The strong negative association between IgG and IgM levels

The strong negative association between IgG and IgM levels and CHD events needs to be considered in the context of other biomarkers that have been evaluated as adjuncts to traditional risk assessments. Although the ASCOT-CRP substudy concluded that measuring CRP had little utility in refining CV risk assessment beyond classical risk factors in the study population (Sever et al., 2012), a meta-analysis concluded that adding CRP to the risk assessment led to predicting one additional event over a glycoprotein iib iiia inhibitors of 10years for every 400–500 people screened (Kaptoge et al., 2012). Not only did IgG levels remain highly significant in predicting protection from events after adjustment for CRP, they were also independent from NtProBNP which was previously shown to be a predictor of events in ASCOT (Welsh et al., 2014). A particularly important outcome of the study was the reclassification of more cases and less controls into the clinically relevant >10% risk categories and more controls with less cases in the <10% risk category by incorporating total serum IgG in the analysis. If confirmed in further cohorts, this has the potential to be used for more robust risk stratification in hypertension, thus redirecting primary prevention therapies towards those who would benefit the most. Our findings are at odds with those of Kovanen et al. who showed that serum IgG levels (as well as IgA and IgE), but not IgM, were predictive of MI (Kovanen et al., 1998). However the two studies differ in entrance requirements, with that of Kovanen et al. being selected for dyslipidemia whilst ours was based on hypertension. It is possible that IgG levels in our study population might have been affected by hypertension, although we did not detect any correlations with SBP, DBP or MAP (Chan et al., 2014). It therefore remains to be seen to what degree our findings on the ASCOT population generalize to wider populations. In particular, raised Ig levels are probably not associated with freedom from CV events in patients with autoimmune conditions such rheumatoid arthritis and systemic lupus erythematosus in which there is a disease-related increase in risk of CV events and in which a polyclonal expansion of Ig levels signifies disease activity. Furthermore, our study has focused on the prediction of first adverse cardiovascular incidents in a high risk population, and does not address the relevance of immunoglobulins or specific antibodies during and after acute coronary events.
Conclusion
Author Contributions
Conflict of Interest
Acknowledgements The work was funded by a grant from the National Institute for Health Research Comprehensive Biomedical Research Centre (RDB02_P46385) at Imperial College Healthcare NHS Trust. The parent ASCOT study was an independent, investigator-initiated, investigator-designed, and investigator-led study funded by a grant program from Pfizer UK. DH receives BHF Professorial Support. CK is supported by Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad. RYK was funded as a Wellcome Trust Clinical Research Fellow. DOH has professorial support from the British Heart Foundation. JJB acknowledges the British Heart Foundation SCRF03 for his financial support. The original ASCOT study was supported by an investigational grant from Pfizer International, New York, NY, USA. The principal funding source for ASCOT was Pfizer, New York, NY, USA. Servier Research Group, Paris, France, and Leo Laboratories, Copenhagen, Denmark provided additional funding. The investigators acknowledge the invaluable support of the clinical trial doctors, nurses, and support staff for their important contributions. We thank Dr. John Morris (Imperial College Healthcare NHS Trust) contribution to standard sera measurements, as well as the ASCOT study team, collaborators and co-investigators. In addition, we thank all study participants.