What is the clinical evidence from this study?

Study design: Cohort. Population: Cardiovascular disease (n=8740). Intervention: Human cytomegalovirus (HCMV) seropositivity vs. HCMV seronegativity. Primary outcome: Incident cardiovascular disease (CVD) events (HR 1.00, 95% CI 0.86-1.15).

What does this research mean for the field?

Human cytomegalovirus seropositivity is not significantly associated with incident cardiovascular disease or all-cause mortality in fully adjusted models. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

November 6, 2025Philosophical Transactions of the Royal Society B Biological Sciences1 citationsOpen Access

Acyclic graphs to define models of relationships between human cytomegalovirus, cardiovascular disease and all-cause mortality in UK Biobank

RDRobert DoorlyCentre for Human Genetics ACAmanda Y. ChongCentre for Human Genetics EHElizabeth HamiltonUniversity of Edinburgh

Key Result

Human cytomegalovirus seropositivity was not significantly associated with incident cardiovascular disease (HR 1.00) or all-cause mortality in fully adjusted models.

Study Design

Type

Cohort (n=8,740)

Multicenter

Yes

Structured PICO

Does human cytomegalovirus seropositivity increase the risk of incident cardiovascular disease, ischaemic heart disease, stroke, and all-cause mortality in middle-aged to older adults?

Population

8,740 UK Biobank participants aged 40-69 years, mean age 56.5, 42.5% male, 94.2% White.

Intervention

Human cytomegalovirus (HCMV) seropositivity

Comparator

Human cytomegalovirus (HCMV) seronegativity

Outcome

Incident cardiovascular disease (CVD), ischaemic heart disease (IHD), stroke, and all-cause mortalityhard clinical

Human cytomegalovirus seropositivity is not independently associated with an increased risk of cardiovascular disease, ischaemic heart disease, stroke, or all-cause mortality when adjusting for relevant sociodemographic and health-related confounders.

Main Result

Effect estimate: HR 1.00 (95% CI 0.86-1.15)

Limitations

Volunteer bias in the UK Biobank cohort, which is older, more female, and less ethnically diverse than the general population.
Lower prevalence of CVD and HCMV in the cohort compared to the general population, which could introduce collider bias.
Inability to determine the age or timing of when participants became infected with HCMV.
Possible under-representation of HCMV-related mortality due to the exclusion of external causes of death.

Abstract

Human cytomegalovirus seropositivity has shown varying levels of association with cardiovascular disease and all-cause mortality in previous studies. This study uses updated data from the UK Biobank to test these associations. The association between human cytomegalovirus seropositivity and outcomes of incident cardiovascular disease, ischaemic heart disease, stroke and all-cause mortality was determined using multivariate Cox proportional-hazards models in 8740 UK Biobank participants aged 40-69 years. Two directed acyclic graphs depicting the hypothesized relationship between human cytomegalovirus infection (either in childhood or adulthood) and cardiovascular disease/all-cause mortality controlled the selection of biological and socioeconomic confounders to be adjusted for in each model. Human cytomegalovirus seropositivity was not significantly associated with cardiovascular disease, ischaemic heart disease, stroke or all-cause mortality when applying either the fully adjusted adulthood or childhood infection models. We found no significant association between human cytomegalovirus seropositivity and any of the measured outcomes. Further research is expected to include larger sample sizes, younger participants and more ethnically diverse cohorts.This article is part of the discussion meeting issue 'The indirect effects of cytomegalovirus infection: mechanisms and consequences'.

Ask AI

Helpful

Bookmark

View Full Paper