Mary uhttps://chs-nhlbi.org/node/134902824nas a2200397 4500008004100000022001400041245011600055210006900171260001300240300001100253490000700264520170200271653000901973653002201982653002802004653003002032653001102062653001202073653001102085653001402096653002502110653000902135653001702144100002202161700002002183700002402203700001802227700002002245700002202265700002102287700001802308700002402326700002102350700001902371856003602390 2013 eng d a1935-554800aFetuin-A, type 2 diabetes, and risk of cardiovascular disease in older adults: the cardiovascular health study.0 aFetuinA type 2 diabetes and risk of cardiovascular disease in ol c2013 May a1222-80 v363 aOBJECTIVE: Fetuin-A, a hepatic secretory protein that simultaneously inhibits arterial calcification and insulin action, is associated with type 2 diabetes, but its association with cardiovascular disease (CVD) is uncertain. Preliminary studies suggest that the association of fetuin-A with CVD might differ among individuals with or without type 2 diabetes.
RESEARCH DESIGN AND METHODS: This was a prospective study of 3,810 community-living individuals older than 65 years (511 with type 2 diabetes) and free of CVD in 1992 when fetuin-A levels were measured. Participants were followed-up for incident CVD through June 2008.
RESULTS: Mean age was 75 years, and 61% were women; 1,456 participants had an incident CVD event (248 among individuals with type 2 diabetes). The association of fetuin-A with CVD was modified by type 2 diabetes (P interaction = 0.02). Higher fetuin-A was associated with lower CVD risk among persons without type 2 diabetes [hazard ratio per SD 0.1 g/L higher fetuin-A, 0.93 (95% CI, 0.88-0.99)], whereas a trend in the opposite direction was observed among individuals with type 2 diabetes, although it was not statistically significant [1.07 (0.93-1.22)]. Among individuals without type 2 diabetes, similar effect modification was observed by obesity and insulin resistance. Consistently, higher fetuin-A was associated with lower CVD risk only in the subgroups without obesity or with HOMA-IR below the median [0.91 (0.85-0.97) and 0.87 (0.79-0.95), respectively].
CONCLUSIONS: The association of fetuin-A with risk of CVD differs among elderly individuals with and without insulin resistance or type 2 diabetes.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aDiabetes Mellitus, Type 210aFemale10aFetuins10aHumans10aIncidence10aLongitudinal Studies10aMale10aRisk Factors1 aJensen, Majken, K1 aBartz, Traci, M1 aMukamal, Kenneth, J1 aDjoussé, Luc1 aKizer, Jorge, R1 aTracy, Russell, P1 aZieman, Susan, J1 aRimm, Eric, B1 aSiscovick, David, S1 aShlipak, Michael1 aIx, Joachim, H uhttps://chs-nhlbi.org/node/155202403nas a2200361 4500008004100000022001400041245009100055210006900146260001700215300001000232490000700242520142400249653000901673653001001682653000901692653002101701653002101722653001101743653003101754653001101785653001101796653001101807653000901818653002401827653003101851100002601882700001601908700002101924700002001945700002101965700001901986856003602005 2014 eng d a1873-124400aDietary protein intake and change in estimated GFR in the Cardiovascular Health Study.0 aDietary protein intake and change in estimated GFR in the Cardio c2014 Jul-Aug a794-90 v303 aOBJECTIVE: With aging, kidney function declines, as evidenced by reduced glomerular filtration rate. It is controversial whether or not high protein intake accelerates this decline. The aim of this study was to determine whether high protein intake was associated with declines in kidney function among older patients.
METHODS: We examined whether dietary protein is associated with change in kidney function (mean follow-up 6.4 y [SD = 1.4, range = 2.5-7.9] in the Cardiovascular Health Study (N = 3623). We estimated protein intake using a food frequency questionnaire and estimated glomerular filtration rate from cystatin C. Associations between protein intake and kidney function were determined by linear and logistic regression models.
