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We conducted a multi-institutional study in Taiwan and a systematic review of the literature for reports of Guillain-​Barré syndrome after coronavirus disease vaccination. This condition, mostly the classic form and the acute inflammatory demyelinating polyneuropathy subtype, has been reported in 39 cases and has occurred within 2 weeks of vaccine administration.

Aims To investigate the risk of diabetic macular oedema (DMO) associated with the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM). Materials and methods We conducted a retrospective cohort study by analysing a large multi-institutional electronic medical records database in Taiwan. We included adult patients with T2DM without DMO newly receiving either SGLT2 inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1RAs) during the period 2016 to 2018. We used propensity scores with inverse probability of treatment weighting to generate comparable groups. The study outcome was incident DMO, determined by clinical diagnosis during outpatient visits or admissions. We followed patients from the index date to either DMO occurrence, last clinical visit, patient death, or December 31, 2020. We performed Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of DMO. Results We included 9986 new users of SGLT2 inhibitors (mean [SD] age 59.6 (12.1) years, median [interquartile range {IQR}] glycated haemoglobin [HbA1c] 70 (61-81)mmol/mol, estimated glomerular filtration rate [eGFR] 89.1 [71.4-108.7] mL/min/1.73 m2 and urine albumin-creatinine ratio [UACR] 26.1 [9.7-117.6] mg/g) and 1067 new users of GLP-1RAs (mean [SD] age 58.4 (41.5) years, median [IQR] HbA1c 73 [64-84] mmol/mol, eGFR 91.6 [68.6-114.0] mL/min/1.73 m2 and UACR 37.6 [11.1-153.2] mg/g) with similar baseline characteristics. Lower DMO risks were observed among patients newly receiving SGLT2 inhibitors (7.9/1000 person-years), compared to those receiving GLP-1RAs (10.7/1000 person-years) with an HR of 0.75 (95% CI 0.64-0.88). Conclusions Our findings suggest use of SGLT2 inhibitors was associated with lower risk of DMO in T2DM patients in clinical practice, compared to use of GLP-1RAs. Future studies are necessary to confirm this observation.

Background: Non-diabetic coronary artery spasm (CAS) without obstructive coronary artery disease increases insulin resistance. We investigated the risk of incident type 2 diabetes (diabetes) associated with CAS. Methods: Patient records were retrospectively collected from the Taiwan National Health Insurance Research Database during the period 2000-2012. The matched cohorts consisted of 12,413 patients with CAS and 94,721 patients in the control group. Results: During the entire follow-up, the incidence of newly-diagnosed diabetes was 22.2 events per 1000 person-years in the CAS group and 13.9 events per 1000 person-years in the control group. The increased risk of CAS-related incident diabetes was observed regardless of sex and length of follow-up. The median time to incident diabetes was 2.9 and 3.5 years in the CAS and the control group (P

Background Cardiac troponins are important markers for diagnosis of acute myocardial infarction (AMI) in general population; however, chronically-elevated troponins levels are often seen in patients with renal insufficiency, which reduce their diagnostic accuracy. The aim of our study was to access the diagnostic values of initial high-sensitive cardiac troponin T (hs-cTnT) and relative change of hs-cTnT for AMI in patients with and without renal insufficiency. Methods Cardiac care unit patients with elevated hs-cTnT levels in 2017–2018 were enrolled. Receiver operating characteristic (ROC) curves were used to evaluate initial hs-cTnT levels and relative changes after 3 h of enrollment for diagnosis of AMI in patients with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (low), and eGFR ≥ 60 mL/min/1.73 m2 (normal). Results Of 359 patients, 240 patients had low eGFR, and 119 patients had normal eGFR. The area under the ROC curve (AUC) for the initial hs-cTnT levels was 0.58 (95% CI, 0.5–0.65, p = 0.053) among patients with low eGFR and 0.54 (95% CI, 0.4–0.67, p = 0.612) among patients with normal eGFR. AUCs for relative changes of hs-cTnT were 0.82 (95% CI, 0.76–0.88, p

Not applicable. Acute kidney injury Confidence interval Coronavirus disease 2019 Ali H, Daoud A, Mohamed MM, Salim SA, Yessayan L, Baharani J, Murtaza A, Rao V, Soliman KM. Survival rate in acute kidney injury superimposed COVID-19 patients: a systematic review and meta-analysis. Ren Fail. 2020;42(1):393–7. CAS Article Google Scholar Ronco C, Reis T. Kidney involvement in COVID-19 and rationale for extracorporeal therapies. Nat Rev Nephrol. 2020;16(6):308–10. CAS Article Google Scholar Naicker S, Yang CW, Hwang SJ, Liu BC, Chen JH, Jha V. The novel coronavirus 2019 epidemic and kidneys. Kidney Int. 2020;97(5):824–8. CAS Article Google Scholar Alberici F, Delbarba E, Manenti C, Econimo L, Valerio F, Pola A, Maffei C, Possenti S, Zambetti N, Moscato M, et al. A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia. Kidney Int. 2020;97(6):1083–8. CAS Article Google Scholar Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX, Chong M, Lee M. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington state. JAMA. 2020;323(16):1612–4. CAS Article Google Scholar Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M. COVID-19 infection in kidney transplant recipients. Kidney Int. 2020;97(6):1076–82. CAS Article Google Scholar Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–13. CAS Article Google Scholar Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, Ma K, Xu D, Yu H, Wang H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020;368:m1091. Article Google Scholar Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, Li J, Yao Y, Ge S, Xu G. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020;97(5):829–38. CAS Article Google Scholar Deng Y, Liu W, Liu K, Fang YY, Shang J, Zhou L, Wang K, Leng F, Wei S, Chen L, et al. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 (COVID-19) in Wuhan, China: a retrospective study. Chin Med J. 2020. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–20. CAS Article Google Scholar Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, Wang H, Wan J, Wang X, Lu Z. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. CAS Article Google Scholar Lei S, Jiang F, Su W, Chen C, Chen J, Mei W, Zhan LY, Jia Y, Zhang L, Liu D, et al. Clinical characteristics and outcomes of patients undergoing surgeries during the incubation period of COVID-19 infection. EClinicalMedicine. 2020:100331. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, and the Northwell C-RC, Barnaby DP, Becker LB, Chelico JD, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the new York City area. JAMA. 2020. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, Gong W, Liu X, Liang J, Zhao Q, et al. Association of Cardiac Injury with Mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020. Wang L, Li X, Chen H, Yan S, Li D, Li Y, Gong Z. Coronavirus disease 19 infection does not result in acute kidney injury: an analysis of 116 hospitalized patients from Wuhan, China. Am J Nephrol. 2020;51(5):343–8. 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CAS Article Google Scholar Hoste EAJ,...

