Effect of rifampicin administration on CYP induction in a dermatomyositis patient with vasospastic angina attributable to nilmatrelvir/ritonavir-induced blood tacrolimus elevation: A case report.

Ritonavir (RTV), which is used in combination with nilmatrelvir (NMV) to treat coronavirus disease 2019 (COVID-19), inhibits cytochrome P450 (CYP) 3A, thereby increasing blood tacrolimus (TAC) levels through a drug-drug interaction (DDI). We experienced a case in which a DDI between the two drugs led to markedly increased blood TAC levels, resulting in vasospastic angina (VSA) and acute kidney injury (AKI). Rifampicin (RFP) was administered to induce CYP3A and promote TAC metabolism. A 60-year-old man with dermatomyositis who was taking 3 mg/day TAC contracted COVID-19. The patient started oral NMV/RTV therapy, and he was admitted to the hospital after 4 days because of chest pain and AKI. On day 5, his blood TAC level increased markedly to 119.8 ng/mL. RFP 600 mg was administered once daily for 3 days, and his blood TAC level decreased to the therapeutic range of 9.6 ng/mL on day 9, leading to AKI improvement. Transient complete atrioventricular block and nonsustained ventricular tachycardia were present during chest pain. In the coronary spasm provocation test, complete occlusion was observed in the right coronary artery, leading to a diagnosis of VSA. VSA and AKI are possible side effects of high blood TAC levels caused by DDI, and attention should be paid to cardiovascular side effects such as VSA and AKI associated with increased blood levels of TAC when it is used together with NMV/RTV. When blood levels of TAC increase, oral RFP can rapidly decrease TAC blood levels and potentially reduce its toxicity.

Mobilization of Endogenous CD34+/CD133+ Endothelial Progenitor Cells by Enhanced External Counter Pulsation for Treatment of Refractory Angina.

Adult stem cell therapy via intramyocardial injection of autologous CD34+ stem cells has been shown to improve exercise capacity and reduce angina frequency and mortality in patients with refractory angina (RA). However, the cost of such therapy is a limitation to its adoption in clinical practice. Our goal was to determine whether the less costly, less invasive, and widely accessible, FDA-approved alternative treatment for RA patients, known as enhanced external counterpulsation (EECP), mobilizes endogenous CD34+ stem cells and whether such mobilization is associated with the clinical benefits seen with intramyocardial injection. We monitored changes in circulating levels of CD34+/CD133+ and CD34+/KDR+ cells in RA patients undergoing EECP therapy and in a comparator cohort of RA patients undergoing an exercise regimen known as cardiac rehabilitation. Changes in exercise capacity in both cohorts were monitored by measuring treadmill times (TT), double product (DP) scores, and Canadian Cardiovascular Society (CCS) angina scores between pre- and post-treatment treadmill stress tests. Circulating levels of CD34+/CD133+ cells increased in patients undergoing EECP and were significant (ß = -2.38, p = 0.012) predictors of improved exercise capacity in these patients. CD34+/CD133+ cells isolated from RA patients could differentiate into endothelial cells, and their numbers increased during EECP therapy. Our results support the hypothesis that mobilized CD34+/CD133+ cells repair vascular damage and increase collateral circulation in RA patients. They further support clinical interventions that can mobilize adult CD34+ stem cells as therapy for patients with RA and other vascular diseases.

Optimizing the Use of High-Sensitivity Troponin Assays for the Early Rule-out of Myocardial Infarction in Patients Presenting with Chest Pain: A Systematic Review.

