Association of multiple preventive therapies postdischarge and long-term health outcomes after acute myocardial infarction.

BACKGROUND: Statins, beta-blockers, and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers have been advocated by guidelines as secondary prevention medications to improve the long-term outcomes of post-acute myocardial infarction (AMI) patients. However, adequate drug adherence has always been challenging, and different treatment regimens may lead to divergent outcomes that remain unclear under current myocardial infarction (MI) care standards. This study investigated the association between use of different preventive regimens post-AMI and patients' long-term outcomes. METHODS: This cohort study used data files from the Taiwan National Health Insurance Research Database. A total of 77 520 people who were hospitalized with AMI between 2002 and 2015 were assessed. On the basis of medication possession ratio (MPR) to individual medications, eight treatment groups were examined in this study. Receiving therapy was defined as MPR ≥40%. We investigated the association between different treatment groups and all-cause mortality in 24 months. RESULTS: Overall, 51 322 patients with ST-elevation MI and 26 198 with non-ST-elevation MI were included in the study. Patients received all three preventive medications show the lowest mortality in 24 months follow-up periods among all treatment groups. Patients who did not usage of any of these three preventive medications had the highest mortality in 24 months (adjusted hazard ratio, 1.78; 95% CI, 1.64-1.93). This mortality rate had the same pattern across the three cohort generations (2002-2005, 2006-2010, and 2011-2015). CONCLUSION: In this large population-based real-world study, usage of three preventive therapies post-MI was associated with the lowest rate of all-cause mortality.

Effectiveness and safety of rivaroxaban versus warfarin in Taiwanese patients with end-stage renal disease and nonvalvular atrial fibrillation: A real-world nationwide cohort study.

BACKGROUND: The optimal anticoagulant for end-stage renal disease patients for stroke prophylaxis is unknown. The efficacy and safety of warfarin in this population are debatable. In addition, real-world evidence of direct oral anticoagulants in patients with end-stage renal disease is limited. The aim of this study was to evaluate the clinical outcomes of rivaroxaban compared with warfarin in Taiwanese patients with end-stage renal disease with nonvalvular atrial fibrillation in a real-world setting. METHODS AND RESULTS: This was a retrospective population-based cohort study conducted using Taiwan's National Health Insurance Research Database. Patients with nonvalvular atrial fibrillation and end-stage renal disease who started on rivaroxaban or warfarin between February 2013 and September 2017 were eligible to participate in the study. The inverse probability of treatment weighting approach was used to balance baseline characteristics. Bleeding and thromboembolic outcomes were compared using competing risk analyses. The study population consisted of 3358 patients (173 and 3185 patients on rivaroxaban and warfarin, respectively). In the rivaroxaban group, 50.8%, 38.7%, and 10.4% of the patients received 10, 15, and 20 mg of the drug, respectively. The cumulative incidence of major bleeding was similar between the two groups; however, the gastrointestinal bleeding rate was lower in the rivaroxaban group (adjusted subdistribution hazard ratio [SHR]: 0.56, 95% confidence interval [CI]: 0.34-0.91) than in the warfarin group. Furthermore, the composite risk of ischemic stroke or systemic embolism was significantly lower in the rivaroxaban group (adjusted SHR: 0.36, 95% CI: 0.17-0.79). Similar findings were observed for patients who received 10 mg of rivaroxaban. CONCLUSIONS: In Taiwanese patients with end-stage renal disease and nonvalvular atrial fibrillation, rivaroxaban may be associated with a similar risk of major bleeding but a lower risk of thromboembolism compared with warfarin. The potential benefit of 10 mg of rivaroxaban in this population requires further investigation.

Circulating level of microRNA-142-5p is a potential biomarker for predicting in-stent restenosis: a case-control study.

