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Background The aim was to determine the prevalence and impact of an occluded “culprit” artery (OCA) in patients with non-ST segment elevation myocardial infarction (NSTEMI). Methods We searched PubMed, EMBASE, and Web of Science, with no language restrictions, up to 1 Jul. 2016. Observational cohorts or clinical trials of adult NSTEMI were eligible for inclusion to determine the prevalence if the proportion of OCA on coronary angiography was reported. Studies were further eligible for inclusion to determine the outcome if the association between OCA and clinical endpoints was reported. Results Among the 60,898 patients with NSTEMI enrolled in 25 studies, 17,212 were found to have OCA. The average proportion of OCA in NSTEMI was 34% (95% CI 30–37%). Patients with OCA were more likely to have left circumflex artery as their culprit artery (odds ratio (OR) 1.65, 95% CI 1.15–2.37, p  = 0.007), and this was associated with lower left ventricular ejection fraction (standard mean difference -0.29, 95% CI -0.34 to -0.34, p  < 0.001), higher peak enzyme level (standard mean difference 0.43, 95% CI 0.27–0.58, p  < 0.001), and higher risk for cardiogenic shock (OR 1.66, 95% CI 1.35–2.04, p  < 0.001), compared with patients with a non-occlusive culprit artery. Death rate (OR 1.72, 95% CI 1.49–1.98, p  < 0.001) and recurrent myocardial infarction (OR 1.7, 95% CI 1.06–2.75, p  = 0.029) were also higher in patients with OCA, compared with patients with a non-occlusive culprit artery. Conclusions Patients with OCA comprised a substantial portion of the NSTEMI population. These patients present with more severe symptoms and worse clinical outcome. Whether these patients should be treated with more aggressive strategy warrants further study.

In the diagnosis of diabetes mellitus, hemoglobin A1c (HbA1c) is sometimes measured to determine the need of an oral glucose tolerance test (OGTT). However, HbA1c does not accurately reflect glycemic status in certain conditions. This study was performed to test the possibility that measurement of serum glycated albumin (GA) better assesses the need for OGTT. From 2006 to 2012, 1559 subjects not known to have diabetes or to use anti-diabetic medications were enrolled. Serum GA was measured, and a 75-g OGTT was then performed to diagnose diabetes. Serum GA correlated significantly to age (r = 0.27, p<0.001), serum albumin (r = -0.1179, age-adjusted p = 0.001), body mass index (r = -0.24, age-adjusted p<0.001), waist circumference (r = -0.16, age-adjusted p<0.001), and plasma GA (r = 0.999, p<0.001), but was unaffected by diet (p = 0.8). Using serum GA at 15% for diagnosis of diabetes, the sensitivity, specificity, and area under the receiver-operating characteristic curve were 74%, 85%, and 0.86, respectively. Applying a fasting plasma glucose (FPG) value of < 100 mg/dL to exclude diabetes and of ≥ 126 mg/dL to diagnose diabetes, 14.4% of the study population require an OGTT (OGTT%) with a sensitivity of 78.8% and a specificity of 100%. When serum GA value of 14% and 17% were used to exclude and diagnose diabetes, respectively, the sensitivity improved to 83.3%, with a slightly decrease in specificity (98.2%), but a significant increase in OGTT% (35%). Using combined FPG and serum GA cutoff values (FPG < 100 mg/dL plus serum GA < 15% to exclude diabetes and FPG ≥ 126 mg/dL or serum GA ≥ 17% to diagnose diabetes), the OGTT% was reduced to 22.5% and the sensitivity increased to 85.6% with no change in specificity (98.2%). In the diagnosis of diabetes, serum GA measurements can be used to determine the need of an OGTT.

