Association and predictive value of immunoglobulin and complement levels for incident coronary heart disease: a nested case-control study in Chinese adults

AIMS: To investigate the associations of serum immunoglobulin (Ig) and complement levels with incident coronary heart disease (CHD), and to explore the potential mediating role of C-reactive protein (CRP). METHODS AND RESULTS: We measured serum levels of IgA, IgE, IgG, IgM, complement 3 (C3), complement 4 (C4), and CRP in a nested case-control study within the Dongfeng-Tongji cohort, consisting of 1605 CHD cases and 1605 age- and sex-matched controls. We quantified the associations of serum Ig and complement levels with incident CHD using conditional logistic regression and restricted cubic spline models. Mediation analysis was conducted to explore the role of CRP in these associations. The additional predictive ability of an immune indicator score beyond traditional risk factors was also evaluated. Higher IgA and C3 levels were associated with an increased risk of CHD in a linear manner [odds ratio (OR) (95% confidence interval, CI): 1.35 (1.11-1.62), P = 0.002; OR (95% CI): 2.01 (1.17-3.44), P = 0.01, respectively]. Conversely, higher IgG exhibited a significant linear decrease in CHD risk [OR (95% CI): 0.55 (0.36-0.83), P = 0.005]. C-reactive protein mediated 5.70% and 12.51% in the associations of IgA and C3 with incident CHD, respectively. Adding an immune indicator score to the traditional risk model improved CHD prediction more effectively than adding CRP [area under receiver operating characteristic curve (AUC): 0.85% vs. 0.21%; net reclassification improvement (NRI): 15.33% vs. 7.85%; integrated discrimination improvement (IDI): 0.80% vs. 0.17%]. CONCLUSION: Our study identified IgA and C3 as independent risk factors and IgG as a protective factor for CHD. These immune markers may improve CHD risk prediction beyond traditional and CRP models, highlighting their potential for better risk assessment.