Russell P Tracy

University of Vermont, Burlington, Vermont, United States

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Publications (571)4062.32 Total impact

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    ABSTRACT: Nuclear magnetic resonance (NMR) spectra of serum obtained under quantitative conditions for lipoprotein particle analyses contain additional signals that could potentially serve as useful clinical biomarkers. One of these signals that we named GlycA originates from a subset of glycan N-acetylglucosamine residues on enzymatically glycosylated acute-phase proteins. We hypothesized that the amplitude of the GlycA signal might provide a unique and convenient measure of systemic inflammation. We developed a spectral deconvolution algorithm to quantify GlycA signal amplitudes from automated NMR LipoProfile® test spectra and assessed analytic precision and biological variability. Spectra of acute-phase glycoproteins and serum fractions were analyzed to probe the origins of the GlycA signal. GlycA concentrations obtained from archived NMR LipoProfile spectra of baseline plasma from 5537 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) were used to assess associations with demographic and laboratory parameters including measures of inflammation. Major acute-phase protein contributors to the serum GlycA signal are α1-acid glycoprotein, haptoglobin, α1-antitrypsin, α1-antichymotrypsin, and transferrin. GlycA concentrations were correlated with high-sensitivity C-reactive protein (hsCRP) (r = 0.56), fibrinogen (r = 0.46), and interleukin-6 (IL-6) (r = 0.35) (all P < 0.0001). Analytic imprecision was low (intra- and interassay CVs 1.9% and 2.6%, respectively) and intraindividual variability, assessed weekly for 5 weeks in 23 healthy volunteers, was 4.3%, lower than for hsCRP (29.2%), cholesterol (5.7%), and triglycerides (18.0%). GlycA is a unique inflammatory biomarker with analytic and clinical attributes that may complement or provide advantages over existing clinical markers of systemic inflammation. © 2015 American Association for Clinical Chemistry.
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    ABSTRACT: Coagulation factor VIII and von Willebrand factor (VWF) are key proteins in procoagulant activation. Higher FVIII coagulant activity (FVIII:C) and VWF antigen (VWF:Ag) are risk factors for cardiovascular disease and venous thromboembolism. Beyond associations with ABO blood group, genetic determinants of FVIII and VWF are not well understood, especially in non European-American populations. We performed a genetic association study of FVIII:C and VWF:Ag that assessed 50,000 gene-centric single nucleotide polymorphisms (SNPs) in 18,556 European Americans (EAs) and 5,047 African Americans (AAs) from five population-based cohorts. Previously unreported associations for FVIII:C were identified in both AAs and EAs with KNG1 (most significantly associated SNP rs710446, Ile581Thr, p=5.10 x10(-7) in EAs and p=3.88x10(-3) in AAs) and VWF rs7962217 (Gly2705Arg, p=6.30 x10(-9) in EAs and p=2.98 x 10(-2) in AAs). Significant associations for FVIII:C were also observed with F8/TMLHE region SNP rs12557310 in EAs (p=8.02 x10(-10) ), with VWF rs1800380 in AAs (p=5.62x10(-11) ), and with MAT1A rs2236568 in AAs (p=1.69 x10(-6) ). We replicated previously reported associations of FVIII:C and VWF:Ag with the ABO blood group, VWF rs1063856 (Thr789Ala), rs216321 (Ala852Gln), and VWF rs2229446 (Arg2185Gln). Findings from this study expand our understanding of genetic influences for FVIII:C and VWF:Ag in both EAs and AAs. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    American Journal of Hematology 03/2015; DOI:10.1002/ajh.24005 · 3.48 Impact Factor
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    ABSTRACT: Fibrosis has been implicated in a number of pathological, organ-based conditions of the liver, kidney, heart, and lungs. The objective of this study was to determine whether biomarkers of fibrosis are associated with vascular disease in the large and/or small vessels. We evaluated the associations of two circulating biomarkers of fibrosis, transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP), with incident peripheral artery disease (PAD) and subclinical macrovascular (carotid intima-media thickness, flow-mediated vasodilation, ankle-brachial index, retinal vein diameter), and microvascular (retinal artery diameter and retinopathy) disease among older adults in the Cardiovascular Health Study. We measured TGF-β and PIIINP from samples collected in 1996 and ascertained clinical PAD through 2011. Measurements of large and small vessels were collected between 1996 and 1998. After adjustment for sociodemographic, clinical, and biochemical risk factors, TGF-β was associated with incident PAD (hazard ratio [HR] = 1.36 per doubling of TGF-β, 95% confidence interval [CI] = 1.04, 1.78) and retinal venular diameter (1.63 μm per doubling of TGF-β, CI = 0.23, 3.02). PIIINP was not associated with incident PAD, but was associated with carotid intima-media thickness (0.102 mm per doubling of PIIINP, CI = 0.029, 0.174) and impaired brachial artery reactivity (-0.20% change per doubling of PIIINP, CI = -0.39, -0.02). Neither TGF-β nor PIIINP were associated with retinal arteriolar diameter or retinopathy. Serum concentrations of fibrosis-related biomarkers were associated with several measures of large vessel disease, including incident PAD, but not with small vessel disease. Fibrosis may contribute to large vessel atherosclerosis in older adults. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Atherosclerosis 02/2015; 239(2):539-546. DOI:10.1016/j.atherosclerosis.2015.02.020 · 3.71 Impact Factor
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    ABSTRACT: 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. Copyright © 2015 by the American Society of Nephrology.