BACKGROUND: We assessed the accuracy and clinical effectiveness of high-sensitivity cardiac troponin (hs-cTn) assays for early rule-out of non-ST-segment elevation myocardial infarction (NSTEMI) in adults presenting with acute chest pain. METHODS: Sixteen databases were searched to September 2019. Review methods followed published guidelines. The bivariate model was used to estimate summary sensitivity and specificity with 95% confidence intervals for meta-analyses involving 4 or more studies, otherwise random-effects logistic regression was used. RESULTS: Thirty-seven studies (124 publications) were included in the review. The hs-cTn test strategies evaluated in the included studies were defined by the combination of 4 factors (assay, number of tests, timing of tests, and threshold concentration or change in concentration between tests). Clinical opinion indicated a minimum acceptable sensitivity of 97%. A single test at presentation using a threshold at or near the assay limit of detection could reliably rule-out NSTEMI for a range of hs-cTn assays. Serial testing strategies, which include an immediate rule-out step, increased the proportion ruled out without loss of sensitivity. Finally, serial testing strategies without an immediate rule-out step had excellent sensitivity and specificity, but at the expense of the option for immediate patient discharge. CONCLUSION: Test strategies that comprise an initial rule-out step, based on low hs-cTn concentrations at presentation and a minimum symptom duration, and a second step for those not ruled-out that incorporates a small absolute change in hs-cTn at 1, 2, or 3 hours, produce the highest rule-out rates with a very low risk of missed NSTEMI. PROSPERO REGISTRATION: CRD42019154716.

Patients discharged with elevated baseline high-sensitive cardiac troponin T from the emergency department.

BACKGROUND: Elevated levels of high-sensitive cardiac troponin T (hs-cTnT) are linked to poor prognosis among emergency department (ED) patients. OBJECTIVE: Examine the effect of our ED risk assessment among patients with suspected acute coronary syndrome (ACS) and elevated baseline hs-cTnT levels. DESIGN: Observational cohort study of 16776 ED patients with chest pain or dyspnoea and a hs-cTnT sample analyzed at the time of the ED visit. Of these 1480 patients were sent home with elevated hs-cTnT levels (>14 ng/L). METHODS: Analysis of clinical and laboratory data from the local hospital and data from the National Board of Health and Welfare. RESULTS: Admitted patients had 11% and discharged patients had 1.2% 90-day mortality indicating effective risk assessment of patients with suspected ACS. However, if the suspected ACS patient presented with hs-cTnT between 14 and 22 ng/L, the 90-day mortality was 4.1% among discharged and 6.7% among admitted patients. Among discharged patients, an hs-cTnT level above 14 ng/L was a higher independent risk factor for 90-day mortality (HR 3.3, 95% CI 2.9-3.7, p < 0.001) than if the patient was triaged as a high-risk patient (HR 1.6, 95% CI 1.1-1.8, p < 0.001). CONCLUSIONS: Our ED risk assessment was less effective among patients presenting with elevated hs-cTnT levels.

Complement component 7 is associated with total- and cardiac death in chest-pain patients with suspected acute coronary syndrome.

BACKGROUND: Complement activation has been associated with atherosclerosis, atherosclerotic plaque destabilization and increased risk of cardiovascular events. Complement component 7 (CC7) binds to the C5bC6 complex which is part of the terminal complement complex (TCC/C5b-9). High-sensitivity C-reactive protein (hsCRP) is a sensitive marker of systemic inflammation and may reflect the increased inflammatory state associated with cardiovascular disease. AIM: To evaluate the associations between CC7 and total- and cardiac mortality in patients hospitalized with chest-pain of suspected coronary origin, and whether combining CC7 with hsCRP adds prognostic information. METHODS: Baseline levels of CC7 were related to 60-months survival in a prospective, observational study of 982 patients hospitalized with a suspected acute coronary syndrome (ACS) at 9 hospitals in Salta, Argentina. A cox regression model, adjusting for conventional cardiovascular risk factors, was fitted with all-cause mortality, cardiac death and sudden cardiac death (SCD) as the dependent variables. A similar Norwegian population of 871 patients was applied to test the reproducibility of results in relation to total death. RESULTS: At follow-up, 173 patients (17.7%) in the Argentinean cohort had died, of these 92 (9.4%) were classified as cardiac death and 59 (6.0%) as SCD. In the Norwegian population, a total of 254 patients (30%) died. In multivariable analysis, CC7 was significantly associated with 60-months all-cause mortality [hazard ratio (HR) 1.26 (95% confidence interval (CI), 1.07-1.47) and cardiac death [HR 1.28 (95% CI 1.02-1.60)], but not with SCD. CC7 was only weakly correlated with hsCRP (r = 0.10, p = 0.002), and there was no statistically significant interaction between the two biomarkers in relation to outcome. The significant association of CC7 with total death was reproduced in the Norwegian population. CONCLUSIONS: CC7 was significantly associated with all-cause mortality and cardiac death at 60-months follow-up in chest-pain patients with suspected ACS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01377402, NCT00521976.

Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation.

An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease. The serum of patients with coronary artery disease or cerebrovascular disease displayed an increased propensity to form CPPs in combination with elevated ionised calcium as well as reduced albumin levels, altogether indicative of reduced Ca2+-binding capacity. Intravenous administration of CPPs to normolipidemic and normotensive Wistar rats provoked intimal hyperplasia and adventitial/perivascular inflammation in both balloon-injured and intact aortas in the absence of other cardiovascular risk factors. Upon the addition to primary human arterial endothelial cells, CPPs induced lysosome-dependent cell death, promoted the release of pro-inflammatory cytokines, stimulated leukocyte adhesion, and triggered endothelial-to-mesenchymal transition. We concluded that CPPs, which are formed in the blood as a result of altered mineral homeostasis, cause endothelial dysfunction and vascular inflammation, thereby contributing to the development of cardiovascular disease.

Progenitor Cells and Clinical Outcomes in Patients With Acute Coronary Syndromes.

RATIONALE: Circulating progenitor cells (CPCs) mobilize in response to ischemic injury, but their predictive value remains unknown in acute coronary syndrome (ACS). OBJECTIVE: We aimed to investigate the number of CPCs in ACS compared with those with stable coronary artery disease (CAD), relationship between bone marrow PCs and CPCs, and whether CPC counts predict mortality in patients with ACS. METHODS AND RESULTS: In 2028 patients, 346 had unstable angina, 183 had an acute myocardial infarction (AMI), and the remaining 1499 patients had stable CAD. Patients with ACS were followed for the primary end point of all-cause death. CPCs were enumerated by flow cytometry as mononuclear cells expressing a combination of CD34+, CD133+, vascular endothelial growth factor receptor 2+, or chemokine (C-X-C motif) receptor 4+. CPC counts were higher in subjects with AMI compared those with stable CAD even after adjustment for age, sex, race, body mass index, renal function, hypertension, diabetes mellitus, hyperlipidemia, and smoking; CD34+, CD34+/CD133+, CD34+/CXCR4+, and CD34+/VEGFR2+ CPC counts were 19%, 25%, 28%, and 142% higher in those with AMI, respectively, compared with stable CAD. There were strong correlations between the concentrations of CPCs and the PC counts in bone marrow aspirates in 20 patients with AMI. During a 2 (interquartile range, 1.31-2.86)-year follow-up period of 529 patients with ACS, 12.4% died. In Cox regression models adjusted for age, sex, body mass index, heart failure history, estimated glomerular filtration rate, and AMI, subjects with low CD34+ cell counts had a 2.46-fold (95% confidence interval, 1.18-5.13) increase in all-cause mortality, P=0.01. CD34+/CD133+ and CD34+/CXCR4+, but not CD34+/VEGFR2+ PC counts, had similar associations with mortality. Results were validated in a separate cohort of 238 patients with ACS. CONCLUSIONS: CPC levels are significantly higher in patients after an AMI compared with those with stable CAD and reflect bone marrow PC content. Among patients with ACS, a lower number of hematopoietic-enriched CPCs are associated with a higher mortality.

Diagnostic accuracy of troponin T measured ≥6h after symptom onset for ruling out myocardial infarction.

