This submission is the renewal of a project that was funded 6 years ago in response to an RFA that sought to determine the factors associated with cardiovascular disease in HI V-infected individuals. Our original project described predictors of abnormal surrogate markers of CVD (carotid intimal medial thickness and coronary calcium score) done at a 3 year interval. Antiretroviral regimens, markers of HIV disease activity, C- reactive protein and lipid profiles (including conventional lipid profiles, triglyceride-rich remnant lipoproteins, Lp(a), homocysteine, fasting blood glucose, free fatty acids and insulin levels), BMI, body composition by anthropometery , BIA and DXA as well as traditional risk factors (smoking, diet, blood pressure, age, gender, family history) were examined. Analyses from our original grant as well as others have suggested that traditional cardiovascular risk factors are the most common predictors for abnormal surrogate markers in this patient population;the impact of the dyslipidemia induced by Pis or other antiretroviral agents and the role of HIV and its associated inflammation on this increased risk remain unclear. To date no HIV surrogate marker studies have followed HIV-infected patients for the 6 year period that may be optimal detect the impact of the dyslipidemia or HIV on progression of disease in individuals. It remains clear that HIV infection itself induces low HDL-cholesterol levels and we have preliminary data that suggest that HIV infected individuals have an atherogenic HDL subpopulation profile. It appears that HDL-subpopulations may have a greater predictive value for risk of CVD than HDL-C alone. We now know that it is selected antiretroviral agents, not classes of agents, that are associated with more severe dyslipidemia in HIV-infected populations and propose to examine the impact of these agents (lopinavir/ritonavir, d4t, efavirenz) as well as traditional and emerging risk factors on HDL subprofiles and on surrogate markers of CVD. Markers of chronic inflammation are considered to be independent predictors of CVD;they also predict progression in HIV-infection and may reflect the cumulative burden of HIV disease in an infected individual. We propose to expand our studies of chronic inflammation adding CRP isoforms and sPLA2 to the determination of CRP to examine the association of these with atherogenic lipid profiles and with abnormal surrogate makers in our cohort. We propose to extend the duration of our surrogate marker studies in this continuation of our R01, to study the progression of c-IMT and coronary calcium score in an HIV infected population over 6 years and to document the changes in HDL subpopulations and inflammatory markers over the new grant period in our HIV infected cohort. The longitudinal determination of HDL subpopulations, the simultaneous determination of both cIMT and coronary calcium scores at 6 years in an HIV infected cohort are novel to this project.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL065947-10
Application #
8081756
Study Section
Special Emphasis Panel (ZRG1-AARR-A (06))
Program Officer
Mcdonald, Cheryl
Project Start
2000-07-12
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
10
Fiscal Year
2011
Total Cost
$549,775
Indirect Cost
Name
Tufts University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02111
Krsak, Martin; Kent, David M; Terrin, Norma et al. (2015) Myocardial Infarction, Stroke, and Mortality in cART-Treated HIV Patients on Statins. AIDS Patient Care STDS 29:307-13
Smit, E; Wanke, C; Dong, K et al. (2015) FRAILTY, FOOD INSECURITY, AND NUTRITIONAL STATUS IN PEOPLE LIVING WITH HIV. J Frailty Aging 4:191-7
Mangili, Alexandra; Ahmad, Raabia; Wolfert, Robert L et al. (2014) Lipoprotein-associated phospholipase A2, a novel cardiovascular inflammatory marker, in HIV-infected patients. Clin Infect Dis 58:893-900
Asztalos, Bela F; Matera, Robert; Horvath, Katalin V et al. (2014) Cardiovascular Disease-Risk Markers in HIV Patients. J AIDS Clin Res 5:
Paranandi, Anu; Asztalos, Bela F; Mangili, Alexandra et al. (2014) Short communication: effects of omega-3 fatty acids on triglycerides and high-density lipoprotein subprofiles in HIV-infected persons with hypertriglyceridemia. AIDS Res Hum Retroviruses 30:800-5
Volpe, Gretchen E; Tang, Alice M; Polak, Joseph F et al. (2013) Progression of carotid intima-media thickness and coronary artery calcium over 6 years in an HIV-infected cohort. J Acquir Immune Defic Syndr 64:51-7
McMahon, James H; Wanke, Christine A; Elliott, Julian H et al. (2011) Repeated assessments of food security predict CD4 change in the setting of antiretroviral therapy. J Acquir Immune Defic Syndr 58:60-3
Falcone, E Liana; Mangili, Alexandra; Skinner, Sally et al. (2011) Framingham risk score and early markers of atherosclerosis in a cohort of adults infected with HIV. Antivir Ther 16:1-8
Mangili, Alexandra; Polak, Joseph F; Quach, Lien A et al. (2011) Markers of atherosclerosis and inflammation and mortality in patients with HIV infection. Atherosclerosis 214:468-73
McMahon, James; Wanke, Christine; Terrin, Norma et al. (2011) Poverty, hunger, education, and residential status impact survival in HIV. AIDS Behav 15:1503-11

Showing the most recent 10 out of 18 publications