02942nas a2200445 4500008004100000022001400041245010400055210006900159260001300228300001000241490000700251520170200258653000901960653002501969653002301994653001102017653001502028653002202043653001102065653001402076653002502090653000902115653002302124653003202147653001502179653001702194653001502211100002102226700001902247700002402266700001902290700002302309700002402332700001802356700002402374700002002398700001802418700002402436856003602460 2014 eng d a1524-456300aMetabolic syndrome and risk of incident peripheral artery disease: the cardiovascular health study.0 aMetabolic syndrome and risk of incident peripheral artery diseas c2014 Feb a413-90 v633 a

Prior studies evaluating metabolic syndrome (MetS) and incident peripheral artery disease (PAD) have been limited by use of modified MetS criteria and restriction to clinical PAD end points. We investigated MetS and risk of developing a low ankle-brachial index (ABI) and clinical PAD in the Cardiovascular Health Study, a population-based cohort of adults aged ≥65 years. Participants with MetS met at least 3 of 5 Adult Treatment Panel III criteria. Baseline C-reactive protein-MetS or fibrinogen-MetS were defined as presence of 3 of 6 components, with elevated C-reactive protein (>3 mg/L) or fibrinogen (>341 mg/dL) as a sixth component. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15, was assessed among a subset of 1899 individuals with 2 ABI measurements 6 years apart. Over a median follow-up of 13.7 years, 4632 individuals were followed up for clinical PAD, defined as revascularization or diagnosed claudication. Adult Treatment Panel III MetS was associated with both incident low ABI (risk ratio, 1.26; 95% confidence interval [CI], 1.00-1.58) and clinical PAD (hazard ratio, 1.47; 95% CI, 1.11-1.94). Incorporating C-reactive protein or fibrinogen into Adult Treatment Panel III criteria identified an additional 16% to 20% of individuals as having MetS, and both C-reactive protein-MetS and fibrinogen-MetS were associated with incident low ABI (risk ratio, 1.36; 95% CI, 1.07-1.72 and risk ratio, 1.43; 95% CI, 1.13-1.81, respectively) and clinical PAD (hazard ratio, 1.56; 95% CI, 1.17-2.08 and hazard ratio, 1.55; 95% CI, 1.17-2.07, respectively). Among Adult Treatment Panel III MetS criteria, risk of PAD was most strongly associated with hypertension.

10aAged10aAnkle Brachial Index10aC-Reactive Protein10aFemale10aFibrinogen10aFollow-Up Studies10aHumans10aIncidence10aLongitudinal Studies10aMale10aMetabolic Syndrome10aPeripheral Arterial Disease10aPrevalence10aRisk Factors10aVasculitis1 aGarg, Parveen, K1 aBiggs, Mary, L1 aCarnethon, Mercedes1 aIx, Joachim, H1 aCriqui, Michael, H1 aBritton, Kathryn, A1 aDjoussé, Luc1 aSutton-Tyrrell, Kim1 aNewman, Anne, B1 aCushman, Mary1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/614803299nas a2200517 4500008004100000022001400041245013500055210006900190260001300259300001000272490000700282520181000289653005102099653001602150653000902166653001002175653002502185653001502210653002802225653001102253653001102264653001402275653002702289653002002316653000902336653001502345653003202360653001402392653003202406653002002438653001702458653001702475653001802492653001802510100002102528700002102549700003302570700001602603700002002619700002402639700002302663700002102686700002002707700001802727856003602745 2016 eng d a1524-463600aLipoprotein-Associated Phospholipase A2 and Incident Peripheral Arterial Disease in Older Adults: The Cardiovascular Health Study.0 aLipoproteinAssociated Phospholipase A2 and Incident Peripheral A c2016 Apr a750-60 v363 a

OBJECTIVE: Although prior studies report a relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) and incident cardiovascular disease, the prospective association of Lp-PLA2 with incident peripheral arterial disease (PAD) has not been studied. We investigated the association between Lp-PLA2 mass and activity and the risk of developing clinical PAD and low ankle-brachial index (ABI).