    Journal of the American Society of Nephrology 02/2015; DOI:10.1681/ASN.2014070696 · 9.47 Impact Factor
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    ABSTRACT: Rationale: Inflammation is associated with symptoms in many chronic illnesses; however, this link has not been established in pulmonary arterial hypertension. Objectives: The objective of this study was to investigate the association between inflammatory markers and quality of life-related symptoms in patients with pulmonary arterial hypertension. We hypothesized that higher circulating interleukin-6 and tumor necrosis factor-alpha levels would be associated with worse quality of life-related symptoms. Methods: We performed a secondary analysis using baseline and 3 month assessments of 62 subjects in a clinical trial of aspirin and simvastatin to determine the association between plasma interleukin-6 and tumor necrosis factor-alpha levels and the Medical Outcomes Study Short Form-36 subscales (pain, vitality, mental health). Measurements and Main Results: The mean age was 49.7 + 13.4 years; 87% were female. Higher interleukin-6 levels were significantly associated with lower Medical Outcomes Study Short Form-36 subscale scores indicating worse bodily pain, vitality and mental health (all p < .01). Higher tumor necrosis factor-alpha levels were significantly associated with increased bodily pain, but better mental health scores. Conclusions: Interleukin-6 and tumor necrosis factor-alpha levels are associated with certain quality of life domains in patients with pulmonary arterial hypertension. Primary Sources of Funding: This study was partially funded by the National Institutes of Health grant K23 NR014885, R01 HL082895 and HL082895-S1, the American Nurses Foundation and the Biobehavioral Research Center at the University of Pennsylvania School of Nursing. Clinical trial registered with www.clinicaltrials.gov (NCT00384865) Word Count: 238.
    01/2015; DOI:10.1513/AnnalsATS.201410-463OC
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    ABSTRACT: With the advent of antiretroviral therapy that can control virus replication below the detection levels of conventional assays, a new clinical landscape of AIDS emerged, in which non-AIDS complications prevail over AIDS-defining conditions. These comorbidities are diverse and affect multiple organs, thus resulting in cardiovascular, kidney, neurocognitive and liver disease, osteopenia/osteoporosis, and cancers. A common feature of these conditions is that they are generally associated with accelerated aging. The mechanism behind these comorbidities is chronic excessive inflammation induced by HIV infection, which persists under antiretroviral therapy. Progressive simian immunodeficiency virus (SIV) infection of nonhuman primates (NHPs) closely reproduces these comorbidities and offers a simplified system in which most of the traditional human risk factors for comorbidities (i.e., smoking, hyperlipidemia) are absent. Additionally, experimental conditions can be properly controlled during a shorter course of disease for SIV infection. As such, NHPs can be employed to characterize new paradigms of AIDS pathogenesis and to test the efficacy of interventions aimed at alleviating non-AIDS-related comorbidities.
    Current HIV/AIDS Reports 01/2015; DOI:10.1007/s11904-014-0245-5
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    ABSTRACT: Levels of circulating of sex hormones are associated with glucose metabolism and adiposity, but little is known about their association with ectopic fat. We aimed to characterize the association between circulating sex hormones and liver fat.
