@article {855, title = {Risk factors for declining ankle-brachial index in men and women 65 years or older: the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {165}, year = {2005}, month = {2005 Sep 12}, pages = {1896-902}, abstract = {

BACKGROUND: An ankle-brachial index (ABI) of less than 0.9 is a noninvasive measure of lower extremity arterial disease and a predictor of cardiovascular events. Little information is available on longitudinal change in ABI or on risk factors for declining ABI in a community-based population.

METHODS: To assess risk factors for ABI decline, we studied 5888 participants in the Cardiovascular Health Study cohort (men and women 65 years or older). We measured ABI in 1992-1993 and again in 1998-1999. At baseline, we excluded individuals with an ABI less than 0.9, ABI greater than 1.4, or confirmed symptomatic lower extremity arterial disease (n = 823). The group with ABI decline included 218 participants with decline greater than 0.15 and to 0.9 or less. The comparison group comprised the remaining 2071 participants with follow-up ABI.

RESULTS: The percentage of participants with ABI decline was 9.5\% over 6 years of follow-up. The mean +/- SD decline was 0.33 +/- 0.12 in cases of ABI decline and 0.02 +/- 0.13 in non-cases. Independent predictors of ABI decline, reported as odds ratios, were age, 1.96 (95\% confidence interval [CI], 1.42-2.71) for 75 to 84 years and 3.79 (95\% CI, 1.36-10.5) for those older than 85 years compared with those younger than 75 years; current cigarette use, 1.74 (95\% CI, 1.02-2.96); hypertension, 1.64 (95\% CI, 1.18-2.28); diabetes, 1.77 (95\% CI, 1.14-2.76); higher low-density lipoprotein cholesterol level, 1.60 (95\% CI, 1.03-2.51), and lipid-lowering drug use 1.74 (95\% CI, 1.05-2.89).

CONCLUSION: Worsening lower extremity arterial disease, assessed as ABI decline, occurred in 9.5\% of this elderly cohort over 6 years and was associated with modifiable vascular disease risk factors.

}, keywords = {Aged, Aged, 80 and over, Ankle, Brachial Artery, Cardiovascular Diseases, Female, Humans, Male, Peripheral Vascular Diseases, Risk Assessment, Risk Factors}, issn = {0003-9926}, doi = {10.1001/archinte.165.16.1896}, author = {Kennedy, Margaret and Solomon, Cam and Manolio, Teri A and Criqui, Michael H and Newman, Anne B and Polak, Joseph F and Burke, Gregory L and Enright, Paul and Cushman, Mary} } @article {948, title = {Ethnic-specific prevalence of peripheral arterial disease in the United States.}, journal = {Am J Prev Med}, volume = {32}, year = {2007}, month = {2007 Apr}, pages = {328-33}, abstract = {

BACKGROUND: Individuals diagnosed with peripheral arterial disease (PAD) are at increased risk for future functional limitations as well as cardiovascular morbidity and mortality. The aim of this study was to estimate the age-, gender-, and ethnic-specific burden of PAD in the United States for the year 2000.

METHODS: Data were collected from seven community-based studies that assessed subjects for the presence of PAD using the ankle-brachial index (ABI). Using standardized weighting criteria, age-, gender-, and ethnic-specific prevalence rates were computed and then multiplied by the corresponding 2000 Census population totals to estimate the burden of PAD in the United States for that year. Evidence-based adjustments for studies which did not consider possible subclavian stenosis, prior revascularization for PAD, or both were employed.

RESULTS: In 2000, it is conservatively estimated that at least 6.8 million (5.8\%) individuals aged 40 years or older had PAD based on an ABI of less than 0.9 or previous revascularization for PAD, and that that there are an additional 1.7 million Americans with PAD but "normal" ABIs. Including this group gives a total of 8.5 million (7.2\%) individuals with PAD.

CONCLUSIONS: Roughly one in 16 individuals residing in the United States in 2000 who were aged 40 years and older had PAD. Clinicians are encouraged to screen for the presence of PAD using the ABI.