APPROACH AND RESULTS: Among Cardiovascular Health Study participants, a population-based cohort of 5888 adults aged ≥65 years enrolled in 1989 to 1990, Lp-PLA2 mass and activity were measured in 4537 individuals without baseline PAD. Clinical PAD, defined as leg artery revascularization or diagnosed claudication, was ascertained through 2011. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15, was assessed among 3537 individuals who had an ABI >0.9 at baseline and a second ABI measurement 3 or 6 years later. Analyses were adjusted for demographics, cholesterol, smoking, comorbidities, and C-reactive protein. Each standard deviation increment in Lp-PLA2 mass (117 ng/mL) was associated with a higher risk of developing clinical PAD (hazard ratio 1.28; 95% confidence interval 1.13, 1.45) and incident low ABI (odds ratio 1.16; 95% confidence interval 1.00, 1.33). Results per standard deviation increment in Lp-PLA2 activity (13 nmol/min per mL) were similar for clinical PAD (hazard ratio 1.24; 95% confidence interval 1.07, 1.44) and low ABI (odds ratio 1.28; 95% confidence interval 1.09, 1.50).

CONCLUSIONS: Higher Lp-PLA2 mass and activity were associated with development of both incident clinical PAD and low ABI. Future studies are needed to determine whether pharmacological inhibition of Lp-PLA2 reduces the incidence of PAD.

10a1-Alkyl-2-acetylglycerophosphocholine Esterase10aAge Factors10aAged10aAging10aAnkle Brachial Index10aBiomarkers10aChi-Square Distribution10aFemale10aHumans10aIncidence10aInflammation Mediators10aLogistic Models10aMale10aOdds Ratio10aPeripheral Arterial Disease10aPrognosis10aProportional Hazards Models10aRisk Assessment10aRisk Factors10aTime Factors10aUnited States10aUp-Regulation1 aGarg, Parveen, K1 aArnold, Alice, M1 aStukovsky, Karen, D Hinckley1 aKoro, Carol1 aJenny, Nancy, S1 aMukamal, Kenneth, J1 aCriqui, Michael, H1 aFurberg, Curt, D1 aNewman, Anne, B1 aCushman, Mary uhttps://chs-nhlbi.org/node/699602682nas a2200253 4500008004100000022001400041245011600055210006900171260001600240300001200256490000600268520189400274100002102168700002102189700002302210700001902233700002202252700002702274700002402301700002702325700002102352700001902373856003602392 2016 eng d a1664-545600aRisk Factors for Incident Carotid Artery Revascularization among Older Adults: The Cardiovascular Health Study.0 aRisk Factors for Incident Carotid Artery Revascularization among c2016 Nov 16 a129-1390 v63 a

BACKGROUND: Population-based risk factors for carotid artery revascularization are not known. We investigated the association between demographic and clinical characteristics and incident carotid artery revascularization in a cohort of older adults.

METHODS: Among Cardiovascular Health Study participants, a population-based cohort of 5,888 adults aged 65 years or older enrolled in two waves (1989-1990 and 1992-1993), 5,107 participants without a prior history of carotid endarterectomy (CEA) or cerebrovascular disease had a carotid ultrasound at baseline and were included in these analyses. Cox proportional hazards multivariable analysis was used to determine independent risk factors for incident carotid artery revascularization.

RESULTS: Over a mean follow-up of 13.5 years, 141 participants underwent carotid artery revascularization, 97% were CEA. Baseline degree of stenosis and incident ischemic cerebral events occurring during follow-up were the strongest predictors of incident revascularization. After adjustment for these, factors independently associated with an increased risk of incident revascularization were: hypertension (HR 1.53; 95% CI: 1.05-2.23), peripheral arterial disease (HR 2.57; 95% CI: 1.34-4.93), and low-density lipoprotein cholesterol (HR 1.23 per standard deviation [SD] increment [35.4 mg/dL]; 95% CI: 1.04-1.46). Factors independently associated with a lower risk of incident revascularization were: female gender (HR 0.51; 95% CI: 0.34-0.77) and older age (HR 0.69 per SD increment [5.5 years]; 95% CI: 0.56-0.86).

CONCLUSIONS: Even after accounting for carotid stenosis and incident cerebral ischemic events, carotid revascularization is related to age, gender, and cardiovascular risk factors. Further study of these demographic disparities and the role of risk factor control is warranted.

