Cardiovascular disease (CVD) stands as the world’s leading cause of both morbidity and mortality, with an increased threat to vulnerable populations such as people living with HIV (PWH). Despite the progress made in HIV treatment and care, those with HIV continue to experience a higher incidence of cardiovascular conditions, making CVD a key concern for healthcare providers globally. The development of prediction models, particularly atherosclerotic cardiovascular disease (ASCVD) risk scores, has been essential in estimating the risk of heart disease in individuals. However, the validity of these models in different populations—especially in the context of low- and middle-income countries (LMICs)—remains uncertain.
The Need for Accurate CVD Prediction Models in HIV
ASCVD risk models have become a cornerstone in preventive cardiology, helping clinicians estimate an individual’s risk of heart disease and tailor preventative strategies accordingly. These models take into account risk factors such as age, blood pressure, cholesterol levels, smoking status, and diabetes, among others. However, recent studies have cast doubt on whether these models provide accurate predictions for people living with HIV, who face unique health challenges, including chronic inflammation and a higher prevalence of coexisting conditions.
Further complicating matters is the issue of using these models in diverse regions, such as LMICs. The global distribution of HIV cases is unequal, with a higher proportion of people living with HIV residing in low-resource settings. Despite their growing importance, prediction models like ASCVD have not been rigorously tested for their applicability in these regions, where healthcare systems, risk factor profiles, and access to medical care differ considerably from those in high-income countries (HICs).
A Global Study to Address These Gaps
To address these critical concerns, a team of international researchers—including scientists from Massachusetts General Hospital (MGH), part of the Mass General Brigham health care system—set out to assess the performance of ASCVD risk models in global populations living with HIV. The study, published in Lancet HIV, offers a comprehensive evaluation of how well existing risk scores predict cardiovascular outcomes in individuals with HIV from varying economic and geographical backgrounds.
The researchers leveraged data from the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), a multinational cohort study involving participants from HICs, LMICs, and middle-income countries. The diverse nature of the REPRIEVE cohort allowed the researchers to examine cardiovascular outcomes in a way that reflects the global variability in HIV populations.
Key Findings: Underestimations and Overestimations
The findings from the REPRIEVE study reveal some striking results that highlight significant discrepancies between current risk models and the actual cardiovascular risk faced by PWH in different settings. One of the most important revelations was that, in high-income countries, the existing ASCVD risk models significantly underestimated the risk of cardiovascular events, particularly in women and Black men. This suggests that these subgroups of the population may not be receiving the necessary attention or appropriate preventive measures despite their heightened risk.
On the other hand, in LMICs, the ASCVD risk scores were found to overestimate cardiovascular risk for people living with HIV. This discrepancy likely stems from differences in lifestyle, risk factors, and access to healthcare in these regions. In many LMICs, PWH may not have the same level of medical surveillance and chronic disease management, and the use of risk models originally designed for high-resource settings may not accurately capture the dynamics of cardiovascular risk in these populations.
The Importance of Tailored Risk Models for PWH
These findings underscore the urgent need for more refined and region-specific cardiovascular risk models that are tailored to the unique health profiles of people living with HIV. As Dr. Patrice Desvigne-Nickens, a medical officer at the National Heart, Lung, and Blood Institute (NHLBI), pointed out, accurately assessing cardiovascular risk in diverse subgroups requires careful study design, targeted outreach, and the inclusion of a global population. This study’s cross-sectional diversity allowed the research team to fine-tune the existing prediction models based on the specific needs of different subgroups.
Dr. Steven Grinspoon, co-lead study author and chief of the MGH Metabolism Unit, emphasized the importance of these nuanced findings: “This study demonstrates the necessity for population-specific risk models that more accurately reflect the cardiovascular risks faced by PWH, particularly in LMICs. These models need to account for the multifaceted nature of CVD risk in these populations.”
Markella Zanni, another co-lead author and director of Women’s Health Research at the MGH Metabolism Unit, also noted that further work will be required to validate these findings. “We have calculated adjustment factors for the underestimates found in high-income countries,” Zanni explained. “Our hope is that these findings will be integrated into future treatment guidelines and will lead to stronger recommendations for preventive treatments, especially for women and Black or African American men living with HIV.”
Correction Factors and Next Steps
Building on these findings, the researchers have proposed correction factors that can be applied to the current ASCVD risk scores. For example, in high-income countries, the correction factors would adjust for the underestimation of cardiovascular risk among certain at-risk groups like women and Black men. Validation of these correction factors in external cohorts remains a crucial next step. The team aims to test these adjustment factors in different global settings to ensure their generalizability and effectiveness. Moreover, broader studies need to assess how incorporating these refinements might influence prevention strategies and treatment plans for PWH in various socioeconomic and geographical settings.
There is an emerging consensus among public health experts that the current approach to cardiovascular risk prediction needs to evolve to better accommodate the unique risks faced by people living with HIV. As Dr. Desvigne-Nickens highlighted, the current study represents a critical move toward better addressing these disparities. “By improving risk assessments and refining clinical approaches to care, we can better target prevention efforts for high-risk individuals in both high- and low-income settings.”
Implications for Global Health Policy
The REPRIEVE study’s findings could have far-reaching implications for global health policy and practice, especially as the HIV epidemic continues to disproportionately impact populations in lower-resource settings. The lack of accuracy in ASCVD risk models may mean that individuals at risk of heart disease are either overlooked or receive unnecessary treatment, leading to inadequate prevention strategies or undue healthcare expenditure. By addressing these issues with region-specific and population-specific models, healthcare providers can deliver more precise care and effectively allocate resources to those who need them most.
For health organizations and policymakers, the study highlights the critical need for developing a more nuanced approach to cardiovascular care for people living with HIV. This includes ensuring that people in both high- and low-income countries are evaluated using prediction models that reflect their unique health and demographic characteristics. Additionally, fostering international collaborations and data sharing will be important for the development of evidence-based guidelines that promote equitable health outcomes worldwide.
Conclusion
As cardiovascular disease continues to pose a serious threat to people living with HIV, it is essential for healthcare systems and scientists to refine and adapt existing risk prediction models. The REPRIEVE study provides invaluable insights into the gaps in cardiovascular risk assessments for global populations and highlights the need for tailored models that accurately reflect the cardiovascular health of people with HIV, particularly in low-resource settings. While there is much work to be done in validating and implementing these refined models, the study represents a critical step toward more equitable, effective, and precise cardiovascular care for individuals living with HIV worldwide. By refining our approach to predicting cardiovascular risk, we can ensure that people living with HIV receive the most appropriate and timely interventions to prevent heart disease and improve their long-term health outcomes.
Reference: Performance of the Pooled Cohorts Equations and D:A:D Risk Scores among Individuals with HIV in a Global Cardiovascular Disease Prevention Trial: A Cohort Study Leveraging Data from REPRIEVE, The Lancet HIV (2025). DOI: 10.1016/S2352-3018(24)00276-5