}, keywords = {Adult, Aged, Aged, 80 and over, Databases as Topic, Female, Humans, Male, Middle Aged, Peripheral Vascular Diseases, United States}, issn = {0749-3797}, doi = {10.1016/j.amepre.2006.12.010}, author = {Allison, Matthew A and Ho, Elena and Denenberg, Julie O and Langer, Robert D and Newman, Anne B and Fabsitz, Richard R and Criqui, Michael H} } @article {994, title = {Alcohol consumption and lower extremity arterial disease among older adults: the cardiovascular health study.}, journal = {Am J Epidemiol}, volume = {167}, year = {2008}, month = {2008 Jan 01}, pages = {34-41}, abstract = {

Few studies of the relation of alcohol intake to lower-extremity arterial disease (LEAD) have included clinical events and objective measurements repeated longitudinally. As part of the Cardiovascular Health Study, a study of older adults from four US communities, 5,635 participants reported their use of beer, wine, and spirits yearly. Incident LEAD was identified by hospitalization surveillance. Technicians measured ankle-brachial index 6 years apart in 2,298 participants. A total of 172 cases of LEAD were documented during a mean of 7.5 years of follow-up between 1989 and 1999. Compared with abstention, the multivariable-adjusted hazard ratios were 1.10 (95\% confidence interval (CI): 0.71, 1.71) for <1 alcoholic drink per week, 0.56 (95\% CI: 0.33, 0.95) for 1-13 drinks per week, and 1.02 (95\% CI: 0.53, 1.97) for > or =14 drinks per week (p for quadratic trend = 0.04). These relations were consistent within strata of sex, age, and apolipoprotein E genotype, and neither lipids nor inflammatory markers appeared to be important intermediates. Change in ankle-brachial index showed a similar relation (p for quadratic trend = 0.01). Alcohol consumption of 1-13 drinks per week in older adults may be associated with lower risk of LEAD, but heavier drinking is not associated with lower risk.

}, keywords = {Aged, Alcohol Drinking, Female, Follow-Up Studies, Health Surveys, Humans, Intermittent Claudication, Male, Prevalence, Prospective Studies, Risk Factors, Surveys and Questionnaires, Time Factors, United States}, issn = {1476-6256}, doi = {10.1093/aje/kwm274}, author = {Mukamal, Kenneth J and Kennedy, Margaret and Cushman, Mary and Kuller, Lewis H and Newman, Anne B and Polak, Joseph and Criqui, Michael H and Siscovick, David S} } @article {1130, title = {Association of chronic kidney disease with the spectrum of ankle brachial index the CHS (Cardiovascular Health Study).}, journal = {J Am Coll Cardiol}, volume = {54}, year = {2009}, month = {2009 Sep 22}, pages = {1176-84}, abstract = {

OBJECTIVES: This study sought to determine the association of chronic kidney disease (CKD) with high ankle brachial index (ABI) measurement and to compare its strength with that of CKD with a low ABI.

BACKGROUND: CKD is an important risk factor for cardiovascular disease (CVD) events. A high ABI, a marker of lower extremity arterial stiffness, is associated with CVD events and mortality. The association between CKD and high ABI is unknown.

METHODS: The CHS (Cardiovascular Health Study) enrolled community-living people >65 years of age and measured kidney function and ABI. Glomerular filtration rate (GFR) was estimated using equations that incorporated either cystatin C or creatinine, and CKD was defined by estimated GFR <60 ml/min/1.73 m(2). The ABI was categorized as low (<0.90), low-normal (0.90 to 1.09), normal (1.10 to 1.40), and high (>1.40 or incompressible). Multinomial logistic regression was used to evaluate the associations of CKD with ABI categories.

RESULTS: Among 4,513 participants, 23\% had CKD, 13\% had a low ABI, and 3\% had a high ABI. In models adjusted for age, sex, race, hypertension, diabetes, smoking, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and C-reactive protein, cystatin C-based CKD was associated with both low ABI (relative risk [RR]: 2.0; 95\% confidence interval [CI]: 1.6 to 2.5; p <0.001) and high ABI (RR: 1.6; 95\% CI: 1.0 to 2.3; p = 0.03). Results were similar when CKD was defined by creatinine.

CONCLUSIONS: CKD is associated with both the high and the low extremes of ABI in community-living older people. Future studies should evaluate whether arterial stiffness is an important mechanism leading to CVD in people with CKD.