1 aGarg, Parveen, K1 aKoh, Willam, J H1 aDelaney, Joseph, A1 aHalm, Ethan, A1 aHirsch, Calvin, H1 aLongstreth, William, T1 aMukamal, Kenneth, J1 aKucharska-Newton, Anna1 aPolak, Joseph, F1 aCurtis, Lesley uhttps://chs-nhlbi.org/node/724402582nas a2200337 4500008004100000022001400041245012500055210006900180260001300249300001000262490000800272520156200280100002101842700002001863700001901883700002301902700002501925700002801950700001701978700002401995700002202019700001902041700002002060700002002080700002402100700002402124700001802148700001902166700002302185856003602208 2018 eng d a1097-674400aAssociation of lipoprotein-associated phospholipase A and risk of incident atrial fibrillation: Findings from 3 cohorts.0 aAssociation of lipoproteinassociated phospholipase A and risk of c2018 Mar a62-690 v1973 a

BACKGROUND: Multiple prospective studies have established an association between inflammation and higher risk of atrial fibrillation (AF), but the association between lipoprotein-associated phospholipase A (Lp-PLA) mass and activity and incident AF has not been extensively evaluated.

METHODS: Using data from 10,794 Atherosclerosis Risk In Communities (ARIC) study participants aged 53-75 years, 5,181 Cardiovascular Health Study (CHS) participants aged 65 to 100 years, and 5,425 Multi-Ethnic Study of Atherosclerosis (MESA) participants aged 45-84 years, we investigated the association between baseline Lp-PLA levels and the risk of developing AF. Incident AF was identified in each cohort by follow-up visit electrocardiograms, hospital discharge coding of AF, or Medicare claims data.

RESULTS: Over a mean of 13.1, 11.5, and 10.0 years of follow-up, 1,439 (13%), 2,084 (40%), and 615 (11%) incident AF events occurred in ARIC, CHS, and MESA, respectively. In adjusted analyses, each SD increment in Lp-PLA activity was associated with incident AF in both ARIC (hazard ratio [HR] 1.13, 95% CI 1.06-1.20) and MESA (HR 1.24, 95% CI 1.05-1.46). Each SD increment in Lp-PLA mass was also associated with incident AF in MESA (HR 1.25, 95% CI 1.11-1.41). No significant associations were observed among CHS participants.

CONCLUSIONS: Although higher Lp-PLA mass and activity were associated with development of AF in ARIC and MESA, this relationship was not observed in CHS, a cohort of older individuals.

1 aGarg, Parveen, K1 aBartz, Traci, M1 aNorby, Faye, L1 aJorgensen, Neal, W1 aMcClelland, Robyn, L1 aBallantyne, Christie, M1 aChen, Lin, Y1 aGottdiener, John, S1 aGreenland, Philip1 aHoogeveen, Ron1 aJenny, Nancy, S1 aKizer, Jorge, R1 aRosenson, Robert, S1 aSoliman, Elsayed, Z1 aCushman, Mary1 aAlonso, Alvaro1 aHeckbert, Susan, R uhttps://chs-nhlbi.org/node/767801810nas a2200253 4500008004100000022001400041245015300055210006900208260001600277300002100293520097900314100002101293700001901314700002101333700001801354700001901372700001901391700002001410700002201430700002001452700002401472700002401496856003601520 2019 eng d a1752-898400aAdvanced glycation end product carboxymethyl-lysine and risk of incident peripheral artery disease in older adults: The Cardiovascular Health Study.0 aAdvanced glycation end product carboxymethyllysine and risk of i c2019 May 08 a14791641198474813 a

Carboxymethyl-lysine is an advanced glycation end product that is detectable in the serum. Higher carboxymethyl-lysine levels have been associated with increased risk of coronary heart disease, stroke and cardiovascular mortality. We determined whether high carboxymethyl-lysine levels are also associated with the risk of peripheral artery disease in Cardiovascular Health Study participants who were all aged 65 years and older at baseline. Multivariate Cox proportional hazards models were used to determine the association of baseline carboxymethyl-lysine levels with incident peripheral artery disease in 3267 individuals followed for a median length of 10.0 years. A total of 157 cases of incident peripheral artery disease occurred during follow-up. No significant relationship between carboxymethyl-lysine and risk of peripheral artery disease was found (hazard ratio per standard deviation increment = 1.03; 95% confidence interval = 0.87, 1.23).

