No abstract

BackgroundThyroid function is closely involved in cardiovascular diseases. The free triiodothyronine (fT3) to free thyroxine (fT4) ratio has been reported as a risk factor for coronary artery disease, but its prognostic value in euthyroid patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) remains unclear.MethodsA total of 1162 euthyroid patients with MINOCA were enrolled and divided according to decreased tertiles of fT3/fT4 ratio. The study endpoint was major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, nonfatal stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan-Meier, Cox regression, and receiver-operating characteristic analyses were performed.ResultsPatients with lower fT3/fT4 tertile levels had a significantly higher incidence of MACE (10.0%, 13.9%, 18.2%; p=0.005) over the median follow-up of 41.7 months. The risk of MACE increased with the decreasing fT3/fT4 tertiles even after multivariate adjustment (tertile1 as reference, tertile2: HR 1.58, 95% CI: 1.05-2.39, p=0.030; tertile3: HR 2.06, 95% CI: 1.17-3.11, p=0.006). Lower level of fT3/fT4 ratio remained a robust predictor of MACE in overall (HR 1.64, 95% CI: 1.18-2.29, p=0.003) and in subgroups. When adding fT3/fT4 ratio [area under the curve (AUC) 0.61] into the thrombolysis in myocardial infarction (TIMI) risk score (AUC 0.69), the combined model (AUC 0.74) yielded a significant improvement in discrimination for MACE (ΔAUC 0.05, p=0.023).ConclusionsLow level of fT3/fT4 ratio was strongly associated with a poor prognosis in euthyroid patients with MINOCA. Routine assessment of fT3/fT4 ratio may facilitate risk stratification in this specific population.

Background Abnormal glucose metabolism including diabetes (DM) and prediabetes (pre-DM) have been reported as predictors of poorer outcomes after acute myocardial infarction (AMI). However, the prognostic value of pre-DM in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) remains unclear. Methods A total of 1179 MINOCA patients were prospectively recruited and divided into normoglycemia (NG), pre-DM, and DM groups according to glycated hemoglobin (HbA1c) levels or past history. The primary endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, nonfatal stroke, revascularization and hospitalization for unstable angina or heart failure. Kaplan–Meier and Cox regression analyses were performed. Results Patients with pre-DM and DM had a significantly higher incidence of MACE compared with NG group (10.8%, 16.1%, 19.4%; p = 0.003) over the median follow-up of 41.7 months. After multivariate adjustment, both pre-DM and DM were significantly associated with an increased risk of MACE (NG as reference; pre-DM: 1.45, 95% CI 1.03–2.09, p = 0.042; DM: HR 1.79, 95% CI 1.20–2.66, p = 0.005). At subgroup analysis, pre-DM remained a robust risk factor of MACE compared to NG. In addition, pre-DM had a similar impact as DM on long-term prognosis in patients with MINOCA. Conclusions Pre-DM defined as raised HbA1c was associated with a poor prognosis in patients with MINOCA. Routine assessment of HbA1c enables an early recognition of pre-DM and thus may facilitate risk stratification in this specific population.

Background Kawasaki disease (KD) is a systemic vasculitis that predominantly occurs in children, but the pathogenesis of KD remains unclear. Here, we explored key genes and underlying mechanisms potentially involved in KD using bioinformatic analyses. Material/Methods The shared differentially expressed genes (DEGs) in KD compared to control samples were identified using the microarray data from the Gene Expression Omnibus Series (GSE) 18606, GSE68004, and GSE73461. Analyses of the functional annotation, protein-protein interaction (PPI) network, microRNA-target DEGs regulatory network, and immune cell infiltration were performed. The expression of hub genes before and after intravenous immunoglobulin (IVIG) treatment in KD was further verified using GSE16797. Results A total of 195 shared DEGs (164 upregulated and 31 downregulated genes) were identified between KD and healthy controls. These shared DEGs were mainly enriched in immune and inflammatory responses. Ten upregulated hub genes ( ITGAX, SPI1, LILRB2, MMP9, S100A12, C3AR1, RETN, MAPK14, TLR5, MYD88 ) and the most significant module were identified in the PPI network. There were 309 regulatory relationships detected within 70 predicted microRNAs and 193 target DEGs. The immune cell infiltration analysis showed that monocytes, neutrophils, activated mast cells, and activated natural killer cells had relatively high proportions and were significantly more infiltrated in KD samples. Six hub genes of ITGAX, LILRB2, C3AR1, MAPK14, TLR5, and MYD88 were markedly downregulated after IVIG treatment for KD. Conclusions Our study identified the candidate genes and associated molecules that may be related to the KD process, and provided new insights into potential mechanisms and therapeutic targets for KD.

Background: Sex differences in clinical profiles and prognosis after acute myocardial infarction have been addressed for decades. However, the sex-based disparities among patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) remain largely unreported. Here, we investigated sex-specific characteristics and long-term outcomes in MINOCA population.Methods: A total of 1,179 MINOCA patients were enrolled, including 867 men and 312 women. The mean follow-up was 41.7 months. The primary endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, non-fatal reinfarction, revascularization, non-fatal stroke, and hospitalization for unstable angina or heart failure. Baseline data and outcomes were compared. Kaplan-Meier curves and Cox regression analyses were used to identify association between sex and prognosis.Results: Female patients with MINOCA had more risk profiles with regard to older age and higher prevalence of hypertension and diabetes compared with men. The evidence-based medical treatment was similar in men and women. The incidence of MACE (men vs. women: 13.8 vs. 15.3%, p = 0.504) did not differ significantly between the sexes. The Kaplan-Meier analysis also indicated that women had a similar incidence of MACE compared to men (log rank p = 0.385). After multivariate adjustment, female sex was not associated with the risk of MACE in overall (adjusted hazard ratio 1.02, 95% confidence interval: 0.72–1.44, p = 0.916) and in subgroups of MINOCA patients.Conclusion: The long-term outcomes were similar for men and women presenting with MINOCA despite older age and more comorbidities in women. Future research should aim to improve in-hospital and post-discharge care for both sexes with MINOCA.