}, keywords = {Aged, Aged, 80 and over, Ankle Brachial Index, C-Reactive Protein, Cardiovascular Diseases, Chronic Disease, Cohort Studies, Cross-Sectional Studies, Female, Glomerular Filtration Rate, Humans, Kidney Diseases, Lipids, Male, Risk Factors}, issn = {1558-3597}, doi = {10.1016/j.jacc.2009.06.017}, author = {Ix, Joachim H and Katz, Ronit and de Boer, Ian H and Kestenbaum, Brian R and Allison, Matthew A and Siscovick, David S and Newman, Anne B and Sarnak, Mark J and Shlipak, Michael G and Criqui, Michael H} } @article {1326, title = {Association of body mass index with peripheral arterial disease in older adults: the Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {174}, year = {2011}, month = {2011 Nov 01}, pages = {1036-43}, abstract = {

The authors hypothesized that the absence of cross-sectional associations of body mass index (BMI; weight (kg)/height (m)(2)) with peripheral arterial disease (PAD) in prior studies may reflect lower weight among persons who smoke or have poor health status. They conducted an observational study among 5,419 noninstitutionalized residents of 4 US communities aged >= 65 years at baseline (1989-1990 or 1992-1993). Ankle brachial index was measured, and participants reported their history of PAD procedures. Participants were followed longitudinally for adjudicated incident PAD events. At baseline, mean BMI was 26.6 (standard deviation, 4.6), and 776 participants (14\%) had prevalent PAD. During 13.2 (median) years of follow-up through June 30, 2007, 276 incident PAD events occurred. In cross-sectional analysis, each 5-unit increase in BMI was inversely associated with PAD (prevalence ratio (PR) = 0.92, 95\% confidence interval (CI): 0.85, 1.00). However, among persons in good health who had never smoked, the direction of association was opposite (PR = 1.20, 95\% CI: 0.94, 1.52). Similar results were observed between BMI calculated using weight at age 50 years and PAD prevalence (PR = 1.30, 95\% CI: 1.11, 1.51) and between BMI at baseline and incident PAD events occurring during follow-up (hazard ratio = 1.32, 95\% CI: 1.00, 1.76) among never smokers in good health. Greater BMI is associated with PAD in older persons who remain healthy and have never smoked. Normal weight maintenance may decrease PAD incidence and associated comorbidity in older age.

}, keywords = {Aged, Ankle Brachial Index, Body Mass Index, Cross-Sectional Studies, Health Status, Humans, Kaplan-Meier Estimate, Longitudinal Studies, Male, Obesity, Peripheral Arterial Disease, Prevalence, Sex Factors, Smoking, United States}, issn = {1476-6256}, doi = {10.1093/aje/kwr228}, author = {Ix, Joachim H and Biggs, Mary L and Kizer, Jorge R and Mukamal, Kenneth J and Djouss{\'e}, Luc and Zieman, Susan J and de Boer, Ian H and Nelson, Tracy L and Newman, Anne B and Criqui, Michael H and Siscovick, David S} } @article {1359, title = {Association between chromosome 9p21 variants and the ankle-brachial index identified by a meta-analysis of 21 genome-wide association studies.}, journal = {Circ Cardiovasc Genet}, volume = {5}, year = {2012}, month = {2012 Feb 01}, pages = {100-12}, abstract = {

BACKGROUND: Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts.

METHODS AND RESULTS: Continuous ABI and PAD (ABI <=0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the ≈2.5 million single nucleotide polymorphisms (SNPs) in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fixed effects inverse variance weighted meta-analyses. There were a total of 41 692 participants of European ancestry (≈60\% women, mean ABI 1.02 to 1.19), including 3409 participants with PAD and with genome-wide association study data available. In the discovery meta-analysis, rs10757269 on chromosome 9 near CDKN2B had the strongest association with ABI (β=-0.006, P=2.46{\texttimes}10(-8)). We sought replication of the 6 strongest SNP associations in 5 population-based studies and 3 clinical samples (n=16 717). The association for rs10757269 strengthened in the combined discovery and replication analysis (P=2.65{\texttimes}10(-9)). No other SNP associations for ABI or PAD achieved genome-wide significance. However, 2 previously reported candidate genes for PAD and 1 SNP associated with coronary artery disease were associated with ABI: DAB21P (rs13290547, P=3.6{\texttimes}10(-5)), CYBA (rs3794624, P=6.3{\texttimes}10(-5)), and rs1122608 (LDLR, P=0.0026).