ObjectivesThe effect of subclinical leaflet thrombosis, characterised by hypoattenuated leaflet thickening (HALT), on the valve haemodynamic function and durability of the bioprosthetic valve, is not yet determined. We determined the impact of HALT on valve haemodynamics after transcatheter aortic valve replacement (TAVR) and the predictors of haemodynamic structural valve deterioration (SVD).MethodsThe Anticoagulation vs Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization after Transcatheter Aortic Valve Replacement(ADAPT-TAVR) trial is a multicenter, randomised trial that compared edoxaban and dual antiplatelet therapy in patients who had undergone successful TAVR. The presence of HALT was evaluated by four-dimensional CT at 6 months and serial echocardiography performed at baseline, immediately post-TAVR and after 6 months. SVD was defined as at least one of the following: (1) mean transprosthetic gradient ≥20 mm Hg, (2) change in the mean gradient ≥10 mm Hg from baseline, or (3) new or increase in intraprosthetic aortic regurgitation of at least ≥1 grade, resulting in moderate or greater regurgitation.ResultsAt 6 months, HALT was found in 30 of 211 (14.2%) patients. The presence of HALT did not significantly affect aortic valve mean gradients (with vs without HALT; 14.0±4.8 mm Hg vs 13.7±5.5 mm Hg; p=0.74) at 6 months. SVD was reported in 30 of 206 patients (14.6%) at 6-month follow-up echocardiography. Older age (OR: 1.138; 95% CI: 1.019 to 1.293; p=0.033), use of aortic valve size ≤23 mm (OR: 6.254; 95% CI: 2.230 to 20.569; p=0.001) and mean post-TAVR pressure gradient (OR: 1.233; 95% CI: 1.123 to 1.371; p<0.001) were independent predictors of haemodynamic SVD; however, the presence of HALT was not identified as a predictor of SVD.ConclusionsIn patients who had undergone successful TAVR, aortic valve haemodynamic status was not influenced by the presence of HALT. Although HALT was not a predictor of haemodynamic SVD at 6 months, it warrants further longer-term follow-up to evaluate the effect on long-term valve durability.Trial registration numberNCT03284827 (https://www.clinicaltrials.gov).

Abstract Context Angiopoietin-like protein 6 (ANGPTL6) is a hepatokine that improves insulin sensitivity in animals. However, serum ANGPTL6 concentration was found to be higher in human participants with diabetes or metabolic syndrome in cross-sectional studies, implying that ANGPTL6 may be induced to counteract hyperglycemia. Objective To investigate whether serum ANGPTL6 can predict incident diabetes and explore whether glucose or insulin can regulate ANGPTL6 expression and secretion. Design This cohort study included adults without diabetes at baseline who were followed every 2 years for incident diabetes. Serum ANGPTL6 concentrations were measured at baseline and during oral glucose tolerance tests (OGTTs). A hepatic cell line, HepG2, and diet-induced obesity mouse model were used to evaluate the response of ANGPTL6 expression and secretion to hyperglycemia and the metabolic syndrome. Results We recruited 1103 participants without diabetes at baseline. During the 4.22-year follow-up, 113 (10.2%) participants developed incident diabetes. Serum ANGPTL6 was negatively associated with the incidence of diabetes (adjusted hazard ratio, 0.77; P = 0.042). However, serum ANGPTL6 level was higher in participants with prediabetes (P = 0.018) and was elevated during OGTT. In HepG2 cells, treatment with glucose, but not insulin, induced ANGPTL6 expression. Hepatic ANGPTL6 expression and serum ANGPTL6 concentrations were significantly higher in mice fed with a high-fat diet than in those fed with a standard chow (both P < 0.05). Conclusion A high serum ANGPTL6 level is associated with a low incidence of diabetes in humans. ANGPTL6 is expressed and secreted in response to hyperglycemia to maintain glucose homeostasis.

Successful collateral channel (CC) crossing is an essential step in retrograde chronic total occlusion (CTO) percutaneous coronary interventions (PCIs). We previously developed a dedicated CC score based on CC size and tortuosity to facilitate target CC selection. Validation and comparison to other scoring systems were lacking. Thus, the aims of this study were to (1) validate the CC score in a larger independent cohort, and (2) compare its accuracy and clinical usefulness with the J-channel score. All coronary CTO PCIs attempted by experienced high-volume operators from January 2017 to December 2021 were enrolled. The CC and J-channel scores were calculated for all attempted CCs with bi-plane high-resolution cine angiography images. CC crossing success was defined as guidewire reaching the distal true lumen retrogradely. In total, 502 patients who received CTO PCI were included. The retrograde approach was utilized in 244 target CTOs, and a total of 329 CCs were attempted. The overall CC crossing rate was 67.8% (223 of 329) and final technical success rate 92.2% (225 of 244). The average CC score was 2.0 and average J-channel score was 0.71. The sensitivity and specificity of successful CC crossing with the CC score ≥2 were 81.2%, and 84.0%, respectively. Comparison between the CC score (area under the curve 0.87; 95% confidence interval 0.83 to 0.90) and the J-channel score (area under the curve 0.61, 95% confidence interval 0.55 to 0.67) demonstrated superior predictive performance of the CC score (p <0.001). The CC score was an easy-to-use and accurate tool for the prediction of successful CC crossing in retrograde CTO PCI. The CC score can help operators select the ideal target CC, thereby facilitating final procedural success.

