Heart Artery Walls Thicker in Young Adults With HIV Than in HIV-Negatives

Compared with healthy HIV-negative adults, young adults infected with HIV early in life had significantly thicker coronary artery walls -- a possible signal of future heart disease.¹ Statistical analysis determined that HIV infection itself -- as well as more cigarette smoking and high cholesterol -- raised the risk of greater coronary artery wall thickness regardless of a person's other major risk factors. HIV-positive people in this study were 15 to 29 years old.

Several studies,²⁻⁴ including the one reviewed in the preceding pages of this issue,⁵ show a higher risk of cardiovascular disease in people with HIV than in comparison groups of HIV-negative people. Higher heart disease risk in people with HIV may be partly explained by traditional risk factors (like smoking, high blood pressure, and diabetes), long-term use of certain antiretroviral drugs, and ongoing inflammation and activation of immune system cells caused by HIV itself.

Previous comparisons of heart disease rates in people with and without HIV involved middle-aged and older adults, many of them approaching the age when people in the general population start having heart disease. Few heart risk studies have involved young adults with HIV, some of whom have had HIV infection and taken antiretrovirals all their life.

Young HIV-positive adults differ from other heart-risk study groups in that they usually do not have traditional cardiovascular risk factors like diabetes and high blood pressure. So studying young adults with HIV infection would fill an important gap in HIV heart disease research and could tell HIV providers what heart risk factors are most important in this young group.

To address these issues, researchers at the National Institutes of Health (NIH) conducted this comparison of young adults with HIV and healthy young adults without HIV. Because advanced heart disease is rare in young adults, the researchers used two scans that create images of the heart to look for three signals of future heart disease -- heart artery wall thickness, plaque in the coronary arteries that supply blood to the heart, and fat around the heart.

How the Study Worked

Researchers invited young adults infected with HIV early in life to join the study between April 2010 and April 2013. These people could not have inherited cardiovascular disease or cardiovascular disease that developed in their lifetime. To create a comparison group, the NIH team invited HIV-negative people at least 18 years old to enter the study. People in the HIV-negative group could not have any significant medical conditions.

Everyone in the study had two types of heart scans. First, coronary CT angiography assessed (1) artery blockage, (2) number of plaques, and (3) epicardial fat, which is fat surrounding the heart. Second, a sophisticated magnetic resonance imaging (MRI) scan called TRAPD measured thickness of the right coronary artery wall (Figure 1).

Thickness was measured as the average distance between inner and outer boundaries of the right coronary artery wall. Coronary artery wall thickening is a possible early indicator or developing heart disease -- earlier than development of plaques in arteries.

All study participants had a detailed physical exam and review of their medical records to find measures of possible interest to this study. The researchers used accepted statistical methods to identify predictors of coronary artery wall thickness. This type of statistical analysis finds predictors that affect artery wall thickness regardless of whatever other possible predictors a person might have.

What the Study Found

The study involved 35 people with HIV (19 men, 16 women) and 11 healthy people without HIV (3 men, 8 women). Age ranged from 15 to 29 years in the HIV group and from 22 to 29 in the HIV-negative group. Average age was significantly younger in the HIV group, 22 versus 25 years. In the HIV group, 48% were black, 34% were white, and the others were Hispanic or mixed race. These proportions did not differ significantly in the HIV-negative comparison group.

Average blood pressure was higher among young adults with HIV than among those without HIV, but the HIV group had lower body mass index (weight) and lower total cholesterol than the HIV-negative group. A higher proportion of people with HIV ever smoked, and they smoked more pack-years than people without HIV, but these differences were not statistically significant.

Among the 35 people with HIV, 25 (71%) were taking antiretroviral therapy but only 15 (43%) had an undetectable viral load. CD4 count averaged 502 among people with HIV, though 5 (14%) had a CD4 count below 200.

Epicardial fat volume did not differ significantly between people with HIV and those without HIV. Coronary CT angiography detected plaque in 6 people (19%) with HIV and in 5 (45%) without HIV. No plaques in any study participant caused significant artery narrowing.

Right coronary artery wall thickness averaged 1.32 millimeters (mm) in young adults with HIV, which was significantly greater than the average thickness of 1.09 mm in young adults without HIV (Figure 2). Because the HIV group was younger than the HIV-negative group, the researchers ran a separate analysis excluding HIV-positive people younger than 20. In this analysis, coronary artery wall thickness was still significantly greater in the HIV group than in the comparison group (1.31 versus 1.09 mm).

Smoking pack-years (the amount people smoked) correlated positively with coronary artery wall thickness in people with HIV -- in other words, the more a person smoked, the thicker the artery wall. This correlation was not seen in people without HIV. Among all study participants, higher total cholesterol and higher low-density lipoprotein (LDL or "bad") cholesterol correlated with detection of coronary artery plaque.