Background: Carbon monoxide (CO) poisoning is the leading cause of poisoning death worldwide, but associations between CO poisoning and weather remain unclear.Objective: To quantify the influence of climate parameters (e.g., temperature, relative humidity, and wind speed) on the incidence risk of acute CO poisoning in Taiwan.Methods: We used negative binomial mixed models (NBMMs) to evaluate the influence of weather parameters on the incidence risk of acute CO poisoning. Subgroup analyses were conducted, based on the seasonality and the intentionality of acute CO poisoning cases.Results: We identified a total of 622 patients (mean age: 32.9 years old; female: 51%) with acute CO poisoning in the study hospital. Carbon monoxide poisoning was associated with temperature (beta: −0.0973, rate ratio (RR): 0.9073, p < 0.0001) but not with relative humidity (beta: 0.1290, RR: 1.1377, p = 0.0513) or wind speed (beta: −0.4195, RR: 0.6574, p = 0.0806). In the subgroup analyses, temperature was associated with the incidence of intentional CO poisoning (beta: 0.1076, RR: 1.1136, p = 0.0333) in spring and unintentional CO poisoning (beta: −0.1865, RR: 0.8299, p = 0.0184) in winter.Conclusion: Changes in temperature affect the incidence risk for acute CO poisoning, but the impact varies with different seasons and intentionality in Taiwan. Our findings quantify the effects of climate factors and provide fundamental evidence for healthcare providers to develop preventative strategies to reduce acute CO poisoning events.

Background The treatment effects on hospitalization for heart failure (hHF) from sodium-glucose cotransporter 2 (SGLT2) inhibitors may vary among type 2 diabetes (T2D) patients depending on whether or not they have established atherosclerotic cardiovascular diseases (ASCVD). We aimed to examine differences in hHF outcomes after dapagliflozin or empagliflozin use between T2D patients with and without a history of established ASCVD. Methods We conducted a retrospective multi-institutional cohort study in Taiwan. We included T2D patients newly receiving dapagliflozin or empagliflozin during 2016–2019, and followed them up until December 31, 2020. We implemented 1:1 propensity score matching to create homogenous groups for comparisons. We generated Cox proportional hazard models to compare the risk of hHF between dapagliflozin and empagliflozin (reference group). We included interaction terms of SGLT2 inhibitor and ASCVD history in the regression models to examine effect modification by ASCVD. Results We included a total cohort of 9,586 dapagliflozin new users and 9,586 matched empagliflozin new users. The overall hHF risks were similar for dapagliflozin and empagliflozin (HR: 0.90, 95% CI 0.74–1.09). However, differential hHF risks between dapagliflozin and empagliflozin were observed only in the subgroup without ASCVD (HR: 0.67, 95% CI 0.49–0.90), while not in the subgroup with ASCVD (HR: 1.12, 95% 0.87–1.45), and the p-value for examining interaction was 0.0097. Conclusion In this study, history of established ASCVD was associated with different hHF risks among SGLT2 inhibitors. For T2D patients without ASCVD, dapagliflozin may offer a more favorable hHF reduction effect, compared to empagliflozin, in clinical practice. Future prospective studies should be conducted to validate our findings.

Clinical trials have indicated that sodium-glucose co-transporter-2 (SGLT2) inhibitors have a favourable effect on serum alanine aminotransferase (ALT) levels in people with type 2 diabetes (T2D), but supporting evidence from real-world studies is lacking. We identified patients with T2D who initiated SGLT2 inhibitors during the period 2016 to 2017 from Chang Gung Research Database, which covers 1.3 million individuals from seven hospitals (6% of the Taiwan population). We classified patients by baseline ALT level and evaluated changes in ALT values from baseline to 1 year after initiation of SGLT2 inhibitors. We identified 11 690 new users of SGLT2 inhibitors with a mean (SD) age of 59.3 (11.8) years. The mean (SD) glycated haemoglobin and ALT levels were 8.9 (1.7)% and 34.7 (28.9) U/L at baseline, respectively. The mean change in ALT levels was -5.0 U/L (95% confidence interval [CI] -6.4, -3.5) 1 year after initiation of SGLT2 inhibitors. In patients with ALT levels ≤1× the upper limit of normal (ULN), the change in ALT levels was 1.6 U/L (95% CI -0.1, 3.4), while in those with ALT levels >1× ULN, the change in ALT levels was -26.5 U/L (95% CI -28.6, -24.3). The higher the baseline ALT level, the greater the decline after SGLT2 inhibitor treatment. Our findings suggest the initiation of SGLT2 inhibitors for T2D management could improve serum ALT levels in clinical practice, particularly in patients with especially high ALT levels.