RESULTS: Average protein intake was 19% of energy intake (SD = 5%). Twenty-seven percent (n = 963) of study participants had rapid decline in kidney function, as defined by (ΔeGFRcysC > 3 mL•min•1.73 m(2)). Protein intake (characterized as g/d and % energy/d), was not associated with change in estimated glomerular filtration rate (P > 0.05 for all comparisons). There were also no significant associations when protein intake was separated by source (animal and vegetable).
CONCLUSION: These data suggest that higher protein intake does not have a major effect on kidney function decline among elderly men and women.
10aAged10aAging10aDiet10aDietary Proteins10aFeeding Behavior10aFemale10aGlomerular Filtration Rate10aHealth10aHumans10aKidney10aMale10aRegression Analysis10aSurveys and Questionnaires1 aBeasley, Jeannette, M1 aKatz, Ronit1 aShlipak, Michael1 aRifkin, Dena, E1 aSiscovick, David1 aKaplan, Robert uhttps://chs-nhlbi.org/node/654603491nas a2200493 4500008004100000022001400041245012600055210006900181260001300250300001100263490000600274520211000280653002402390653001602414653000902430653002202439653001602461653001502477653001502492653001502507653001102522653003002533653003102563653002002594653001102614653002302625653001102648653002502659653000902684653001402693653003202707653002402739653001702763653001702780100002302797700001602820700001902836700002002855700002402875700002102899700002102920700002002941856003602961 2014 eng d a1555-905X00aFibroblast growth factor-23 and the long-term risk of hospital-associated AKI among community-dwelling older individuals.0 aFibroblast growth factor23 and the longterm risk of hospitalasso c2014 Feb a239-460 v93 aBACKGROUND AND OBJECTIVES: AKI occurs frequently in older persons. Elevated circulating fibroblast growth factor-23 (FGF-23), a known marker of impaired mineral metabolism, may also reflect tubular dysfunction and risk of AKI. This study evaluated FGF-23 as well as traditional markers of kidney disease, namely urine albumin-to-creatinine ratio (UACR) and creatinine-cystatin C estimated GFR (eGFRCrCyC), as risk factors for AKI in elderly individuals.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma FGF-23, UACR, and eGFRCrCyC were measured in 3241 community-dwelling elderly individuals in the Cardiovascular Health Study. Hospitalization for AKI was defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Associations of each biomarker with AKI were evaluated using Cox proportional hazards models adjusted for demographics, cardiovascular risk factors, and biomarkers of kidney function.
RESULTS: The mean participant age was 78 years; 60% of participants were women and 16% were African American. The median (interquartile range) values of biomarkers were as follows: FGF-23, 70 RU/ml (53, 99); UACR, 8.88 mg/g (4.71, 20.47); and eGFRCrCyC, 71 ml/min per 1.73 m(2) (59, 83). Hospitalized AKI occurred in 119 participants over 10.0 years of median follow-up. In fully adjusted analyses, compared with the lowest quartiles, the highest quartiles of FGF-23 (≥100 RU/ml) and UACR (≥20.9 mg/g) were associated with AKI (FGF-23: hazard ratio [HR], 1.99; 95% confidence interval [95% CI], 1.04 to 3.80; and UACR: HR, 3.35; 95% CI, 1.83 to 6.13). Compared with the highest quartile, the lowest quartile of eGFRCrCyC (<57 ml/min per 1.73 m(2)) was associated with AKI with an HR of 2.15 (95% CI, 1.21 to 3.82).
CONCLUSIONS: FGF-23 adjusted for albuminuria, cardiovascular disease risk factors, and baseline eGFR is independently associated with a higher risk of AKI hospitalizations in community-dwelling elderly individuals. Further studies to understand the nature of this association are warranted.