Statistical analysis that considered the impact of age, gender, and body mass index on coronary artery wall thickness pinpointed three factors that predicted thicker walls regardless of these other risk factors:

• HIV infection

• More smoking pack-years

• Higher LDL cholesterol

An analysis focused only on people with HIV determined that a longer time taking antiretroviral therapy and a longer time taking any class of antiretroviral drugs correlated positively with coronary artery wall thickness. In other words, the longer a person took antiretrovirals, the thicker the coronary artery wall. But this correlation proved true for only one individual antiretroviral, stavudine (d4T), a drug no longer routinely prescribed in the United States or other Western countries. Among people with HIV, higher total cholesterol, LDL cholesterol, and triglycerides correlated with thicker coronary artery walls.

What the Results Mean for You

This is the first study to use the most up-to-date imaging scans to assess three indicators of potentially developing heart disease in young adults infected with HIV for most of their lives and in a comparison group of healthy HIV-negative young adults. The most important finding is that coronary artery wall thickness -- a possible heart danger signal -- was significantly greater in young adults with HIV than in those without HIV.

Statistical analysis that considered the impact of three heart risk factors -- age, body mass index, and gender -- identified HIV infection as an independent risk factor for thicker coronary artery walls. This analysis also pinpointed heavier cigarette smoking and higher LDL cholesterol ("bad cholesterol") as independent predictors of thicker coronary artery walls.

The study linked longer time taking antiretrovirals to greater coronary artery wall thickness. This finding does not mean youngsters and young adults should avoid antiretroviral therapy to lower their risk of heart disease. The benefits of antiretroviral therapy far outweigh the potential heart disease risk possibly related to thicker coronary arteries. In this study the only individual antiretroviral linked to thicker coronary artery walls was stavudine, an old drug no longer prescribed in the United States.

Indeed, some studies have linked antiretroviral therapy to better heart health. For example, people who stopped antiretroviral therapy in a trial of treatment interruptions had more than a 50% higher risk of cardiovascular disease than people who never stopped their antiretrovirals.⁶ US antiretroviral guidelines for adults and adolescents stress that HIV control with antiretroviral therapy may decrease the inflammation and immune system cell activation that contribute to higher rates of cardiovascular disease in people with HIV.⁷

Smoking and high LDL ("bad") cholesterol also emerged as predictors of thicker coronary artery walls in this study. Both of these risk factors can be changed -- smokers can stop smoking and people with high LDL cholesterol can lower their cholesterol through diet, exercise, or drug therapy, often with drugs called statins. (See "Statin Therapy Reduces Heart Artery Plaque Size and Number in People With HIV" and "Statin Therapy for 1 Year Linked to Gains in Bone Density With HIV" in this issue of HIV Treatment Alerts for findings on statin benefits in people with HIV.)

Abundant research links smoking to heart disease, lung cancer, other cancers, lung disease, and shorter life. Because HIV infection itself may raise the risk of heart disease, HIV-positive people should work hard to avoid or stop smoking. Quitting is not easy, but many longtime smokers do manage to stop. Your HIV provider can work with you to kick the smoking habit, perhaps by prescribing nicotine replacement therapy or other therapies, or perhaps through strategies like those described by the Centers for Disease Control and Prevention (visit the link at reference 8 below).

The researchers noted that their study is limited by its small size and by its snapshot design -- it measured coronary artery walls and looked for plaque and heart fat at a single point in time. This kind of study cannot prove that HIV or smoking or high LDL cholesterol caused artery wall thickening in these young adults. But the findings do show possible links between these factors and coronary artery wall thickness. For this reason, people infected with HIV and treated for HIV from early in life should be aware that they may run a higher risk of heart disease than people without HIV. Therefore they should work with their HIV provider to avoid or control heart disease risk factors throughout their life. Table 1 lists heart disease risk factors that can be avoided or reversed.

References

1. Abd-Elmoniem KZ, Unsal AB, Eshera S, et al. Increased coronary vessel wall thickness in HIV-infected young adults. Clin Infect Dis. 2014;59:1779-1786.

2. Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab. 2007;92:2506-2512.

3. Lang S, Mary-Krause M, Cotte L, et al. Increased risk of myocardial infarction in HIV-infected patients in France, relative to the general population. AIDS. 2010;24:1228-1230.

4. Islam FM, Wu J, Jansson J, Wilson DP. Relative risk of cardiovascular disease among people living with HIV: a systematic review and meta-analysis. HIV Med. 2012;13:453-468.

5. Paisible AL, Chang CCH, So-Armah KA, et al. HIV infection, cardiovascular disease risk factor profile, and risk for acute myocardial infarction. J Acquir Immune Defic Syndr. 2015;68:209-216.

6. Phillips AN, Carr A, Neuhaus J, et al. Interruption of antiretroviral therapy and risk of cardiovascular disease in persons with HIV-1 infection: exploratory analyses from the SMART trial. Antivir Ther. 2008;13:177-187.

7. Department of Health and Human Services. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. November 13, 2014.

8. Centers for Disease Control and Prevention. Smoking and tobacco use. How to quit.