BackgroundTo compare the cardiovascular event risk in type 2 diabetes patients newly receiving dapagliflozin vs. empagliflozin.MethodsWe conducted a retrospective cohort study by analyzing a multi-institutional electronic medical records database (Chang Gung Research Database) in Taiwan and included adult type 2 diabetes patients who were newly receiving sodium–glucose co-transporter 2 (SGLT2) inhibitors from 2016 to 2017. The primary outcome was a composite of cardiovascular death, myocardial infarction, ischemic stroke and heart failure. We followed up patients from initiation of SGLT2 inhibitors until the occurrence of cardiovascular events before December 31, 2018. We performed multivariable Cox proportional hazard modeling, adjusting for patients’ age, sex, laboratory data, co-morbidities, and concomitant medications.ResultsWe identified 12,681 new SGLT2 inhibitor users with a mean age of 58.9 (SD 11.8) years, of whom 43.9% were female and 45.8% were new dapagliflozin users. A total of 10,442 person-years of dapagliflozin use and 12,096 person-years of empagliflozin use were included. Compared to empagliflozin users, new users of dapagliflozin were found to have similar risks for primary composite outcome (adjusted HR: 0.91; 95% CI 0.73–1.14), cardiovascular death (adjusted HR: 0.54; 95% CI 0.14–2.12), myocardial infarction (adjusted HR: 0.77, 95% CI 0.49–1.19) and ischemic stroke (adjusted HR: 1.15; 95% CI 0.80–1.65), but a lower risk of heart failure (adjusted HR: 0.68; 95% CI 0.49–0.95).ConclusionThe risk of cardiovascular events was similar between dapagliflozin and empagliflozin new users, but dapagliflozin may have a better outcome in the reduction of heart failure in type 2 diabetes patients. Future prospective studies are required to confirm the findings.

Background and objectives: Chronic musculoskeletal (MS) pain is common in chronic kidney disease (CKD) patients. The association of chronic MS pain and CKD progression has not yet been established. Method: We conducted a prospective cohort study to evaluate the association of chronic MS pain and CKD progression of pre-dialysis CKD patients. Result: A total of 53.2% of pre-dialysis CKD patients had chronic MS pain. Patients classified as progression and non-progression had a similar prevalence of chronic MS pain at baseline, and similar baseline use of NSAIDs and Chinese herbal medicines. Univariate Cox analysis indicated that chronic MS pain and baseline NSAID or Chinese herbal medicine use were not significantly associated with progression of CKD. But multivariate Cox regression found chronic MS pain was independently significantly associated with all-cause mortality (HR, 2.912, 95% CI, 1.004–8.444; p = .049). However, serum levels of hs-CRP were similar between those chronic MS pain patients and without chronic MS pain patients (4.96 ± 9.4 vs. 4.25 ± 13.3 mg/L, p = .535). Conclusion: The CKD patients with chronic MS pain was independently and significantly associated with all-cause mortality, but not independently and significantly associated with CKD progression and composite endpoints. The inflammatory marker-hs-CRP was similar between CKD patients with and without chronic MS pain.

This is a retrospective cohort study by analyzing a multi-institutional electronic medical records database covering 1.3 million individuals (6% of Taiwan's population) to compare the risk of heart failure (HF) in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor-α (TNF-α) inhibitors or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). We included patients with RA aged 20 years and older who had treatment failure with at least 2 different csDMARD regimens and newly switched to another csDMARD regimen or TNFis from 2009 to 2019. We followed patients from initiation of the new therapies to the occurrence of hospitalization for heart failure (hHF), death, to the last clinical visit or December 31, 2020. We performed multivariable Cox proportional hazard models to compare TNF-α inhibitors and csDMARD groups for the risk of hHF, with adjustment for patients' characteristics. A total of 1,278 TNF-α inhibitors and 1,932 csDMARDs treated patients were identified, with 78% being women and having an average age of 55 (SD 13.28) years. The incidence rates of hHF for the TNF-α inhibitors and csDMARD groups were 3.66 and 4.72 per 1,000 person-years, respectively (adjusted hazard ratio (aHR) 0.59; 95% confidence interval (CI) 0.35-0.97), and the results remained consistent in patients both with an HF history (aHR 0.66; 95% CI 0.03-14.46) and without (aHR 0.49; 95% CI, 0.27-0.89). The findings suggest that those who switched to TNF-α inhibitors had a reduced risk of hHF, compared with those who switched to another csDMARD regimen.

Atorvastatin 40 mg (ATOR 40) and ezetimibe 10 mg/simvastatin 20 mg (EZ-SIM 20) have similar reductions of low-density lipoprotein cholesterol (LDL-C) but cardiovascular (CV) outcomes between these two therapies are unclear. Our real-world cohort study is to test the hypothesis of pleiotropic effects of purely higher dose statin on CV outcomes beyond similar reductions of LDL-C, especially for extremely CV risk patients. Between January 1, 2007 and December 31, 2013, a total of 3,372 patients with type 2 diabetes mellitus (T2DM) admitted due to acute coronary syndrome (ACS) or acute ischemic stroke (AIS) were selected as the study cohort from the Taiwan National Health Insurance Research Database. Clinical outcomes were evaluated by ATOR 40 group (n = 1686) matched with EZ-SIM 20 group (n = 1686). Primary composite outcome includes CV death, non-fatal myocardial infarction, and non-fatal stroke. Secondary composite outcome includes hospitalization for unstable angina (HUA), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). With a mean follow-up of 2.4 years, no significant difference of primary composite outcome was observed between ATOR 40 and EZ-SIM 20 groups (subdistribution hazard ratio [SHR], 1.09; 95% confidence interval [CI], 0.95–1.25). Nevertheless, ATOR 40 group had lower risks of HUA (SHR, 0.50; 95% CI, 0.35–0.72), PCI (SHR, 0.82; 95% CI, 0.69–0.97) and CABG (SHR, 0.62; 95% CI, 0.40–0.97) than EZ-SIM 20 group. For T2DM patients after ACS or AIS, ATOR 40 and EZ-SIM 20 had similar major CV outcomes, which still supported the main driver for CV risk reductions is LDL-C lowering.

