The effects of brominated flame retardants (BFRs) on pro-atherosclerosis mechanisms.

Brominated flame-retardants (BFRs) are environmental endocrine disruptors, comprising several pollutants, which potentially affect the endocrine system and cause dysfunction and disease. Widespread BFR exposure may cause multisystem toxicity, including cardiovascular toxicity in some individuals. Studies have shown that BFRs not only increase heart rate, induce arrhythmia and cardiac hypertrophy, but also cause glycolipid metabolism disorders, vascular endothelial dysfunction, and inflammatory responses, all of which potentially induce pre-pathological changes in atherosclerosis. Experimental data indicated that BFRs disrupt gene expression or signaling pathways, which cause vascular endothelial dysfunction, lipid metabolism-related disease, inflammation, and possibly atherosclerosis. Considerable evidence now suggests that BFR exposure may be a pro-atherosclerotic risk factor. In this study, we reviewed putative BFR effects underpinning pro-atherosclerosis mechanisms, and focused on vascular endothelial cell dysfunction, abnormal lipid metabolism, pro-inflammatory cytokine production and foam cell formation. Consequently, we proposed a scientific basis for preventing atherosclerosis by BFRs and provided concepts for further research.

Higher than recommend dosage of sublingual isosorbide dinitrate for treating angina pectoris: a case report and review of the literature.

Nitrates primarily cause arterial and venous vasodilation effects, which increases coronary artery blood supply, and decreases cardiac preload and afterload by enhancing nitric oxide (NO) levels. The dosage of nitrates used for angina pectoris widely differs among individuals, and therapeutic resistance and tolerance gradually occur. Increasing doses of nitrates are needed to abolish ischemia chest pain onset in patients with angina pectoris, and to obtain satisfactory therapeutic effects. Here, we report the case of a 37-year-old male who was hospitalized six times, from September 2013 to April 2018, with recurrent angina pectoris. Although the patient was implanted with stents, he still presented with chest pain associated with physical efforts. Diagnosis with acute myocardial infarction was based on his ST-segment changes on electrocardiogram (ECG), elevated troponin-T level and coronary angiography. After the stents were implanted, his chest pain had no relief. Following three times of coronary angiography revealed that distal and small branch vessels still had stenosis, but was not required to revascularization. Due to serious headache resulted from sublingual or oral nitroglycerin; he had to take sublingual isosorbide dinitrate, from 20 mg to 150 mg each time, to obtain rapid relief from angina pectoris without doctor's consent. Followed up to April 2019, the patient has continued to take 100-150 mg sublingual isosorbide dinitrate for angina pectoris onset triggered by physical efforts, and has obtained remarkable relief within a few minutes, without blood pressure decrease and other side effects. Higher than recommend dosage of sublingual isosorbide dinitrate might establish better efficacy for angina pectoris in rarely patient.

Combination of D-dimer and simplified pulmonary embolism severity index to improve prediction of hospital death in patients with acute pulmonary embolism.

OBJECTIVE: To investigate whether the combination of D-dimer and simplified pulmonary embolism severity index (sPESI) could improve prediction of in-hospital death from pulmonary embolism (PE). METHODS: Patients with PE (n = 272) were divided into a surviving group (n = 249) and an in-hospital death group (n = 23). RESULTS: Compared with surviving patients, patients who died in hospital had significantly higher rates of hypotension and tachycardia, reduced SaO2 levels, elevated D-dimer and troponin T levels, higher sPESI scores, and were more likely to be classified as high risk. Elevated D-dimer levels and high sPESI scores were significantly associated with in-hospital death. Using thresholds for D-dimer and sPESI of 3.175 ng/mL and 1.5, respectively, the specificity for prediction of in-hospital death was 0.357 and 0.414, respectively, and the area under the receiver operating characteristic curve (AUC) was 0.665 and 0.668, respectively. When D-dimer and sPESI were considered together, the specificity for prediction of in-hospital death increased to 0.838 and the AUC increased to 0.74. CONCLUSIONS: D-dimer and sPESI were associated with in-hospital death from PE. Considering D-dimer levels together with sPESI can significantly improve the specificity of predicting in-hospital death for patients with PE.

Successful treatment of amniotic fluid embolism complicated by disseminated intravascular coagulation with rivaroxaban: A case report.

