Common viruses sharply raise heart attack and stroke risk, major global review shows

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

Shingles showed an immediate stroke threat: Beyond long-term risks, self-controlled studies found stroke risk spiked 61% in the critical 1-3 weeks following a shingles outbreak. Image Credit: Stocktrek Images / Shutterstock

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

Cytomegalovirus hinted at a deadly link: While evidence for heart attacks or strokes remained unclear, this common virus was tied to a 28% higher risk of dying from cardiovascular causes in cohort studies. Image Credit: Kateryna Kon / Shutterstock

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

HPV infection carried a stark warning for women: Two South Korean studies found women with high-risk HPV strains faced a 25% higher risk of cardiovascular disease and a nearly 4-fold (391%) increased risk of cardiovascular death.

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:

1. Cohort studies
2. Case-control studies
3. 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

Heart failure risk stood out for HIV: Among the viruses studied, HIV was uniquely linked to a substantially higher (89% increased) risk of developing heart failure based on the meta-analysis.

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

Underlying factors might still muddy the waters: The researchers cautioned that unmeasured influences, like genetic predispositions or simultaneous infections with other pathogens, could still affect the observed links between viruses and heart problems.

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