IntroductionSodium glucose co-transporter 2 (SGLT2) inhibitors have been reported to benefit liver functions in patients with type 2 diabetes (T2D) with non-alcoholic fatty liver disease (NAFLD). The aim of this study is to critically appraise existing systematic reviews in order to consolidate evidence associating the use of SGLT2 inhibitors with beneficial hepatic results for patients with T2D with NAFLD.MethodsThis umbrella review searched relevant published systematic reviews of clinical trials from PubMed and Embase between inception and September 16, 2020. Two independent investigators appraised study quality using AMSTAR2 (Assessment of Multiple Systematic Reviews 2). The hepatic effects from SGLT2 inhibitors were summarized based on liver enzymes, liver fat, liver histology, liver cirrhosis and liver cancer.ResultsOf 25 screened potential systematic reviews, we ultimately included 7 in this study. However, none of them could be rated as being of high methodological quality. Five systematic reviews indicated that SGLT2 inhibitors could effectively decrease liver fat and liver parameters of alanine aminotransferase and gamma-glutamyl transferase in patients with NAFLD. Two systematic reviews indicated that SGLT2 inhibitors could reduce hepatosteatosis, as supported by biopsy-proven evidence of improvement from a small clinical trial, but no evidence of liver fibrosis improvement was found.ConclusionsThere is some association between SGLT2 inhibitor use and observed benefits to liver functions in patients with T2D with NAFLD, although the quality of current systematic reviews remains relatively low. Further evaluation of long-term liver outcomes with SGLT2 inhibitors in cases of liver cirrhosis and liver cancer is warranted.

BackgroundNon-diabetic coronary artery spasm (CAS) without obstructive coronary artery disease increases insulin resistance. We investigated the risk of incident type 2 diabetes (diabetes) associated with CAS.MethodsPatient records were retrospectively collected from the Taiwan National Health Insurance Research Database during the period 2000-2012. The matched cohorts consisted of 12,413 patients with CAS and 94,721 patients in the control group. ResultsDuring the entire follow-up, the incidence of newly-diagnosed diabetes was 22.2 events per 1000 person-years in the CAS group and 13.9 events per 1000 person-years in the control group. The increased risk of CAS-related incident diabetes was observed regardless of sex and length of follow-up. The median time to incident diabetes was 2.9 and 3.5 years in the CAS and the control group (P

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Heart failure (HF) is a global pandemic public health burden affecting one in five of the general population in their lifetime. For high-risk individuals, early detection and prediction of HF progression reduces hospitalizations, reduces mortality, improves the individual’s quality of life, and reduces associated medical costs. In using an artificial intelligence (AI)-assisted genome-wide association study of a single nucleotide polymorphism (SNP) database from 117 asymptomatic high-risk individuals, we identified a SNP signature composed of 13 SNPs. These were annotated and mapped into six protein-coding genes (GAD2, APP, RASGEF1C, MACROD2, DMD, and DOCK1), a pseudogene (PGAM1P5), and various non-coding RNA genes (LINC01968, LINC00687, LOC105372209, LOC101928047, LOC105372208, and LOC105371356). The SNP signature was found to have a good performance when predicting HF progression, namely with an accuracy rate of 0.857 and an area under the curve of 0.912. Intriguingly, analysis of the protein connectivity map revealed that DMD, RASGEF1C, MACROD2, DOCK1, and PGAM1P5 appear to form a protein interaction network in the heart. This suggests that, together, they may contribute to the pathogenesis of HF. Our findings demonstrate that a combination of AI-assisted identifications of SNP signatures and clinical parameters are able to effectively identify asymptomatic high-risk subjects that are predisposed to HF.

Background Sodium glucose cotransporter 2 (SGLT2) inhibitors have shown greater reductions of cardiovascular event risks than dipeptidyl peptidase-4 (DPP4) inhibitors, whereby possible mechanisms may involve the better pleiotropic effects of SGLT2 inhibitors. However, no published data are currently available to directly compare glycemic and pleiotropic effects in real-world type 2 diabetes patients initiating SGLT2 inhibitors or DPP4 inhibitors. Method We conducted a retrospective cohort study by analyzing the Chang Gung Research Database, the largest multi-institutional electronic medical records database in Taiwan. We included patients newly receiving SGLT2 inhibitor or DPP4 inhibitor intensification therapy for type 2 diabetes from 2016 to 2017. We matched SGLT2 inhibitor users to DPP4 inhibitor users (1:4) by propensity scores to ensure comparable characteristics between the groups. We primarily evaluated 1-year post-treatment changes of hemoglobin A1c (HbA1c) after SGLT2 inhibitor or DPP4 inhibitor initiation, using two-tailed independent t-test. We also evaluated post-treatment changes in body weight, systolic blood pressure (SBP), alanine aminotransferase (ALT) and estimated glomerular filtration rate (eGFR) values, associated with SGLT2 inhibitors and DPP4 inhibitors. Results We identified a cohort of 2028 SGLT2 inhibitors and 8112 matched DPP4 inhibitors new users. SGLT2 inhibitors and DPP4 inhibitors showed similar HbA1c reductions (− 1.0 vs. − 1.1%; P = 0.076), but patients receiving SGLT2 inhibitors had greater improvements in body weight (− 1.5 vs. − 1.0 kg; P = 0.008), SBP (− 2.5 vs. − 0.7 mmHg; P 2; P Conclusion SGLT2 inhibitors had glucose-lowering effects comparable to those of DPP4 inhibitors but more favorable pleiotropic effects on body weight, ALT and eGFR changes, potentially improving type 2 diabetes patients’ cardio-metabolic disease risks.

