Antibodies to human herpesviruses and rate of incident cardiovascular events and all-cause mortality in the UK Biobank Infectious Disease pilot study

Background Associations between human herpesviruses (HHVs) and cardiovascular disease/mortality have been reported, but evidence is inconsistent. We investigated associations between three common herpesviruses and i) incident stroke or myocardial infarction (MI) and ii) all-cause mortality. Methods We included participants from the UK Biobank Infectious Disease pilot study with valid serum antibody (IgG) measurements taken at cohort entry (2006-2010) for herpes simplex virus type 1 (HSV1), varicella zoster virus (VZV), and cytomegalovirus (CMV). Linked hospital and mortality records up to 30/12/2019 provided information on rates of i) incident first stroke or MI and ii) all-cause mortality. Hazard ratios (HRs) from Cox proportional hazards regression models were used to assess relationships between (i) HHV seropositivity, (ii) HHV titre and incident stroke/MI and death outcomes. Fully adjusted models accounted for sociodemographic information (age, sex, ethnicity, education, deprivation quintile, birthplace, population density), baseline comorbidities (including diabetes and hypertension), smoking status, body mass index and serum cholesterol. Results Of 9429 study participants (56% female, 95% White, median age 58 years), 41% were seropositive for all three HHVs. HHV seropositivity was not associated with stroke/MI (fully-adjusted HRs and 95% confidence intervals: HSV1; 0.93 [0.72-1.22], VZV; 0.78 [0.51-1.20], CMV; 0.91 [0.71-1.16]) or all-cause mortality (HSV1; 1.21 [1.00-1.47], VZV: 0.79 [0.58-1.07], CMV: 0.90 [0.76-1.06]). HHV titres were not associated with outcomes. Conclusions In this mostly White UK Biobank subset, neither HHV seropositivity nor titres were associated with stroke/MI or all-cause mortality.