Human cytomegalovirus neutralising antibodies and increased risk of coronary artery disease in Indian population
- Lakshmi Ashutosh Mundkur1,
- Hemapriys Shivanandan1,
- Sridhara Hebbagudi2,
- Valeria Endrész3,
- Meenakshi Varma1,
- Veena Rao4,
- Eva Gonczol5,
- Vijay Vir Kakkar1,6
- 1Molecular Immunology, Thrombosis Research Institute, Bangalore, India
- 2Bioinformatics and Statistics, Thrombosis Research Institute, Bangalore, India
- 3Microbiology and Immunology, University of Szeged, Szeged, Hungary
- 4Proteomics and coagulation, Thrombosis Research Institute, Bangalore, India
- 5Virology, National Center for Epidemiology, Budapest, Hungary
- 6Thrombosis Research Institute, Bangalore, India; and President, Thrombosis Research Institute, London, UK
- Correspondence to Professor Vijay Vir Kakkar, Thrombosis Research Institute (Bangalore), Narayana Hrudayalaya, 258/A, Bommasandra Industrial Area, Anekal Taluk, Bangalore-560099, India;
Contributors The study was conceptualised by VVK and EG, while LM designed and coordinated the same. VE and EG standardised the protocol and HS and MV carried out the antibody assays under the supervision of LM. Statistical analysis were designed and carried out by SH. Interpretation of the results were carried out by SH and LM. VSR designed and carried out the assays for inflammatory markers. LM wrote the first draft of the paper. VE and EG participated in the scientific discussions and improvement of the draft and it was finalised by VVK.
- Accepted 24 April 2012
Background Several studies have reported a conflicting association between cytomegalovirus (CMV) infection and coronary artery disease (CAD) based on the levels of total anti-CMV antibodies. However, none have estimated the levels of specific neutralising antibodies (NA) to CMV, which may be clinically more relevant.
Objective To determine whether CMV–NA titres show a better association with CAD compared with total anti-CMV antibody levels.
Design CMV–NA titres were measured by micro-neutralisation assay and anti-CMV IgG antibodies using ELISA in 391 consecutive CAD patients compared with the same number of controls (N=782), and 91 patients reporting recurrent cardiac events during a 4-year follow-up compared with those without a recurrent event (N=182). Levels of inflammatory markers, interleukin 6, high-sensitivity C reactive protein, fibrinogen and secretory phospholipase A2 (sPLA2), were measured by ELISA. Analysis of variance and logistic regression were used for statistical analyses.
Results High CMV–NA titres showed a positive association with CAD occurrence (OR 2.24, 95% CI 1.31 to 3.85, p=0.003) and recurrent cardiac events in CAD patients (OR 4.65, 95% CI 1.21 to 17.86, p=0.025) compared with total CMV antibodies (OR 1.67, 95% CI 1.04 to 2.69, p=0.034, and 2.70, 1.04 to 7.02, p=0.040, respectively). Patients with higher quartile of CMV–NA titres and sPLA2 levels had an adjusted OR of 7.82 (95% CI 1.87 to 32.65, 0.005) for recurrent cardiac events compared with those with the lowest quartiles for both markers.
Conclusion These findings suggest that high CMV–NA titres in combination with inflammatory markers improve prediction of cardiac events in the Asian Indian population.
- CMV infection
- neutralising antibodies
- inflammatory biomarkers
- coronary artery disease
- Asian Indian population
- risk factors
Funding Tata Social Welfare Trust, India (TSWT/IG/SNB/JP/Sdm), and the Department of Biotechnology, Ministry of Science and Technology, Government of India (BT/01/CDE/08/07).
Competing interests None.
Patient consent Obtained.
Ethics approval Ethics approval was provided by Indian Council of Medical Research.
Provenance and peer review Not commissioned; internally peer reviewed.