Rationale: Takotsubo syndrome (TTS) is a form of acute and usually reversible heart failure syndrome. Transient left ventricular dysfunction and electrocardiographic changes could mimic acute coronary syndrome but there are actually no obstructive coronary lesions. Patient concerns: A 76-year-old woman with chronic lung disease developed spontaneous tension pneumothorax with the presentation of severe dyspnea, respiratory failure, left ventricular dysfunction, and anterior wall ST-segment elevation on 12-lead electrocardiogram. Acute coronary syndrome was excluded by normal coronary angiograms. Diagnosis: The patient was diagnosed as tension pneumothorax complicated by TTS. Interventions: The woman underwent tubal thoracostomy for tension pneumothorax-induced obstructive shock. However, the patient further underwent ligation bullectomy for persistent air leakage 2 weeks later. Outcomes: The left ventricular dysfunction recovered 1 week after resolution of tension pneumothorax. Anterior wall ST-segment elevation resolved 25 days after admission. Lessons: Concurrent electrocardiograms and echocardiographic serial evaluations should be performed to provide more comprehensive information when dealing with tension pneumothorax patients.

Aims/Introduction The cardiovascular (CV) outcomes of vildagliptin – a dipeptidyl peptidase‐4 inhibitor – in patients with type 2 diabetes mellitus after acute coronary syndrome or acute ischemic stroke are unclear. Materials and Methods We analyzed data from the Taiwan National Health Insurance Research Database on 3,750 type 2 diabetes mellitus patients with acute coronary syndrome or acute ischemic stroke within 3 months between 1 August 2011 and 31 December 2013. Clinical outcomes were evaluated by comparing 1,250 participants receiving vildagliptin with 2,500 propensity score‐matched participants. The primary composite outcome included CV death, non‐fatal myocardial infarction and non‐fatal stroke. Results The primary composite outcome occurred in 122 patients (9.8%) in the vildagliptin group and 263 patients (10.5%) in the control group (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.72–1.11) with a mean follow‐up period of 9.9 months. No significant between‐group differences were observed for CV death (HR 0.93, 95% CI 0.56–1.52), non‐fatal myocardial infarction (HR 0.79, 95% CI 0.46–1.36) and non‐fatal stroke (HR 0.96, 95% CI 0.74–1.24). The vildagliptin group was at similar risks of hospitalization for heart failure (HF) or coronary intervention to the control group (P = 0.312 and 0.430, respectively). For patients with HF at baseline, the risk of hospitalization for HF was similar between the vildagliptin and control groups (HR 1.04, 95% CI 0.57–1.88). Conclusions Among patients with type 2 diabetes mellitus after a recent acute coronary syndrome or acute ischemic stroke, treatment with vildagliptin was not associated with increased risks of CV death, non‐fatal myocardial infarction, non‐fatal stroke and hospitalization for HF., Among patients with type 2 diabetes mellitus after a recent acute coronary syndrome or acute ischemic stroke, treatment with vildagliptin was not associated with increased risks of cardiovascular death, non‐fatal myocardial infarction, non‐fatal stroke and hospitalization for heart failure.

ObjectiveTo understand the efficacy of aspirin use for preventing ischaemic stroke after central retinal artery occlusion (CRAO).DesignThe retrospective cohort study was conducted using the National Health Insurance Research Database from 1998 to 2013.SettingA population-based study.ParticipantsA total of 9437 participants with newly diagnosed CRAO were identified. Participants who had a previous stroke and/or retinal vascular occlusion, were aged MethodsCox proportional hazard models and cumulative survival curves were used to assess ischaemic stroke in the study groups, along with log-rank tests to compare group differences.Main outcome measuresIncidence of ischaemic stroke in the aspirin and aspirin-naive groups 1 year after CRAO.ResultsOf the 3778 patients with newly diagnosed CRAO, 151 (4%) had a subsequent ischaemic stroke within 1 year. The risk was especially high during the first week of the CRAO. No difference between the aspirin and aspirin-naive groups was found in risk of ischaemic stroke, haemorrhagic stroke, gastrointestinal bleeding, major bleeding, acute coronary syndrome, retinal vein occlusion, new-onset glaucoma, undergoing panretinal photocoagulation or all-cause mortality. Risk factors for ischaemic stroke within 1 year of CRAO included male gender (p=0.031; HR=1.46) and age (p=0.032; HR=1.14).ConclusionsAspirin use after a CRAO showed no benefit on attenuating the risk of ischaemic stroke. The risk of ischaemic stroke was increased after CRAO especially during the first week. Male gender and age were risk factors for ischaemic stroke after CRAO.

Background To investigate the cardiovascular (CV) outcomes of drug-eluting stents (DESs) versus bare-metal stents (BMSs) in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). Methods Data from the Taiwan National Health Insurance Research Database was analyzed between January 1, 2007 and December 31, 2011. A total of 3051 AMI patients in CS were selected as the study cohort. Their clinical outcomes were evaluated by comparing 1017 subjects who used DESs to 2034 matched subjects who used BMSs. Results The risk of the primary composite outcome (i.e., death, myocardial infarction, stroke, and coronary revascularization) was significantly lower in the DES group compared with the BMS group [56.1% vs. 66.2%, hazard ratio (HR), 0.74; 95% CI, 0.67–0.81] with a mean follow-up of 1.35years. The patients who received DESs had a lower risk of coronary revascularization (HR, 0.78; 95% CI, 0.67–0.91) and death (HR, 0.70; 95% CI, 0.62–0.79) than those who used BMSs. However, the risks of myocardial infarction (HR, 0.89; 95% CI, 0.66–1.18), ischemic stroke (HR, 1.02; 95% CI, 0.67–1.53) and major bleeding (HR, 0.80; 95% CI, 0.56–1.14) were similar between the two groups. Conclusions Among patients with CS complicating AMI, DES implantation significantly reduced the risk of percutaneous coronary revascularization and death compared to BMS implantation.