RATIONALE: An amniotic fluid embolism (AFE) is a rare, lethal syndrome that is commonly associated with disseminated intravascular coagulation (DIC). Anticoagulation therapy is the most important strategy to inhibit excessive activation of the coagulation cascade in patients with AFE and DIC. At present, treatment of AFE with rivaroxaban has not been reported. PATIENT CONCERNS: We report a 37-year-old woman (gravida 2, para 1) at 39 weeks' gestation with irregular contractions of the uterus was admitted to the obstetrical department. Ten minutes after the spontaneous rupture of the membranes, the patient complained of dyspnea and dysphoria and exhibited cyanosis of her lips. The patient's blood pressure decreased and heart rate increased rapidly, and 2100 mL of unclotted blood flowed from her vagina within 1 hour. Her platelet count dropped to 21 × 10/L, and the results from routine coagulation tests, and D-dimer and fibrin degradation product tests were obviously abnormal. DIAGNOSES: According to the current research consensus, AFE with DIC should be considered immediately when sudden cardiovascular collapse occurs around the time of labor and delivery, followed by the development of coagulopathy and hemorrhage. INTERVENTIONS: In addition, the variety of supportive treatments, rivaroxaban was used in anticoagulant therapy. OUTCOMES: At follow-up 30 and 60 days, there were no complaints of discomfort or abnormal laboratory assays. The patient recovered completely. LESSONS: This case highlights that rivaroxaban, as a direct inhibitor of activated factor Xa, demonstrates a good therapeutic efficacy for treating AFE with DIC.

Considerations for routine coagulation monitoring with rivaroxaban: A case report and review of the literature.

BACKGROUND: Rivaroxaban is a non-vitamin K antagonist oral anticoagulant that does not require coagulation monitoring based on current recommendations. Our goal is to explore whether routine coagulation monitoring should not be required for all patients receiving oral rivaroxaban, what relationship between routine coagulation abnormalities and bleeding, and how to deal with the above clinical situations through our case and review of the literature. CASE SUMMARY: We report a 67-year-old woman with a history of atrial fibrillation who presented to the hospital with worsening dyspnea and cough. Based on electrocardiogram, venous compression ultrasonography, and computed tomography pulmonary angiography, the diagnosis of atrial fibrillation, deep venous thrombosis, and acute pulmonary embolism was confirmed. Her coagulation assays and renal function were normal on admission; she was not underweight, did not have a history of hemorrhagic disease, and her CHA2DS2-VAS, HAS-BLED, and simplified Pulmonary Embolism Severity Index scores were 3, 0, and 0, respectively. Oral rivaroxaban (15 mg twice daily) was administered. The following day, she presented gastrointestinal and gum bleeding, combined with coagulation abnormalities. Following cessation of rivaroxaban, her bleeding stopped and tests improved over the next 2 d. Rivaroxaban was begun again 3 d after recovery. However, she again presented with gastrointestinal and gum bleeding and the abnormal tests, and the therapy was discontinued. At 30-d follow-up after discharge, she presented normal coagulation tests without bleeding. CONCLUSION: Although current guidelines recommend that using non-vitamin K antagonist oral anticoagulants including rivaroxaban do not require coagulation monitoring, a small number of patients may develop routine coagulation test changes and bleeding during rivaroxaban therapy, especially in the elderly. Clinicians should pay attention to these patients and further obtain evidence in practice.

LPA Gene Polymorphisms and Gene Expression Associated with Coronary Artery Disease.

The aim of our study was to investigate the influence of LPA gene polymorphisms for CAD risk and Lp(a) in a case-control study of Chinese Han population. In addition, we further analyzed the effect of LPA gene expression on plasma levels of Lp(a) and CAD risk. First, five SNPs (rs1367211, rs3127596, rs6415085, rs9347438, and rs9364559) in LPA gene were genotyped using the SEQUENOM Mass-ARRAY system in two groups. Second, we used quantitative real-time PCR to examine the mRNA expression levels of LPA gene in 92 cases and 32 controls. Results showed that the frequency of rs6415085-T allele was significantly higher in case group than that in control group (P < 0.05). Haplotypes were not associated with CAD risk (P > 0.05). And cases with the TT/TG genotype had significantly higher plasma Lp(a) levels compared with those that have the rs6415085 GG genotype (P < 0.05). Additionally, the mRNA expression levels in case group are significantly higher than that in control group (P < 0.05). Our study confirmed that rs6415085 was associated with CAD and increased plasma Lp(a) levels. And increased mRNA expression level of LPA gene may be a mechanism in development of CAD.

A Case-Control Study of the Relationship Between SLC22A3-LPAL2-LPA Gene Cluster Polymorphism and Coronary Artery Disease in the Han Chinese Population.