BACKGROUND: Patients who receive percutaneous coronary intervention (PCI) have different chances of developing in-stent restenosis (ISR). To date, no predictable biomarker can be applied in the clinic. MicroRNAs (miRNAs or miRs) play critical roles in transcription regulation, and their circulating levels were reported to have potential as clinical biomarkers. METHODS: In total, 93 coronary stent-implanted patients without pregnancy, liver or renal dysfunction, malignancy, hemophilia, or autoimmune diseases were recruited in this clinical study. All recruited participants were divided into an ISR group (n = 45) and a non-ISR group (n = 48) based on their restenotic status as confirmed by cardiologists at the first follow-up visit (6 months after surgery). Blood samples of all participants were harvested to measure circulating levels of miRNA candidates (miR-132, miR-142-5p, miR-15b, miR-24-2, and miR-424) to evaluate whether these circulating miRNAs can be applied as predictive biomarkers of ISR. RESULTS: Our data indicated that circulating levels of miR-142-5p were significantly higher in the ISR population, and results from the receiver operating characteristic (ROC) curve analysis also demonstrated superior discriminatory ability of miR-142-5p in predicting patients' restenotic status. In addition, circulating levels of miR-15b, miR-24-2, and miR-424 had differential expressions in participants with diabetes, hyperlipidemia, and hypertension, respectively. CONCLUSIONS: The current study revealed that the circulating level of miR-142-5p has potential application as a clinical biomarker for predicting the development of ISR in stent-implanted patients.

Reversible left ventricular apical ballooning associated with jet lag in a Taiwanese woman: A case report.

Reversible left ventricular apical ballooning, without coronary artery stenosis, is a novel heart syndrome mimicking acute myocardial infarction, and is very rare in Taiwan. A 74-year-old Taiwanese woman returned from travelling abroad for one week and suffered from persistent, severe jet lag with sleep disturbance. She had a cold exacerbated by bronchial asthma for three days. She presented with sudden onset of chest pain after drinking three cups of coffee and taking a sauna for more than 1 h. On admission, an electrocardiogram showed ST segment elevation in leads II, III, aVF and V(3-6), and cardiac enzyme tests revealed minimal elevation. An echocardiogram showed apical ballooning and basal hyperkinesias of the left ventricle (LV) in systole. A coronary angiogram on the second day was normal, while the ST segment was still elevated, and the patient continued to experience chest pain. A negative T wave developed three days later. The electrocardiogram abnormality and LV dysfunction resolved completely six months later. A takotsubo (ampulla) cardiomyopathy was diagnosed. The activated myocardial adrenergic nervous system, stimulated by acute and marked stress in this patient, with more adrenergic innervations distributed in the apex of the LV, may be the trigger for this novel cardiac syndrome.

Inhibition of cyclic strain-induced endothelin-1 secretion by tetramethylpyrazine.

1. Chuanxiong is a Chinese herb that has been used widely in China to treat vascular disorders. 2,3,5,6-Tetramethylpyrazine (TMP) is one of the major components purified from chuanxiong. Many studies have demonstrated that TMP is effective in the treatment of cardiovascular diseases. However, the mechanism of action by which TMP exerts relaxation in vascular vessels remains unclear. 2. Endothelin (ET)-1 is a potent vasopressor synthesised by endothelial cells both in culture and in vivo. The aims of the present study were to test the hypothesis that TMP may alter strain-induced ET-1 secretion and to identify the putative underlying signalling pathways in endothelial cells. 3. We showed that TMP inhibits strain-induced ET-1 secretion. 2,3,5,6-Tetramethylpyrazine also inhibits the strain-induced formation of reactive oxygen species (ROS) and phosphorylation of extracellular signal-regulated kinases (ERK) 1/2. Furthermore, pretreating cells with TMP or the anti-oxidant N-acetyl-cysteine decreased strain-induced increases in ET-1 secretion and ERK1/2 phosphorylation. Using a reporter gene assay, TMP and N-acetyl-cysteine were demonstrated to also attenuate the strain-induced activity of the activator protein-1 reporter. 4. In summary, we have demonstrated, for the first time, that TMP inhibits strain-induced ET-1 gene expression, in part by interfering with the ERK1/2 pathway via attenuation of ROS formation. Thus, the present study provides important new insights into the molecular pathways that may contribute to the proposed beneficial effects of TMP in the vascular system.