ObjectiveWhether the cardiovascular (CV) outcomes of second-generation limus-eluting stents (LESs) differ from those of paclitaxel-eluting stents (PESs) in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) is still unclear.MethodsWe used the Taiwan National Health Insurance Research Database to analyse data of 516 patients with AMI and CS diagnosed from January 2007 to December 2011. We used propensity score matching to adjust for the imbalance in covariate baseline values between these two groups. We evaluated clinical outcomes by comparing 197 subjects who used second-generation LESs to 319 matched subjects who used PESs.ResultsThe risk of the primary composite outcomes (i.e., myocardial infarction, coronary revascularisation or CV death) was significantly lower in the second-generation LES group than in the PES group [37.3% vs. 51.8%; hazard ratio (HR), 0.73; 95% CI: 0.56-0.95] at the 12-month follow-up. The patients who received second-generation LESs had a lower risk of coronary revascularisation (HR 0.62; 95% CI: 0.41-0.93) than those who used PESs. However, the risks of myocardial infarction (HR 0.56; 95% CI: 0.26-1.24), ischemic stroke (HR 0.73; 95% CI: 0.23-2.35), or CV death (HR 0.90; 95% CI: 0.63-1.28) were not significantly different between the two groups.ConclusionsAmong patients with CS-complicating AMI, second-generation LES implantation significantly reduced the risk of coronary revascularisation and composite CV events compared to PES implantation at the 12-month follow-up.

Article history: Received 22 November 2015 Accepted 23 November 2015 Available online 24 November 2015 scale (GCS) score of 3 (E1VeM1), a body temperature of 35.2 °C, a heart rate of 83 beats/min, a respiratory rate of 18 breaths/min, a blood pressure of 146/83 mmHg, and a body mass index of 23.2 kg/m. There was no evidence of cardiac murmur and the results of other physical examinations were unremarkable. Blood hemograms and biochemical test results, including hematocrit, electrolytes, troponin-I, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein levels, were

Objective Proteoglycans and glycosoaminoglycans play many roles in connective tissue formation, their accumulation in myxomatous tissues may influence the associated mechanical behaviour of the mitral valve, as well as the extracellular matrix of the eye. Open-angle glaucoma (OAG) and mitral valve prolapse (MVP) may share similar phathophysiology. We hypothesised that MVP increased the risk of developing glaucoma. Methods The research was a retrospective cohort study using a longitudinal health insurance database from the National Health Insurance programme. The database was a randomly sampled population of 1 073 891 followed for 13 years from 1996 to 2008. There were 21 677 subjects with MVP, and 86 708 subjects without MVP were propensity score matched and served as a comparison group. Cox proportional hazards analysis was performed and adjusted for several comorbidities to evaluate the adjusted HR for OAG in the MVP group. Results The incidence rate of OAG in patients in the non-MVP and MVP groups were 10.17 and 16.05 per 10 000 person-years, respectively. The adjusted HR for OAG in the MVP group was 1.88 (95% CI 1.58 to 2.23). A significantly elevated risk of OAG in patients with MVP was also identified in the four stratified age groups. The cumulative incidence of OAG was assessed by Kaplan–Meier analysis. The analysis revealed that the MVP group had a higher incidence of OAG than the comparison group during the follow-up period (p Conclusions This population-based study demonstrated that pre-existing MVP is a significant predictor for the development of OAG, after adjusting for possible confounding factors.

The prevalence of coronary vasospasm and also the factors associated with coronary vasospasm in CKD is still unclear. In this cross-sectional study of 859 consecutive CKD patients with angina pectoris received coronary catheterization, we evaluated the factors associated with coronary vasospasm. Patients with vasospasm were older and had higher peripheral blood white cell counts, higher peripheral blood monocyte cell counts, higher haemoglobin levels, higher hs-CRP levels, and lower levels of serum creatinine than patients without vasospasm. The results of multivariate logistic regression analysis revealed that peripheral blood monocyte count and hs-CRP level were independently associated with coronary vasospasm in patients with stage 1 CKD. Only peripheral blood monocyte count but not hs-CRP was independently associated with coronary vasospasm in patients with stages 2 and 3 of CKD. In conclusion, peripheral blood monocyte count is independently associated with coronary vasospasm in patients with stage 1–3 CKD, whereas hs-CRP is only independently associated with coronary vasospasm in patients with stage 1 CKD.

Coronary artery spasm (CAS), an intense vasoconstriction of coronary arteries that causes total or subtotal vessel occlusion, plays an important role in myocardial ischemic syndromes including stable and unstable angina, acute myocardial infarction, and sudden cardiac death. Coronary angiography and provocative testing usually is required to establish a definitive diagnosis. While the mechanisms underlying the development of CAS are still poorly understood, CAS appears to be a multifactorial disease but is not associated with the traditional risk factors for coronary artery disease. The diagnosis of CAS has important therapeutic implications, as calcium antagonists, not β-blockers, are the cornerstone of medical treatment. The prognosis is generally considered benign; however, recurrent episodes of angina are frequently observed. We provide a review of the literature and summarize the current state of knowledge regarding the pathogenesis of CAS.

