Low CD4 Count Linked to Higher Heart Attack Risk With HIV

A latest CD4 count below 200 raised the risk of acute myocardial infarction (MI, or heart attack) in a large study of people with HIV, regardless of what other heart risk factors those people had.¹ A viral load above 100,000 copies also made a heart attack more likely in this study, but that higher risk was not independent of a low CD4 count and other heart risk factors.

Heart disease has emerged as a growing concern in HIV-positive people now living longer thanks to antiretroviral therapy. Researchers are trying to sort out the specific risk factors for heart disease in general -- and heart attacks in particular -- in people with HIV. These risk factors fall into three groups: (1) traditional risk factors such as high blood pressure and diabetes, (2) HIV itself, and (3) individual antiretrovirals and groups of antiretrovirals.

Two earlier studies found evidence that a low CD4 count makes heart disease more likely in people with HIV,^2,3 but those studies did not look specifically at acute MI (heart attacks). The new study weighed the impact of CD4 count, viral load, antiretroviral therapy, and traditional risk factors on heart attack risk in a big group of HIV-positive people in a large healthcare system in Boston.

• How the study worked. Researchers at two Boston medical centers that care for many HIV-positive people searched through electronic medical records for everyone with HIV who made at least two hospital or clinic visits between December 1998 and February 2008. They determined how many people had an acute MI (heart attack) during that period, and they noted the latest CD4 count and viral load recorded before the heart attack or the last CD4 count and viral load during the study period.

  The researchers also used medical records to note each person's antiretroviral use and standard heart disease risk factors, including high blood pressure (hypertension), diabetes, abnormal lipids (cholesterol and triglycerides), chronic kidney disease, and smoking. They used accepted statistical methods to determine the impact of CD4 count, viral load, antiretrovirals, and traditional heart disease risk factors on the risk of heart attacks.

• What the study found. Of the 6517 HIV-positive people studied, 273 (4%) had a heart attack during the study period. The study group included 1993 women (31%), and women accounted for 85 of the heart attacks (31%). Whites made up 55% of the study group, blacks 24%, and Hispanics 18%; but blacks acounted for 35% of the heart attacks.

  In the whole study group, 26% had high blood pressure (including 57% with an acute MI), 16% had diabetes (28% with an MI), 29% had abnormal lipids (33% with an MI), 50% smoked (55% with an MI), 7% had chronic kidney disease (14% with an MI), and 10% had coronary heart disease (35% with an MI). Rates of all of these risk factors were significantly higher in people who had an MI than in those who did not.

  Among people who had a heart attack, median time from most recent CD4 count and viral load to the heart attack was 55 days. Thus, for most people with an MI, the CD4 count and viral load recorded in the study were likely to be close to the measurements at the time of the heart attack. Half of the study group was taking antiretroviral therapy, including 155 people (57%) with a heart attack. There were 1969 people (30%) taking a protease inhibitor, including 84 (31%) with a heart attack.

  The study group had been infected with HIV for a median of 5.1 years and had a median of 42 clinic or hospital visits. CD4 counts were available for 3887 study participants (60%) and viral loads for 3424 people (52.5%). Among people with a CD4 count available, 1018 (26%) had a count under 200, including 79 (8% of 1018) with an MI. Among people with a viral load available, 342 (10%) had a load above 100,000 copies, including 22 (6% of 342) with an MI. Rates of low CD4 counts or high viral loads were significantly higher in people who had a heart attack than in those who did not.

  Figure 1. In two separate statistical analyses, a low CD4 count raised the risk of a heart attack and a high CD4 count lowered the risk -- regardless of what other heart risk factors a person had. Left, a latest CD4 count below 200 was associated with an increased risk of acute MI: odds ratio 1.74, 95% confidence interval 1.07 to 2.81, in an analysis adjusted for CD4 count, viral load, age, gender, race, hypertension, diabetes, abnormal lipids, chronic kidney disease, smoking, years since first antiretroviral use, and antiretroviral medications. Right, in an analysis considering both CD4 count and viral load, every 50-cell higher latest CD4 count was associated with a 7% decreased risk of acute MI: odds ratio 0.93, 95% confidence interval 0.89 to 0.97.

