RESUMO
Background: Heart disease is the leading cause of premature death for women in Canada. Ischemic heart disease is categorized as myocardial infarction (MI) with no obstructive coronary artery disease (MINOCA), ischemia with no obstructive coronary arteries (INOCA), and atherosclerotic obstructive coronary artery disease (CAD) with MI (MI-CAD) or without MI (non-MI-CAD). This study aims to study the prevalence of traditional and nontraditional ischemic heart disease risk factors and their relationships with (M)INOCA, compared to MI-CAD and non-MI-CAD in young women. Methods: This study investigated women who presented with premature (at age ≤ 55 years) vasomotor entities of (M)INOCA or obstructive CAD confirmed by coronary angiography, who are currently enrolled in either the Leslie Diamond Women's Heart Health Clinic Registry (WHC) or the Study to Avoid Cardiovascular Events in British Columbia (SAVEBC). Univariable and multivariable regression models were applied to investigate associations of risk factors with odds of (M)INOCA, MI-CAD, and non-MI-CAD. Results: A total of 254 women enrolled between 2015 and 2022 were analyzed, as follows: 77 with INOCA and 37 with MINOCA from the registry, and 66 with non-MI-CAD and 74 with MI-CAD from the study. Regression analyses demonstrated that migraines and preeclampsia or gestational hypertension were the most significant risk factors, with a higher likelihood of being associated with premature (M)INOCA, relative to obstructive CAD. Conversely, the presence of diabetes and a current or previous smoking history had the highest likelihood of being associated with premature CAD. Conclusions: The risk factor profiles of patients with premature (M)INOCA, compared to obstructive CAD, have significant differences.
Contexte: Au Canada, la cardiopathie est la principale cause de décès prématuré chez les femmes. La cardiopathie ischémique est catégorisée comme suit : infarctus du myocarde (IM) en l'absence de coronaropathie obstructive (MINOCA), ischémie sans obstruction des artères coronaires (INOCA) et athérosclérose coronaire obstructive accompagnée d'un IM ou sans IM. La présente étude vise à examiner la prévalence des facteurs de risque classiques et non classiques de cardiopathie ischémique et leurs liens avec le (M)INOCA, comparativement à l'athérosclérose coronaire obstructive accompagnée d'un IM ou sans IM chez les femmes jeunes. Méthodologie: Cette étude portait sur des femmes qui avaient prématurément (55 ans ou moins) souffert d'un (M)INOCA ou d'une coronaropathie obstructive confirmés par coronarographie et qui étaient inscrites au registre de la Leslie Diamond Women's Heart Health Clinic (WHC) ou qui participaient à l'étude visant à éviter les événements cardiovasculaires en Colombie-Britannique (Study toAvoid CardiovascularEvents inBC; SAVEBC). Des modèles de régression univariés et multivariés ont été utilisés pour explorer les associations entre les facteurs de risque et les probabilités de (M)INOCA, ainsi que d'athérosclérose coronaire obstructive accompagnée ou non d'un IM. Résultats: Au total, 254 femmes inscrites de 2015 à 2022 ont été recensées, soit 77 présentant une INOCA et 37, un MINOCA selon le registre WHC, et 66 présentant une athérosclérose coronaire obstructive sans IM et 74, une athérosclérose coronaire obstructive accompagnée d'un IM selon l'étude SAVEBC. Les analyses de régression ont démontré que les migraines et la prééclampsie ou l'hypertension gestationnelle étaient les facteurs de risque les plus importants associés à une probabilité la plus élevée de (M)INOCA comparativement à une coronaropathie obstructive. En revanche, la présence d'un diabète et d'un tabagisme actuel ou passé était associée à la probabilité la plus élevée de coronaropathie prématurée. Conclusions: Il existe d'importantes différences pour ce qui est des profils de facteurs de risque des patientes ayant prématurément souffert d'un (M)INOCA en comparaison d'une coronaropathie obstructive.
RESUMO
BACKGROUND: Fetal alcohol spectrum disorders (FASD) have a strong genetic component although the genes that underlie this are only beginning to be elucidated. In the present study, one of the most common phenotypes of FASD, cell death within the early developing neural tube, was examined across a genetic reference population in a reverse genetics paradigm with the goal of identifying genetic loci that could influence ethanol (EtOH)-induced apoptosis in the early developing neural tube. METHODS: BXD recombinant inbred mice as well as the parental strains were used to evaluate genetic differences in EtOH-induced cell death after exposure on embryonic day 9.5. Dams were given either 5.8 g/kg EtOH or isocaloric maltose-dextrin in 2 doses via intragastric gavage. Embryos were collected 7 hours after the initial exposure and cell death evaluated via TUNEL staining in the brainstem and forebrain. Genetic loci were evaluated using quantitative trait locus (QTL) analysis at GeneNetwork.org. RESULTS: Significant strain differences were observed in the levels of EtOH-induced cell death that were due to genetic effects and not confounding variables such as differences in developmental maturity or cell death kinetics. Comparisons between the 2 regions of the developing neural tube showed little genetic correlation with the QTL maps exhibiting no overlap. Significant QTLs were found on murine mid-chromosome 4 and mid-chromosome 14 only in the brainstem. Within these chromosomal loci, a number of interesting candidate genes were identified that could mediate this differential sensitivity including Nfia (nuclear factor I/A) and Otx2 (orthodenticle homeobox 2). CONCLUSIONS: These studies demonstrate that the levels of EtOH-induced cell death occur in strain- and region-dependent manners. Novel QTLs on mouse Chr4 and Chr14 were identified that modulate the differential sensitivity to EtOH-induced apoptosis in the embryonic brainstem. The genes underlying these QTLs could identify novel molecular pathways that are critical in this phenotype.
