From flu and COVID-19 to HIV and shingles, a sweeping analysis reveals that viral infections can trigger or accelerate cardiovascular disease, reinforcing the role of vaccination in protecting the heart.
Study: Viral Infections and Risk of Cardiovascular Disease: Systematic Review and Meta‐Analysis. Image Credit: sportoakimirka / Shutterstock
In a recent systematic review and meta-analysis published in the Journal of the American Heart Association, researchers synthesized and reanalyzed data from 155 different studies to investigate associations between viral pathogens and cardiovascular disease (CVD).
Study findings confirm that several common viruses, including those responsible for influenza, COVID-19, HIV, hepatitis C, and shingles, are significantly associated with an increased risk of coronary heart disease and stroke. This work suggests that preventing infections, through measures like vaccination, may be a critical strategy for protecting future heart and cardiovascular health.
Global Burden and Traditional CVD Risk Factors
Cardiovascular diseases (CVDs), which encompass heart attacks and strokes, are the world’s leading cause of human mortality. Responsible for over 20 million deaths in 2021 alone, public health campaigns have rightly and for decades focused on modifying traditional risk factors like high blood pressure, elevated cholesterol, smoking, and poor diet.
Viral Infections as Emerging Cardiovascular Triggers
While these traditional risk factors are well-researched, the role of viral infections is often overlooked. However, the COVID-19 pandemic brought this “other” potential trigger into sharp focus. Previous investigations in both animal models and human clinical trials have revealed this mechanism: when a virus invades, the body mounts an intense inflammatory response.
Inflammatory Mechanisms Driving Vascular Damage
This systemic inflammation can damage the delicate lining of blood vessels (endothelial dysfunction) and make the blood more likely to clot (a hypercoagulable state). In COVID-19, an additional mechanism involving neutrophil extracellular traps (NETs), webs of DNA and proteins released by immune cells, has been implicated in triggering blood clots and heart attacks. In people with existing atherosclerotic plaques (hardening of the arteries), this acute response can cause a plaque to rupture, leading directly to a heart attack or stroke.
Gaps in Comprehensive Viral-CVD Research
While many studies have linked individual viruses to CVD, a comprehensive, large-scale assessment comparing the risks across a wide range of infections has been lacking.
Systematic Review and Meta-Analysis Scope
The present study addressed this pressing need and informed future cardiovascular public health advice by conducting a systematic review and meta-analysis leveraging more than 150 recent publications investigating the association between viral infections and subsequent CVD events.
Study Selection and Data Sources
Studies for inclusion in the present work were identified through a custom keyword search of five major scientific databases, including MEDLINE and Web of Science, for relevant studies published up to July 3, 2024. Title, abstract, and full-text screening of more than 52,000 scientific records resulted in the inclusion of 155 high-quality studies in subsequent analyses.
Geographic Representation and Study Design
Notably, most studies originated from North America, Europe, and East Asia, with underrepresentation from Latin America, Africa, and South/Southeast Asia, regions facing high burdens of both infectious and cardiovascular diseases. The included studies comprised three main types:
Cohort studies
Case-control studies
A self-controlled case series (SCCS) is a powerful and relatively novel method that compares an individual’s risk of an event (such as a heart attack) in the time window immediately following an infection to their own baseline risk at other times.
For influenza, the SCCS studies captured primarily severe cases (as lab testing is typically reserved for these).
Analytical Approach and Key Outcomes
Data from all 155 publications were pooled to measure the association between specific viral infections and key cardiovascular outcomes, including coronary heart disease (CHD), stroke, and heart failure. This data was leveraged to calculate a pooled risk ratio (RR) for long-term risk and an incidence rate ratio (IRR) for acute-phase risk.
Acute and Chronic Viral Infections Increase CVD Risk
Meta-analyses revealed significant links between several common viruses and major cardiovascular events, though the strength of evidence varied across pathogens. Both acute infections (like influenza and SARS-CoV-2) and chronic infections (such as HIV, Hepatitis C Virus [HCV], and Herpes Zoster [Shingles]) were found to increase CVD risk.
Influenza Strongly Elevates Short-Term Heart Attack Risk
Laboratory-confirmed flu was associated with a 4-fold increase (IRR of 4.01) in the risk of acute myocardial infarction (MI), or heart attack, and a 5-fold increase (IRR of 5.01) in the risk of stroke during the first month after infection. The danger was revealed to be highest in the first seven days, when MI risk surged by over 7-fold (IRR of 7.20) but declined sharply to a 1.87-fold risk by days 8–14.
COVID-19 and Long-Term Cardiovascular Complications
COVID-19 infections were similarly associated with an increased long-term risk of CHD (RR 1.74) and stroke (RR 1.69). SCCS studies confirmed the acute risk, showing a 3.35-fold increase in MI risk within the first 14 weeks. Substantial heterogeneity was observed in these SARS-CoV-2 findings, reflecting the methodological challenges encountered during the pandemic.
Chronic Viral Infections and Persistent Heart Risk
Chronic infections presented a long-term threat. HIV infection was linked to a 60% higher risk of CHD (RR 1.60) and a 45% higher risk of stroke (RR 1.45) and was the only virus with robust evidence for heart failure risk (RR 1.89). HCV was associated with a 27% higher risk of CHD (RR 1.27), a 23% higher risk of stroke (RR 1.23), and doubled the risk of cardiovascular death (RR 2.11).
Shingles and Cardiovascular Events After Infection
Shingles, a reactivation of the chickenpox virus, was associated with a 12% higher risk of CHD (RR 1.12) and an 18% higher risk of stroke (RR 1.18). Acute-phase SCCS data showed stroke risk peaked 1–3 weeks post-infection (IRR 1.61). Notably, the review did not find a positive association between the hepatitis B virus and concluded that the evidence for cytomegalovirus remains insufficient, despite a tentative link to cardiovascular death (RR 1.28).
Emerging Viral Links Requiring Further Validation
Viruses such as HPV, dengue, and chikungunya have shown associations in single studies but require further validation due to limited evidence.
Mechanisms Connecting Viruses to Heart Disease
Review findings demonstrate that the impact of a virus often extends far beyond the initial sickness, concluding that these viruses likely contribute to heart disease by promoting persistent, low-grade inflammation, activating pro-coagulant pathways, and even directly invading arterial endothelial cells.
Vaccination and Prevention of Infection-Driven CVD
Vaccination emerged as a key preventive strategy, with direct trial evidence supporting influenza vaccines (34% CVD risk reduction), while herpes zoster vaccines show promising indirect potential. The authors stress that research gaps persist in underrepresented regions and for understudied viruses.
Journal reference:
Source: Kawai, K., Muhere, C. F., Lemos, E. V., & Francis, J. M. (2025). Viral Infections and Risk of Cardiovascular Disease: Systematic Review and Meta‐Analysis. Journal of the American Heart Association. DOI – 10.1161/jaha.125.042670