CONCLUSIONS: Genome-wide association studies in more than 40 000 individuals identified 1 genome wide significant association on chromosome 9p21 with ABI. Two candidate genes for PAD and 1 SNP for coronary artery disease are associated with ABI.

}, keywords = {Adult, Age Factors, Aged, Aged, 80 and over, Alleles, Ankle Brachial Index, Chromosomes, Human, Pair 9, Cohort Studies, Cyclin-Dependent Kinase Inhibitor p15, Female, Genome-Wide Association Study, Genotype, HapMap Project, Humans, Logistic Models, Male, Middle Aged, Peripheral Vascular Diseases, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, Sex Factors}, issn = {1942-3268}, doi = {10.1161/CIRCGENETICS.111.961292}, author = {Murabito, Joanne M and White, Charles C and Kavousi, Maryam and Sun, Yan V and Feitosa, Mary F and Nambi, Vijay and Lamina, Claudia and Schillert, Arne and Coassin, Stefan and Bis, Joshua C and Broer, Linda and Crawford, Dana C and Franceschini, Nora and Frikke-Schmidt, Ruth and Haun, Margot and Holewijn, Suzanne and Huffman, Jennifer E and Hwang, Shih-Jen and Kiechl, Stefan and Kollerits, Barbara and Montasser, May E and Nolte, Ilja M and Rudock, Megan E and Senft, Andrea and Teumer, Alexander and van der Harst, Pim and Vitart, Veronique and Waite, Lindsay L and Wood, Andrew R and Wassel, Christina L and Absher, Devin M and Allison, Matthew A and Amin, Najaf and Arnold, Alice and Asselbergs, Folkert W and Aulchenko, Yurii and Bandinelli, Stefania and Barbalic, Maja and Boban, Mladen and Brown-Gentry, Kristin and Couper, David J and Criqui, Michael H and Dehghan, Abbas and den Heijer, Martin and Dieplinger, Benjamin and Ding, Jingzhong and D{\"o}rr, Marcus and Espinola-Klein, Christine and Felix, Stephan B and Ferrucci, Luigi and Folsom, Aaron R and Fraedrich, Gustav and Gibson, Quince and Goodloe, Robert and Gunjaca, Grgo and Haltmayer, Meinhard and Heiss, Gerardo and Hofman, Albert and Kieback, Arne and Kiemeney, Lambertus A and Kolcic, Ivana and Kullo, Iftikhar J and Kritchevsky, Stephen B and Lackner, Karl J and Li, Xiaohui and Lieb, Wolfgang and Lohman, Kurt and Meisinger, Christa and Melzer, David and Mohler, Emile R and Mudnic, Ivana and Mueller, Thomas and Navis, Gerjan and Oberhollenzer, Friedrich and Olin, Jeffrey W and O{\textquoteright}Connell, Jeff and O{\textquoteright}Donnell, Christopher J and Palmas, Walter and Penninx, Brenda W and Petersmann, Astrid and Polasek, Ozren and Psaty, Bruce M and Rantner, Barbara and Rice, Ken and Rivadeneira, Fernando and Rotter, Jerome I and Seldenrijk, Adrie and Stadler, Marietta and Summerer, Monika and Tanaka, Toshiko and Tybjaerg-Hansen, Anne and Uitterlinden, Andr{\'e} G and van Gilst, Wiek H and Vermeulen, Sita H and Wild, Sarah H and Wild, Philipp S and Willeit, Johann and Zeller, Tanja and Zemunik, Tatijana and Zgaga, Lina and Assimes, Themistocles L and Blankenberg, Stefan and Boerwinkle, Eric and Campbell, Harry and Cooke, John P and de Graaf, Jacqueline and Herrington, David and Kardia, Sharon L R and Mitchell, Braxton D and Murray, Anna and M{\"u}nzel, Thomas and Newman, Anne B and Oostra, Ben A and Rudan, Igor and Shuldiner, Alan R and Snieder, Harold and van Duijn, Cornelia M and V{\"o}lker, Uwe and Wright, Alan F and Wichmann, H-Erich and Wilson, James F and Witteman, Jacqueline C M and Liu, Yongmei and Hayward, Caroline and Borecki, Ingrid B and Ziegler, Andreas and North, Kari E and Cupples, L Adrienne and Kronenberg, Florian} } @article {5864, title = {Genetic determinants of the ankle-brachial index: a meta-analysis of a cardiovascular candidate gene 50K SNP panel in the candidate gene association resource (CARe) consortium.}, journal = {Atherosclerosis}, volume = {222}, year = {2012}, month = {2012 May}, pages = {138-47}, abstract = {

BACKGROUND: Candidate gene association studies for peripheral artery disease (PAD), including subclinical disease assessed with the ankle-brachial index (ABI), have been limited by the modest number of genes examined. We conducted a two stage meta-analysis of \~{}50,000 SNPs across \~{}2100 candidate genes to identify genetic variants for ABI.

