High Serum Immunoglobulin G and M Levels Predict Freedom From Adverse Cardiovascular Events in Hypertension: A Nested Case-Control Substudy of the Anglo-Scandinavian Cardiac Outcomes Trial

• We studied whether immunoglobulins predict cardiovascular events in hypertension.
• Total serum IgG was strongly associated with freedom from adverse events.
• The predictive power of total IgG was superior to antibodies against MDA-LDL.
• Total serum IgG significantly improved cardiovascular risk reclassification.
• Further work is needed to determine whether these observations extend to other populations.Current clinical tools for stratifying cardiovascular risk remain relatively imprecise. In view of interests in the immune system in atherosclerosis, our study explored whether measuring IgG and IgM immunoglobulin levels provides any improvement in determining risk in hypertensive patients. We found that high levels of total serum IgG, and to a lesser extent IgM, were strongly associated with freedom from coronary events. We also found that antibodies against one type of oxidized LDL conferred protection, but the effect was weaker than with total immunoglobulins. Our results support a link between robust humoral immunity and cardiac health.

AimsWe aimed to determine whether the levels of total serum IgM and IgG, together with specific antibodies against malondialdehyde-conjugated low-density lipoprotein (MDA-LDL), can improve cardiovascular risk discrimination.Methods and ResultsThe Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) randomized 9098 patients in the UK and Ireland into the Blood Pressure-Lowering Arm. 485 patients that had cardiovascular (CV) events over 5.5 years were age and sex matched with 1367 controls. Higher baseline total serum IgG, and to a lesser extent IgM, were associated with decreased risk of CV events (IgG odds ratio (OR) per one standard deviation (SD) 0.80 [95% confidence interval, CI 0.72,0.89], p < 0.0001; IgM 0.83[0.75,0.93], p = 0.001), and particularly events due to coronary heart disease (CHD) (IgG OR 0.66 (0.57,0.76); p < 0.0001, IgM OR 0.81 (0.71,0.93); p = 0.002). The association persisted after adjustment for a basic model with variables in the Framingham Risk Score (FRS) as well as following inclusion of C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NtProBNP). IgG and IgM antibodies against MDA-LDL were also associated with CV events but their significance was lost following adjustment for total serum IgG and IgM respectively. The area under the receiver operator curve for CV events was improved from the basic risk model when adding in total serum IgG, and there was improvement in continuous and categorical net reclassification (17.6% and 7.5% respectively) as well as in the integrated discrimination index.ConclusionHigh total serum IgG levels are an independent predictor of freedom from adverse cardiovascular events, particularly those attributed to CHD, in patients with hypertension.