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1.  CD8+ T-Cells Count in Acute Myocardial Infarction in HIV Disease in a Predominantly Male Cohort 
BioMed Research International  2015;2015:246870.
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/mm3) 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/mm3 had increased AMI risk with high CD8+ T-cell count, while those with CD4+ T-cell counts <200 cells/mm3 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.
doi:10.1155/2015/246870
PMCID: PMC4320893
2.  Prehypertension, Hypertension, and the Risk of Acute Myocardial Infarction in HIV-Infected and -Uninfected Veterans 
We found increased acute myocardial infarction risk among hypertensive and prehypertensive HIV-infected veterans compared to normotensive uninfected veterans, independent of confounding comorbidities.
Background. Compared to uninfected people, human immunodeficiency virus (HIV)–infected individuals may have an increased risk of acute myocardial infarction (AMI). Currently, HIV-infected people are treated to the same blood pressure (BP) goals (<140/90 or <130/80 mm Hg) as their uninfected counterparts. Whether HIV-infected people with elevated BP have excess AMI risk compared to uninfected people is not known. This study examines whether the association between elevated BP and AMI risk differs by HIV status.
Methods. The Veterans Aging Cohort Study Virtual Cohort (VACS VC) consists of HIV-infected and -uninfected veterans matched 1:2 on age, sex, race/ethnicity, and clinical site. For this analysis, we analyzed 81 026 people with available BP data from VACS VC, who were free of cardiovascular disease at baseline. BP was the average of the 3 routine outpatient clinical measurements performed closest to baseline (first clinical visit after April 2003). BP categories used in the analyses were based on criteria of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Analyses were performed using Cox proportional hazards regression.
Results. Over 5.9 years (median), 860 incident AMIs occurred. Low/high prehypertensive and untreated/treated hypertensive HIV-infected individuals had increased AMI risk compared to uninfected, untreated normotensive individuals (hazard ratio [HR], 1.60 [95% confidence interval {CI}, 1.07–2.39]; HR, 1.81 [95% CI, 1.22–2.68]; HR, 2.57 [95% CI, 1.76–3.76]; and HR, 2.76 [95% CI, 1.90–4.02], respectively).
Conclusions. HIV, prehypertensive BP, and hypertensive BP were associated with an increased risk of AMI in a cohort of HIV-infected and -uninfected veterans. Future studies should prospectively investigate whether HIV interacts with BP to further increase AMI risk.
doi:10.1093/cid/cit652
PMCID: PMC3864500  PMID: 24065316
blood pressure; prehypertension; HIV; myocardial infarction
3.  Dysregulated Mineral Metabolism in Patients with Acute Kidney Injury and Risk of Adverse Outcomes 
Clinical endocrinology  2013;79(4):491-498.
Objective
Numerous studies have evaluated the prevalence and importance of vitamin D deficiency among patients with chronic kidney disease and end-stage renal disease, however, little is known about vitamin D levels in acute kidney injury (AKI). We evaluated the association between vitamin D metabolites and clinical outcomes among patients with AKI.
Design
Prospective cohort study.
Patients
30 participants with AKI and 30 controls from general hospital wards and intensive care units at a tertiary care hospital.
Measurements
Plasma levels of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], 24R,25-dihydroxyvitamin D3, vitamin D binding protein (VDBP), and fibroblast growth factor 23 (FGF23) were measured within 24 hours of AKI onset and 5 days later. Bioavailable 25(OH)D and 1,25(OH)2D levels, defined as the sum of free- and albumin-bound 25(OH)D and 1,25(OH)2D, were estimated using equations.
Results
Compared to controls, participants with AKI had lower levels of 1,25(OH)2D [17 (10-22) versus 25 (15-35) pg/ml, p=0.01], lower levels of VDBP [23 (15-31) versus 29 (25-36) mg/dl, p=0.003], and similar levels of bioavailable 25(OH)D and 1,25(OH)2D at enrollment. Levels of bioavailable 25(OH)D were inversely associated with severity of sepsis in the overall sample (p<0.001). Among participants with AKI, bioavailable 25(OH)D, but not other vitamin D metabolites, was significantly associated with mortality after adjusting for age and serum creatinine (adjusted odds ratio per 1 SD ln [bioavailable 25(OH)D]=0.16, 95% confidence interval=0.03 to 0.85).