    Clinical Gastroenterology and Hepatology 01/2015; DOI:10.1016/j.cgh.2014.12.033 · 6.53 Impact Factor
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    ABSTRACT: Human Immunodeficiency Virus- (HIV-) infected persons have a higher risk for acute myocardial infarction (AMI) than HIV-uninfected persons. Earlier studies suggest that HIV viral load, CD4(+) T-cell count, and antiretroviral therapy are associated with cardiovascular disease (CVD) risk. Whether CD8(+) T-cell count is associated with CVD risk is not clear. We investigated the association between CD8(+) T-cell count and incident AMI in a cohort of 73,398 people (of which 97.3% were men) enrolled in the U.S. Veterans Aging Cohort Study-Virtual Cohort (VACS-VC). Compared to uninfected people, HIV-infected people with high baseline CD8(+) T-cell counts (>1065 cells/mm(3)) had increased AMI risk (adjusted HR = 1.82, P < 0.001, 95% CI: 1.46 to 2.28). There was evidence that the effect of CD8(+) T-cell tertiles on AMI risk differed by CD4(+) T-cell level: compared to uninfected people, HIV-infected people with CD4(+) T-cell counts ≥200 cells/mm(3) had increased AMI risk with high CD8(+) T-cell count, while those with CD4(+) T-cell counts <200 cells/mm(3) had increased AMI risk with low CD8(+) T-cell count. CD8(+) T-cell counts may add additional AMI risk stratification information beyond that provided by CD4(+) T-cell counts alone.
    BioMed Research International 01/2015; 2015:246870. DOI:10.1155/2015/246870 · 2.71 Impact Factor
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    ABSTRACT: Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance. When MI occurs early in life, genetic inheritance is a major component to risk. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families, whereas common variants at more than 45 loci have been associated with MI risk in the population. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (≤50 years in males and ≤60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol16. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol > 190 mg dl−1. At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase15, 17 and apolipoprotein C-III. Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.
    Nature 12/2014; advance online publication. DOI:10.1038/nature13917 · 42.35 Impact Factor
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    ABSTRACT: BACKGROUND: Ezetimibe lowers plasma levels of low-density lipoprotein (LDL) cholesterol by inhibiting the activity of the Niemann-Pick C1-like 1 (NPC1L1) protein. However, whether such inhibition reduces the risk of coronary heart disease is not known. Human mutations that inactivate a gene encoding a drug target can mimic the action of an inhibitory drug and thus can be used to infer potential effects of that drug. METHODS: We sequenced the exons of NPC1L1 in 7364 patients with coronary heart disease and in 14,728 controls without such disease who were of European, African, or South Asian ancestry. We identified carriers of inactivating mutations (nonsense, splice-site, or frameshift mutations). In addition, we genotyped a specific inactivating mutation (p.Arg406X) in 22,590 patients with coronary heart disease and in 68,412 controls. We tested the association between the presence of an inactivating mutation and both plasma lipid levels and the risk of coronary heart disease. RESULTS: With sequencing, we identified 15 distinct NPC1L1 inactivating mutations; approximately 1 in every 650 persons was a heterozygous carrier for 1 of these mutations. Heterozygous carriers of NPC1L1 inactivating mutations had a mean LDL cholesterol level that was 12 mg per deciliter (0.31 mmol per liter) lower than that in noncarriers (P=0.04). Carrier status was associated with a relative reduction of 53% in the risk of coronary heart disease (odds ratio for carriers, 0.47; 95% confidence interval, 0.25 to 0.87; P=0.008). In total, only 11 of 29,954 patients with coronary heart disease had an inactivating mutation (carrier frequency, 0.04%) in contrast to 71 of 83,140 controls (carrier frequency, 0.09%). CONCLUSIONS: Naturally occurring mutations that disrupt NPC1L1 function were found to be associated with reduced plasma LDL cholesterol levels and a reduced risk of coronary heart disease. (Funded by the National Institutes of Health and others.).