10aAcute Kidney Injury10aAge Factors10aAged10aAged, 80 and over10aAlbuminuria10aBiomarkers10aCreatinine10aCystatin C10aFemale10aFibroblast Growth Factors10aGlomerular Filtration Rate10aHospitalization10aHumans10aIndependent Living10aKidney10aLongitudinal Studies10aMale10aPrognosis10aProportional Hazards Models10aProspective Studies10aRisk Factors10aTime Factors1 aBrown, Jeremiah, R1 aKatz, Ronit1 aIx, Joachim, H1 ade Boer, Ian, H1 aSiscovick, David, S1 aGrams, Morgan, E1 aShlipak, Michael1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/630803861nas a2200565 4500008004100000022001400041245010700055210006900162260001500231300001100246490000700257520230700264653001602571653000902587653001002596653001502606653001502621653002402636653001102660653003102671653001102702653001402713653001102727653001802738653002502756653000902781653003102790653002202821653003002843653001402873653003202887653002402919653003302943653001702976653001702993653001503010653001803025653001803043100001803061700001603079700002203095700001703117700002703134700002203161700001703183700001703200700002103217700002103238856003603259 2015 eng d a1555-905X00aNT-proBNP and troponin T and risk of rapid kidney function decline and incident CKD in elderly adults.0 aNTproBNP and troponin T and risk of rapid kidney function declin c2015 Feb 6 a205-140 v103 aBACKGROUND AND OBJECTIVES: Elevations in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T are associated with poor cardiovascular outcomes. Whether elevations in these cardiac biomarkers are associated with decline in kidney function was evaluated.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: N-terminal pro-B-type natriuretic peptide and troponin T were measured at baseline in 3752 participants free of heart failure in the Cardiovascular Health Study. eGFR was determined from the Chronic Kidney Disease Epidemiology Collaboration equation using serum cystatin C. Rapid decline in kidney function was defined as decline in serum cystatin C eGFR≥30%, and incident CKD was defined as the onset of serum cystatin C eGFR<60 among those without CKD at baseline (n=2786). Cox regression models were used to examine the associations of each biomarker with kidney function decline adjusting for demographics, baseline serum cystatin C eGFR, diabetes, and other CKD risk factors.
RESULTS: In total, 503 participants had rapid decline in serum cystatin C eGFR over a mean follow-up time of 6.41 (1.81) years, and 685 participants developed incident CKD over a mean follow-up time of 6.41 (1.74) years. Participants in the highest quartile of N-terminal pro-B-type natriuretic peptide (>237 pg/ml) had an 67% higher risk of rapid decline and 38% higher adjusted risk of incident CKD compared with participants in the lowest quartile (adjusted hazard ratio for serum cystatin C eGFR rapid decline, 1.67; 95% confidence interval, 1.25 to 2.23; hazard ratio for incident CKD, 1.38; 95% confidence interval, 1.08 to 1.76). Participants in the highest category of troponin T (>10.58 pg/ml) had 80% greater risk of rapid decline compared with participants in the lowest category (adjusted hazard ratio, 1.80; 95% confidence interval, 1.35 to 2.40). The association of troponin T with incident CKD was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.92 to 1.50).
CONCLUSIONS: Elevated N-terminal pro-B-type natriuretic peptide and troponin T are associated with rapid decline of kidney function and incident CKD. Additional studies are needed to evaluate the mechanisms that may explain this association.
10aAge Factors10aAged10aAging10aBiomarkers10aCystatin C10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHumans10aIncidence10aKidney10aLinear Models10aLongitudinal Studies10aMale10aNatriuretic Peptide, Brain10aPeptide Fragments10aPredictive Value of Tests10aPrognosis10aProportional Hazards Models10aProspective Studies10aRenal Insufficiency, Chronic10aRisk Factors10aTime Factors10aTroponin T10aUnited States10aUp-Regulation1 aBansal, Nisha1 aKatz, Ronit1 aDalrymple, Lorien1 ade Boer, Ian1 aDeFilippi, Christopher1 aKestenbaum, Bryan1 aPark, Meyeon1 aSarnak, Mark1 aSeliger, Stephen1 aShlipak, Michael uhttps://chs-nhlbi.org/node/666102478nas a2200241 4500008004100000022001400041245012400055210007000179260001600249300000700265490000700272520174300279100001702022700002102039700002002060700001802080700002102098700002402119700002102143700001902164700001702183856003602200 2017 eng d a1471-236900aHigher plasma transforming growth factor (TGF)-β is associated with kidney disease in older community dwelling adults.0 aHigher plasma transforming growth factor TGFβ is associated with c2017 Mar 21 a980 v183 aBACKGROUND: TGF-β is induced in the vasculature with aging suggesting that high plasma TGF-β levels may be a risk factor for chronic kidney disease (CKD) in older adults.