METHODS AND RESULTS: We studied subjects of European ancestry from 8 studies (n=21,547, 55\% women, mean age 44-73 years) and African American ancestry from 5 studies (n=7267, 60\% women, mean age 41-73 years) involved in the candidate gene association resource (CARe) consortium. In each ethnic group, additive genetic models were used (with each additional copy of the minor allele corresponding to the given beta) to test each SNP for association with continuous ABI (excluding ABI>1.40) and PAD (defined as ABI<0.90) using linear or logistic regression with adjustment for known PAD risk factors and population stratification. We then conducted a fixed-effects inverse-variance weighted meta-analyses considering a p<2{\texttimes}10(-6) to denote statistical significance.

RESULTS: In the European ancestry discovery meta-analyses, rs2171209 in SYTL3 (β=-0.007, p=6.02{\texttimes}10(-7)) and rs290481 in TCF7L2 (β=-0.008, p=7.01{\texttimes}10(-7)) were significantly associated with ABI. None of the SNP associations for PAD were significant, though a SNP in CYP2B6 (p=4.99{\texttimes}10(-5)) was among the strongest associations. These 3 genes are linked to key PAD risk factors (lipoprotein(a), type 2 diabetes, and smoking behavior, respectively). We sought replication in 6 population-based and 3 clinical samples (n=15,440) for rs290481 and rs2171209. However, in the replication stage (rs2171209, p=0.75; rs290481, p=0.19) and in the combined discovery and replication analysis the SNP-ABI associations were no longer significant (rs2171209, p=1.14{\texttimes}10(-3); rs290481, p=8.88{\texttimes}10(-5)). In African Americans, none of the SNP associations for ABI or PAD achieved an experiment-wide level of significance.

CONCLUSIONS: Genetic determinants of ABI and PAD remain elusive. Follow-up of these preliminary findings may uncover important biology given the known gene-risk factor associations. New and more powerful approaches to PAD gene discovery are warranted.

}, keywords = {Adult, African Americans, Aged, Ankle Brachial Index, Aryl Hydrocarbon Hydroxylases, Cytochrome P-450 CYP2B6, European Continental Ancestry Group, Female, Humans, Male, Middle Aged, Oxidoreductases, N-Demethylating, Peripheral Arterial Disease, Polymorphism, Single Nucleotide, Risk Factors, Transcription Factor 7-Like 2 Protein}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2012.01.039}, author = {Wassel, Christina L and Lamina, Claudia and Nambi, Vijay and Coassin, Stefan and Mukamal, Kenneth J and Ganesh, Santhi K and Jacobs, David R and Franceschini, Nora and Papanicolaou, George J and Gibson, Quince and Yanek, Lisa R and van der Harst, Pim and Ferguson, Jane F and Crawford, Dana C and Waite, Lindsay L and Allison, Matthew A and Criqui, Michael H and McDermott, Mary M and Mehra, Reena and Cupples, L Adrienne and Hwang, Shih-Jen and Redline, Susan and Kaplan, Robert C and Heiss, Gerardo and Rotter, Jerome I and Boerwinkle, Eric and Taylor, Herman A and Eraso, Luis H and Haun, Margot and Li, Mingyao and Meisinger, Christa and O{\textquoteright}Connell, Jeffrey R and Shuldiner, Alan R and Tybj{\ae}rg-Hansen, Anne and Frikke-Schmidt, Ruth and Kollerits, Barbara and Rantner, Barbara and Dieplinger, Benjamin and Stadler, Marietta and Mueller, Thomas and Haltmayer, Meinhard and Klein-Weigel, Peter and Summerer, Monika and Wichmann, H-Erich and Asselbergs, Folkert W and Navis, Gerjan and Mateo Leach, Irene and Brown-Gentry, Kristin and Goodloe, Robert and Assimes, Themistocles L and Becker, Diane M and Cooke, John P and Absher, Devin M and Olin, Jeffrey W and Mitchell, Braxton D and Reilly, Muredach P and Mohler, Emile R and North, Kari E and Reiner, Alexander P and Kronenberg, Florian and Murabito, Joanne M} } @article {6366, title = {Coronary heart disease risks associated with high levels of HDL cholesterol.}, journal = {J Am Heart Assoc}, volume = {3}, year = {2014}, month = {2014 Mar 13}, pages = {e000519}, abstract = {