Whether retroperitoneal fat should be included in the measurement of visceral fat remains controversial. We compared the relationships of fat areas in peritoneal, retroperitoneal, and subcutaneous compartments to metabolic syndrome, adipokines, and incident hypertension and diabetes. We enrolled 432 adult participants (153 men and 279 women) in a community-based cohort study. Computed tomography at the umbilicus level was used to measure the fat areas. Retroperitoneal fat correlated significantly with metabolic syndrome (adjusted odds ratio (OR), 5.651, p<0.05) and the number of metabolic abnormalities (p<0.05). Retroperitoneal fat area was significantly associated with blood pressure, plasma glycemic indices, lipid profile, C-reactive protein, adiponectin (r =  -0.244, P<0.05), and leptin (r = 0.323, p<0.05), but not plasma renin or aldosterone concentrations. During the 2.94 ± 0.84 years of follow-up, 32 participants developed incident hypertension. Retroperitoneal fat area (hazard ration (HR) 1.62, p = 0.003) and peritoneal fat area (HR 1.62, p = 0.009), but not subcutaneous fat area (p = 0.14) were associated with incident hypertension. Neither retroperitoneal fat area, peritoneal fat area, nor subcutaneous fat areas was associated with incident diabetes after adjustment. Retroperitoneal fat is similar to peritoneal fat, but differs from subcutaneous fat, in terms of its relationship with metabolic syndrome and incident hypertension. Retroperitoneal fat area should be included in the measurement of visceral fat for cardio-metabolic studies in human.

It is unknown whether edoxaban versus dual antiplatelet therapy (DAPT) has differential treatment effects on leaflet thrombosis, cerebral thromboembolism, and neurologic or neurocognitive dysfunction according to clinical and anatomic factors after transcatheter aortic valve implantation. To investigate the relative effects of edoxaban and DAPT on leaflet and cerebral thromboembolism in patients with major risk factors. The primary end point of this study was the incidence of leaflet thrombosis on computed tomography at 6 months. The secondary end points were new cerebral lesions on brain magnetic resonance imaging and neurologic and neurocognitive dysfunction between baseline and 6-month follow-up. Cox regression models assessed the consistency of the treatment effects in the prespecified subgroups. The favorable effect of edoxaban versus DAPT on the leaflet thrombosis was consistent across multiple clinical or anatomic subgroups, without significant interaction between the drug effect and each subgroup (p for interaction for age = 0.597, gender = 0.557, body mass index = 0.866, Society of Thoracic Surgeons score = 0.307, valve type = 0.702, edoxaban reduction criteria = 0.604, and valve morphology = 0.688). However, the incidence of new cerebral lesions on brain magnetic resonance imaging and worsening of neurologic and neurocognitive function were not significantly different between the groups among the various key subgroups. The relative effects of edoxaban and DAPT on the risk of leaflet thrombosis, cerebral thromboembolism, and neurologic dysfunction were consistent across a diverse spectrum of clinical or anatomical factors. Further studies are required to define tailored antithrombotic therapy for high-risk groups with specific clinical or anatomic characteristics.

