Highlight
This population-based cohort study from Singapore highlights that acute dengue-virus infection is associated with a marked increase in the odds of cardiovascular events within 30 days post-infection. Elevated risks include major adverse cardiac events (MACE), dysrhythmias, and ischemic heart disease. While the relative risks are high, the overall excess burden among young adults is modest, with patients aged 60 years and older particularly vulnerable. These findings stress the importance of cardiovascular monitoring in older dengue patients to mitigate potential complications.
Study Background and Disease Burden
Dengue virus (DENV) is a major mosquito-borne pathogen endemic in tropical and subtropical regions, causing an estimated 100-400 million infections annually worldwide. Most acute DENV infections manifest as self-limited febrile illness; however, severe complications can arise, including hemorrhagic fever and shock. Cardiovascular manifestations, although less frequently reported, have been increasingly recognized in clinical anecdotes and small case series, ranging from arrhythmias to myocarditis and ischemic events.
Given the rising incidence of dengue driven by climate change, urbanization, and mosquito vector proliferation, a clearer understanding of the cardiovascular risk profile associated with acute DENV infection is critical. Cardiovascular complications contribute substantially to morbidity and healthcare burden globally. Yet, before this study, empirical estimates of cardiovascular event incidence in DENV-infected populations were limited, with no large-scale population-based comparative analyses available.
Study Design
This retrospective, population-based cohort study was conducted in Singapore using data from the national dengue registry and population databases spanning 2017-2023. The study included 65,207 adults diagnosed with acute laboratory-confirmed dengue infection and a control group of 1,616,865 adults without dengue infection, matched temporally and demographically.
Baseline covariates were balanced using overlap weighting techniques to reduce confounding effects. The primary outcome was the occurrence of cardiovascular events within 30 days following index date (T0): the notification date for dengue cases or a randomly assigned date in controls correlating with case distribution.
Cardiovascular outcomes analyzed included: any cardiovascular event, major adverse cardiac events (MACE), dysrhythmias, and ischemic heart disease. Subgroup analyses explored effects across ambulatory and hospitalized dengue cases, IgG serostatus (indicating previous dengue exposure), and predominant dengue serotypes (DENV1, DENV2, DENV3).
Key Findings
The study demonstrated a significant increase in odds for various cardiovascular events among dengue-infected adults compared to uninfected controls during the first 30 days post-infection:
- Any cardiovascular event: adjusted odds ratio (aOR) = 10.63 (95% CI: 7.56 to 15.48)
- Major adverse cardiac events (MACE): aOR = 2.92 (95% CI: 1.81 to 4.88)
- Dysrhythmias: aOR = 18.44 (95% CI: 11.25 to 32.96)
- Ischemic heart disease: aOR = 3.00 (95% CI: 1.83 to 5.15)
These increased odds were consistent across subgroups including both ambulatory and hospitalized patients, those with positive or negative dengue IgG (indicative of primary or secondary infection), and different predominant DENV serotypes.
Despite high relative risks, the absolute excess burden (EB) was relatively modest overall, with less than one excess cardiovascular event per 100 dengue cases. However, among patients aged 60 years and older, excess burden was higher (EB = 1.25; 95% CI: 1.05 to 1.44), indicating an important at-risk group.
Expert Commentary
This study provides the most comprehensive population-level evidence to date linking acute dengue infection with a transiently increased risk of cardiovascular complications. The biological plausibility may relate to viral myocarditis, systemic inflammation, endothelial dysfunction, and prothrombotic states triggered by dengue infection, which can exacerbate underlying cardiovascular disease or precipitate new events. The high risk of dysrhythmias warrants particular clinical vigilance.
Limitations include potential residual confounding despite overlap weighting and reliance on registry-based diagnostic coding, which may underreport mild or subclinical cardiac events. The study was conducted in a developed healthcare system with robust dengue surveillance, which may limit extrapolation to regions with different healthcare access or dengue epidemiology.
These findings align with previous smaller reports and support recent guideline discussions recommending cardiac monitoring in dengue patients with risk factors. Further prospective studies with cardiac biomarkers and imaging could deepen mechanistic understanding and refine risk stratification.
Conclusion
Acute dengue infection confers a markedly increased relative risk of cardiovascular complications within 30 days of infection, with the highest burden observed in older adults. Although the overall absolute increase in cardiovascular events is modest, these data underscore the need for heightened clinical awareness and targeted monitoring strategies—especially in elderly dengue patients—to mitigate cardiac morbidity. The intersection of infectious disease and cardiovascular health surfaces as a growing area of clinical importance given the expanding global burden of dengue.
Funding
This research was supported by the National Medical Research Council, Singapore.
References
Wee LE, Tan WZ, Chow JY, Lim JT, Chiew C, Chia PY, Ng LC, Amanullah MR, Yap J, Yeo KK, Yee Chan MY, Hausenloy DJ, Leo YS, Lye DC, Tan KB. Cardiovascular complications in acute dengue infection: a population-based cohort study. Lancet Reg Health West Pac. 2025 Oct 16;64:101713. doi: 10.1016/j.lanwpc.2025.101713. PMID: 41146673; PMCID: PMC12554185.