Objectives: Guidelines recommend a single high-sensitivity cardiac troponin T (hs-cTnT) ≤14 ng/L measured ≥6 h after chest pain onset combined with a GRACE score <140 and the patient being pain-free for ruling out myocardial infarction (MI). There is however little data on the performance of this strategy. We therefore aimed to evaluate the diagnostic accuracy of a hs-cTnT ≤14 ng/L measured ≥6 h after chest pain onset when combined with GRACE score or other clinical risk stratification tools. Design: This was a secondary analysis of a prospective observational study, which enrolled emergency department (ED) chest pain patients. The hs-cTnT strategy was combined with HEART, TIMI, EDACS, GRACE score and ED physician's overall assessment of patient history and ECG. The primary outcome was MI, and the secondary outcome was 30-day major adverse cardiac events (MACE). Results: All tested diagnostic strategies were shown to have a negative predictive value (NPV) ≥99.5% for ruling out MI. Using HEART, TIMI, EDACS or ECG + patient history also resulted in a NPV ≥98% for ruling out 30-day MACE. An isolated hs-cTnT ≤14 ng/L measured ≥6 h after chest pain onset and the combination with GRACE score both had a NPV <98% for ruling out 30-day MACE. Conclusion: A single hs-cTnT ≤14 ng/L obtained ≥6 h from chest pain onset, with and without GRACE score, reliably ruled out MI but did not perform well for ruling out 30-day MACE. These results question current guideline recommendations, and indicate that HEART, EDACS, TIMI, or ECG + patient history strategies should be the preferred risk stratification tools.

Prognostic Value of Pre-Infarction Angina Combined with Mean Platelet Volume to Lymphocyte Count Ratio for No-Reflow and Short-Term Mortality in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

BACKGROUND The aim of the present study was to investigate the clinical predictive value of pre-infarction angina (PIA) combined with mean platelet volume to lymphocyte count ratio (MPVLR) for no-reflow phenomenon and short-term mortality in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). MATERIAL AND METHODS A total of 1009 STEMI patients who had undergone PCI were enrolled and subdivided into 4 groups based on the occurrence of PIA and the presence of MPVLR above or below the cutoff value. Analysis of the predictors of the no-reflow phenomenon and 90-day mortality was conducted. Further, evaluation and comparison of the clinical predictive value of PIA, MPVLR, and their combination were done. RESULTS Both MPVLR (odds ratio [OR]=1.476, 95% confidence interval [CI]: 1.401 to 1.756, P<0.001; hazard ratio [HR]=1.430, 95% CI: 1.287 to 1.643, P<0.001) and PIA (OR=0.905, 95% CI: 0.783 to 0.986, P<0.001; HR=0.878, 95% CI: 0.796 to 0.948, P<0.001) were independent predictors of no-reflow phenomenon and 90-day mortality. Spearman's rank correlation test revealed that MPVLR (r=-0.297, P<0.001), monocyte to lymphocyte count ratio (MLR) (r=-0.211, P<0.001) and neutrophil to lymphocyte count ratio (NLR) (r=-0.389, P<0.001) in peripheral blood were significantly negatively correlated with postoperative left ventricular ejection fraction (LVEF). Upon comparing the area under curve (AUC), the MPVLR combined with PIA achieved better performance in differentiating no-reflow phenomenon (AUC=0.847, 95% CI: 0.821 to 0.874) and 90-day mortality (AUC=0.790, 95% CI: 0.725 to 0.855), than the GRACE score, MPVLR and PIA alone, and had similar performance to all other pairwise combinations of the GRACE score, MPVLR and PIA. CONCLUSIONS High MPVLR and PIA were independent predictors of the no-reflow phenomenon and 90-day mortality in patients with STEMI after PCI. Moreover, Combined application of MPVLR and PIA can effectively predict the occurrence of the no-reflow phenomenon and 90-day mortality.

Effects of Altered Levels of Pro- and Anti-Inflammatory Mediators on Locations of In-Stent Reocclusions in Elderly Patients.

