Exploring Global Connections

For Answers in the Bronx, a Look at Rwanda

As antiretroviral therapy (ART) becomes more available and people with HIV live longer, the combination of HIV and cardiovascular disease has created a health crisis that is projected to surpass infectious disease as the leading cause of mortality in Sub-Saharan Africa. Recognizing that better understanding is needed of how HIV/AIDS and ART affect cardiovascular disease, Dr. Elizabeth Kiefer, assistant professor of medicine, is exploring the relationship between risk of cardiovascular disease and ART in HIV-infected Rwandan women, supported by an American Heart Association Clinical Research Program Award. As a general internist with an interest in international health, she is working to identify patients in Rwanda at risk for heart attack and stroke so that physicians can recognize and treat cardiovascular disease before its devastating consequences can occur.

Dr. Elizabeth Kiefer
Dr. Elizabeth Kiefer
Just as Dr. Kiefer’s clinical practice in the Bronx helps to inform her research abroad, she also hopes the knowledge gained from her global investigation will aid the patients she treats in New York. "As antiretroviral therapy becomes more available in Africa and people live longer with HIV, they are dealing with some of the same issues that we see in this country, like hypertension, cardiovascular disease, and diabetes," she said. "My research in Rwanda allows me to merge two interests: the patients with cardiovascular disease I care for every day and the serious health issues emerging in the developing world."

Sub-Saharan Africa accounts for 67 percent of the world’s HIV infection, with 60 percent of the estimated HIV infections occurring in women. Cardiovascular disease is rapidly climbing in this region as a result of urbanization and shifting lifestyle factors such as increasingly sedentary jobs and exposure to different diets. While the correlation between HIV and higher risk of cardiovascular disease is still unclear, evidence is emerging that HIV infection and ART may create a high inflammatory state that might increase cardiovascular disease risk. Compounding things further is the specter of malnutrition, which also may cause inflammation and is a prevalent issue in developing countries. Nearly one-quarter of the individuals who Dr. Kiefer is studying have a body mass index under 18.5 – a level that may indicate malnutrition.

Closer to home, about two percent of Bronx residents are HIV positive – the second highest prevalence in the nation. A recent study among patients seen at the Montefiore AIDS Center’s Center for Positive Living/Infectious Diseases Clinic, conducted by internal medicine resident Dr. Yehuda Cohen, found that diagnoses of acute myocardial infarction (heart attack) have been increasing, mirroring trends seen nationwide. Contributors to this trend include high rates of cardiovascular disease risk factors (such as smoking, hypertension, diabetes, obesity and elevated lipid levels) and living longer with HIV.

"We look forward to the information that Dr. Kiefer’s study will reveal about cardiovascular disease risk factors in people with HIV, especially more information on the role of HIV itself and resultant inflammation," said Dr. Barry Zingman, director of the AIDS Center.

To better understand the relationship between risk of cardiovascular disease and ART, Dr. Kiefer will measure C-reactive protein (CRP), which is released into the bloodstream during inflammation and thought to be a predictor of cardiovascular disease. CRP levels are elevated in HIV-infected individuals, and independently predict HIV mortality, HIV disease progression, and risk for AIDS and non-AIDS events.

doctor and patient in rowanda
Samples for Dr. Kiefer’s research will be drawn from those collected through the Rwanda Women’s Interassociation Study and Assessment
While ART has been shown to decrease the risk of death from cardiovascular disease, possibly as a result of decreased inflammation, it remains unclear how CRP levels change with ART use in HIV-infected individuals, or whether they are related to cardiovascular disease risk factors before or after ART. Dr. Kiefer will use the high-sensitivity CRP test, a relatively inexpensive blood test that costs between $10 and $120, to evaluate the relationship between CRP and cardiovascular disease risk factors in both HIV-infected and uninfected women. She also will use the test to examine the change in CRP and its relationship to traditional cardiovascular risk factors (such as body mass index and cholesterol) in HIV-infected women before and after ART.

In the course of her study, Dr. Kiefer will measure CRP from collected, stored serum obtained through the Rwanda Women’s Interassociation Study and Assessment (RWISA), a longitudinal cohort study investigating the effectiveness and toxicity of antiretroviral therapy and the effect of traumatic rape, HIV infection and immune suppression on multiple clinical outcomes in Rwandan women. Developed by her mentor, Dr. Kathryn Anastos, professor of medicine and of epidemiology & population health, and initiated in 2005, RWISA has enrolled and followed 1,000 women with and without HIV, 50 percent of who were survivors of rape during the country’s 1994 genocide.

"The large majority – about 89 percent – of the HIV-positive women in the RWISA cohort now receive ART, so Dr. Kiefer's new studies will address extremely important clinical and public health questions for Africans living with HIV," noted Dr. Anastos.  "Very little is known about the interactions of inflammation, malnutrition, and HIV disease or treatment, and Dr. Kiefer’s work also can help elucidate the pathophysiology of these processes."

"The work that we’re doing in Rwanda is one piece of the puzzle of what happens when people start antiretroviral therapy," said Dr. Kiefer. "We hope it will be helpful in determining what happens to peoples’ cardiovascular risk profiles as they stay longer on ART."

Posted on: Thursday, June 30, 2011