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ASCOT: Immunoglobulin G antibody levels may be predictive of risk for MI
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The amount of immunoglobulin G antibodies in the blood is associated with a person’s likelihood of being protected against adverse cardiac events, according to data from the ASCOT trial reported in EBioMedicine.
“In this specific hypertensive population, those in the upper third of total IgG [immunoglobulin G] levels had a lower risk [for CV] events and, in particular, those relating to the heart, [MI] included. The other antibody levels (total [immunoglobulin M] as well as IgG and IgM that are specific to oxidized cholesterol) also predicted protection from heart events, but IgG was the strongest predictor,” Ramzi Khamis, MD, consultant cardiologist and independent clinical research fellow at the National Heart and Lung Institute, Imperial College London, told Cardiology Today.
During the original ASCOT trial, patients with hypertension in the BP-lowering arm were treated with a beta-blocker with a thiazide diuretic as required or a dihydropyridine calcium channel blocker with an ACE inhibitor as required. In this arm, those with a fasting total cholesterol of 6.5 mmol/L (250 mg/dL) or less were further randomly assigned to 10 mg atorvastatin daily or matching placebo.
Improving prediction
The present nested case-control study measured adverse CV events (CHD, MI, coronary revascularization, stroke) in patients in the ASCOT BP-lowering arm between February 1998 and October 2005. During a median follow-up of 5.5 years, 485 of the participants experienced CV events (355 CHD and 130 strokes). They were then matched by age, sex and study entry time to a control group (n = 1,367).
The final analysis included 1,753 participants (mean age, 65 years; 84.8% men).
According to the results, IgM anti-malondialdehyde-conjugated (MDA)-LDL antibody levels had a strong correlation with total serum IgM (Spearman rank correlation = 0.78; P < .0001) and IgG anti-MDA-LDL had a weaker correlation with total serum IgG (Spearman rank correlation = 0.36; P < .0001). In addition, total IgG and IgG anti-MDA-LDL antibodies were weakly linked to C-reactive protein (Spearman rank correlation = 0.13 and rho = 0.09, respectively). An inverse association, although weak, also was found between IgG anti-MDA-LDL antibodies and LDL (Spearman rank correlation = –0.085; P < .001). The OR for total serum IgG was 0.62 (95% CI, 0.46-0.82) or 0.81 (95% CI, 0.72-0.91) per 1 standard deviation increase in total IgG levels. Total serum IgG also improved the area under the receiver operating curve for CV events from the basic risk model.
The researchers also found that in the integrated discrimination index, adding serum IgG to the basic risk model improved continuous net reclassification by 17.6% and categorical net reclassification by 7.5%.
Next steps
Khamis said in an interview that the findings are not yet generalizable on the population level. Further work must be done on confirming these findings in other populations and exploring the reasons behind these associations.
“An important caveat is that levels of IgG can be abnormally raised in pathological conditions such as autoimmune diseases, and pathologically abnormal levels of IgG should not be ignored or considered as a biomarker for CVD at all and should be investigated.”
Khamis told Cardiology Today, “If these findings are confirmed in other studies, and this is essential, antibody levels may be integrated into risk-factor profiling to improve the current way CV risk is estimated using conventional risk factors.”
Dorian Haskard, PhD, British Heart Foundation professor at Imperial College London, said in a press release, “These very interesting findings linking the immune system to protection from heart disease have grown out of years of previous research funded by the British Heart Foundation. The study focused on patients under treatment for high [BP], and we now need to know if this applies to other groups at risk.” – by Tracey Romero
Disclosure: ASCOT is funded by Pfizer, Servier Research Group and Leo Laboratories. The present analysis was funded in part by the British Heart Foundation. Khamis reports no relevant financial disclosures. Please see full study for a list of all other researchers’ relevant financial disclosures.
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