Imbalances of proatherogenic inflammatory and antiatherogenic inflammatory mediators were involved in the pathogenesis of atherosclerosis. This study sought to investigate the effects of proatherogenic inflammatory and antiatherogenic inflammatory mediators on the proximal, middle, and distal coronary artery reocclusions in elderly patients after coronary stent implantations. We measured the expression levels of proatherogenic inflammatory/antiatherogenic inflammatory cytokines. This included interleukin-1 ß (IL-1 ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), interleukin-10 (IL-10), interleukin-17 (IL-17), interleukin-13 (IL-13), and interleukin-37 (IL-37) in the elderly patients with the proximal, middle, and distal coronary artery reocclusions after coronary stent implantations. Levels of IL-1 ß, IL-6, IL-8, TNF-α, and hs-CRP were remarkably increased (P < 0.001), and levels of IL-10, IL-17, IL-13, and IL-37 were remarkably lowered (P < 0.001) in the elderly patients with the proximal, middle, and distal coronary artery reocclusions. Imbalances of proatherogenic inflammatory and antiatherogenic inflammatory mediators may be involved in the formation and progression of proximal, middle, and distal coronary artery reocclusions in elderly patients after coronary stent implantations.

Brain-Derived Neurotrophic Factor during Oral Glucose Tolerance Test Predicts Cardiovascular Outcomes.

We investigated if brain-derived neurotrophic factor (BDNF) accumulation after glucose intake could predict cardiovascular outcomes. We enrolled patients admitted for angiography due to angina. After their conditions stabilized, serum BDNF levels were detected at 0, 30, and 120 min during oral glucose tolerance test (OGTT). Area under the curve (AUC) of BDNF was calculated. The first occurrence of nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality served as the primary composite endpoint. Of 480 enrolled patients, 428 completed the follow-up, and 36 primary endpoint events occurred during a median follow-up of 4.4 years. The area under the receiver operating characteristic curve significantly increased from 0.61 (95% confidence interval (CI): 0.52-0.73) for the Framingham risk score (FRS) alone model to 0.72 (95%CI: 0.63-0.81) for the AUC of BDNF plus FRS model (p = 0.016) for predicting the primary endpoint, but not to 0.65 (95%CI: 0.55-0.75) for the fasting BDNF plus FRS model (p = 0.160). Grouped by median AUC of BDNF of 38.0 (ng/mL) × h, the low BDNF group had a significantly higher risk of the endpoint than the high BDNF group (hazard ratio = 3.410, 95%CI: 1.520-7.653, p = 0.003). In conclusion, AUC of BDNF during OGTT could be superior to fasting BDNF for predicting a low cardiovascular risk.

Circulating microRNA-1 in the diagnosis and predicting prognosis of patients with chest pain: a prospective cohort study.

BACKGROUND: To investigate the early diagnostic and prognostic value of microRNA-1 in patients with acute chest pain. METHODS: This study enrolled 341 patients attacked by chest pain within 3 h, and another 100 volunteers as control group. Circulating microRNA-1 was collected and determined by real-time quantitative reverse transcription-polymerase chain reaction. The clinical follow-up period was 720 days. RESULTS: There were 174 patients in acute myocardial infarction (AMI) group, 167 in non-AMI group. The relative expression of microRNA-1 was significantly increased within 3 h in AMI group, and it continued rising within 12 h, lower at 24 h than that 12 h in AMI group without reperfusion therapy. Otherwise, microRNA-1 concentration was markedly low at 12 h after primary percutaneous coronary intervention in AMI group. The 95% reference range of circulating microRNA-1 was 0.171-0.653. It was significantly available for microRNA-1 to early diagnose AMI with an optimal cutoff value of 2.215 and diagnostic accuracy could be improved when combined with cardiac troponin I. It was not statistically significant for microRNA-1 to forecast future AMI but might prognose mortality of 720 days in chest pain patients. In patients with chest pain, microRNA-1 concentration was high with major adverse cardiac events within 30 days, low with high overall survival within 720 days. CONCLUSIONS: Circulating microRNA-1 might diagnose early AMI and predict the prognosis of patients with chest pain.

