Asymptomatic Obstructive Coronary Artery Disease (CAD) in Suppressed HIV-infected Patients ≥ 45 Years and 2 or More CV Risk Factors. Associations With Persistent Immune Activation and Microbial Translocation

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. Coronary artery disease (CAD), especially myocardial infarction (MI), is the leading cause of death in Europe [Eurostat 2013]. Cardiovascular deaths are responsible for 8% of deaths among HIV-infected patients in France and for 15% of deaths among HIV-infected patients in US [Lewden C JAIDS 08, Palella FJ JAIDS 06]. Multiple cohort studies have shown that HIV-infected patients are at a higher risk of myocardial infarction than the general population [Triant VA J Clin Endocrinol 07, Freiberg MS JAMA Intern Med 13] and there is some evidence that HIV-infected patients have a 38% greater risk of mortality from MI than controls [Pearce D AM J Cardiol 12].

Several tools for cardiovascular risk stratification are available but current risk scores seem to underestimate this risk in HIV-infected patients. Indeed, a significant proportion of cardiovascular events occur in subjects with none or few risk factors. A European study comparing first episode of MI among HIV-infected patients with uninfected controls showed that 40% had none or only one traditional cardiovascular risk factor [Boccara F Eur Heart J 11]. Another study in general population demonstrates that almost 50% of patients with a MI had no previous history of coronary symptoms [Tunstall-Pedoe H Circulation 96].

The true prevalence of CAD in asymptomatic HIV-infected patients is unknown. Older studies performed in tissue samples from deceased patients demonstrated 3-times greater odds of having obstructive CAD in HIV-infected patients compared with non-infected controls after controlling for age and sex [Micheletti RG Cardiovasc Pathol 09]. A recent meta-analysis shows that the prevalence of coronary stenosis and calcified coronary plaques is similar in comparison with non-HIV age and sex-matched controls but HIV-infected patients have a 3-fold higher prevalence of non-calcified coronary plaques [D'Ascenzo Atherosclerosis 15].

CAD severity detected by coronary computed tomographic angiography (CCTA) is associated with cardiac death or MI and all-cause mortality [Habib F Int J Cardiol 12]. 64 slice or greater CCTA is reported to have a sensitivity of 93 to 97% and specificity of 80 to 90% compared to standard coronary angiography [Fihn SD J Am Coll Cardiol 12]. There is a high correlation between CCTA and invasive coronary angiography in the determination of CAD extent and severity [Miller JM N Engl J Med 08].

Whether routine CCTA screening in high-risk populations can effect changes in treatment (such as pre-emptive coronary revascularization or more aggressive medical therapy) remains unproven. The 2013 AHA guidelines about stable ischemic heart disease states that either stress test or anatomic imaging in higher-risk individuals may be appropriate [J Am Coll Cardiol 14].