  The researchers conducted a statistical analysis that considered many heart attack risk factors, including CD4 count, viral load, age, gender, race, hypertension, diabetes, abnormal lipids, chronic kidney disease, smoking, years since first antiretroviral therapy, and individual antiretrovirals. A latest CD4 count below 200 raised the heart attack risk almost 75%, regardless of what other heart risk factors a person had (including a high viral load) (Figure 1). A latest viral load above 100,000 copies raised the heart attack risk about 60%, but this higher risk was not independent of other factors in the analysis, including a low CD4 count.

  Four other factors raised the heart attack risk independently of all other risk factors -- older age, male gender, nonwhite race, and high blood pressure. Of these four factors, only high blood pressure had a greater impact on heart attack risk than a CD4 count below 200.

  The researchers performed a separate statistical analysis in which they considered the impact of higher or lower CD4 count (in blocks of 50 cells) and higher or lower viral load (in 10-fold blocks). In this analysis, every 50-cell higher CD4 count was associated with a 7% lower risk of a heart attack, regardless of other risk factors including a high viral load. Again, a high viral load did not raise the heart attack risk independently of a low CD4 count.

  However, when the researchers eliminated CD4 count from this analysis, a viral load above 100,000 copies more than doubled the risk of a heart attack, regardless of other risk factors (except CD4 count). In this analysis:

  1. Every 10-times higher viral load raised the heart attack risk almost 25%.
  2. Every 10-times higher peak viral load raised the risk almost 25%.
  3. A viral load under 400 copies lowered the MI risk 40%.
• What the results mean for you. This large, well-designed study found strong evidence that a CD4 count below 200 raises the risk of heart attacks in people with HIV -- regardless of what other heart risk factors a person may have. Other risk factors that had this independent impact on heart attack risk were older age, male gender, nonwhite race, and high blood pressure. Of these four traditional risk factors, only high blood pressure raised the heart attack risk more than a CD4 count under 200.

  A viral load above 100,000 copies made heart attacks more likely in this study group, and a viral load below 400 copies made heart attacks less likely. But these associations between viral load and heart attacks were not independent of a low CD4 count.

  Some of the heart attack risk factors identified in this study -- gender, age, and race -- cannot be changed. But CD4 count, viral load, and high blood pressure respond to drug therapy. High blood pressure can also be controlled by lifestyle changes, such as stopping certain illegal drugs (cocaine, amphetamines), being physically active, controlling weight, stopping smoking, and limiting alcohol drinking.⁴ (See Table 1.) People with HIV should work with their doctors to lower high blood pressure and to get care for other problems that may raise the risk of a heart attack (such as diabetes, kidney disease, and high cholesterol or triglycerides).

  Smoking did not emerge as an independent heart attack risk factor in this study, possibly because smoking habits were not adequately recorded in the medical records used in this analysis. But countless other studies in people with and without HIV confirm that smoking is bad for the heart, lungs, and general health. People who smoke should get help trying to stop.

  The CD4 count and viral load findings in this study add to the evidence that controlling HIV infection through antiretroviral therapy may lower the risk of heart disease. Although individual antiretrovirals or groups of antiretrovirals may add to the risk of heart disease, the overall impact of antiretroviral therapy seems to help lower that risk. As the researchers who ran this study write, "treatment of HIV infection to improve immunologic function [CD4 count] is likely to be an important component of cardiovascular prevention in patients with HIV."

References

1. Triant VA, Regan S, Lee H, Sax PE, Meigs JB, Grinspoon SK. Association of immunologic and virologic factors with myocardial infarction rates in a US healthcare system. J Acquir Immune Defic Syndr. 2010;55:615-619.
2. van Lelyveld S, Gras L, Kesselring A, et al. Incomplete immune recovery on HAART is associated with significantly more cardiovascular events and a trend towards more non-AIDS-related malignancies in Dutch ATHENA cohort. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 714. www.retroconference.org/2010/PDFs/714.pdf. Accessed December 27, 2010.
3. Lichtenstein KA, Armon C, Buchacz K, et al. Low CD4+ T cell count is a risk factor for cardiovascular disease events in the HIV Outpatient Study. Clin Infect Dis. 2010;51:435-447.
4. Mayo Clinic. High blood pressure (hypertension). www.mayoclinic.com/health/high-blood-pressure/DS00100. Accessed December 27, 2010.