Gender differences in thrombogenicity among patients with angina and non-obstructive coronary artery disease.

Women more often present with angina and non-obstructive coronary artery disease (ANOCA) and have poorer clinical outcomes than men. These findings may be related to sex associated differences in inflammation and thrombogenicity. Consecutive patients (n = 134) with ANOCA (luminal diameter stenosis < 50%) undergoing elective cardiac catheterization were included in post hoc analysis of Multi-Analyte, thrombogenic, and Genetic Markers of Atherosclerosis (MAGMA, NCT01276678) study. Patients with prior revascularization, coronary artery bypass grafting or myocardial infarction were excluded. Blood for thromboelastography, oxidized LDL ß2-glycoprotein complex (AtherOx), oxidized-LDL, lipid profile, and urine for 11-dehydrothromboxane B2 (dTxB2) were obtained before catheterization. All women (n = 75) were post-menopausal and tended to be older than men (61.4 ± 10.6 vs. 58.6 ± 9.9 year, p = 0.12), and were significantly more thrombogenic with higher thrombin-induced platelet-fibrin strength (TIP-FCS, mm) (68.0 ± 4.5 vs. 64.5 ± 6.2 mm, p = 0.001), clotting index (0.35 ± 2.22 vs. - 0.72 ± 2.75, p = 0.02), K (measure of the speed to reach 20 mm of clot strength from an amplitude of 2 mm) (2.2 ± 1.6 vs. 1.7 ± 0.5 min, p = 0.01), and fibrinogen activity (degrees) (66.6 ± 7.1 vs. 62.9 ± 7.5, p = 0.009). Markers of inflammation were not significantly different between the two groups. Women had higher total cholesterol, total LDL, LDL subtypes 1 and 2, total HDL, HDL subtypes 2 and 3, and ApoA1 (p < 0.05 for all). On multivariate regression, TIP-FCS remained significantly higher in women (p < 0.0001). Women with ANOCA are more thrombogenic than men. This fundamental difference in thrombogenicity may affect gender-related outcomes and warrants further investigation.

Long-term statin persistence is poor among high-risk patients with dyslipidemia: a real-world administrative claims analysis.

BACKGROUND: A decade ago, statin persistence was < 50% after 1 year, and recent short-term analyses have revealed very little progress in improving statin persistence, even in patients with a prior cardiovascular (CV) event. Data on longer-term statin persistence are lacking. We measured long-term statin persistence in patients with high CV risk. METHODS: This retrospective administrative claims analysis of the Optum Research Database included patients aged ≥ 45 years with diabetes and/or atherosclerotic CV disease (ASCVD) who had a statin prescription filled in 2010. It included an elevated triglycerides (TG) cohort of patients with index date in 2010 and TG ≥ 150 mg/dL (n = 23,181) and a propensity-matched comparator cohort with TG < 150 mg/dL and high-density lipoprotein cholesterol > 40 mg/dL (n = 23,181). Both cohorts were followed for ≥ 6 months up to March 2016. RESULTS: The probability of remaining on a prescription fill for index statin therapy was 47% after 1 year and 19% after 5 years in both cohorts. Statin persistence was worse among women than men, and among younger versus older patients (P < 0.001 for all comparisons). After 5 years, the probability of remaining on a prescription fill for index statin was < 25% across all subgroups assessed including patients with and without baseline revascularization, heart failure, peripheral artery disease and renal disease. Similar results were observed in a subcohort analysis of patients with TG 200-499 mg/dL. CONCLUSIONS: Long-term statin persistence after 5 years is alarmingly low (< 25%) and is a public health concern.

Corn silk decoction for blood lipid in patients with angina pectoris: A systematic review and meta-analysis.