Concentration-dependent differential effects of quercetin on rat aortic smooth muscle cells.

Quercetin is one of the most ubiquitous bioflavonoids in foods of plant origin. Although quercetin is generally considered to provide protection against oxidative injury and inflammation, recent studies have demonstrated that its cytoprotective effects occur within a narrow concentration range. We attempted to examine the concentration-dependent effect on proliferation and inflammation in the primary culture of rat aortic smooth muscle cells. We demonstrate that quercetin inhibited [3H]thymidine incorporation into rat aortic smooth muscle cells only at concentrations < or =50 microM in a concentration-dependent manner. Nevertheless, quercetin, at concentrations > or =100 microM, reduced cell viability; this was further characterized as being due to apoptosis, which occurred through the proteolytic activation of pro-caspase-3. Additionally, the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) substantially increased in rat aortic smooth muscle cells exposed to 100 microM quercetin, results which differ from observations by others and ourselves of cells exposed to < or =50 microM quercetin. Unlike P-JNK and P-p38, the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/ERK2) was not significantly affected by the concentration-dependent effects of quercetin. Surprisingly, the adverse effects of higher concentrations of quercetin could be ameliorated by adding the antioxidants, catalase, and N-acetylcysteine (NAC). Furthermore, the electrophoretic mobility shift assay (EMSA) showed that rat aortic smooth muscle cells exposed to quercetin at concentrations of < or =50 microM caused concentration-dependent inhibition of nuclear factor kappa B (NF-kappaB) activity, whereas concentrations of > or =100 microM resulted in increased NF-kappaB binding activity. We demonstrate for the first time that quercetin at low concentrations has antiproliferative and antiinflammatory effects, but at concentrations of > or =100 microM, is likely to induce the opposite effects on rat aortic smooth muscle cells.

Fosinopril improves left ventricular diastolic function in young mildly hypertensive patients without hypertrophy.

To clarify whether fosinopril monotherapy can improve left ventricular diastolic function (LVDF) in young mildly hypertensives without hypertrophy, we studied 66 patients (pts) with diastolic blood pressure 90-100 mmHg, aged <45 years, with normal 2-dimensional echocardiography (2-D echo), and impaired DF. Impaired DF was defined as a Doppler transmitral early (E) to atrial (A) filling velocity ratio (E/A ratio) <1. Thirty-eight pts were selected for fosinopril monotherapy. Mean age was 36 years. Duration of documented hypertension was 5.4 years. Mean daily dose of fosinopril was 20 mg. Twenty-eight controls were treated with hydrochlorothiazide and hydralazine combination. Sixty-six age- and sex-matched healthy subjects served to establish normal reference values of 2-D and Doppler echo measurements. All hypertensives were treated for 30 months and re-examined 4 weeks after cessation of treatment. The fosinopril-treated group showed improvements in transmitral E (52 +/- 8 cm/s, vs. 61 +/- 9 cm/s, p < 0.01), A (56 +/- 9 cm/s, vs. 47 +/- 6 cm/s, p < 0.05), and E/A ratio (0.93 +/- 0.16, vs. 1.29 +/- 0.18, p < 0.01). Moreover, the early to atrial velocity-time integral ratio (1.31 +/- 0.10, vs. 2.24 +/- 0.10, p < 0.001) improved. The pulmonary venous flow pattern normalized after fosinopril therapy. LV mass index, relative wall thickness, LV dimension, left atrial dimension, fractional shortening, heart rate, and body mass index did not change. The hydrochlorothiazide-hydralazine combination-treated group did not show an improved diastolic function. It is concluded that long-term fosinopril monotherapy leads to an improvement of impaired LVDF in young mildly hypertensives without hypertrophy.