Cardiovascular disease (CVD) is a significant problem for HIV-infected patients, yet the extent to which the newest CVD risk prediction tools accurately predict risk for HIV patients is not known. In this grant, we will evaluate the new American College of Cardiology (ACC)/ American Heart Association (AHA) CVD risk prediction algorithm, released in November 2013, to assess its performance in HIV patients. We will then develop a new risk prediction algorithm incorporating HIV and HIV-related factors to attempt to improve risk prediction. The rationale for performing this study is the uniqu pathophysiology underlying HIV-associated CVD, which is thought to be incompletely explained by traditional risk factors and driven in large part by inflammation and immune dysregulation. While established CVD risk prediction tools have been applied to HIV groups, there is not evidence that they are appropriate for use as they do not reflect these underlying immunologic and inflammatory changes. Accurate prediction of CVD risk is particularly important as it is a key component of the newly released 2013 cholesterol guidelines, which guide clinicians in identifying patients in need of CVD risk modifying treatment. Through Aim 1 of the proposed study, we will evaluate the new ACC/AHA CVD risk prediction algorithm, assessing the degree to which it accurately predicts CVD risk for HIV patients and hypothesizing that it will under predict risk. We will conduct a parallel analysis of the longstanding Framingham Risk Score.
In Aim 2, we will develop a new CVD risk prediction algorithm tailored for use in HIV populations, for the first time incorporating HIV status as a CVD risk factor within a prediction function and hypothesizing that its inclusion will improve risk prediction beyond that by traditional CVD risk factors alone. We will refine this analysis by assessing whether inclusion of HIV-related variables indicating disease and treatment status further improve risk prediction beyond inclusion of HIV status alone. To achieve these aims, we will leverage an established cohort uniquely suited to perform the study to be conducted by a cross- disciplinary team assembled with specific expertise in the relevant fields. We will collaborate with Dr. Ralph D'Agostino and his team, who have decades of experience in risk prediction statistical analysis, to apply sophisticated risk prediction methodology in order to rigorously compare established and new risk prediction functions. Cardiovascular risk prediction is a critical aspect of HIV-related heart disease as it underlies a clinician's ability to identify high-risk individuals in need of risk-modifying therapy. Validating the new ACC/AHA risk prediction algorithm in diverse settings and assessing the benefit of novel risk markers were specific priorities identified in the new 2013 ACC/AHA risk assessment guidelines, both of which will be performed through this study. The proposed study presents an opportunity to answer a timely question with a significant clinical and public health impact, optimizing methods for CVD risk prediction in HIV and thereby improving CVD preventative strategies for this at-risk group.

Public Health Relevance

It is unknown how to accurately predict cardiovascular disease (CVD) risk HIV patients. CVD significantly impacts the long term health and well-being of HIV populations and is likely caused by a different set of risk factors related t the presence of a chronic infection. Our study will evaluate how well the newly-released American College of Cardiology (ACC)/ American Heart Association (AHA) CVD risk prediction algorithm works for patients with HIV and whether it is appropriate for adoption into HIV clinical practice. We will then develop a CVD risk prediction tool tailored to HIV patients, which reflects the unique interplay of traditional and non-traditional, HIV-related factors specific to this population. The results of the study will inform public health strategies by improving physicians'ability to identify HIV patients at high cardiovascular risk and enhancing cardiovascular disease prevention for HIV patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
High Priority, Short Term Project Award (R56)
Project #
1R56HL125029-01
Application #
8915903
Study Section
Special Emphasis Panel (ZHL1-CSR-B (M1))
Program Officer
Wei, Gina
Project Start
2014-09-06
Project End
2015-08-31
Budget Start
2014-09-06
Budget End
2015-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$820,763
Indirect Cost
$349,060
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Triant, Virginia A; Perez, Jeremiah; Regan, Susan et al. (2018) Cardiovascular Risk Prediction Functions Underestimate Risk in HIV Infection. Circulation 137:2203-2214
Janjua, Sumbal A; Triant, Virginia A; Addison, Daniel et al. (2017) HIV Infection and Heart Failure Outcomes in Women. J Am Coll Cardiol 69:107-108
Hyle, Emily P; Mayosi, Bongani M; Middelkoop, Keren et al. (2017) The association between HIV and atherosclerotic cardiovascular disease in sub-Saharan Africa: a systematic review. BMC Public Health 17:954
Rhodes, Corinne M; Chang, Yuchiao; Regan, Susan et al. (2017) Human Immunodeficiency Virus (HIV) Quality Indicators Are Similar Across HIV Care Delivery Models. Open Forum Infect Dis 4:ofw240
Mosepele, Mosepele; Hemphill, Linda C; Moloi, Walter et al. (2017) Pre-clinical carotid atherosclerosis and sCD163 among virally suppressed HIV patients in Botswana compared with uninfected controls. PLoS One 12:e0179994
Mosepele, Mosepele; Hemphill, Linda C; Palai, Tommy et al. (2017) Cardiovascular disease risk prediction by the American College of Cardiology (ACC)/American Heart Association (AHA) Atherosclerotic Cardiovascular Disease (ASCVD) risk score among HIV-infected patients in sub-Saharan Africa. PLoS One 12:e0172897
Feinstein, Matthew J; Kim, June-Ho; Bibangambah, Prossy et al. (2017) Ideal Cardiovascular Health and Carotid Atherosclerosis in a Mixed Cohort of HIV-Infected and Uninfected Ugandans. AIDS Res Hum Retroviruses 33:49-56
Rhodes, Corinne M; Chang, Yuchiao; Regan, Susan et al. (2017) Non-Communicable Disease Preventive Screening by HIV Care Model. PLoS One 12:e0169246
Siedner, Mark J; Kim, June-Ho; Nakku, Ruth Sentongo et al. (2016) Persistent Immune Activation and Carotid Atherosclerosis in HIV-Infected Ugandans Receiving Antiretroviral Therapy. J Infect Dis 213:370-8
Regan, Susan; Meigs, James B; Grinspoon, Steven K et al. (2016) Determinants of Smoking and Quitting in HIV-Infected Individuals. PLoS One 11:e0153103

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