BACKGROUND: The association between high-density lipoprotein cholesterol (HDL-C) and coronary heart disease (CHD) events is not well described in individuals with very high levels of HDL-C (>80 mg/dL).

METHODS AND RESULTS: Using pooled data from 6 community-based cohorts we examined CHD and total mortality risks across a broad range of HDL-C, including values in excess of 80 mg/dL. We used Cox proportional hazards models with penalized splines to assess multivariable, adjusted, sex-stratified associations of HDL-C with the hazard for CHD events and total mortality, using HDL-C 45 mg/dL and 55 mg/dL as the referent in men and women, respectively. Analyses included 11 515 men and 12 925 women yielding 307 245 person-years of follow-up. In men, the association between HDL-C and CHD events was inverse and linear across most HDL-C values; however at HDL-C values >90 mg/dL there was a plateau effect in the pattern of association. In women, the association between HDL-C and CHD events was inverse and linear across lower values of HDL-C, however at HDL-C values >75 mg/dL there were no further reductions in the hazard ratio point estimates for CHD. In unadjusted models there were increased total mortality risks in men with very high HDL-C, however mortality risks observed in participants with very high HDL-C were attenuated after adjustment for traditional risk factors.

CONCLUSIONS: We did not observe further reductions in CHD risk with HDL-C values higher than 90 mg/dL in men and 75 mg/dL in women.

}, keywords = {Aged, Biomarkers, Cholesterol, HDL, Coronary Disease, Female, Humans, Linear Models, Male, Middle Aged, Multivariate Analysis, Prognosis, Proportional Hazards Models, Risk Assessment, Risk Factors, Time Factors, United States, Up-Regulation}, issn = {2047-9980}, doi = {10.1161/JAHA.113.000519}, author = {Wilkins, John T and Ning, Hongyan and Stone, Neil J and Criqui, Michael H and Zhao, Lihui and Greenland, Philip and Lloyd-Jones, Donald M} } @article {6148, title = {Metabolic syndrome and risk of incident peripheral artery disease: the cardiovascular health study.}, journal = {Hypertension}, volume = {63}, year = {2014}, month = {2014 Feb}, pages = {413-9}, abstract = {

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.

}, keywords = {Aged, Ankle Brachial Index, C-Reactive Protein, Female, Fibrinogen, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Metabolic Syndrome, Peripheral Arterial Disease, Prevalence, Risk Factors, Vasculitis}, issn = {1524-4563}, doi = {10.1161/HYPERTENSIONAHA.113.01925}, author = {Garg, Parveen K and Biggs, Mary L and Carnethon, Mercedes and Ix, Joachim H and Criqui, Michael H and Britton, Kathryn A and Djouss{\'e}, Luc and Sutton-Tyrrell, Kim and Newman, Anne B and Cushman, Mary and Mukamal, Kenneth J} } @article {6996, title = {Lipoprotein-Associated Phospholipase A2 and Incident Peripheral Arterial Disease in Older Adults: The Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {36}, year = {2016}, month = {2016 Apr}, pages = {750-6}, abstract = {

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.

}, keywords = {1-Alkyl-2-acetylglycerophosphocholine Esterase, Age Factors, Aged, Aging, Ankle Brachial Index, Biomarkers, Chi-Square Distribution, Female, Humans, Incidence, Inflammation Mediators, Logistic Models, Male, Odds Ratio, Peripheral Arterial Disease, Prognosis, Proportional Hazards Models, Risk Assessment, Risk Factors, Time Factors, United States, Up-Regulation}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.115.306647}, author = {Garg, Parveen K and Arnold, Alice M and Hinckley Stukovsky, Karen D and Koro, Carol and Jenny, Nancy S and Mukamal, Kenneth J and Criqui, Michael H and Furberg, Curt D and Newman, Anne B and Cushman, Mary} }