The aims of this study were to evaluate the efficacy of corn silk decoction on lipid profile in patients with angina pectoris. PubMed, Cochrane, Embase, Google Scholar, Chongqing VIP Chinese Science and Technology Periodical Database, China National Knowledge Infrastructure, and Wanfang database were searched up to January 2019 for randomized controlled trials that assessed the impact of corn silk decoction on total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in patients with angina pectoris. Study evaluation and synthesis methods were in accordance with the Cochrane Handbook, and data were analyzed using Review Manager (version 5.3) software. Random effects model was applied in this systematic review and meta-analysis to compensate for potential heterogeneity among the included studies. A total of four randomized controlled trials were eligible for meta-analysis. Pooled results of these studies indicated that corn silk decoction might improve high-density lipoprotein cholesterol and reduce total cholesterol, triglycerides, and low-density lipoprotein cholesterol in patients with angina pectoris. Subgroup analyses showed that corn silk decoction or modified corn silk decoction plus conventional pharmaceutical treatment could have favorable effects on blood lipids. However, the lack of blinding in most studies may have led to overestimation of these effects. Further studies with better design are needed to confirm these findings.

Co-administration of cyclosporine and ticagrelor may lead to a higher exposure to cyclosporine: a case report of a 49-year-old man.

ADVERSE EVENT: A drug interaction leading to higher exposure to cyclosporine. DRUGS IMPLICATED: Cyclosporine and ticagrelor. THE PATIENT: A 49-year-old man with a stable renal graft, managed with cyclosporine with stable trough blood concentrations for several years, was treated with ticagrelor for unstable angina pectoris. EVIDENCE THAT LINKS THE DRUG TO THE EVENT: The timeline was consistent with the appearance of an interaction, the interaction was confirmed by an increase in trough concentration of cyclosporine, and there were no alternative causes that by themselves could have caused the increase in cyclosporine exposure. MANAGEMENT: Cessation of ticagrelor. MECHANISM: Inhibition of CYP3A4 and P-glycoprotein by ticagrelor. IMPLICATIONS FOR THERAPY: Clinicians should be aware of this potential interaction as ticagrelor is frequently prescribed in individuals using cyclosporine. Close monitoring of cyclosporine serum concentrations is warranted to avoid overdosing of cyclosporine. A pharmacokinetic study is needed to further examine the probable interaction between cyclosporine and ticagrelor.

Interrelationships of Cadmium, Smoking, and Angina in the National Health and Nutrition Examination Survey, a Cross-Sectional Study.

The interrelationships between cadmium biomarker levels, smoking, and myocardial infarction and stroke have been established. In this cross-sectional analysis, we explored the interrelationships of blood cadmium levels, smoking, and angina. We analyzed the National Health and Nutrition Examination Survey (NHANES, 2003-2014) accounting for the multi-staged complex sampling design. Participants 40-79 years of age with blood cadmium levels but without a history of myocardial infarction and/or stroke were included (n = 14,832). We examined blood cadmium levels (3 tertile groups) in relation to 3 (diagnosed, undiagnosed, and composite diagnosed and/or undiagnosed) angina outcomes. Multivariable logistic regression models adjusted for age, diabetes, smoking status, and household income were used to estimate odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). Of 14,832 participants, 741 (4.2%) had positive composite angina. The crude and adjusted ORs comparing those in the lowest tertile (referent group) of blood cadmium to those in the highest tertile for the composite outcome were 1.82 (95% CI 1.42-2.34) and 1.45 (95% CI 1.12-1.88), respectively. These cross-sectional data from a nationally representative sample contribute to the hypothesis that there are interrelationships between smoking, cadmium, and angina.

