Mora, Samia

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.

Abstract Background Premature coronary heart disease (CHD) is a major cause of death in women. We aimed to characterize biomarker profiles of women who developed CHD before and after age 65 years. Methods In the Women’s Health Study (median follow-up 21.5 years), women were grouped by age and timing of incident CHD: baseline age <65 years with premature CHD by age 65 years (25 042 women; 447 events) and baseline age ≥65 years with nonpremature CHD (2982 women; 351 events). Associations of 44 baseline plasma biomarkers measured using standard assays and a nuclear magnetic resonance (NMR)-metabolomics assay were analyzed using Cox models adjusted for clinical risk factors. Results Twelve biomarkers showed associations only with premature CHD and included lipoprotein(a), which was associated with premature CHD [adjusted hazard ratio (HR) per SD: 1.29 (95% CI 1.17–1.42)] but not with nonpremature CHD [1.09(0.98–1.22)](Pinteraction = 0.02). NMR-measured lipoprotein insulin resistance was associated with the highest risk of premature CHD [1.92 (1.52–2.42)] but was not associated with nonpremature CHD (Pinteraction <0.001). Eleven biomarkers showed stronger associations with premature vs nonpremature CHD, including apolipoprotein B. Nine NMR biomarkers showed no association with premature or nonpremature CHD, whereas 12 biomarkers showed similar significant associations with premature and nonpremature CHD, respectively, including low-density lipoprotein (LDL) cholesterol [1.30(1.20–1.45) and 1.22(1.10–1.35)] and C-reactive protein [1.34(1.19–1.50) and 1.25(1.08–1.44)]. Conclusions In women, a profile of 12 biomarkers was selectively associated with premature CHD, driven by lipoprotein(a) and insulin-resistant atherogenic dyslipoproteinemia. This has implications for the development of biomarker panels to screen for premature CHD.

Abstract In a prospective study with records of heart failure (HF) incidence, we present metabolite profiling data from individuals without HF at baseline. We uncovered the interconnectivity of metabolites using data-driven and causal networks augmented with polygenic factors. Exploring the networks, we identified metabolite broadcasters, receivers, mediators, and subnetworks corresponding to functional classes of metabolites, and provided insights into the link between metabolomic architecture and regulation in health. We incorporated the network structure into the identification of metabolites associated with HF to control the effect of confounding metabolites. We identified metabolites associated with higher or lower risk of HF incidence, the associations that were not confounded by the other metabolites, such as glycine, ureidopropionic and glycocholic acids, and LPC 18:2. We revealed the underlying relationships of the findings. For example, asparagine directly influenced glycine, and both were inversely associated with HF. These two metabolites were influenced by polygenic factors and only essential amino acids which are not synthesized in the human body and come directly from the diet. Metabolites may play a critical role in linking genetic background and lifestyle factors to HF progression. Revealing the underlying connectivity of metabolites associated with HF strengthens the findings and facilitates a mechanistic understanding of HF progression.

Introduction: The association of patient satisfaction with hospital ACS care and risk for long-term outcomes is incompletely described. This is particularly relevant to the Gulf region, where the ACS burden is high and literature on patient satisfaction and outcomes is lacking. The aim was to compare determinants of 1-year mortality based on patient satisfaction with ACS care in the Gulf region. Methods: In a prospective registry of 3566 ACS patients from Bahrain, Kuwait, Oman, and UAE (Gulf COAST registry), we grouped patients by their self-reported overall satisfaction with ACS care reported at 1-month following ACS (low satisfaction [n=1654] vs. high satisfaction [n=1912]; Table). We examined associations of baseline characteristics and risk for 1-year mortality in logistic regression models adjusted for Global Registry of Acute Coronary Events (GRACE) score. Results: Mortality at 1-year following ACS was higher in patients reporting low satisfaction (8.8%; n=146/1654) vs. high satisfaction (5.4%; n=103/1912) ( P <.0001). Women, compared with men, had higher 1-year mortality risk in both satisfaction groups, and statistically significant risk in the low satisfaction group (aOR 1.45 [1.01–2.07]; P <.05). Lack of employment (vs. any employment) was associated with higher 1-year mortality risk in both the low satisfaction (aOR 6.44 [2.58–16.03]) and high satisfaction (aOR 2.58 [1.35–4.93]) groups with borderline significant interaction ( P interaction = .08). In both satisfaction groups, lack of education, hypertension and prior angina were associated with higher 1-year mortality risk, whereas dyslipidemia and diabetes showed no association. Conclusions: Low patient satisfaction with ACS care was associated with higher 1-year mortality risk. Socioeconomic factors such as employment and education were associated with higher 1-year mortality, independent of patient satisfaction, and may guide mortality reduction interventions.

This JAMA Insights Clinical Update discusses updated recommendations on the use of aspirin for primary prevention of atherosclerotic cardiovascular disease in women and stresses the importance of shared clinical decision-making.

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.