    New England Journal of Medicine 11/2014; 371(22):2072-82. DOI:10.1056/NEJMoa1405386 · 54.42 Impact Factor
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    ABSTRACT: : In HIV negatives, markers of hemostasis, including D-dimer, factor VIII, plasminogen activator inhibitor-1 antigen (PAI-1), and total protein S are associated with all-cause and cardiovascular disease mortality. In HIV positives, studies of D-dimer and factor VIII with death were limited to short follow-up; associations of PAI-1 and total protein S with death have not been examined. In 674 HIV-infected women from the Women's Interagency HIV Study, markers from the first visit after enrollment were exposures of interest in multivariate analyses of death (AIDS and non-AIDS) in separate models at 5 and 16 years. There were 87 AIDS and 44 non-AIDS deaths at 5 years, and 159 AIDS and 113 non-AIDS deaths at 16 years. An inverse association of total protein S quartiles with non-AIDS deaths was observed at 5 (P trend = 0.002) and 16 years (P trend = 0.02); there was no association with AIDS deaths. The third quartile of PAI-1 was associated with AIDS deaths at 5 [hazard ratio (HR) = 4.0; 95% confidence interval (CI): 1.9 to 8.4] and 16 years (HR = 3.4; 95% CI: 1.9 to 5.9); and with non-AIDS deaths at 5 years (HR = 4.8; 95% CI: 1.6 to 13.9). D-dimer and factor VIII were not associated with AIDS or non-AIDS death at 5 or 16 years. Lower total Protein S was a consistent marker of non-AIDS death. We found no association between D-dimer with AIDS or non-AIDS death, in contrast to previous studies showing increased short-term (<5 years) mortality, which may represent sex differences or population heterogeneity. Given longer survival on highly active antiretroviral therapy, further studies of these markers are needed to determine their prognostic value.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 11/2014; 67(3):287-294. DOI:10.1097/QAI.0000000000000306 · 4.39 Impact Factor
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    ABSTRACT: Background Endothelial intercellular adhesion molecule (ICAM) 1 binds neutrophils and facilitates their transmigration into the lung; E-selectin facilitates leukocyte rolling. As neutrophils contribute to tissue destruction in emphysema and chronic obstructive pulmonary disease, we hypothesized that soluble ICAM-1 (sICAM-1) and E-selectin (sE-selectin) would be associated with longitudinal progression of emphysema and lung function decline. Methods The Multi-Ethnic Study of Atherosclerosis (MESA) enrolled participants 45-84 years old without clinical cardiovascular disease in 2000-02. The MESA Lung Study assessed percent emphysema (<-950 Hounsfield units) on cardiac (2000-07) and full-lung CT scans (2010-12), and spirometry was assessed twice over five years. sICAM-1 and sE-selectin were measured at baseline. Mixed-effect models adjusted for demographics, anthropometry, smoking, C-reactive protein, sphingomyelin and scanner factors. Results Among 1,865 MESA Lung participants with measurement of sICAM-1 and percent emphysema the mean log-sICAM-1 was 5.5±0.3 ng/mL and percent emphysema increased 0.73 percentage points (95% CI: 0.34, 1.12; P<0.001) over ten years. A one SD increase in sICAM-1 was associated with an accelerated increase in percent emphysema of 0.23 percentage points over ten years (95% CI: 0.06, 0.39; P=0.007). No significant association was found for sE-selectin, or between any adhesion molecule and lung function. Conclusions Higher levels of sICAM-1 were independently associated with progression of percent emphysema in a general population sample.
    Respiratory Medicine 10/2014; DOI:10.1016/j.rmed.2014.10.004 · 2.92 Impact Factor
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    ABSTRACT: Background Inflammation biomarkers are associated with the venous thromboembolism (VTE) risk factors obesity and age, however the relationships of inflammation with VTE risk remain controversial.Objectives To examine associations of four inflammation biomarkers, C-reactive protein (CRP), serum albumin, white blood cell count (WBC), and platelet count (PLTC), with incident VTE, and determine whether they mediate the association of age or obesity with VTE.Patients/Methods Hazards models adjusted for VTE risk factors were used to calculate prospective associations of each biomarker with incident VTE in 30,239 participants of the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Mediation of the associations of obesity and age with VTE were examined by bootstrapping. Over 4.6 years, there were 268 incident VTE events. Adjusting for VTE risk factors, the hazard ratio (HR) (95% confidence interval (CI)) was 1.25 (1.09, 1.43) per standard deviation (SD) higher log-CRP and 1.25 (1.06, 1.48) per SD lower albumin, with no associations for WBC or PLTC. The association of BMI, but not age, with VTE was partially mediated by CRP and albumin. In risk factor-adjusted models, the percent attenuation of the BMI HR for VTE by introducing CRP or albumin to the models was 15.4% (95% CI: 7.7%, 33.3%) and 41.0% (95% CI: 12.8%, 79.5%), respectively.Conclusion Higher CRP and lower serum albumin were associated with increased VTE risk, and statistically mediated part of the association of BMI with VTE. These data suggest inflammation may be a potential mechanism underlying the relationship of obesity and VTE risk.This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 10/2014; 12(12). DOI:10.1111/jth.12742 · 6.08 Impact Factor
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    ABSTRACT: Even with prolonged antiretroviral therapy (ART), many HIV infected individuals have<500 CD4+ T cells/µL and CD4+ T cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical T cell zone (TZ) that impairs homeostatic mechanisms required for T cell survival. We therefore used antifibrotic therapy in SIV infected rhesus macaques to determine if decreased TZ fibrosis would improve reconstitution of peripheral and lymphoid CD4+ T cells. Treatment with the antifibrotic drug pirfenidone preserved TZ architecture and was associated with significantly larger populations of CD4+ T cells in peripheral blood and lymphoid tissues. Combining pirfenidone with an ART regimen was associated with greater preservation of CD4+ T cells than ART alone and was also associated with higher pirfenidone concentrations. These data support a potential role for antifibrotic drug treatment as adjunctive therapy with ART to improve immune reconstitution.
