Background: Numerous reports suggest an increased rate of ischemic heart disease (IHD) among human immunodeficiency virus (HIV) infected patients. Several data showed that endothelial dysfunction is a major mechanism in the development of coronary atherosclerosis in non-HIV infected patients. Some regulators of coronary blood flow, as potassium channels (i.e. KATP and Kv) and eNOS have been showed as involved in IHD susceptibility.
Aim: In HIV patients on HAART and an apparently low risk for cardiovascular events we aim to assess coronary anatomy, coronary plaque morphology and microvascular integrity correlating it with the presence of some genetic variants encoding for coronary ion channels.
Methods: We will enrol 100 HIV-infected patients on HAART with Framingham risk score 50% stenosis (expected almost 30 subjects) will undergo coronary angiography, virtual histology-intravascular ultrasound (VH-IVUS) and Doppler-flow wire in order to identified plaque components as dense calcium, necrotic core, fibro-fatty tissue, or fibrous tissue, with the cross-sectional area and percentage of total plaque area reported for each component. Moreover, microvascular function will be assessed by measuring coronary flow velocity reserve (CFR) evaluating both endothelium-dependent and non-endothelium-dependent microvascular function. Patients from group A and B will undergo genetic analysis for polymorphisms of genes encoding for coronary ion channels (i.e. KATP and Kv) and eNOS by PCR.
Expected results: Using multiparametric approach, we expected to observe different pathophysiological mechanisms for HIV-related IHD with a peculiar genetic susceptibility.
To our knowledge, the present project will be the first evaluating HIV infected patients in therapy with HAART by in-vivo coronary anatomy and function and by genetic profile. In fact, coronary plaques composition will be assessed by VH-IVUS and the coronary microcirculation vasomotility by CFR. Moreover, genetic polymorphisms encoding for coronary ion channels will be evaluated by DNA sequencing. The strict selection of the studied population will be another strength of the present project. In particular, all enrolled patients will be at low cardiovascular risk, according to their calculated Framingham risk score, confirmed by an echocardiographic stress-test negative for inducible ischemia. In HIV+ patients we will assess presence and composition of coronary plaques; coronary flow reserve analysis will study the microcirculation including endothelial and non-endothelial function.
As previously reported, several observational studies showed that HIV infected patients on HAART are at increased cardiovascular risk. These observations were confirmed by several studies using different imaging modalities, such as carotid ultrasound, coronary computed tomography angiography, brachial artery ultrasound, 18-fluorodeoxyglucose PET. However, the pathophysiologic mechanism of the increased cardiovascular morbidity and mortality is not yet totally understood. This project has the potentiality to focus on the pathophysiology of ischemic heart diseaes in HIV+ patients. In fact, as demonstrated by the PROSPECT Trial, the largest prospective clinical study to assess the ability of VH-IVUS to identify atherosclerotic plaque at risk of ulceration, a plaque burden characterized by a necrotic core represents the finger print of unstable plaques and a frequent cause of acute coronary syndrome.
In addition, endothelial dysfunction precedes the development of atherosclerotic plaque and its clinical syndromes. Patients with cardiovascular risk factors and with coronary artery disease (CAD) typically present endothelial dysfunction. We hypothesize that this pathophysiologic process could be different in HIV population.
We consider that the different methodological approaches, in particular in term of diverse approaches, including genetic analysis and different imaging modalities used to investigate coronary anatomy and function, could be able to obtain interesting results on this setting.