Hydoub, Yousif M.

Abstract Background Glycosylation, a key post-translational modification, plays a crucial role in biological pathways related to atherosclerosis. Purpose To investigate whether specific immunoglobulin G (IgG) N-glycosylation patterns are associated with premature myocardial infarction (MI) and to evaluate whether a glycan-based score improves case identification beyond traditional cardiovascular risk factors. Methods We measured 27 IgG N-glycans using capillary gel electrophoresis in 377 cases of premature first MI (men ≤55 years; women ≤65 years) and 377 controls matched for age (±5 years), sex, and nationality from the Gulf PREVENT study, a case-control study investigating risk factors for premature MI in the United Arab Emirates. We performed conditional logistic regression to evaluate associations between IgG N-glycans and premature MI, adjusting for age, body mass index, LDL-C, HDL-C, hs-CRP, hypertension, diabetes, and smoking. Using LASSO regression, we derived a novel IgG glycan score as a linear combination of selected glycans associated with premature MI. We evaluated model performance using likelihood ratio tests and the area under the curve (AUC) adapted for the case-control design, using 10-fold cross-validation. Results After adjusting for cardiovascular risk factors, glycan peaks (P) 4, 13, 23, and 27 were positively associated with premature MI (false discovery rate [FDR]<0.05). Bisecting N-acetylglucosamine (GlcNAc) was the consistent glycosylation pattern among these four glycans. In contrast, P 22, a core-fucosylated and monogalactosylated glycan, had inverse association (FDR=0.02) with premature MI. An IgG glycan score, composed of Ps 2, 4, 8, 17, 20, and 24, was associated with twofold increase in premature MI risk per standard deviation increment (aOR,1.98 [95%CI,1.56–2.52]; P<0.001) after adjusting for cardiovascular risk factors. Further, the IgG glycan score significantly improved model fit and performance, as indicated by a significant improvement in the likelihood ratio test and AUC (P<0.001). Conclusion We identified novel IgG N-glycosylation patterns that were associated with premature MI independent of cardiovascular risk factors. Glycans enriched with bisecting GlcNAc had increased risk, while core fucosylation and monogalactosylation had decreased risk. A novel IgG glycan score had 2-fold increased risk of premature MI independent of other risk factors and improved model performance. These findings highlight the potential of IgG N-glycans as biomarkers and therapeutic targets for premature MI.

The Middle East and North Africa (MENA) region has a high burden of morbidity and mortality due to premature (≤55 years in men; ≤65 years in women) myocardial infarction (MI) and acute coronary syndrome (ACS). Despite this, the prevalence of risk factors in patients presenting with premature MI or ACS is incompletely described. We compared lifestyle, clinical risk factors, and biomarkers associated with premature MI/ACS in the MENA region with selected non-MENA high-income countries. We identified English-language, peer-reviewed publications through PubMed (up to March 2018). We used the World Bank classification system to categorize countries. Patients with premature MI/ACS in the MENA region had a higher prevalence of smoking than older patients with MI/ACS but a lower prevalence of diabetes, hypertension, and dyslipidemia. Men with premature MI/ACS had a higher prevalence of smoking than women but a lower prevalence of diabetes and hypertension. The MENA region had sparse data on lifestyle, diet, psychological stress, and physical activity. To address these knowledge gaps, we initiated the ongoing Gulf Population Risks and Epidemiology of Vascular Events and Treatment (Gulf PREVENT) case–control study to improve primary and secondary prevention of premature MI in the United Arab Emirates, a high-income country in the MENA region.