Update on the VACS HIV CVD Substudy and Preliminary Analyses Matthew S. Freiberg, MD, MSc University of Pittsburgh April 8, 2010

Specific Aims (1) Evaluate whether HIV is an independent risk factor for cardiovascular disease (CVD) and whether HIV viral load; CD4 counts; duration, type, and adherence to combination antiretroviral therapy (CART); HCV and substance use increase CVD risk (2) Evaluate the cross-sectional association of HIV infection and CART and (3) Hepatitis C and substance use with potential mechanisms of CVD among HIV infected and uninfected persons.

VACS Conceptual Model for Alcohol, HIV and CVD Freiberg et al. Alcohol Research and Health 2010

Self-reported CVD events within and outside the VA Health Care system Cardiovascular Disease Events among 1496 surveyed VACS Participants Site VA Events Non-VA Events Atlanta 38 13 Bronx 34 7 Houston 32 6 Los Angeles 14 18 New York 4 2 Baltimore Washington, D.C. 39 24 Pittsburgh 1 Total 172  75  There are a total of 247 cardiovascular events.

MI/CHD events within VA by screening criteria VA screening process for MI/CHD: -1601 participants who have a diagnostic ICD-9 codes -148 participants had procedure ICD-9 codes (e.g., PTCA, CABG) -881 participants have met pharmacy criteria (e.g., nitroglycerine) -3345 participants have laboratory criteria (e.g., CPK or Troponin values)

Sample of Online Web Adjudication Site

Mechanistic Studies The 600 Substudy participants Exercise treadmill test Complete echocardiogram study CT scan (measuring 10 endpoints) Coronary artery, aortic valve, and mitral value annular calcium Left ventricular size and thoracic aorta calcium Liver : spleen fat ratio Abdominal visceral and subcutaneous fat, epicardial fat, and thigh fat Laboratory testing (serum biomarkers) Endothelial function: (eg., sICAM-1) Thrombosis: (e.g., D-dimer) Other: (e.g., IL-6)

Mechanistic Substudy Current Enrollment and Completed Testing Site Current Enrollment and Target Completed Testing Blood GXT/6MW Echo CT scan Baltimore 24 / 275 10 13 / 0 12 2 LA 17 / 275 7 / 0 7 Pittsburgh 5 / 50 3 / 3 3 Total 46 / 600 22 23 / 3 5

Ischemic Heart Disease Quality Enhancement Research Initiative (IHD QUERI) The overall mission of the IHD QUERI is to improve the quality of care and health outcomes of veterans with IHD To this end, all myocardial infarctions occurring within the VA from 2003 to 2008 were chart reviewed using standardized protocols

QUERI and Virtual Cohort Merger Virtual Cohort and IHD QUERI merger Virtual Cohort (40594 HIV+, 81188 HIV-) Acute Myocardial Infarctions (2003-2008) 993 total events 379 events among HIV infected veterans 614 events among HIV uninfected veterans These numbers do NOT include PTCA, stent, or CABG performed without preceding AMI nor do these account for events outside VA system

Preliminary Data

Acknowledgements PI and Co-PI: AC Justice, DA Fiellin Scientific Officer (NIAAA): K Bryant Participating VA Medical Centers: Atlanta (D. Rimland), Baltimore (KA Oursler, R Titanji), Bronx (S Brown, S Garrison), Houston (M Rodriguez-Barradas, N Masozera), Los Angeles (M Goetz, D Leaf), Manhattan-Brooklyn (M Simberkoff, D Blumenthal, H Leaf, J Leung), Pittsburgh (A Butt, E Hoffman), and Washington DC (C Gibert, R Peck) Core Faculty: K Mattocks (Deputy Director), K Akgun, S Braithwaite, C Brandt, K Bryant, R Cook, K Crothers, J Chang, S Crystal, N Day, R Dubrow, M Duggal, J Erdos, M Freiberg, M Gaziano, M Gerschenson, A Gordon, J Goulet, N Kim, M Kozal, K Kraemer, V LoRe, S Maisto, P Miller, P O’Connor, C Parikh, C Rinaldo, J Samet Staff: H Bathulapalli, T Bohan, D Cohen, A Consorte, P Cunningham, A Dinh, C Frank, K Gordon, J Huston, F Kidwai, F Levin, K McGinnis, C Rogina, J Rogers, L Sacchetti, M Skanderson, J Tate, E Williams Major Collaborators: VA Public Health Strategic Healthcare Group, VA Pharmacy Benefits Management, Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), Yale Center for Interdisciplinary Research on AIDS (CIRA), Center for Health Equity Research and Promotion (CHERP), ART-CC, NA-ACCORD, HIV-Causal Major Funding by: National Institutes of Health: NIAAA (U10-AA13566), NIA (R01-AG029154), NHLBI (R01-HL095136; R01-HL090342; RCI-HL100347) , NIAID (U01-A1069918), NIMH (P30-MH062294), and the Veterans Health Administration Office of Research and Development (VA REA 08-266) and Office of Academic Affiliations (Medical Informatics Fellowship).