    The Journal of Infectious Diseases 09/2014; 211(5). DOI:10.1093/infdis/jiu519 · 5.78 Impact Factor
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    ABSTRACT: Cerebral white matter lesions (WMLs) are considered a reflection of cerebral and systemic small vessel disease (SVD), and are associated with reductions in brain volume. Like the brain, the kidney is also sensitive to factors that affect vasculature. Glomerular dysfunction due to renal vascular damage can be measured with different biochemical parameters, such as creatinine or cystatin C, although cystatin C is considered to be more accurate than creatinine in the elderly. The purpose of the study was to determine whether manifestations of SVD in the kidney can predict SVD-based damage to the brain. We examined the relationship between glomerular dysfunction as a measure of SVD on WMLs, gray matter (GM) volume, and cognition in 735 cognitively normal participants from the Cardiovascular Health Study Cognition Study. The multivariate analyses controlled for demographic characteristics, hypertension, heart disease, diabetes, Apolipoprotein 4 allele, C reactive protein, lipids, physical activity, smoking, and body mass index (BMI). Elevated cystatin C levels were associated with lower neuropsychological test scores, the presence of MRI-identified brain infarcts, the severity of WMLs, and GM atrophy five years later. In adjusted models, GM volume was significantly associated with cystatin-C only until BMI and severity of WMLs were added to the model, meaning that the effect of SVD on GM volume is mediated by these two variables. These findings suggest that age-related SVD is a process that leads to altered brain structure, and creates a vulnerability state for cognitive decline.
    Journal of Alzheimer's disease: JAD 09/2014; 44(1). DOI:10.3233/JAD-141077 · 3.61 Impact Factor
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    ABSTRACT: C-reactive protein (CRP) concentration is a heritable systemic marker of inflammation that is associated with cardiovascular disease risk. Genome Wide Association Studies have identified CRP-associated common variants associated in approximately 25 genes. Our aims were to apply exome sequencing to 1) assess whether the candidate loci contain rare coding variants associated with CRP levels and; 2) perform an exome-wide search for rare variants in novel genes associated with CRP levels. We exome sequenced 6,050 European Americans and 3,109 African Americans from the NHLBI-ESP and the CHARGE consortia and performed association tests of sequence data with measured CRP levels. In single variant tests across candidate loci, a novel rare (MAF=0.16%) CRP coding variant (rs77832441-A; p.Thr59Met) was associated with 53% lower mean CRP levels (P=2.9x10(-6)). We replicated the association of rs77832441 in an exome array analysis of 11,414 European Americans (P=3.0x10(-15)). Despite a strong effect on CRP levels, rs77832441 was not associated with inflammation-related phenotypes including Coronary Heart Disease. We also found evidence for an African American-specific association of APOE-ϵ2 rs7214 with higher CRP levels. At the exome-wide significance level (P<5.0x10(-8)), we confirmed associations for reported common variants of HNF1A, CRP, IL6R, and TOMM40-APOE. In gene-based tests, a burden of rare/low frequency variation in CRP in European Americans (P≤6.8 x10(-4)) and RORA in African Americans (P=1.7 x10(-3)) were associated with CRP levels at the candidate gene-level (P<2.0 x10(-3)). This inquiry did not elucidate novel genes, but instead demonstrated that variants distributed across the allele-frequency spectrum within candidate genes contribute to CRP levels.
