## 4 Ischemic Heart Disease
### Mechanisms of IHD  
Atherosclerosis remains the main cause of ischemic heart disease (IHD). It is well-known that atherosclerosis is a chronic inflammatory, active process characterized by the development of arterial atherosclerotic plaques. A key contributor to this condition is hypercholesterolemia, where high levels of low-density lipoprotein (LDL) cholesterol initiate endothelial dysfunction, promote lipid accumulation, and lead to the buildup of macrophage foam cells in the subendothelial space. Research has shown a negative association between antiretroviral therapy and early-onset atherosclerosis [29]. Seminari and colleagues found that HIV patients receiving protease inhibitors had higher triglyceride and apoB levels. Additionally, these patients exhibited significantly increased carotid intima-media thickening (IMT) compared to untreated or HIV-negative individuals [29]. The introduction of HAART led to an increased incidence of lipodystrophy syndrome, a condition characterized by hyperlipidemia and impaired glucose tolerance--both well known risk factors for coronary artery disease in both HIV-positive and HIV-negative individual [30; 31; 32]. Table 1 lists the most common adverse effects of HIV medications. However, these findings were not confirmed in a systematic review and meta-analysis of observational studies conducted by Hulten et al. Their analysis of 26 studies focused on subclinical atherosclerotic lesions assessed via carotid ultrasound or coronary artery calcium scores in patients receiving protease inhibitors versus non-recipients. They concluded that PI exposure did not significantly impact carotid intima-media thickness (IMT) or coronary calcium scores [42]. However, for patients interrupting treatment, there was a 70% increased hazard of cardiovascular events [43]. A separate large prospective study spanning seven years investigated the link between HIV infection and the progression of subclinical atherosclerosis. After adjusting for demographic, behavioral, and cardiometabolic risk factors, the study found that HIV-infected individuals had a 1.6-fold greater risk of developing new plaques compared to uninfected individuals. Notably, this increased risk was observed even in those with optimal viral suppression, suggesting the involvement of additional complex mechanisms [44]. Another study found that young, asymptomatic men with long-standing HIV infection had a twofold higher prevalence and burden of coronary atherosclerosis (24% vs. 12%) compared to non-infected individuals, as assessed by coronary computed tomography [45]. Moreover, a higher prevalence of non-calcific coronary plaques in HIV-positive patients with low CD4+ T-cell counts was reported, suggesting the role of systemic inflammation and immune activation [46]. Fluorodeoxyglucose positron emission tomography (18F-FDG-PET) imaging further supported these findings by revealing increased arterial inflammation in HIV-positive individuals. Additionally, plasma-soluble CD163 (sCD163), a monocyte/macrophage-specific activation marker, correlated with 18F-FDG-PET data, indicating a higher presence of inflammatory macrophages in the ascending aortas of HIV-infected individuals [47].