Conclusions
Bioavailable 25(OH)D could have a role as a biomarker or mediator of adverse outcomes among patients with established AKI.
doi:10.1111/cen.12172
PMCID: PMC3686895  PMID: 23414198
acute kidney injury; 1-alpha-hydroxylase; 25(OH)D
4.  Association of the Veterans Aging Cohort Study Index with Exercise Capacity in HIV-Infected Adults 
AIDS Research and Human Retroviruses  2013;29(9):1218-1223.
Abstract
Physical disability is a major priority in aging, affecting morbidity, mortality, and quality of life. Despite the large number of adults aging with HIV, our understanding of the physiologic and clinical risk factors for disability is limited. Our goal is to determine whether the Veterans Aging Cohort Study (VACS) Index, based on routine clinical blood tests, could serve as a point of care screening tool to identify HIV-infected adults at high risk for physical disability. HIV-infected adults enrolled in the VACS participated in a cross-sectional exercise study with established measures of strength and endurance. The VACS Index was calculated using recent clinical laboratory values and age; a higher score reflects greater mortality risk. Statistical analyses included correlation and linear regression models adjusted for muscle mass. Fifty-five HIV-infected adults, predominantly African-American men, were included with age mean±SD of 52±7 years. Median (IQR) CD4 cell count was 356 cells/mm3 (212–527). The VACS Index was inversely correlated with quadriceps strength (r=−0.45, p<0.01), grip strength (r=−0.28, p=0.04), and 6-min walk distance (r=−0.27, p=0.05). A 20-point increase in VACS Index score was associated with a 10% lower leg strength (p<0.01), which remained significant after adjustment for muscle cross-sectional area (p=0.02). The VACS Index explained 31% of the variance in specific leg strength. In this group of middle-aged adults with well-controlled HIV infection the VACS Index was significantly associated with upper and lower extremity strength. The VACS Index may be valuable for identification of patients at high risk for disability due to muscle weakness.
doi:10.1089/aid.2012.0388
PMCID: PMC3749694  PMID: 23705911
5.  Plasma FGF23 levels increase rapidly after acute kidney injury 
Kidney international  2013;84(4):776-785.
Emerging evidence suggests that fibroblast growth factor 23 (FGF23) levels are elevated in patients with acute kidney injury (AKI). In order to determine how early this increase occurs we used a murine folic acid nephropathy model and found that plasma FGF23 levels increased significantly from baseline already after 1 hour of AKI, with an 18-fold increase at 24 hours. Similar elevations of FGF23 levels were found when AKI was induced in mice with osteocyte-specific parathyroid hormone receptor ablation or the global deletion of parathyroid hormone or vitamin D receptor, indicating that the increase in FGF23 was independent of parathyroid hormone and vitamin D signaling. Furthermore, FGF23 levels increased to a similar extent in wild-type mice maintained on normal or phosphate-depleted diets prior to induction of AKI, indicating that the marked FGF23 elevation is at least partially independent of dietary phosphate. Bone production of FGF23 was significantly increased in AKI. The half-life of intravenously administered recombinant FGF23 was only modestly increased. Consistent with the mouse data, plasma FGF23 levels rose 15.9-fold by 24 hours following cardiac surgery in patients who developed AKI. The levels were significantly higher than in those without postoperative AKI. Thus, circulating FGF23 levels rise rapidly during AKI in rodents and humans. In mice this increase is independent of established modulators of FGF23 secretion.
doi:10.1038/ki.2013.150
PMCID: PMC3766419  PMID: 23657144
AKI; fibroblast growth factor 23; phosphate; PTH; vitamin D
6.  HIV Status, Burden of Comorbid Disease, and Biomarkers of Inflammation, Altered Coagulation, and Monocyte Activation 
We investigated the association between human immunodeficiency virus (HIV) and prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation in a cohort of HIV-infected and uninfected veterans who had a comparable burden of comorbid conditions.
Background. Biomarkers of inflammation, altered coagulation, and monocyte activation are associated with mortality and cardiovascular disease (CVD) in the general population and among human immunodeficiency virus (HIV)–infected people. We compared biomarkers for inflammation, altered coagulation, and monocyte activation between HIV-infected and uninfected people in the Veterans Aging Cohort Study (VACS).