Association between brain-derived neurotrophic factor and von Willebrand factor levels in patients with stable coronary artery disease.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in angiogenesis and maintenance of endothelial integrity. Whether circulating BDNF levels are associated with von Willebrand factor (vWF) levels, which are indicators of endothelial dysfunction is not known. This study investigated the association between plasma BNDF and vWF levels and whether these biomarkers could predict cardiovascular events at a 12-month follow-up in patients with stable coronary artery disease (CAD). METHODS: We recruited 234 patients with suspected angina pectoris. Subjects were divided into CAD (n = 143) and control (n = 91) groups based on coronary angiography. Plasma BDNF and vWF levels were measured using ELISA. Patients were followed-up for one year, and information on adverse cardiac events was collected. RESULTS: CAD patients exhibited significantly lower plasma BDNF and higher vWF levels than those of control patients. High vWF levels were associated with low BDNF levels even after adjustment for age, gender, low-density lipoprotein (LDL) levels, and the presence of diabetes mellitus. A receiver operating characteristic curve was used to determine whether low BDNF and high vWF levels could predict adverse cardiovascular events. The area under the curve for vWF and the inverse of BDNF were 0.774 and 0.804, respectively. CONCLUSIONS: These findings suggest that endothelial dysfunction is an important determinant of the impaired circulating BDNF levels, and they further reflected cardiovascular prognosis in stable CAD patients.

Comparison of outcomes in emergency department patients with suspected cardiac chest pain: two-centre prospective observational study in Southern China.

BACKGROUND: Hong Kong (HK) and Guangzhou (GZ) are cities in China with different healthcare systems. This study aimed to compare 30-day and 6-month mortality and characteristics of patients with suspected cardiac chest pain admitted to two emergency departments (ED) in HK and GZ. METHODS: A prospective observational study enrolled patients with suspected cardiac chest pain presenting to EDs in the Prince of Wales Hospital (PWH), HK and the Second Affiliated Hospital of Guangzhou Medical University (AHGZMU),GZ. The primary outcome was 30-day and 6-month mortality. RESULTS: In total, 996 patients were recruited, 407 cases from GZ and 589 cases from HK.The 30-day and 6-month mortality of chest patients were 3.7% and 4.7% in GZand 0.3% and 1.9% in HK, respectively. Serum creatinine level (Cr) was an independent factor for 30-day mortality whilst Cr and systolic blood pressure (SBP) were independent factors for 6-month mortality. In Cox regression analysis, unadjusted and adjusted hazard ratios for 30-day and 6-month mortality in GZ were significantly increased. CONCLUSION: The 30-day and 6-month mortality of patients with suspected cardiac chest pain in Guangzhou were higher than in Hong Kong due to due to different baseline clinical characteristics of patients and different distributions of diagnoses, which were associated with different healthcare systems. Serum creatinine and SBP were independent factors for 30-day and 6-month mortality.

The objective CORE score allows early rule out in acute chest pain patients.

OBJECTIVES: Chest pain is a common complaint in the emergency department (ED), and it is a challenge to identify low-risk chest pain patients eligible for early discharge. We aimed to develop a simple objective decision rule to exclude 30-day major adverse cardiac events (MACE) in ED chest pain patients. DESIGN: We analyzed prospectively included patients presenting with chest pain. Low risk patients were identified with the clinical objective rule-out evaluation (CORE). CORE was based on high sensitivity cardiac troponin T (hs-cTnT) tests at ED presentation (0 h) and 2 h later together with a simplified risk score consisting of four objective variables: age ≥65 years and a history of arterial disease, hypertension or diabetes. For the patient to be classified as low risk in the CORE rule, hs-cTnT had to be ≤14 ng/L both at 0 and 2 h, and the sum of the risk score had to be 0. The primary outcome was MACE within 30 days. RESULTS: Among the 751 patients in the final analysis, 90 (11.9%) had a MACE. CORE identified 248 (33%) of patients as low risk with a sensitivity of 98.9% (CI 93.1-99.9) and a negative predictive value of 99.6% (95% CI 97.4-100) for 30-day MACE. Adding the ED physician's interpretation of the ECG to CORE did not improve diagnostic performance. CONCLUSION: A simple objective decision rule (CORE) identified one-third of all patients as having a very low 30-day risk of MACE. These patients may potentially be discharged without additional investigations for acute coronary syndrome.