A comprehensive systematic review and meta-analysis published in the Journal of the American Heart Association found that several viral infections are associated with elevated cardiovascular disease risk, including HIV, SARS-CoV-2, influenza, hepatitis C, and herpes zoster.
SARS-CoV-2 infection was linked to increased coronary heart disease (CHD) risk and stroke risk in the pooled analysis of 155 studies examining associations between viral infection and cardiovascular outcomes.
The investigation, led by Kosuke Kawai, ScD, of the Department of Medicine at the David Geffen School of Medicine, University of California, Los Angeles, and colleagues, searched MEDLINE, Embase, Web of Science, African-Wide Information, and the Cochrane Library database from inception to July 2024.
Laboratory-confirmed influenza infection showed strong temporal associations in self-controlled case series (SCCS) studies, with an incidence rate ratio (IRR) of 4.01 for acute myocardial infarction and 5.01 for stroke during the first month after infection. Risk varied by time period, with a pooled IRR of 7.20 during the first 7 days and 1.87 during days 8 to 14.
HIV infection showed elevated cardiovascular disease risk across multiple outcomes, with a pooled adjusted risk ratio of 1.60 for CHD and 1.45 for stroke.
Among chronic viral infections, the hepatitis C virus (HCV) demonstrated a persistent cardiovascular impact across cohort studies. HCV infection was associated with elevated CHD risk and stroke risk, and patients with HCV infection showed 2-fold higher cardiovascular disease (CVD) mortality risk compared with those without HCV across 3 cohort studies.
Herpes zoster was also associated with higher CHD risk and stroke risk. SCCS studies revealed increased stroke risk during the first 3 months following infection, with IRRs of 1.61 at 1 to 3 weeks and 1.24 at 5 to 12 weeks.
For SARS-CoV-2 infection, 3 SCCS studies found elevated risk for acute myocardial infarction (IRR 3.35) and stroke risk (IRR 3.36) during the first 14 weeks following infection.
Evidence for cytomegalovirus remained inconclusive, showing mixed results across study designs. While cytomegalovirus seropositivity showed no CVD risk association in prevalence studies across 8 cohorts, cytomegalovirus-seropositive patients demonstrated higher CVD mortality risk compared with seronegative patients in mortality analyses.
Other viral infections showed preliminary associations requiring additional research, including hepatitis A virus, herpes simplex virus type 1, respiratory syncytial virus, human papillomavirus, dengue, and chikungunya. Hepatitis B virus showed no statistically significant cardiovascular associations with CVD, CHD, or stroke risk.
The study used the DerSimonian-Laird random effects model with inverse variance weighting and assessed across 4 domains: exposure and outcome assessment, confounding bias, and selection bias. Researchers separated analyses by study design, and meta-analyses were performed when at least 3 studies evaluated specific virus-outcome relationships.
Of 155 included studies, 105 were cohort, 31 were case-control, 2 were case-cohort, and 15 were SCCS studies. Most studies were conducted in North America (67 studies), Europe (46 studies), and East Asia (32 studies). Approximately 71% of studies adjusted for age, sex, and traditional cardiovascular risk factors.
Study limitations included moderate to high heterogeneity in effect estimates across viral infections and potential variations due to differences in study design, country setting, and patient characteristics. Additionally, most case-control studies were small and potentially overestimated effect sizes, leading researchers to emphasize findings from cohort studies.
Disclosures: The study authors reported no conflicts of interest.