1 aGarg, Parveen, K1 aBiggs, Mary, L1 aBarzilay, Joshua1 aDjoussé, Luc1 aHirsch, Calvin1 aIx, Joachim, H1 aKizer, Jorge, R1 aTracy, Russell, P1 aNewman, Anne, B1 aSiscovick, David, S1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/804501835nas a2200229 4500008004100000022001400041245009100055210006900146260001700215300001200232490000700244520114300251100002101394700002001415700002301435700002201458700002001480700002001500700002501520700002401545856003601569 2020 eng d a1546-415600aBrachial Flow-mediated Dilation and Risk of Dementia: The Cardiovascular Health Study.0 aBrachial Flowmediated Dilation and Risk of Dementia The Cardiova c2020 Jul-Sep a272-2740 v343 a

INTRODUCTION: Brachial flow-mediated dilation (FMD) is a physiologic measure of endothelial function. We determined the prospective association of brachial FMD with incident dementia among older adults.

METHODS: We included 2777 Cardiovascular Health Study participants who underwent brachial FMD measurement. Incident dementia was ascertained by medication use, International Classification of Diseases-9 codes, requirement for a proxy, and death certificates and calibrated to gold-standard assessments performed in a subset of the cohort.

RESULTS: Mean participant age at time of brachial FMD measurement was 77.9 years. We identified 1650 incident dementia cases (median follow-up=10.5 y). After adjusting for age, race, sex, education, clinic site, and baseline arterial diameter, risk of dementia for participants in the highest quartile of percent brachial FMD did not differ from those in lowest quartile (hazard ratio=0.89, 95% confidence interval: 0.77, 1.03).

CONCLUSIONS: Brachial FMD, measured late in life, is not associated with an increased risk of incident dementia.

1 aGarg, Parveen, K1 aTan, Annabel, X1 aOdden, Michelle, C1 aGardin, Julius, M1 aLopez, Oscar, L1 aNewman, Anne, B1 aRawlings, Andreea, M1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/839202530nas a2200229 4500008004100000022001400041245007700055210006900132260001300201300001200214490000700226520185800233100002402091700002102115700002302136700002002159700002102179700002402200700002002224700002002244856003602264 2020 eng d a1532-841400aSoluble CD14 and Risk of Heart Failure and Its Subtypes in Older Adults.0 aSoluble CD14 and Risk of Heart Failure and Its Subtypes in Older c2020 May a410-4190 v263 a

BACKGROUND: CD14 is a membrane glycoprotein primarily expressed by myeloid cells that plays a key role in inflammation. Soluble CD14 (sCD14) levels carry a poor prognosis in chronic heart failure (HF), but whether elevations in sCD14 precede HF is unknown. We tested the hypothesis that sCD14 is associated with HF incidence and its subtypes independent of major inflammatory biomarkers among older adults.

METHODS AND RESULTS: We included participants in the Cardiovascular Health Study without preexisting HF and available baseline sCD14. We evaluated the associations of sCD14, high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and white blood cell count (WBC) with incident HF and subtypes using Cox regression. Among 5217 participants, 1878 had incident HF over 13.6 years (609 classifiable as HF with preserved ejection fraction [HFpEF] and 419 as HF with reduced ejection fraction [HFrEF]). After adjusting for clinical and laboratory covariates, sCD14 was significantly associated with incident HF (hazard ratio [HR]: 1.56 per doubling, 95% confidence interval [CI]: 1.29-1.89), an association that was numerically stronger than for hsCRP (HR per doubling: 1.10, 95% CI: 1.06-1.15), IL-6 (HR: 1.18, 95% CI: 1.10-1.25), and WBC (HR: 1.24, 95% CI: 1.09-1.42), and that remained significant after adjustment for the other markers of inflammation. This association for sCD14 was observed with HFpEF (HR: 1.50, 95% CI: 1.07-2.10) but not HFrEF (HR: 0.99, 95% CI: 0.67-1.49).

CONCLUSIONS: Plasma sCD14 was associated with incident HF independently and numerically more strongly than other major inflammatory markers. This association was only observed with HFpEF in the subset with classifiable HF subtypes. Pending replication, these findings have potentially important therapeutic implications.

1 aAl-Kindi, Sadeer, G1 aBůzková, Petra1 aShitole, Sanyog, G1 aReiner, Alex, P1 aGarg, Parveen, K1 aGottdiener, John, S1 aPsaty, Bruce, M1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/837602773nas a2200349 4500008004100000022001400041245011200055210006900167260001600236300000800252490000700260520176200267653000902029653002802038653001102066653001202077653001102089653002302100653000902123653003402132653003102166100002102197700001902218700002002237700002002257700001702277700002402294700002402318700002102342700002402363856003602387 2022 eng d a1475-284000aGlucose dysregulation and subclinical cardiac dysfunction in older adults: The Cardiovascular Health Study.0 aGlucose dysregulation and subclinical cardiac dysfunction in old c2022 Jun 20 a1120 v213 a

OBJECTIVE: We evaluated whether measures of glucose dysregulation are associated with subclinical cardiac dysfunction, as assessed by speckle-tracking echocardiography, in an older population.