The current method of diagnosing diabetes mellitus (DM) using fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) without oral glucose tolerance tests (OGTT) results in inaccuracy and underdiagnosis of diabetes. This study aimed to investigate the mortality of individuals with improperly classified glycemic status and suggest new screening methods for diabetes. A total of 1935 subjects were prospectively followed for 10 years, with vital status obtained through linkage to the National Health Insurance Research Database (NHIRD). Hazard ratios (HR) of all-cause mortality were analyzed. The percentage of all-cause mortality was significantly higher in subjects with improperly classified glycemic status than those correctly classified (8.3% vs. 3.6%, p  = 0.004; unadjusted HR 2.537, p  = 0.002). The risk of mortality associated with underdiagnosis was highest in those over the age of 60 (adjusted HR 2.043, p  = 0.036). Using components of metabolic syndrome, three screening strategies were developed to determine the need for OGTT in elderly subjects with improved sensitivity in diagnosing DM. Diagnosis of diabetes based solely on FPG and HbA1c leads to underdiagnosis of glycemic status and higher all-cause mortality in older adults. Age and the presence of components of metabolic syndrome-based screening strategies can improve diagnostic accuracy and reduce the need for OGTT.

To quantify the societal impact of disability in patients with non-small cell lung cancer (NSCLC), this study estimated the disability-free life expectancy (DFLE), loss-of-DFLE and explored their associations with quality-adjusted life expectancy (QALE) and loss-of-QALE. We interlinked national databases and applied a rolling-over algorithm to estimate the lifetime survival function for patients with NSCLC. Using the EuroQOL-5 Dimension (EQ-5D) and Barthel index (BI), we repeatedly measured the quality-of-life and disability functions of NSCLC patients who visited our hospital from 2011 to 2020. Age-, sex-matched referents were simulated from lifetables of the same calendar year of diagnosis. We categorized BI scores ≤ 70 as in need of long-term care and constructed linear mixed models to estimate the utility values and disability scores. We collected 960 cases and 3088 measurements. The proportions of measurements without disability at age 50–64 and in stage I–IIIa, 50–64 and stage IIIb–IV, 65–89 and stage I–IIIa and 65–89 and stage IIIb–IV were 97.3%, 89.3%, 94.8%,78.3%, corresponding to DFLEs of 15.3, 2.4, 6.8, 1.2 years and losses-of-DFLE of 8.1, 20.7, 4.0, 8.6 years, respectively, indicating that advanced stage had a stronger effect than old age. Survivors in advanced stages showed increased demands for assistance in almost all subitems. The DFLEs seemed to be approximate to the QALEs and the latter were shorter than the former due to discomfort and depression. From a societal perspective, future health technology assessment should consider the impact of lifetime duration of functional disability. Early diagnosis of NSCLC may decrease the burden of long-term care.

Diabetes is the leading cause of end-stage renal disease (ESRD) worldwide. Vascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the deamination of primary amines into aldehydes, hydrogen peroxide, and ammonia, both of which are involved in the pathogenesis of diabetic complications. We have shown that serum VAP-1 is higher in patients with diabetes and in patients with chronic kidney disease (CKD), and can predict cardiovascular mortality in subjects with diabetes. In this study, we investigated if serum VAP-1 can predict ESRD in diabetic subjects. In this prospective cohort study, a total of 604 type 2 diabetic subjects were enrolled between 1996 to 2003 at National Taiwan University Hospital, Taiwan, and were followed for a median of 12.36 years. The development of ESRD was ascertained by linking our database with the nationally comprehensive Taiwan Society Nephrology registry. Serum VAP-1 concentrations at enrollment were measured by time-resolved immunofluorometric assay. Subjects with serum VAP-1 in the highest tertile had the highest incidence of ESRD (p<0.001). Every 1-SD increase in serum VAP-1 was associated with a hazard ratio of 1.55 (95%CI 1.12-2.14, p<0.01) for the risk of ESRD, adjusted for smoking, history of cardiovascular disease, body mass index, hypertension, HbA1c, duration of diabetes, total cholesterol, use of statins, ankle-brachial index, estimated GFR, and proteinuria. We developed a risk score comprising serum VAP-1, HbA1c, estimated GFR, and proteinuria, which could predict ESRD with good performance (area under the ROC curve = 0.9406, 95%CI 0.8871-0.9941, sensitivity = 77.3%, and specificity = 92.8%). We also developed an algorithm based on the stage of CKD and a risk score including serum VAP-1, which can stratify these subjects into 3 categories with an ESRD risk of 0.101%/year, 0.131%/year, and 2.427%/year, respectively. In conclusion, serum VAP-1 can predict ESRD and is a useful biomarker to improve risk stratification in type 2 diabetic subjects.