HIV and Cardiovascular Disease: An Under-recognized, Growing Problem

As if people with HIV/AIDS didn’t have enough to contend with, a growing body of research points to a significantly increased risk of cardiovascular disease (CVD). One of the most recent studies of HIV and CVD surprised even its investigators with its outcome: People with HIV have a rate of sudden cardiac death (SCD) 4.5 times higher than that of the general public.¹

The finding came from an analysis of the first-ever study to investigate the causes of SCD, which kills an estimated 290,000 people a year in the United States. Zian H. Tseng, MD, an associate professor of medicine in residence at the University of California, San Francisco (UCSF), received a $1.9 million National Institutes of Health grant to review all such deaths in San Francisco. The goal is to understand who is at highest risk for the disease and when medical intervention such as defibrillators are most effective. In looking at the data, he noticed that a disproportionately high number of those who died from SCD had HIV. Could there be a connection?

He posed that question to one of the few experts in this country who specializes in CVD in HIV-infected patients, Priscilla Hsue, MD, also at UCSF. Together, the two analyzed the data more thoroughly and found that, after AIDS, SCD was the most common cause of death in this population. It accounted for an estimated 13% of all causes of deaths among HIV-infected individuals in the study. SCD was responsible for fully 86% of all cardiac deaths in this population, compared to about half in the general population. These individuals were also younger than the typical person who dies from SCD, and more likely to have better than average control of their disease. Half had undetectable viral levels, although most had more CVD risk factors than those who died of AIDS.

When the researchers looked back at the medical records of these patients, they found that only between a third and a half had either documented heart disease or other SCD risk factors, such as chest pain, shortness of breath, palpitations, or fainting. Tseng speculates that many HIV-infected patients don’t bring up these symptoms with their doctors-nor do their doctors ask about them-because both are focused on the infection and its treatment.

There are several potential explanations for the increased risk of SCD in this population, said Tseng. For instance, certain anti-retroviral medications increase acute QT interval, which can lead to sudden arrhythmia. In addition, he said, animal and laboratory studies find that the virus itself can affect the electrical properties of the heart, “so patients with HIV may also be more prone to arrhythmias.”

He and Hsue are currently working on a prospective study to elucidate the risk factors for SCD in the HIV-infected population.

Cardiovascular Risks Beyond Sudden Cardiac Death

Sudden cardiac death is only one cardiovascular condition for which HIV-infected people have higher risk. Overall, CVD is responsible for approximately 10% of deaths among HIV-positive patients, a percentage likely to grow as more patients live longer with the disease.^2,3 HIV-positive status is also independently associated with an increased risk for clinical heart failure, cardiomyopathies, and premature atherosclerosis due, in part, to increased levels of systemic inflammation.⁴ Treating the infection itself can mitigate some of these risk factors, although current HIV treatment regimens, particularly the older ART drugs, can also lead to a more atherogenic lipid profile.^{2, 3, 5-7}

What’s more, HIV-infected individuals have higher rates of CVD risk factors, such as smoking, substance abuse, hypertension, and hyperglycemia, than those without the virus. They also tend to be insulin resistant.3 Yet it seems that doctors are less likely to identify or intervene about CVD risk factors in HIV-positive patients than they are for other kinds of patients. For instance, in one study of 593 HIV-positive patients, 43% of whom were active smokers, just 52% of the smokers said their healthcare practitioners had ever questioned them about tobacco use, and only 10% were referred to smoking cessation programs.⁸

In addition, lipid-lowering medications are underprescribed in the HIV population. One study found that just a third of those who experienced a myocardial infarction (MI) received lipid-lowering medications. And while 44.3% of those who didn’t experience an MI had some form of dyslipidemia, only 12% had been prescribed a lipid-lowering medication.9 Even with treatment, there is evidence that more than half of HIV-positive individuals with dyslipidemia do not reach recommended lipid goals. ^10-12

Some of this gap may be due to concomitant hepatitis C and contraindications for statin and fibrate treatment if patients are taking certain ART drugs.¹³

Cardiovascular risk in HIV-infected patients is “not on the radar screen” of primary care physicians and cardiologists, said Tseng. “But as these patients are living longer,” he added, “there has to be more aggressive primary prevention of heart disease and referral of anyone with heart disease symptoms to a cardiologist.”

References:

References

1. Tseng ZH, Secemsky EA, Dowdy D, et al. Sudden cardiac death in patients with human immunodeficiency virus infection. J Am Coll Cardiol. 2012;59(21):1891-1896.

2. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. 2011; http://aidsinfo.nih.gov/guidelines. Accessed January 31, 2011.

3. Petoumenos K, Worm SW. HIV infection, aging and cardiovascular disease: epidemiology and prevention. Sex Health. 2011;8(4):465-473.

4. Zanni MV, Grinspoon SK. HIV-Specific Immune Dysregulation and Atherosclerosis. Current HIV/AIDS reports. 2012.

5. Riddler SA, Smit E, Cole SR, et al. Impact of HIV infection and HAART on serum lipids in men. JAMA. 2003;289(22):2978-2982.

6. Arildsen H, Sorensen K, Ingerslev J, et al. Endothelial dysfunction, increased inflammation, and activated coagulation in HIV-infected patients improve after initiation of highly active antiretroviral therapy. HIV Med. 2012.

7. Dube MP, Cadden JJ. Lipid metabolism in treated HIV Infection. Best Pract Res Clin Endocrinol Metab. 2011;25(3):429-442.

8. Duval X, Baron G, Garelik D, et al. Living with HIV, antiretroviral treatment experience and tobacco smoking: results from a multisite cross-sectional study. Antivir Ther. 2008;13(3):389-397.

9. Worm SW, Sabin C, Weber R, et al. Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study. J Infect Dis. 2010;201(3):318-330.

10. Aberg JA, Zackin RA, Brobst SW, et al. A randomized trial of the efficacy and safety of fenofibrate versus pravastatin in HIV-infected subjects with lipid abnormalities: AIDS Clinical Trials Group Study 5087. AIDS Res Hum Retroviruses. 2005;21(9):757-767.

11. Normen L, Yip B, Montaner J, et al. Use of metabolic drugs and fish oil in HIV-positive patients with metabolic complications and associations with dyslipidaemia and treatment targets. HIV Med. 2007;8(6):346-356.

12. Visnegarwala F, Maldonado M, Sajja P, et al. Lipid lowering effects of statins and fibrates in the management of HIV dyslipidemias associated with antiretroviral therapy in HIV clinical practice. J Infect. 2004;49(4):283-290.

13. Sekhar RV, Balasubramanyam A. Treatment of dyslipidemia in HIV-infected patients. Expert Opin Pharmacother. 2010;11(11):1845-1854.