Human Cytomegalovirus and Risk of Incident Cardiovascular Disease in United Kingdom Biobank

Abstract

Background Previous studies have yielded conflicting results on the association between human cytomegalovirus (HCMV) and cardiovascular disease (CVD). This study aimed to examine associations between HCMV and incident CVD, ischaemic heart disease (IHD) and stroke. Methods This study included 8,531 women and men of predominantly white ethnic background, aged 40–69 without prevalent CVD from the population-based UK Biobank study recruited between 2006–2010 with HCMV antibody levels measured. CVD was ascertained via linkage to health administrative records collected up to 2020. Multivariate Cox proportional-hazards models were used to determine the association between HCMV seropositivity and incident CVD, IHD and stroke. HCMV seropositive antibody levels were split into tertiles to assess dose-response associations. Results Over a mean follow-up period of 10.2 years, HCMV seropositivity was not significantly associated with CVD (Cases = 626, Hazard Ratio (HR) =1.01, 95% Confidence Interval (CI) 0.86–1.20), IHD (Cases = 539, HR=1.03, 95% CI 0.87–1.24) or stroke (Cases = 144, HR=0.96, 95% CI 0.68–1.36). There was no evidence of dose-response associations with any outcome. Conclusion We found no significant association between HCMV seropositivity and risk of CVD, IHD or stroke. Further research within understudied populations, such as those of non-white ethnicity, and other CVD subtypes is warranted.

Human Cytomegalovirus and Risk of Incident Cardiovascular Disease in UK Biobank

“…Cytomegalovirus seropositivity is more prevalent in older individuals, which is partly a cohort effect, with most incident infections occurring in individuals under the age of 40 years [ 6 ]. Seroprevalence in 40- to 49-year-olds in UKBB is 48.0%, similar to that among pregnant white British women in BiB (48.6%), despite the latter having a mean age of 26.6 years [ 1 , 7 ]. Cytomegalovirus is also more prevalent in people of non-white ethnicity [ 4 , 5 , 7 ].…”

“…To The Editor—Hamilton et al’s [ 1 ] analysis of the association between cytomegalovirus (CMV) infection and incident cardiovascular disease (CVD) in 8531 UK Biobank (UKBB) participants is stronger than most observational studies of the CMV-CVD association. There was careful adjustment for age, sex, socioeconomic position, and cardiovascular risk factors.…”

“…This induces a negative correlation between CVD and CMV in the sample that does not hold in the broader population. To evaluate the extent to which collider bias might explain Hamilton et al’s [ 1 ] null findings, we compared CVD risk and CMV exposure in UKBB participants to that in more representative population samples.…”

“…Comparing the age-specific CMV seroprevalence reported by Hamilton et al [ 1 ] with that among pregnant women in the Born in Bradford (BiB) birth cohort [ 7 ] suggests markedly lower CMV prevalence in UKBB. Cytomegalovirus seropositivity is more prevalent in older individuals, which is partly a cohort effect, with most incident infections occurring in individuals under the age of 40 years [ 6 ].…”

“…Seroprevalence among United Kingdom-born pregnant women of South Asian ethnicity in BiB was 89.3% (mean age 27.4 years). Note that CMV seroprevalence in UKBB is similar in men (56.0%) and women (59.3%) [ 1 ].…”