METHODS: Participants were men and women in the Cardiovascular Health Study, age 65+ years and without coronary heart disease, atrial fibrillation, or heart failure at baseline. We evaluated fasting insulin resistance (IR) with the homeostatic model of insulin resistance (HOMA-IR) and estimated the Matsuda insulin sensitivity index (ISI) and insulin secretion with an oral glucose tolerance test. Systolic and diastolic cardiac mechanics were measured with speckle-tracking analysis of echocardiograms. Multi-variable adjusted linear regression models were used to investigate associations of insulin measures and cardiac mechanics.

RESULTS: Mean age for the 2433 included participants was 72.0 years, 33.6% were male, and 3.7% were black. After adjustment for age, sex, race, site, speckle-tracking analyst, echo image and quality score, higher HOMA-IR, lower Matsuda ISI, and higher insulin secretion were each associated with worse left ventricular (LV) longitudinal strain and LV early diastolic strain rate (p-value < 0.005); however, associations were significantly attenuated after adjustment for waist circumference, with the exception of Matsuda ISI and LV longitudinal strain (increase in strain per standard deviation increment in Matsuda ISI = 0.18; 95% confidence interval = 0.03-0.33).

CONCLUSION: In this cross-sectional study of older adults, associations of glucose dysregulation with subclinical cardiac dysfunction were largely attenuated after adjusting for central adiposity.

10aAged10aCross-Sectional Studies10aFemale10aGlucose10aHumans10aInsulin Resistance10aMale10aVentricular Dysfunction, Left10aVentricular Function, Left1 aGarg, Parveen, K1 aBiggs, Mary, L1 aKizer, Jorge, R1 aShah, Sanjiv, J1 aPsaty, Bruce1 aCarnethon, Mercedes1 aGottdiener, John, S1 aSiscovick, David1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/909202505nas a2200277 4500008004100000022001400041245007600055210006900131260001600200300001100216490000700227520169000234100002001924700002101944700002001965700002101985700002002006700002502026700002102051700002302072700002802095700002002123700002502143700002302168856003602191 2023 eng d a1873-205400aNeighborhood greenspace and cognition: The cardiovascular health study.0 aNeighborhood greenspace and cognition The cardiovascular health  c2023 Jan 03 a1029600 v793 a

OBJECTIVES: We examined whether greenspace measures (overall percent greenspace and forest, and number of greenspace types) were associated with clinically adjudicated dementia status.

METHODS: In a sample of non-demented older adults (n = 2141, average age = 75.3 years) from the Cardiovascular Health and Cognition Study, Cox proportional hazard and logistic regression analyses were used to estimate associations of baseline greenspace with risks of incident dementia and MCI, respectively, while adjusting for demographics, co-morbidities, and other neighborhood factors. We derived quartiles of percent greenness (greenspace), forest (percent tree canopy cover), and tertiles of greenspace diversity (number of greenspace types) for 5-km radial buffers around participant's residences at study entry (1989-1990) from the 1992 National Land Cover Dataset. Dementia status and mild cognitive impairment (MCI) over 10 years was clinically adjudicated.

RESULTS: We observed no significant association between overall percent greenspace and risk of mild cognitive impairment or dementia and mostly null results for forest and greenspace diversity. Forest greenspace was associated with lower odds of MCI (OR quartile 4 versus 1: 0.54, 95% CI: 0.29-0.98) and greenspace diversity was associated with lower hazard of incident dementia (HR tertile 2 versus 1: 0.70, 95% CI = 0.50-0.99).

DISCUSSION: We found divergent results for different types of greenspace and mild cognitive impairment or dementia. Improved greenspace type and diversity measurement could better characterize the association between greenspace and cognition.

1 aGodina, Sara, L1 aRosso, Andrea, L1 aHirsch, Jana, A1 aBesser, Lilah, M1 aLovasi, Gina, S1 aDonovan, Geoffrey, H1 aGarg, Parveen, K1 aPlatt, Jonathan, M1 aFitzpatrick, Annette, L1 aLopez, Oscar, L1 aCarlson, Michelle, C1 aMichael, Yvonne, L uhttps://chs-nhlbi.org/node/9238