    Human Molecular Genetics 09/2014; DOI:10.1093/hmg/ddu450 · 6.68 Impact Factor
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    ABSTRACT: HIV infection is associated with increased risk of cardiovascular disease (CVD) in men. Whether HIV is an independent risk factor for CVD in women has not yet been established.
    Journal of the American Heart Association 09/2014; 3(5). DOI:10.1161/JAHA.114.001035
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    ABSTRACT: Plasminogen activator inhibitor 1 (PAI-1) is elevated in obese individuals with type 2 diabetes and may contribute, independently of traditional factors, to increased cardiovascular disease risk. Fiber intake may decrease PAI-1 levels. We examined the associations of fiber intake and its changes with PAI-1 before and during an intensive lifestyle intervention (ILI) for weight loss in 1,701 Look AHEAD (Action for Health in Diabetes) participants with dietary, fitness, and PAI-1 data at baseline and 1 year. Look AHEAD was a randomized cardiovascular disease trial in 5,145 overweight/obese patients with type 2 diabetes, comparing ILI (goal of ≥7% reduction in baseline weight) with a control arm of diabetes support and education. ILI participants were encouraged to consume vegetables, fruits, and grain products low in sugar and fat. At baseline, median fiber intake was 17.9 g/day. Each 8.3 g/day higher fiber intake was associated with a 9.2% lower PAI-1 level (P=0.008); this association persisted after weight and fitness adjustments (P=0.03). Higher baseline intake of fruit (P=0.019) and high-fiber grain and cereal (P=0.029) were related to lower PAI-1 levels. Although successful in improving weight and physical fitness at 1 year, the ILI in Look AHEAD resulted in small increases in fiber intake (4.1g/day, compared with -2.35 g/day with diabetes support and education) that were not related to PAI-1 change (P=0.34). Only 31.3% of ILI participants (39.8% of women, 19.1% of men) met daily fiber intake recommendations. Increasing fiber intake in overweight/obese individuals with diabetes interested in weight loss is challenging. Future studies evaluating changes in fiber consumption during weight loss interventions are warranted.
    Journal of the American Academy of Nutrition and Dietetics 08/2014; 114(11). DOI:10.1016/j.jand.2014.06.357 · 2.44 Impact Factor
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    ABSTRACT: Background: HIV is associated with end-organ diseases of aging via unclear mechanisms. Longitudinally assessing how HIV infection and ART initiation affect biomarkers of end organ function/disease could clarify these mechanisms. We investigated longitudinal changes in clinical biomarkers following 1) HIV infection and 2) ART initiation with evidence of viral suppression. Methods: Cohort: Veterans Aging Cohort Study Virtual Cohort (VACS VC). VACS VC is a longitudinal cohort of HIV infected (HIV+) and race-ethnicity, sex, age, and clinical site-matched uninfected Veterans enrolled in the same calendar year. Inclusion criteria: a negative and successively positive (>six months) HIV antibody test. We used Wilcoxon signedrank tests to analyze 1) the effect of HIV infection on lipids, renal, hepatic and hematologic/cardiovascular biomarkers and 2)whether ART initiation with HIV-1 RNA<500 cpm reverts any changes back to pre-HIV levels. Results: 422 Veterans had at least 1 biomarker measurement available prior to HIV infection and prior to ART initiation. 297 had at least 1 biomarker measurement available prior to HIV infection and after ART initiation with evidence of viral suppression. Mean age prior to HIV infection was 43 years. HIV infection was associated with reduction in total cholesterol, HDL cholesterol, LDL cholesterol, serum albumin, ALT, platelet count, hemoglobin and elevation of FIB-4 score and triglycerides. These changes occurred without significant changes in BMI. ART initiation (with HIV-1 RNA<500cpm) did not reverse alteration in triglycerides, LDL cholesterol, hemoglobin, or FIB-4 to pre-HIV infection levels. Conclusions: HIV infection is associated with longitudinal changes in serum levels of several biomarkers of end-organ function/disease and mortality. Multiple biomarkers (triglycerides, LDL cholesterol, hemoglobin, and FIB-4 ) remain altered from levels prior to HIV infection levels even following inititiation of ART and evidence of viral suppression. These results give insights into underlying mechanisms of increased risk for aging-related chronic diseases in the context of HIV infection.
