Coronary Atherosclerosis in HIV: an issue not solved yet

A hallmark of HIV infection is a state of global immune activation that is only partially restored under highly active antiretroviral therapy. Apart from immune deficiency and impaired immune restoration, this chronic immune activation may result via various mechanisms in non-AIDS linked morbidities such as atherosclerosis. In high-income countries, cardiovascular diseases are the second non-AIDS cause of death in people living with HIV and an important contributor to non-AIDS deaths in the developing world as its demonstrated from the increasing number of publications in the field coming from these countries.

It is widely accepted that people living with HIV have a 1.5 to 2 fold higher risk for coronary artery disease compared to uninfected controls and there is evidence that HIV-infected individuals have a 38% greater risk of mortality after a myocardial infarction.

There are several factors involved in this association, the increased prevalence of classical cardiovascular risk factors in HIV-infected patients, the unfavorable metabolic effects of some drugs, HIV itself, as well as persistent chronic inflammation and immune activation under antiretroviral treatment.

 

Despite this increased risk, there is no consensus on which is the best method to assess risk stratification in HIV-infected patients. Most of the cardiovascular risk equations are not validated in HIV individuals, underestimate the cardiovascular risk in this population, and there are no studies long enough to prospectively capture de novo cardiovascular events in HIV-infected patients.

The current revolution in cardiovascular imaging techniques, with more precise images and less radiation doses, could help identify those individuals at higher risk for acute coronary syndromes. Newer non-invasive technologies such as computed tomography coronary angiography (CTCA) allow a precise assessment of coronary anatomy, degree of stenosis and plaque characteristics.  Some studies in HIV-infected individuals using CTCA have demonstrated an increased prevalence of non-calcified plaques and signs of plaque instability (low attenuation, positive remodeling and spotty calcium) among HIV-infected patients in comparison with uninfected controls. Whether CTCA is valid for screening in asymptomatic high-risk individuals remains unproven.

 

These non-invasive techniques have also helped to explore in vivo associations between innate immunity and coronary atherosclerosis. There are data demonstrating that some activated subsets of monocytes (CD14+CD16+ and CD14^dim CD16+) are more frequent in HIV-infected patients in comparison with non-HIV infected controls. These monocyte subsets were associated with greater progression of coronary artery calcium, independently of traditional cardiovascular risk factors. This intermediate monocyte phenotype independently predicts higher risk for subsequent cardiovascular events (myocardial infarction, stroke or CVD death) in the general population.

 

Further studies are needed to early identify those HIV infected patients at higher risk for acute coronary syndromes.  The new cardiac image techniques offer an excellent opportunity to explore novel pathophysiological mechanisms in atherosclerosis and to discover new biomarkers that could help risk stratification decisions.