Methods. Biomarkers of inflammation (interleukin-6 [IL-6]), altered coagulation (d-dimer), and monocyte activation (soluble CD14 [sCD14]) were measured in blood samples from 1525 HIV-infected and 843 uninfected VACS participants. Logistic regression was used to determine the association between HIV infection and prevalence of elevated (>75th percentile) biomarkers, adjusting for confounding comorbidities.
Results. HIV-infected veterans had less prevalent CVD, hypertension, diabetes, obesity, hazardous drinking, and renal disease, but more dyslipidemia, hepatitis C, and current smoking than uninfected veterans. Compared to uninfected veterans, HIV-infected veterans with HIV-1 RNA ≥500 copies/mL or CD4 count <200 cells/µL had a significantly higher prevalence of elevated IL-6 (odds ratio [OR], 1.54; 95% confidence interval [CI],1.14–2.09; OR, 2.25; 95% CI, 1.60–3.16, respectively) and d-dimer (OR, 1.97; 95% CI, 1.44–2.71, OR, 1.68; 95% CI, 1.22–2.32, respectively) after adjusting for comorbidities. HIV-infected veterans with a CD4 cell count <200 cells/µL had significantly higher prevalence of elevated sCD14 compared to uninfected veterans (OR, 2.60; 95% CI, 1.64–4.14). These associations still persisted after restricting the analysis to veterans without known confounding comorbid conditions.
Conclusions. These data suggest that ongoing HIV replication and immune depletion significantly contribute to increased prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation. This contribution is independent of and in addition to the substantial contribution from comorbid conditions.
doi:10.1093/cid/cis406
PMCID: PMC3493182  PMID: 22534147
7.  Risk of Heart Failure With Human Immunodeficiency Virus in the Absence of Prior Diagnosis of Coronary Heart Disease 
Archives of internal medicine  2011;171(8):737-743.
Background
Whether human immunodeficiency virus (HIV) infection is a risk factor for heart failure (HF) is not clear. The presence of coronary heart disease and alcohol consumption in this population may confound this association.
Methods
To determine whether HIV infection is a risk factor for incident HF, we conducted a population-based, retrospective cohort study of HIV-infected and HIV-uninfected veterans enrolled in the Veterans Aging Cohort Study Virtual Cohort (VACS-VC) and the 1999 Large Health Study of Veteran Enrollees (LHS) from January 1, 2000, to July 31, 2007.
Results
There were 8486 participants (28.2% HIV-infected) enrolled in the VACS-VC who also participated in the 1999 LHS. During the median 7.3 years of follow-up, 286 incident HF events occurred. Age- and race/ethnicity–adjusted HF rates among HIV-infected and HIV-uninfected veterans were 7.12 (95% confidence interval [CI],6.90-7.34) and 4.82 (95% CI, 4.72-4.91) per 1000 person-years, respectively. Compared with HIV-uninfected veterans, those who were HIV infected had an increased risk ofHF (adjusted hazard ratio [HR], 1.81; 95% CI, 1.39-2.36). This association persisted among veterans who did not have a coronary heart disease event or a diagnosis related to alcohol abuse or dependence before the incident HF event (adjusted HR, 1.96; 95% CI, 1.29-2.98). Compared with HIV-uninfected veterans, those who were HIV infected with a baseline Human immunodeficiency virus 1 (HIV-1) RNA level of 500 or more copies/mL had a higher risk of HF (adjusted HR, 2.28; 95% CI, 1.57-3.32), while those with baseline and a recent HIV-1 RNA level less than 500 copies/mL did not (adjusted HR, 1.10; 95% CI, 0.64-1.89; P< .001 for comparison between high and low HIV-1 RNA groups).
Conclusions
Our data suggest that HIV infection is a risk factor for HF. Ongoing viral replication is associated with a higher risk of developing HF.
doi:10.1001/archinternmed.2011.151
PMCID: PMC3687533  PMID: 21518940
8.  Food Insecurity is Associated with Poor Virologic Response among HIV-Infected Patients Receiving Antiretroviral Medications 
Journal of General Internal Medicine  2011;26(9):1012-1018.
ABSTRACT
BACKGROUND AND OBJECTIVE
Food insecurity negatively impacts HIV disease outcomes in international settings. No large scale U.S. studies have investigated the association between food insecurity and severity of HIV disease or the mechanism of this possible association. The objective of this study was to examine the impact of food insecurity on HIV disease outcomes in a large cohort of HIV-infected patients receiving antiretroviral medications.
DESIGN
This is a cross-sectional study.