    Current HIV Research 07/2014; 12(1):50-9. DOI:10.2174/1570162X1201140716101512 · 2.14 Impact Factor

Publication Stats

44k Citations
4,062.32 Total Impact Points

Institutions

  • 1986–2015
    • University of Vermont
      • • Department of Pathology
      • • Department of Biochemistry
      • • College of Medicine
      Burlington, Vermont, United States
  • 2014
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, United States
  • 2006–2013
    • University of California, San Francisco
      • • Division of Hospital Medicine
      • • Veterans Affairs Medical Center
      San Francisco, CA, United States
  • 2003–2013
    • University of Washington Seattle
      • • Department of Medicine
      • • Department of Epidemiology
      Seattle, Washington, United States
    • Northwestern University
      • Department of Preventive Medicine
      Evanston, IL, United States
    • University of Dallas
      Irving, Texas, United States
    • University of Leuven
      Louvain, Flanders, Belgium
  • 2012
    • McGill University
      • Department of Epidemiology, Biostatistics and Occupational Health
      Montréal, Quebec, Canada
    • Albert Einstein College of Medicine
      • Department of Epidemiology & Population Health
      New York City, NY, United States
  • 2010–2012
    • University of Texas Medical Branch at Galveston
      • School of Medicine
      Galveston, TX, United States
    • Hennepin County Medical Center
      Minneapolis, Minnesota, United States
    • George Washington University
      Washington, Washington, D.C., United States
  • 2011
    • Loyola University Medical Center
      • Division of Cardiology
      Maywood, Illinois, United States
    • National Heart, Lung, and Blood Institute
      • Division of Cardiovascular Sciences (DCVS)
      Maryland, United States
  • 1992–2011
    • University of Pittsburgh
      • • Department of Psychiatry
      • • Department of Epidemiology
      Pittsburgh, Pennsylvania, United States
    • Queen's University
      • Department of Medicine
      Kingston, Ontario, Canada
  • 1994–2010
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
  • 2009
    • University of Rochester
      Rochester, New York, United States
  • 1996–2009
    • The University of Arizona
      • Department of Neurology
      Tucson, Arizona, United States
  • 2008
    • University of California, Davis
      • School of Medicine
      Davis, CA, United States
  • 2007
    • Beth Israel Deaconess Medical Center
      • Division of General Medicine and Primary Care
      Boston, MA, United States
    • Lerner Research Institute
      Cleveland, Ohio, United States
    • University of North Carolina at Chapel Hill
      • Department of Genetics
      Chapel Hill, NC, United States
  • 2005–2006
    • Wake Forest School of Medicine
      Winston-Salem, North Carolina, United States
    • Case Western Reserve University
      • Department of Epidemiology and Biostatistics
      Cleveland, OH, United States
    • University of Minnesota Twin Cities
      • Department of Pediatrics
      Minneapolis, MN, United States
    • University of Florida
      • Department of Aging and Geriatric Research
      Gainesville, FL, United States
  • 2002–2006
    • University of Texas at San Antonio
      San Antonio, Texas, United States
    • Burlington College
      Burlington, Vermont, United States
  • 2004
    • Pennington Biomedical Research Center
      Baton Rouge, Louisiana, United States
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2003–2004
    • University of Toronto
      Toronto, Ontario, Canada
  • 1999–2003
    • Johns Hopkins University
      Baltimore, Maryland, United States
    • University of Texas Health Science Center at San Antonio
      • Division of Hospital Medicine
      San Antonio, Texas, United States
  • 2000
    • Baylor College of Medicine
      • Section of Cardiology
      Houston, Texas, United States
  • 1998
    • North Carolina Clinical Research
      Raleigh, North Carolina, United States
  • 1997
    • Armed Forces Institute of Pathology
      Ralalpindi, Punjab, Pakistan
  • 1991–1996
    • University of Massachusetts Medical School
      • Division of Cardiovascular
      Worcester, Massachusetts, United States
  • 1993
    • Brigham and Women's Hospital
      • Department of Radiology
      Boston, MA, United States
  • 1992–1993
    • Wake Forest University
      • • Department of Public Health Sciences
      • • Department of Internal Medicine
      Winston-Salem, North Carolina, United States
  • 1984
    • Sino Biological Inc
      Peping, Beijing, China
    • Mayo Clinic - Rochester
      Рочестер, Minnesota, United States