METHODS: We conducted a cross-sectional analysis of the association between plasma TGF-β levels and CKD including data for 1722 older adults who had participated in the 1996/97 visit of the Cardiovascular Health Study (CHS). Prevalent CKD was defined as eGFR < 60 mL/min/1.73 m(2) or urinary albumin/creatinine ratio (ACR) ≥30 mg/g. We also evaluated whether baseline TGF-β levels predicted change in eGFR, cardiovascular (CV) events, or mortality in longitudinal analysis.
RESULTS: Plasma TGF-β levels were significantly and independently associated with lower eGFR in cross-sectional analysis. Doubling of TGF-β was significantly associated with lower eGFR (β estimate after adjusting for CV risk factors = -1.18, 95% CI -2.03, -0.32). We observed no association with albuminuria. There was no association between baseline TGF-β and change in eGFR, but each doubling of TGF-β at baseline was associated with increased risk of a composite outcome of CV events and mortality, adjusted HR 1.10 (95% C.I. 1.02- 1.20, p = 0.006).
CONCLUSION: In this large cohort of community-dwelling older individuals, high plasma TGF-β levels are modestly, but independently associated with lower eGFR but not with albuminuria in cross-sectional analysis. In addition, TGF-β levels are associated with increased risk of CV events and mortality. Further research is needed to determine the direction of association between plasma TGF-β and the risk of CKD and CKD-associated morbidities in older adults.
1 aMehta, Tapan1 aBůzková, Petra1 aKizer, Jorge, R1 aDjoussé, Luc1 aChonchol, Michel1 aMukamal, Kenneth, J1 aShlipak, Michael1 aIx, Joachim, H1 aJalal, Diana uhttps://chs-nhlbi.org/node/735103207nas a2200337 4500008004100000022001400041245013200055210006900187260001600256300001200272490000800284520218000292100002602472700002202498700002102520700002502541700002102566700001702587700002402604700001702628700002102645700002002666700002402686700002402710700002102734700002202755700002102777700001702798700001802815856003602833 2019 eng d a1535-497000aAlbuminuria, Lung Function Decline, and Risk of Incident Chronic Obstructive Pulmonary Disease. The NHLBI Pooled Cohorts Study.0 aAlbuminuria Lung Function Decline and Risk of Incident Chronic O c2019 Feb 01 a321-3320 v1993 aRATIONALE: Chronic lower respiratory diseases (CLRDs), including chronic obstructive pulmonary disease (COPD) and asthma, are the fourth leading cause of death. Prior studies suggest that albuminuria, a biomarker of endothelial injury, is increased in patients with COPD.
OBJECTIVES: To test whether albuminuria was associated with lung function decline and incident CLRDs.
METHODS: Six U.S. population-based cohorts were harmonized and pooled. Participants with prevalent clinical lung disease were excluded. Albuminuria (urine albumin-to-creatinine ratio) was measured in spot samples. Lung function was assessed by spirometry. Incident CLRD-related hospitalizations and deaths were classified via adjudication and/or administrative criteria. Mixed and proportional hazards models were used to test individual-level associations adjusted for age, height, weight, sex, race/ethnicity, education, birth year, cohort, smoking status, pack-years of smoking, renal function, hypertension, diabetes, and medications.
MEASUREMENTS AND MAIN RESULTS: Among 10,961 participants with preserved lung function, mean age at albuminuria measurement was 60 years, 51% were never-smokers, median albuminuria was 5.6 mg/g, and mean FEV decline was 31.5 ml/yr. For each SD increase in log-transformed albuminuria, there was 2.81% greater FEV decline (95% confidence interval [CI], 0.86-4.76%; P = 0.0047), 11.02% greater FEV/FVC decline (95% CI, 4.43-17.62%; P = 0.0011), and 15% increased hazard of incident spirometry-defined moderate-to-severe COPD (95% CI, 2-31%, P = 0.0021). Each SD log-transformed albuminuria increased hazards of incident COPD-related hospitalization/mortality by 26% (95% CI, 18-34%, P < 0.0001) among 14,213 participants followed for events. Asthma events were not significantly associated. Associations persisted in participants without current smoking, diabetes, hypertension, or cardiovascular disease.