PARTICIPANTS AND SETTING
Participants were HIV-infected patients enrolled in the Veterans Aging Cohort Study between 2002–2008 who were receiving antiretroviral medications.
MAIN MEASUREMENTS
Participants reporting “concern about having enough food for you or your family in the past 30 days” were defined as food insecure. Using multivariable logistic regression, we explored the association between food insecurity and both low CD4 counts (<200 cells/μL) and unsuppressed HIV-1 RNA (>500 copies/mL). We then performed mediation analysis to examine whether antiretroviral adherence or body mass index mediates the observed associations.
KEY RESULTS
Among 2353 HIV-infected participants receiving antiretroviral medications, 24% reported food insecurity. In adjusted analyses, food insecure participants were more likely to have an unsuppressed HIV-1 RNA (AOR 1.37, 95% CI 1.09, 1.73) compared to food secure participants. Mediation analysis revealed that neither antiretroviral medication adherence nor body mass index contributes to the association between food insecurity and unsuppressed HIV-1 RNA. Food insecurity was not independently associated with low CD4 counts.
CONCLUSIONS
Among HIV-infected participants receiving antiretroviral medications, food insecurity is associated with unsuppressed viral load and may render treatment less effective. Longitudinal studies are needed to test the potential causal association between food insecurity, lack of virologic suppression, and additional HIV outcomes.
doi:10.1007/s11606-011-1723-8
PMCID: PMC3157515  PMID: 21573882
food insecurity; HIV; patients; antiretrovirals
9.  The Risk of Incident Coronary Heart Disease Among Veterans with and without HIV and Hepatitis C 
Background
Whether hepatitis C (HCV) confers additional coronary heart disease (CHD) risk among Human Immunodeficiency Virus (HIV) infected individuals is unclear. Without appropriate adjustment for antiretroviral therapy, CD4 count, and HIV-1 RNA, and substantially different mortality rates among those with and without HIV and HCV infection, the association between HIV, HCV, and CHD may be obscured.
Methods and Results
We analyzed data on 8579 participants (28% HIV+, 9% HIV+HCV+) from the Veterans Aging Cohort Study Virtual Cohort who participated in the 1999 Large Health Study of Veteran Enrollees. We analyzed data collected on HIV and HCV status, risk factors for and the incidence of CHD, and mortality from 1/2000–7/2007. We compared models to assess CHD risk when death was treated as a censoring event and as a competing risk. During the median 7.3 years of follow-up, there were 194 CHD events and 1186 deaths. Compared with HIV−HCV− Veterans, HIV+ HCV+ Veterans had a significantly higher risk of CHD regardless of whether death was adjusted for as a censoring event (adjusted hazard ratio (HR)=2.03, 95% CI=1.28–3.21) or a competing risk (adjusted HR=2.45, 95% CI=1.83–3.27 respectively). Compared with HIV+HCV− Veterans, HIV+ HCV+ Veterans also had a significantly higher adjusted risk of CHD regardless of whether death was treated as a censored event (adjusted HR=1.93, 95% CI=1.02–3.62) or a competing risk (adjusted HR =1.46, 95% CI=1.03–2.07).
Conclusions
HIV+HCV+ Veterans have an increased risk of CHD compared to HIV+HCV−, and HIV−HCV− Veterans.
doi:10.1161/CIRCOUTCOMES.110.957415
PMCID: PMC3159506  PMID: 21712519
viruses; coronary disease; mortality; multi morbidity
10.  Association of Age and Comorbidity with Physical Function in HIV-Infected and Uninfected Patients: Results from the Veterans Aging Cohort Study 
AIDS Patient Care and STDs  2011;25(1):13-20.
