Association between Cytomegalovirus Seropositivity or Titres and Cardiovascular Disease: Systematic Review and Meta-Analysis of Prospective Evidence
Established risk factors for cardiovascular disease (CVD) do not fully explain CVD risk. Cytomegalovirus (CMV) has been linked to development of CVD among transplant recipients, but its association with CVD in immunocompetent adults is not established.
Embase®, Medline® and Web of Science® were searched in April 2014. Titles, abstracts and full-text articles were screened and meta-analysed using a priori criteria.
Of 2,658 titles screened, 25 prospective studies met criteria for synthesis. All included studies defined CMV exposure using serological tests with a clinically important CVD outcome, but varied substantially regarding potential bias, confounding, and sample size. Random-effects meta-analysis of studies examining CMV seropositivity and CVD revealed a null association in both 13 population-based studies (effect estimate, 0.99; 95% CI, 0.87–1.12) and in 10 studies of patients with previous history of CVD (1.13; 1.00–1.27). However, in the three population-based studies that examined CMV antibody levels and CVD, there was an indication of increased risk in CVD among participants with higher titres, with the most methodologically robust study reporting an adjusted hazard ratio (95% CI) of 1.21 (1.04–1.41) for participants in the highest tertile of titres versus seronegative subjects.
There appears to be a modest increased risk in CVD associated with higher CMV antibody levels. Given high burden of CVD and high seroprevelance of CMV among adults worldwide, this association is of potential public health relevance. Further research examining this association in other cohorts, and prospective studies correlating CMV antibody levels with direct measurements of active infection are necessary.
E. Gkrania-Klotsas, None