Importance Diabetic retinopathy is the leading cause of blindness in working-age adults. Studies have suggested that statins may reduce the risk of developing diabetic retinopathy. Objective To investigate the association between statin therapy and the development of diabetic retinopathy in patients with diabetes and dyslipidemia. Design, Setting, and Participants This population-based cohort study, conducted among 37 894 Taiwanese patients between January 1, 1998, and December 31, 2013, used the National Health Insurance Research Database to identify patients with type 2 diabetes and dyslipidemia. Outcomes were compared between those taking statins and those not taking statins. Statistical analysis was performed from May 1 to 31, 2018. Exposure Statin therapy with a medication possession rate of 80% or more with no other lipid-lowering medications. Main Outcomes and Measures Any stage of diabetic retinopathy and treatments for vision-threatening diabetic retinopathy. Results Of 1 648 305 patients with type 2 diabetes, 219 359 were eligible for analysis over the study period, including 199 760 patients taking statins and 19 599 patients not taking statins. After propensity score matching, there were 18 947 patients in the statin group (10 436 women and 8511 men; mean [SD] age, 61.5 [10.8] years) and 18 947 patients in the nonstatin group (10 430 women and 8517 men; mean [SD] age, 61.0 [11.0] years), with a mean follow-up of 7.6 years for the statin group and 7.3 years for the nonstatin group. During the study period, 2004 patients in the statin group (10.6%) and 2269 patients in the nonstatin group (12.0%) developed diabetic retinopathy. Patients in the statin group had a significantly lower rate of diabetic retinopathy (hazard ratio [HR], 0.86; 95% CI, 0.81-0.91), nonproliferative diabetic retinopathy (HR, 0.92; 95% CI, 0.86-0.99), proliferative diabetic retinopathy (HR, 0.64; 95% CI, 0.58-0.70), vitreous hemorrhage (HR, 0.62; 95% CI, 0.54-0.71), tractional retinal detachment (HR, 0.61; 95% CI, 0.47-0.79), and macular edema (HR, 0.60; 95% CI, 0.46-0.79) than the nonstatin group, as well as lower rates of interventions such as retinal laser treatment (HR, 0.71; 95% CI, 0.65-0.77), intravitreal injection (HR, 0.74; 95% CI, 0.61-0.89), and vitrectomy (HR, 0.58; 95% CI, 0.48-0.69), along with a smaller number of the interventions (retinal lasers: rate ratio, 0.61; 95% CI, 0.59-0.64; intravitreal injections: rate ratio, 0.68; 95% CI, 0.61-0.76; and vitrectomies: rate ratio, 0.54; 95% CI, 0.46-0.63). Statin therapy was also associated with lower risks of major adverse cardiovascular events (HR, 0.81; 95% CI, 0.77-0.85), new-onset diabetic neuropathy (HR, 0.85; 95% CI, 0.82-0.89), and new-onset diabetic foot ulcers (HR, 0.73; 95% CI, 0.68-0.78). Conclusions and Relevance Statin therapy was associated with a decreased risk of diabetic retinopathy and need for treatments for vision-threatening diabetic retinopathy in Taiwanese patients with type 2 diabetes and dyslipidemia.

Background: Scarce data are available on hemoglobin and platelet in relation to coronary artery spasm (CAS) development. We sought to determine the roles that high-sensitivity C-reactive protein (hs-CRP), hemoglobin and platelet play in CAS patients. Methods: Patients (337 women and 532 men) undergoing coronary angiography with or without CAS but without obstructive coronary artery disease were evaluated during a 12-year period. Results: Among women with high hemoglobin levels, the odds ratios (OR) from the lowest (3 mg/l) of hs-CRP were 1.21, 2.15, and 5.93 (p=0.009). In women with low hemoglobin levels, an elevated risk was found from the middle to the highest tertiles of hs-CRP (OR 0.59 to 3.85) (p=0.004). This relationship was not observed in men. In men, platelet count was the most significant risk factor for CAS (p=0.004). The highest likelihood of developing CAS was found among women with the highest hs-CRP tertile and low platelet counts (OR 8.77; 95% confidence interval [CI] 2.20-35.01) and among men with the highest hs-CRP tertile and high platelet counts (OR 4.58; 95% CI 0.48-43.97). Neither hemoglobin level nor platelet count was associated with frequent recurrent angina in both genders with CAS whereas death and myocardial infarction were rare. Conclusions: There are positive interactions among hs-CRP, hemoglobin and platelet in women with this disease, but not in men. While hemoglobin is a modifier in CAS development in women, platelet count is an independent risk factor for men. Both women and men have good prognosis of CAS.

Statin is the main lipid-lowering therapy for type 2 diabetes mellitus patients. Recent evidence suggested the cardiovascular protective effects of ezetimibe-simvastatin in acute coronary syndrome patients.To investigate the effect of ezetimibe-simvastatin combination therapy on stroke prevention among diabetic stroke patients. Design, Setting, Participants, and Outcome Measures: This is a retrospective cohort study. Between March 1, 2009 and December 31, 2011, all patients with type 2 diabetes mellitus in Taiwan's National Health Insurance Research Database were screened. Those admitted for ischemic stroke (IS) were recruited and divided into 10-mg ezetimibe-20-mg simvastatin (EZ-SIM), 40-mg atorvastatin (ATOR), and 20-mg simvastatin (SIM) groups for further analyses. The primary outcomes were IS, myocardial infarction, and death from any cause. Patients were followed from index hospitalization to the date of death, loss of follow-up, or study termination.During the 34-month follow-up period, the risk of recurrent IS in the SIM group was higher than that of the ATOR (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.46-2.82) and EZ-SIM (HR, 1.69; 95% CI, 1.14-2.50) groups. The risk of recurrent IS was not significantly lower in the EZ-SIM compared with the ATOR group (HR, 1.20; 95% CI, 0.85-1.69). The incidence of composite endpoint was highest in the SIM group (28.2%), followed by the ATOR (16.1%) and EZ-SIM (15.4%) groups. The multivariate adjusted survival curve showed lower trends of recurrent IS in the EZ-SIM and ATOR groups compared with the SIM group.High-potency lipid-lowering therapy effectively reduces the risk of recurrent IS in diabetic patients regardless of ATOR or EZ-SIM combination therapy.