Abstract
HIV clinical care now involves prevention and treatment of age-associated comorbidity. Although physical function is an established correlate to comorbidity in older adults without HIV infection, its role in aging of HIV-infected adults is not well understood. To investigate this question we conducted cross-sectional analyses including linear regression models of physical function in 3227 HIV-infected and 3240 uninfected patients enrolled 2002–2006 in the Veterans Aging Cohort Study-8-site (VACS-8). Baseline self-reported physical function correlated with the Short Form-12 physical subscale (ρ = 0.74, p < 0.001), and predicted survival. Across the age groups decline in physical function per year was greater in HIV-infected patients (βcoef −0.25, p < 0.001) compared to uninfected patients (βcoef −0.08, p = 0.03). This difference, although statistically significant (p < 0.01), was small. Function in the average 50-year old HIV-infected subject was equivalent to the average 51.5-year-old uninfected subject. History of cardiovascular disease was a significant predictor of poor function, but the effect was similar across groups. Chronic pulmonary disease had a differential effect on function by HIV status (Δβcoef −3.5, p = 0.03). A 50-year-old HIV-infected subject with chronic pulmonary disease had the equivalent level of function as a 68.1-year-old uninfected subject with chronic pulmonary disease. We conclude that age-associated comorbidity affects physical function in HIV-infected patients, and may modify the effect of aging. Longitudinal research with markers of disease severity is needed to investigate loss of physical function with aging, and to develop age-specific HIV care guidelines.
doi:10.1089/apc.2010.0242
PMCID: PMC3030913  PMID: 21214375
11.  IMPACT OF CIGARETTE SMOKING ON MORTALITY IN HIV-POSITIVE AND HIV-NEGATIVE VETERANS 
It is unknown whether smoking confers similar mortality risk in HIV-positive as in HIV-negative patients. We compared overall mortality stratified by HIV and smoking of 1,034 HIV-positive block-matched to 739 HIV-negative veterans, enrolled 2001–2002 in the Veterans Aging Cohort 5 Site Study. Adjusted incidence rate ratios (IRR) for mortality were calculated using Poisson regression. Mortality was significantly increased in HIV-positive veterans according to both smoking status and pack-years in unadjusted and adjusted analyses (adjusted IRR 2.31, 95% confidence interval [CI] 1.53–3.49 for HIV-positive current smokers and IRR 1.32, 95% CI 0.67–2.61 for HIV-negative current smokers). Comorbid diseases were also significantly increased according to smoking status and pack-years. Current smoking is associated with poor outcomes; even lower levels of exposure appear to be detrimental in HIV-infected veterans. These findings support the need for improvements in smoking cessation and for studies of mechanisms and diseases underlying increased mortality in smokers with HIV.
doi:10.1521/aeap.2009.21.3_supp.40
PMCID: PMC3118467  PMID: 19537953
12.  Hepatitis C Virus Infection and the Risk of Coronary Disease 
Background
The association between hepatitis C virus (HCV) infection and coronary artery disease (CAD) is controversial. We conducted this study to determine and quantify this association.
Methods
We used an established, national, observational cohort of all HCV-infected veterans receiving care at all Veterans Affairs facilities, the Electronically Retrieved Cohort of HCV Infected Veterans, to identify HCV-infected subjects and HCV-uninfected control subjects. We used the Cox proportional-hazards model to determine the risk of CAD among HCV-infected subjects and control subjects.
Results
We identified 82,083 HCV-infected and 89,582 HCV-uninfected subjects. HCV-infected subjects were less likely to have hypertension, hyperlipidemia, and diabetes but were more likely to abuse alcohol and drugs and to have renal failure and anemia. HCV-infected subjects had lower mean (± standard deviation) total plasma cholesterol (175 ± 40.8 mg/dL vs. 198 ± 41.0 mg/dL), low-density lipoprotein cholesterol (102 ± 36.8 mg/dL vs. 119 ± 38.2 mg/dL), and triglyceride (144 ± 119 mg/dL vs. 179 ± 151 mg/dL) levels, compared with HCV-uninfected subjects. In multivariable analysis, HCV infection was associated with a higher risk of CAD (hazard ratio, 1.25; 95% confidence interval, 1.20–1.30; P < .001 for all comparisons). Traditional risk factors (age, hypertension, chronic obstructive pulmonary disease, diabetes, and hyperlipidemia) were associated with a higher risk of CAD in both groups, whereas minority race and female sex were associated with a lower risk of CAD.
Conclusions
HCV-infected persons are younger and have lower lipid levels and a lower prevalence of hypertension. Despite a favorable risk profile, HCV infection is associated with a higher risk of CAD after adjustment for traditional risk factors.
doi:10.1086/599371
PMCID: PMC3077953  PMID: 19508169
13.  Veterans Aging Cohort Study (VACS) 
Medical care  2006;44(8 Suppl 2):S13-S24.
Background
The Veterans Aging Cohort Study (VACS) is a study of human immunodeficiency virus (HIV) infected and uninfected patients seen in infectious disease and general medical clinics. VACS includes the earlier 3 and 5 site studies (VACS 3 and VACS 5) as well as the ongoing 8 site study.
