Treatment Issues: Newsletter of Current Issues in HIV/AIDS - Volume 21, Number 2, April - June 2007
By Richard Havlik, MD

In the past 10 years, mortality and complication rates for HIV/AIDS have fallen because of the use of highly active antiretroviral therapy (HAART). This experience is a remarkable success story. As a result, many now consider living with HIV a chronic disease. The average age of living HIV/AIDS patients is increasing. This increasing age in HIV patients will raise the risk of cardiovascular disease, which increases with age. Each year, heart disease kills more Americans than cancer. Diseases of the heart alone caused 30% of all deaths, with other diseases of the cardiovascular system causing substantial further death and disability, including stroke. There is increased emphasis on preventing cardiovascular disease by modifying risk factors, such as diet, exercise, and smoking.

Heart Attack and HIV
A possible increase in myocardial infarction (MI) or simply a heart attack in HIV/AIDS patients was first identified in a large study of a predominantly European population (DAD Study Group, 2003). The risk was modest, because the average age was relatively low; the actual number of cases was small. Some studies from the United States did confirm the increase (Currier et al, 2003), while others did not (Bozzette et al, 2003). A few smaller clinical studies of atherosclerosis showed increased frequency of MI with treatment, especially protease inhibitors (Currier, 2002). Other studies identified increased coronary heart disease in untreated HIV/AIDS patients (Klein et al, 2002). Last year the results of a clinical trial evaluation of intermittent HAART therapy (SMART), based on treatment when CD4 cells dropped below a target value versus continuous treatment to minimize exposure time to HAART, were reported (SMART Study Group, 2006). It was hypothesized that cardiovascular complications would be lower in the intermittently treated group. In fact, the study was stopped early because a significantly higher number of individuals developed cardiovascular disease in the intermittent subgroup. The result suggests that rather than treatment, it may be HIV itself that could be contributing to increased cardiovascular risk. However, another recent report from a large observational study, suggests that increased exposure to protease inhibitors is associated with an increase in MI's (DAD Study Group, 2007). Although the scientific explanation for these observations still needs clarification, the immediate conclusion is that more medical attention must be paid to increased cardiovascular risk in current HIV/AIDS patients, whether HAART-treated or not. Prescribing practices by staff for cardiac risk in HIV/AIDS patients will require an array of intensive medical approaches (Stein, 2005).

HIV, Age, and Gender
Obviously, we cannot halt the aging process. We need to recognize the fact that older age and being a male increases cardiac risk. The good news is that cumulative mortality rates for HIV patients exposed to HAART are not significantly different between those older than 50 years and less than 50 years, so there is not an added burden from a treatment differential (Perez, 2003). Results from the DAD Study cohort suggest that for every five-year increment of age, cardiac risk increases about 40%. (DAD Study Group, 2003). The risk for men is about twice that for pre-menopausal women. After menopause the risk of cardiovascular disease increases substantially for older women, reaching the risk of men at approximately age 75. As treated, HIV-positive men and women live longer, their risk of HIV-related death will decrease and their cardiovascular risk will increase. Smoking, HIV, and Coronary Heart Disease Smoking is a major risk factor for coronary heart disease (CHD) as well as cancer and lung disease. Smokers incur about a 1.5-fold increased risk for cardiac disease (Wilson et al, 1998). In the DAD study the risk was twofold (DAD Study Group, 2003). It is significant to note that in the ACRIA ROAH study the frequency of smoking among HIV patients over 50 years of age is very high, with about 60% being current smokers. If this high level is reflected in future studies of older HIV populations, it represents a major risk factor for age-related chronic diseases. Of all the cardiovascular risk factors, smoking is the most potent and yet has the most potential to result in immediate risk reduction with cessation.

Hypertension and HIV
The adverse effects of elevated blood pressure are well known in general populations but less well appreciated in HIV patients. Hypertension is usually defined as a diastolic BP of 90 mm Hg or higher or an SBP of 140 mm Hg or higher. The frequency of hypertension is much more common in African-Americans and persons at older ages. HIV/AIDS and its treatment are probably not directly related to elevated BP (Friis-Moller et al, 2003), but elevated BP has been seen in some HIV patients with lipodystrophy when compared to other HIV patients. This finding might be related to a possible association with the dyslipidemic syndrome in HIV patients (Sattler et al, 2001). Although important risk factors, lipids are not discussed further. Treatment studies show that the avoidance of calcium channel blocker drugs in HIV patients is recommended (Bartlett, 2005). The detection and control of elevated SBP in HIV patients is well justified and cost effective.

Diabetes and HIV
Another important cardiovascular risk factor is diabetes mellitus, usually described as Type 2 (Type 1 occurs early in life and has a different cause). For the aging HIV patient there is the added problem that treatment with protease inhibitors is associated with increased glucose intolerance. This treatment effect increases the likelihood of developing diabetes. If possible, a switch in HIV regimen can be considered. With a successful HAART regimen, however, it may be more appropriate to continue the regimen and use other means to control the elevated blood sugar, such as dietary changes, weight reduction, and exercise. Even small amounts of physical activity can have beneficial effects. Fortunately, there are oral medications or insulin that can be taken safely with HIV drugs to achieve maximal lowering of blood sugar levels and presumably reduced cardiovascular risk. Treatment regimens must be consistent with the dual goal of maintaining optimal treatment of the HIV infection. Good adherence to the HAART regimen cannot be sacrificed because of the additional pills or other treatments being prescribed for lowering cardiac risk. Fortunately, the combination of the two approaches can be achieved with moderate effort and has the potential to provide a longer and healthier life for the HIV patient.

References

Bartlett JG. The Johns Hopkins Hospital 2005–2006 Guide to Medical Care of patients with HIV Infection. Lippincott, Philadelphia, 12th edition, 2005, p. 96.

Bozzette et al. Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection. N Engl J Med. 2003 Feb 20;348(8):702-10.

Currier JS. Cardiovascular risk associated with HIV therapy. J Acquir Immune Defic Syndr. 2002 Sep 1;31 Suppl 1:S16-23; discussion S24-5.

Currier JS et al. Coronary heart disease in HIV-infected individuals. J Acquir Immune Defic Syndr. 2003 Aug 1;33(4):506-12.

The Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study Group: Combination therapy and the risk of myocardial infarction. N Engl J Med. 2003 Nov 20;349(21):1993-2003.

The DAD Study Group. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007 Apr 26;356(17):1723-35.

Friis-Moller N et al. Cardiovascular disease risk factors in HIV patients—association with antiretroviral therapy. AIDS. 2003 May 23;17(8):1179-93.

Klein D et al. Do protease inhibitors increase the risk for coronary heart disease in patients with HIV-1 infection? J Acquir Immune Defic Syndr. 2002 Aug 15;30(5):471-7.

Perez JL, Moore RD. Greater effect of highly active antiretroviral therapy on survival in people aged >50 years compared with younger people in an urban observational cohort. Clin Infect Dis. 2003 Jan 15;36(2):212-8. Epub 2003 Jan 6.

Sattler FR et al. Elevatated blood pressure in subjects with lipodystrophy. AIDS. 2001 Oct 19;15(15):2001-10.

Stein JH. Managing cardiovascular risk in patients with HIV infection. J Acquir Immune Defic Syndr. 2005 Feb 1;38(2):115-23.

Wilson PWF et al. Prediction of coronary heart disease using risk factor categories. Circulation. 1998 May 12;97(18):1837-47.

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