CONCLUSIONS: Albuminuria was associated with greater lung function decline, incident spirometry-defined COPD, and incident COPD-related events in a U.S. population-based sample.
1 aOelsner, Elizabeth, C1 aBalte, Pallavi, P1 aGrams, Morgan, E1 aCassano, Patricia, A1 aJacobs, David, R1 aBarr, Graham1 aBurkart, Kristin, M1 aKalhan, Ravi1 aKronmal, Richard1 aLoehr, Laura, R1 aO'Connor, George, T1 aSchwartz, Joseph, E1 aShlipak, Michael1 aTracy, Russell, P1 aTsai, Michael, Y1 aWhite, Wendy1 aYende, Sachin uhttps://chs-nhlbi.org/node/798003249nas a2200385 4500008004100000022001400041245014700055210006900202260001600271520204100287100001902328700001902347700003002366700002602396700003102422700001902453700002102472700002102493700002502514700001702539700002102556700002502577700001602602700002302618700002102641700002002662700001902682700001902701700002202720700001802742700001802760700002802778700002102806856003602827 2020 eng d a1523-175500aA systematic review and participant-level meta-analysis found little association of retinal microvascular caliber and reduced kidney function.0 asystematic review and participantlevel metaanalysis found little c2020 Aug 153 aPreviously, variation in retinal vascular caliber has been reported in association with chronic kidney disease (CKD) but findings remain inconsistent. To help clarify this we conducted individual participant data meta-analysis and aggregate data meta-analysis on summary estimates to evaluate cross-sectional associations between retinal vascular caliber and CKD. A systematic review was performed using Medline and EMBASE for articles published until October 2018. The aggregate analysis used a two-stage approach combining summary estimates from eleven studies (44,803 patients) while the individual participant analysis used a one-stage approach combining raw data from nine studies (33,222 patients). CKD stages 3-5 was defined as an estimated glomerular filtration rate under 60 mL/min/1.73m. Retinal arteriolar and venular caliber (central retinal arteriolar and venular equivalent) were assessed from retinal photographs using computer-assisted methods. Logistic regression estimated relative risk of CKD stages 3-5 associated with a 20 μm decrease (approximately one standard deviation) in central retinal arteriolar and venular equivalent. Prevalence of CKD stages 3-5 was 11.2 % of 33,222 and 11.3 % of 44,803 patients in the individual participant and aggregate data analysis, respectively. No significant associations were detected in adjusted analyses between central retinal arteriolar and venular equivalent and CKD stages 3-5 in the aggregate analysis for central retinal arteriolar relative risk (0.98, 95% confidence interval 0.94-1.03); venular equivalent (0.99, 0.95- 1.04) or individual participant central retinal arteriolar (0.99, 0.95-1.04) or venular equivalent (1.01, 0.97-1.05). Thus, meta-analysis provided little evidence to suggest that cross sectional direct measurements of retinal vascular caliber was associated with CKD stages 3-5 in the general population. Hence, meta-analyses of longitudinal studies evaluating the association between retinal parameters and CKD stages 3-5 may be warranted.
1 aLye, Weng, Kit1 aPaterson, Euan1 aPatterson, Christopher, C1 aMaxwell, Alexander, P1 aAbdul, Riswana, Banu Binte1 aTai, Shyong, E1 aCheng, Ching, Yu1 aKayama, Takamasa1 aYamashita, Hidetoshi1 aSarnak, Mark1 aShlipak, Michael1 aMatsushita, Kunihiro1 aMutlu, Unal1 aIkram, Mohammad, A1 aKlaver, Caroline1 aKifley, Annette1 aMitchell, Paul1 aMyers, Chelsea1 aKlein, Barbara, E1 aKlein, Ronald1 aWong, Tien, Y1 aSabanayagam, Charumathi1 aMcKay, Gareth, J uhttps://chs-nhlbi.org/node/8628