Objectives
We sought to provide background and context for analyses based upon VACS data, including study design and rationale as well as its basic protocol and the baseline characteristics of the enrolled sample.
Research Design
We undertook a prospectively consented multisite observational study of veterans in care with and without HIV infection.
Measures
Data were derived from patient and provider self report, telephone interviews, blood and DNA samples, focus groups, and full access to the national VA “paperless” electronic medical record system.
Results
More than 7200 veterans have been enrolled in at least one of the studies. The 8 site study (VACS) has enrolled 2979 HIV-infected and 3019 HIV-uninfected age–race–site matched comparators and has achieved stratified enrollment targets for race/ethnicity and age and 99% of its total target enrollment as of October 30, 2005. Participants in VACS are similar to other veterans receiving care within the VA. VACS participants are older and more predominantly black than those reported by the Centers for Disease Control.
Conclusions
VACS has assembled a rich, in-depth, and representative sample of veterans in care with and without HIV infection to conduct longitudinal analyses of questions concerning the association between alcohol use and related comorbid and AIDS-defining conditions.
doi:10.1097/01.mlr.0000223741.02074.66
PMCID: PMC3049942  PMID: 16849964
HIV/AIDS; alcohol; aging veterans; data management/research design
14.  Connexin40 Imparts Conduction Heterogeneity to Atrial Tissue 
Circulation research  2008;103(9):1001-1008.
Impulse propagation in cardiac tissue is a complex process in which intercellular coupling through gap junction channels is a critical component. Connexin40 (Cx40) is an abundant gap junction protein that is expressed in atrial myocytes. Alterations in the expression of Cx40 have been implicated in atrial arrhythmogenesis. The purpose of the current study was to assess the role of Cx40 in atrial impulse propagation. High-resolution optical mapping was used to study conduction in the right and left atrial appendages of isolated Langendorff-perfused murine hearts. Wild-type (Cx40+/+), heterozygous (Cx40+/−), and knockout (Cx40−/−) mice, both adult and embryonic, were studied to assess the effects of reduced Cx40 expression on sinus node function and conduction velocity at different pacing cycle lengths (100 and 60 ms). In both adult and late-stage embryonic Cx40+/+ mice, heterogeneity in CV was found between the right and left atrial appendages. Either partial (Cx40+/−) or complete (Cx40−/−) deletion of Cx40 was associated with the loss of conduction heterogeneity in both adult and embryonic mice. Additionally, sinus node impulse initiation was found to be ectopic in Cx40−/− mice at 15.5 days postcoitus, whereas Cx40+/+ mice showed normal activation occurring near the crista terminalis. Our findings suggest that Cx40 plays an essential role in establishing interatrial conduction velocity heterogeneity in the murine model. Additionally, we describe for the first time a developmental requirement for Cx40 in normal sinus node impulse initiation at 15.5 days postcoitus.
doi:10.1161/CIRCRESAHA.107.168997
PMCID: PMC2925175  PMID: 18599871
arrhythmia; conduction velocity; Cx40; optical mapping; sinus node
15.  HIV Infection and the Risk of Diabetes Mellitus 
AIDS (London, England)  2009;23(10):1227-1234.
Background
The influence of HIV infection on the risk of diabetes is unclear. We determined the association and predictors of prevalent DM in HIV infected and uninfected veterans.
Methods
We determined baseline prevalence and risk factors for diabetes among HIV infected and uninfected veterans in the Veterans Aging Cohort Study. Logistic regression was used to determine the odds of diabetes in HIV infected and uninfected persons.
Results
We studied 3,327 HIV-infected and 3,240 HIV-uninfected subjects. HIV infected subjects were younger, more likely to be black race, male, have HCV coinfection and a lower body mass index (BMI). HIV infected subjects had a lower prevalence of diabetes at baseline (14.9% vs. 21.4%, P<0.0001). After adjustment for known risk factors, HIV infected individuals had a lower risk of diabetes (OR 0.84, 95% CI 0.72-0.97). Increasing age, male gender, minority race, and BMI were associated with an increased risk. The odds ratio for diabetes associated with increasing age, minority race and BMI were greater among HIV infected veterans. HCV coinfection and nucleoside and non-nucleoside reverse transcriptase inhibitor therapy were associated with a higher risk of diabetes in HIV infected veterans.