Acknowledgements Investigator Amy Justice, MD, PhD Co-Investigators John Gottdiener, MD Dan Edmundowicz, MD Adeel Butt, MD, MS Sheldon Brown, MD Joyce Chang, PhD Matthew Budoff, MD Matthew Goetz, MD Cynthia Gilbert, MD David Leaf, MD MPH Maria Rodriguez-Barradas, MD Kris Ann Oursler MD, ScM Stephen Gottlieb, MD Lewis Kuller, MD, DrPH Insert title Elliot Lowy Melissa Skanderson Kathleen McGinnis Elizabeth Sorek Sean Wang Carol Rogina Travis Rabbit Kaku Armah Courtney Watson

Acknowledgements

Studies and Results Testing Protocols for 600 person substudy Echo: ready to start CT: ready to start except one “dummy scan” from LA VA GXT: ready to start Lab protocol: finalizing bar coding procedure and final run through with technician from Russ Tracy’s laboratory Enrollment projected for first week of October 2009

Studies and Results

Studies and Results Currently enrolling all VACS participants (3227 HIV+, 2340HIV-) Survey items quantifying family history of CVD and self-reported CVD events within and outside the VA hospital system Laboratory measurements being collected Hepatitis C antibody and viral RNA levels Fasting lipid panel and glucose testing Physical Measurements being collected Blood pressure Height and weight

Studies and Results On-line Web adjudication system Adjudication process started Virtual Cohort (41,630 HIV+, 66822 HIV-) Acute Myocardial Infarctions (2003-2008) 1021 total events (41% HIV infected) VACS cohort 90 total events (45% HIV infected) These numbers do NOT include PTCA, stent, or CABG performed without preceding AMI nor do these account for events outside VA system Data based on Quality Enhancement Research Initiative (QUERI) IHD

Cardiovascular Disease Mechanisms in HIV Infected and Uninfected Veterans Matthew S. Freiberg, MD, MSc University of Pittsburgh Veterans Aging Cohort Study Meeting New Haven, Connecticut October 14th, 2008

Data Collection: Mechanistic Studies Aim 2 and Aim 3 The 600 Substudy participants Exercise treadmill test Complete echocardiogram study CT scan (measuring 10 endpoints) Coronary artery, aortic valve, and mitral value annular calcium Left ventricular size and thoracic aorta calcium Liver : spleen fat ratio Abdominal visceral and subcutaneous fat, epicardial fat, and thigh fat Laboratory testing (serum biomarkers) Endothelial function: sICAM-1, serum tissue factor, factor VIIIc and von Willebrand Factor Thrombosis: D-dimer, plasminogen, t-PA antigen, PAI-1, TPA/PAI-1 complex, TAF1, thrombin-antithrombin complex (TAT) Other: Lp (a), hs CRP, IL-6, SSA, Cystatin C, Fibrinogen, and insulin

Data Collection: Prospective Studies Aim 1 Traditional and Non-traditional CVD risk factors in VACS Blood pressure measurement, height, and weight* Fasting lipid panel and glucose* Hepatitis C testing and quantification (HCV antibody and viral load) Information on family history of CVD Information on CVD events outside of the VA system Adjudicate CVD outcomes in VACS Coronary Heart Disease (CHD): Myocardial Infarction and coronary revascularization Non-CHD CVD: stroke, peripheral vascular disease, congestive heart failure, deep venous thrombosis, and pulmonary embolism Will include both prevalent and incident events * Will not be obtained at the Atlanta site due to logistic constraints