As HIV becomes a manageable chronic condition, coronary artery disease emerges as a leading cause of mortality, requiring new approaches to risk assessment and prevention.
Thanks to revolutionary advances in antiretroviral therapy (ART), what was once a fatal diagnosis has transformed into a manageable chronic condition for millions of people worldwide. Yet, this remarkable medical success has revealed an unexpected challenge: as people with HIV live longer, they are facing premature heart disease at rates significantly higher than the general population. In fact, coronary artery disease (CAD) has emerged as a leading cause of mortality among people living with HIV, creating an urgent need to understand this connection 1 .
"Men with long-term HIV infections had more plaque in their coronary arteries regardless of other risk factors, with a particularly concerning abundance of noncalcified plaque—the type most likely to rupture and cause heart attacks." 6
The relationship between HIV and heart disease is complex, woven from traditional risk factors like hypertension and unique virus-related elements including chronic inflammation and treatment side effects. This article explores a groundbreaking global systematic review that offers new insights into stratifying and managing CAD risk in HIV-positive individuals, providing both warning and hope for the medical community and affected patients alike 1 5 .
People with HIV face significantly higher rates of coronary artery disease
Multiple factors including chronic inflammation contribute to cardiovascular risk
Systematic analysis of 22 studies with over 100,000 participants
For people living with HIV, the risk of developing coronary artery disease stems from a perfect storm of traditional and HIV-specific factors that accelerate the process of atherosclerosis—the buildup of plaque in coronary arteries.
Many conventional cardiovascular risk factors appear with greater frequency in HIV-positive populations:
These all contribute significantly to CAD risk in this group .
To bring clarity to this complex landscape, researchers recently conducted a comprehensive global systematic review analyzing data from 22 studies involving 103,370 participants across multiple continents. This review applied sophisticated epidemiological frameworks to classify CAD risk factors based on their predictive strength and causal relevance 1 5 .
Comprehensive search across six major databases from inception to January 2024
Epidemiological triangle, Bradford Hill's criteria, Rothman's causal pie model, and Nweke's cumulative risk index 5
Two independent reviewers screened studies, extracted data, and performed narrative synthesis and meta-analysis
| Risk Class | Causality Index | Risk Factors | Odds Ratio | Rw Value |
|---|---|---|---|---|
| First-Class | 7-10 | Hypertension | 4.9 | 4.5 |
| Advanced Age (≥50) | 4.96 | 3.58 | ||
| Dyslipidemia | 2.15 | 2.15 | ||
| Overweight/Obesity | 1.81 | 1.36 | ||
| Second-Class | 5-6 | Family History of CVD | 3.25 | 2.24 |
| Third-Class | ≤4 | Diabetes | 2.64 | 1.32 |
| Antiretroviral Therapy | 1.68 | 0.63 | ||
| Homosexuality | 1.82 | 0.62 |
Key Finding: Advanced age and hypertension were identified as "necessary causes" of CAD among people with HIV, meaning these factors were virtually indispensable for the disease to develop in this population 1 5 .
Included Factors: Age, Hypertension, Dyslipidemia, Family History of CVD, Diabetes, Overweight/Obesity
Cumulative Rw: 15.5
GTT Value: 4.05
Included Factors: Hypertension, Dyslipidemia, Obesity
Cumulative Rw: 8.01
GTT Value: 2.07
These models emphasize that association strength alone cannot determine CAD risk; instead, cumulative risk indexing provides a more robust framework for prediction and prevention 1 5 .
The path from HIV infection to coronary artery disease involves multiple interconnected biological pathways that extend beyond traditional understandings of heart disease.
Even when HIV is well-controlled with antiretroviral therapy, the virus creates a state of chronic immune activation and inflammation. Researchers at Johns Hopkins found that people living with HIV have elevated levels of inflammation that predict future adverse cardiovascular events, even before detectable plaque forms in arteries 6 .
While antiretroviral therapy is lifesaving, some medication classes have been associated with metabolic complications that contribute to heart disease:
"The cardiovascular risks associated with uncontrolled HIV infection far exceed those associated with ART, making treatment essential, but the choice of regimen requires careful consideration of each patient's specific cardiovascular risk profile."
Understanding the relationship between HIV and coronary artery disease requires sophisticated research tools and methodologies. The systematic review employed rigorous approaches, while broader investigation in this field utilizes various specialized techniques.
| Method/Reagent | Primary Function | Research Application |
|---|---|---|
| Coronary CT Angiography | Visualizes coronary plaque | Identifying noncalcified plaque prevalent in HIV patients |
| Inflammatory Biomarkers (IL-6, hs-CRP) | Measure immune activation | Quantifying chronic inflammation levels |
| Immune Cell Assays (CD4 count, viral load) | Assess immune status | Correlating HIV disease control with CAD risk |
| Statistical Models (Cumulative Rw) | Stratify risk factors | Prioritizing clinical interventions |
| Protease Inhibitors | Suppress viral replication | Studying metabolic side effects on cardiovascular system |
| Integrase Inhibitors | Suppress viral replication | Investigating newer ART regimens with better cardiac profiles |
Coronary computed tomography angiography allows researchers to identify and characterize plaque without invasive procedures, leading to the critical discovery that people with HIV tend to have more noncalcified plaque—the type most vulnerable to rupture and cause heart attacks 6 .
The findings from this systematic review have direct, practical applications for improving care for people living with HIV.
Traditional cardiovascular risk calculators often underestimate risk in HIV-positive patients. The hierarchical risk classification offers clinicians more tailored tools.
The identification of hypertension and advanced age as "necessary causes" suggests that all HIV-positive patients over 50 with hypertension should receive comprehensive cardiovascular screening 1 5 .
First-line interventions: Aggressive management of hypertension and dyslipidemia
Secondary targets: Weight management and smoking cessation
HIV-specific considerations: Selecting ART with favorable metabolic profiles and ensuring viral suppression 1
The REPRIEVE trial demonstrated that statin therapy reduces cardiovascular events in people with HIV, offering a powerful prevention tool even for those with normal cholesterol levels but elevated inflammatory markers 3 .
Recent research has added another layer to this complex picture: SARS-CoV-2 infection appears to significantly increase cardiovascular risk in people with pre-existing CAD, with hospitalized COVID-19 patients showing higher rates of major adverse cardiovascular events up to four years post-infection 4 .
One Spanish study presented at the European AIDS Conference found that people with HIV who contracted COVID-19 had a 35% higher risk of major cardiovascular events in the following year, specifically noting increased rates of thrombosis, heart failure, and other heart disorders 7 .
The global systematic review on characterization and risk stratification of coronary artery disease in people living with HIV represents a significant step forward in addressing this critical comorbidity.
"The future of HIV care must encompass both viral control and cardiovascular protection, addressing the whole patient rather than just the virus."
As research continues to refine our understanding, the integration of routine cardiovascular screening and prevention into standard HIV care will be essential. The goal is clear: to ensure that people living with HIV not only live longer lives, but healthier ones, with hearts protected through knowledge, vigilance, and targeted intervention.