Conclusion
While HIV infection itself is not associated with increased risk of diabetes, increasing age, HCV coinfection and BMI have a more profound effect upon the risk of diabetes among HIV infected persons. Further, long term ARV treatment also increases risk. Future studies will need to determine whether incidence of DM differs by HIV status.
doi:10.1097/QAD.0b013e32832bd7af
PMCID: PMC2752953  PMID: 19444074
HIV; diabetes; HCV; risk; antiretroviral therapy
16.  The Association Between the Receipt of Lipid Lowering Therapy and HIV Status Among Veterans Who Met NCEP/ATP III Criteria for the Receipt of Lipid Lowering Medication 
ABSTRACT
OBJECTIVE
To examine the association between HIV infection status and the receipt of lipid lowering therapy based on National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATP III) guidelines and to assess whether HIV viral load and hepatitis C (HCV) status alters that association.
PARTICIPANTS AND DESIGN
A cross-sectional analysis of survey, laboratory, and pharmacy data from 1,577 male participants (59% HIV infected) of the Veterans Aging Cohort Five-Site Study, a prospective observational cohort of U.S. veterans with and without HIV infection.
MEASUREMENTS
Receipt of lipid lowering therapy obtained from the VA pharmacy benefits management system was the main outcome.
RESULTS
The prevalence of lipid lowering therapy among HIV-infected and HIV-uninfected veterans was 15.4% vs. 37.9%, respectively,  < 0.01. Among veterans who met NCEP/ATP III criteria for lipid lowering therapy, HIV-infected veterans had a significantly lower prevalence for the receipt of lipid lowering therapy (adjusted odds ratio (OR) = 0.43, 95% confidence interval (C.I.) 0.28–0.67) as compared with HIV-uninfected veterans. Among HIV-infected veterans, log HIV viral load (adjusted OR = 0.57, 95% CI, 0.41–0.81) and HIV-HCV co-infection (adjusted OR = 0.31, 95% CI = 0.13–0.75) were negatively associated with receipt of lipid lowering therapy. Exposure to HAART was not associated with receipt of lipid lowering therapy.
CONCLUSIONS
Among those who met NCEP/ATP III criteria for lipid lowering therapy, HIV-infected veterans, particularly those with high HIV viral loads and HCV co-infection, were significantly less likely to receive lipid lowering therapy. This may be a modifiable mediator of cardiovascular disease among HIV-infected individuals.
doi:10.1007/s11606-008-0891-7
PMCID: PMC2642578  PMID: 19127386
HIV; cholesterol; hepatitis C; men; veterans; cardiovascular diseases
17.  The Impact of Cigarette Smoking on Mortality, Quality of Life, and Comorbid Illness Among HIV-Positive Veterans 
Journal of General Internal Medicine  2005;20(12):1142-1145.
Background
The impact of smoking on outcomes among those with HIV infection has not been determined in the era of highly active antiretroviral therapy (HAART).
Study Objective
Determine the impact of smoking on morbidity and mortality in HIV-positive patients post-HAART.
Design
Prospective observational study.
Participants
Eight hundred and sixty-seven HIV-positive veterans enrolled in the Veterans Aging Cohort 3 Site Study.
Measurements
Clinical data were collected through patient questionnaire, International Classification of Diseases—9th edition codes, and standardized chart extraction, and laboratory and mortality data through the national VA database. Quality of life was assessed with the physical component summary (PCS) of the Short-Form 12.
Results
Current smokers had increased respiratory symptoms, chronic obstructive pulmonary disease (COPD), and bacterial pneumonia. In analyses adjusted for age, race/ethnicity, CD4 cell count, HIV RNA level, hemoglobin, illegal drug and alcohol use, quality of life was substantially decreased (β=−3.3, 95% confidence interval [CI] −5.3 to −1.4) and mortality was significantly increased (hazard ratio 1.99, 95% CI 1.03 to 3.86) in current smokers compared with never smokers.
Conclusions
HIV-positive patients who currently smoke have increased mortality and decreased quality of life, as well as increased respiratory symptoms, COPD, and bacterial pneumonia. These findings suggest that smoking cessation should be emphasized for HIV-infected patients.
doi:10.1111/j.1525-1497.2005.0255.x
PMCID: PMC1490270  PMID: 16423106
HIV; AIDS; smoking; mortality; health-related quality of life

Results 1-17 (17)