BACKGROUND: Mutations in the solute carrier family 22 member 3 (SLC22A3), lipoprotein (a)-like 2 (LPAL2), and the lipoprotein (a) (LPA) gene cluster, which encodes apolipoprotein (a) [apo (a)] of the lipoprotein (a) [Lp (a)] lipoprotein particle, have been suggested to contribute to the risk of coronary artery disease (CAD), but the precise variants of this gene cluster have not yet been identified in Chinese populations. OBJECTIVES: We sought to investigate the association between SLC22A3-LPAL2-LPA gene cluster polymorphisms and the risk of CAD in the Han Chinese population. PATIENTS AND METHODS: We recruited 551 CAD patients and 544 healthy controls for this case-control study. Four SNPs (rs9346816, rs2221750, rs3127596, and rs9364559) were genotyped in real time using the MassARRAY system (Sequenom; USA) in the SLC22A3-LPAL2-LPA gene cluster. All subjects were Chinese and of Han descent, and were recruited from the First Hospital of Jilin University based on convenience sampling from June 2009 to September 2012. RESULTS: The frequency of the minor allele G (34.8%) in rs9364559 was significantly higher in the CAD patients than in the healthy controls (29.4%) (P = 0.006). There was genotypic association between rs9364559 and CAD (P = 0.022), and these results still remained significant after adjustment for the conventional CAD risk factors through forward logistic regression analysis (P = 0.020, P = 0.019). Haplotype analyses from different blocks indicated that 11 haplotypes were associated with the risk of CAD. Seven haplotypes were associated with a reduced risk of CAD, whereas four haplotypes were associated with an increased risk of CAD. CONCLUSIONS: Rs9364559 in the LPA gene may contribute to the risk of CAD in the Han Chinese population; haplotypes which contain rs9346816-G were all associated with an increased risk of CAD in this study.

The association between the LPA gene polymorphism and coronary artery disease in Chinese Han population.

Lp(a) has been well known as an independent risk factor for coronary artery disease (CAD). The LPA gene, as it encodes apo(a) of the Lp(a) lipoprotein particle, was associated with increased risk of CAD. The purpose of this study was to analyze the relationship between the polymorphisms of LPA gene and CAD in Chinese Han population. Five SNPs (rs1367211, rs3127596, rs6415085, rs9347438, and rs9364559) in the LPA gene were genotyped using Sequenom MassARRAY time-of-flight mass spectrometer (TOF) in 560 CAD patients as case group and 531 non-CAD subjects as control group. The numbers of these two groups were from Chinese Han ancestry. The results showed that allele (P = 0.046) and genotype (P = 0.026) of rs9364559 in the LPA gene was associated with CAD. The frequency of rs9364559 minor allele (G) in case group was obviously higher than that in control group. Results of haplotype analysis showed that 4 haplotypes which contained rs9364559-G were associated with increased risk of CAD in this population. This study explored rs9364559 in the LPA gene may be associated with the pathogenesis of CAD; and the risk of CAD might be higher in the population carrying 4 haplotypes of different blocks in the LPA gene.

Association of genetic polymorphisms in matrix metalloproteinase-9 and coronary artery disease in the Chinese Han population: a case-control study.

OBJECTIVE: Matrix metalloproteinase-9 (MMP-9) plays an important role in inflammation and matrix degradation involved in atherosclerosis and plaque rupture. The T allele of rs3918242 has been reported to lead to a high promoter activity and associate with the extent of coronary artery disease (CAD). And some studies have reported that the G allele of rs17576 might be associated with CAD. The aim of this study was to assess the association between the polymorphisms of the MMP-9 gene and CAD in the Chinese Han population. METHODS: This case-control study comprised 258 CAD cases and 153 controls from the Chinese Han Population. The genomic DNA of MMP-9 was isolated from whole blood. Polymerase chain reaction-based restriction fragment length polymorphism was used to determine the rs3918242 and rs17576 genotypes in the MMP-9 gene and the total serum levels of MMP-9 were measured using enzyme-linked immunosorbent assay in both case and control groups. RESULTS: Analysis of MMP-9 gene polymorphisms showed that the frequencies of the T allele and CT+TT genotypes of rs3918242 were significantly higher in the case group than in the control group (p<0.05). However, the distribution of variant genotypes of rs17576 did not differ between the case and control groups (p>0.05). The total serum level of MMP-9 was significantly higher in the case group than in the control group (p<0.05). The subjects carrying T alleles in the CAD group had higher average serum MMP-9 levels compared with CC genotypes (p<0.05). CONCLUSIONS: Our results suggest that the single-nucleotide polymorphism of rs3918242 in the MMP-9 gene is associated with CAD and high serum levels of MMP-9 are also associated with CAD in the Chinese Han population. Therefore, genetic variation of rs3918242 may participate in the development of CAD through influencing MMP-9 expression.