There is increasing concern over an epidemic of cardiovascular disease (CVD) in patients with HIV infection (HIV+), due to changes in fat distribution and lipid and glucose metabolism that appeared with the introduction of HIV protease inhibitors (PI). However, there is controversy over the role of PI. Data from the study of Fat Redistribution And Metabolic Change in HIV Infection (FRAM) predict increased CVD, but PI drugs are not the major risk factor. We found that other ARV and HIV itself contribute to abnormalities in fat distribution and metabolism. Smoking and microalbuminuria in HIV+ also contribute to CVD risk. It is crucial to determine whether atherosclerosis is increased in HIV+ and, if so, to define the contributors. FRAM is uniquely suited to examine the contributors to atherosclerosis in that a large number of randomly selected HIV-infected men and women from geographic and ethnically diverse populations, and well matched controls from a subset of the CARDIA study were studied with the same rigorous protocol. We assessed regional fat volumes, traditional metabolic risk factors, blood pressure, family history and habits. We propose a follow up to measure carotid intimal medial thickness (IMT) by ultrasound to determine the prevalence of atherosclerosis and contributing factors. We will repeat body composition by MRI, blood pressure, bone density by DXA, and habit survey, plus laboratories for traditional metabolic (e.g., glucose and lipid) and novel inflammatory (e.g., CRP, cytokines) CVD risk factors. Glucose tolerance and fat clearance will be performed. All studies will be done in the subjects from the last FRAM exam, but we will also compare IMT, laboratory results, blood pressure and habits to the larger CARDIA and MESA cohorts. Using multivariate step-wise logistic regression analysis we will assess the association of atherosclerosis by IMT with HIV independent risk factors such as smoking that may be increased in HIV+ cohorts and HIV influenced risk factors (e.g., glucose and lipid metabolism, inflammation). We will assess the association of HIV, ARV and the changes in fat distribution with the CVD risk factors and with IMT. The results will provide essential information on the risk of atherosclerosis and its contributors to aid in patient care, policy and future research. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
9R01HL074814-04
Application #
6696380
Study Section
Special Emphasis Panel (ZRG1-AARR-6 (04))
Program Officer
Olson, Jean
Project Start
1999-09-30
Project End
2007-08-31
Budget Start
2003-09-26
Budget End
2004-08-31
Support Year
4
Fiscal Year
2003
Total Cost
$2,617,565
Indirect Cost
Name
Northern California Institute Research & Education
Department
Type
DUNS #
613338789
City
San Francisco
State
CA
Country
United States
Zip Code
94121
Scherzer, Rebecca; Heymsfield, Steven B; Rimland, David et al. (2017) Association of serum albumin and aspartate transaminase with 5-year all-cause mortality in HIV/hepatitis C virus coinfection and HIV monoinfection. AIDS 31:71-79
Zhi, Degui; Shendre, Aditi; Scherzer, Rebecca et al. (2015) Deep sequencing of RYR3 gene identifies rare and common variants associated with increased carotid intima-media thickness (cIMT) in HIV-infected individuals. J Hum Genet 60:63-7
Manenschijn, Laura; Scherzer, Rebecca; Koper, Jan W et al. (2014) Association of glucocorticoid receptor haplotypes with body composition and metabolic parameters in HIV-infected patients from the FRAM study. Pharmacogenet Genomics 24:156-61
Wheeler, Amber L; Scherzer, Rebecca; Lee, Daniel et al. (2014) HIV/hepatitis C virus coinfection ameliorates the atherogenic lipoprotein abnormalities of HIV infection. AIDS 28:49-58
Kim, Roy J; Vaghani, Sumit; Zifchak, Larisa M et al. (2013) In vitro and in vivo effects of IGF-I on adiposity in HIV-associated metabolic disease: a pilot study. Arch Med Res 44:361-9
Shen, Wei; Scherzer, Rebecca; Gantz, Madeleine et al. (2012) Relationship between MRI-measured bone marrow adipose tissue and hip and spine bone mineral density in African-American and Caucasian participants: the CARDIA study. J Clin Endocrinol Metab 97:1337-46
Scherzer, Rebecca; Heymsfield, Steven B; Lee, Daniel et al. (2011) Decreased limb muscle and increased central adiposity are associated with 5-year all-cause mortality in HIV infection. AIDS 25:1405-14
Yarasheski, Kevin E; Scherzer, Rebecca; Kotler, Donald P et al. (2011) Age-related skeletal muscle decline is similar in HIV-infected and uninfected individuals. J Gerontol A Biol Sci Med Sci 66:332-40
Lake, Jordan E; Wohl, David; Scherzer, Rebecca et al. (2011) Regional fat deposition and cardiovascular risk in HIV infection: the FRAM study. AIDS Care 23:929-38
Jotwani, Vasantha; Scherzer, Rebecca; Choi, Andy et al. (2011) Reduced kidney function and preclinical atherosclerosis in HIV-infected individuals: the study of fat redistribution and metabolic change in HIV infection (FRAM). Am J Nephrol 33:453-60

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