Chronic kidney disease (CKD) is associated with adverse outcomes in patients who undergo coronary artery bypass grafting (CABG). However, the impact of preoperative dialysis dependence and duration in CKD patients on outcomes after CABG has limited research.To evaluate the effect of preoperative dialysis dependence and duration on CABG outcomes in patients with CKD.A total of 33,920 patients without CKD and 2573 patients with CKD, all of whom underwent isolated CABG between 1998 and 2009, were identified using the Taiwan National Health Insurance Research Database. The patients with CKD were divided into non-dialysis (N=1167), dialysis3years (N=749), and dialysis≥3years (N=657) groups. The primary outcomes were cumulative incidence of all-cause mortality, cardiovascular (CV) death, and myocardial infarction (MI) or repeat revascularization.After adjustment of all covariates, a higher all-cause mortality was associated with dialysis≥3years than with dialysis3years (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.35-1.80; P0.001) and with non-dialysis (HR, 1.41; 95% CI, 1.20-1.66; P0.001) after 2years of follow-up. Similar results were observed for CV death. In addition, both the dialysis groups had a higher risk of MI or revascularization than the non-dialysis group. Furthermore, subgroup analysis revealed that longer duration was associated with a higher risk of 30-day mortality (P for linear trend0.001).Among the CABG recipients, dialysis dependence is associated with a higher incidence of MI or repeat revascularization, and longer dialysis duration is associated with a higher risk of mortality.

Background Prior studies have suggested intraaortic balloon pump (IABP) have a neutral effect on acute myocardial infarction (AMI) patients with cardiogenic shock (CS). However, the effects of IABP on patients with severe CS remain unclear. We therefore investigated the benefits of IABP in AMI patients with severe CS undergoing coronary revascularization. Methods and Results This study identified 14,088 adult patients with AMI and severe CS undergoing coronary revascularization from Taiwan’s National Health Insurance Research Database between January 1, 1997 and December 31, 2011, dividing them into the IABP group (n = 7044) and the Nonusers group (n = 7044) after propensity score matching to equalize confounding variables. The primary outcomes included myocardial infarction(MI), cerebrovascular accidents or cardiovascular death. In-hospital events including dialysis, stroke, pneumonia and sepsis were secondary outcomes. Primary outcomes were worse in the IABP group than in the Nonusers group in 1 month (Hazard ratio (HR) = 1.97, 95% confidence interval (CI) = 1.84–2.12). The MI rate was higher in the IABP group (HR = 1.44, 95% CI = 1.16–1.79), and the cardiovascular death was much higher in the IABP group (HR = 2.07, 95% CI = 1.92–2.23). The IABP users had lower incidence of dialysis (8.5% and 9.5%, P = 0.04), stroke (2.6% and 3.8%, P

Although inhibition of Rho-associated coiled-coil containing protein kinase (ROCK) has been shown to prevent coronary vasospastic angina (CVA), direct evidence linking ROCK activity and CVA is lacking. Accordingly, we investigated whether ROCK activity is an independent marker for CVA and is altered after treatment with antispastic medications.We prospectively studied 31 Taiwanese patients who were diagnosed with CVA and 33 control subjects. Subject demographics were recorded, and blood samples were obtained at baseline in all participants and in CVA patients after 3 months of antispastic treatment. Compared with control subjects, leukocyte ROCK activity was greater in CVA patients (136% versus 91%, P0.001). A cutoff value for leukocyte ROCK activity of 104% predicted the presence of CVA with specificity and sensitivity rates of 88% and 84%, respectively. ROCK activity increased with the severity of CVA (P for trend0.001). Following 3-month treatment of antispastic agents, leukocyte ROCK activity, high-sensitivity C-reactive protein, and interleukin-6 levels were reduced by 43%, 42% and 27%, respectively (P0.05 for all).Increased levels of leukocyte ROCK activity independently predicted the presence of CVA and correlated with CVA severity. Treatment with antispastic agents substantially reduced the level of leukocyte ROCK activity.

A quick and effective image diagnosis is necessary for acute Standford type A aortic dissection. A 59-year-old man presented to the emergency department with sudden onset of severe, tearing-type chest pain. Emergency echocardiography demonstrated a dissection intimal flap superior to the sinuses of Valsalva, with extension to the bilateral carotid arteries. Subsequent computed tomography confirmed the diagnosis of acute Standford type A aortic dissection. Transthoracic echocardiography can be used to diagnose rapidly acute Standford type A aortic dissection.

Limited data are available about the cardiovascular (CV) safety and efficacy of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, in ischemic stroke patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Ischemic stroke patients with T2DM and CKD were selected from the Taiwan National Health Insurance Research Database (NHIRD) from March 1, 2009 to December 31, 2011. A total of 1375 patients were divided into 2 age- and gender-matched groups: patients who received sitagliptin (n = 275; 20%) and those who did not (n = 1,100). Primary major adverse cardiac and cerebrovascular events (MACCE), including ischemic stroke, hemorrhagic stroke, myocardial infarction (MI), or CV death, were evaluated. During a mean 1.07-year follow-up period, 45 patients (16.4%) in the sitagliptin group and 165 patients (15.0%) in the comparison group developed MACCEs (Hazard ratio [HR] 1.05; 95% confidence interval [CI], 0.75-1.45). Compared to the non-sitagliptin group, the sitagliptin group had a similar risk of ischemic stroke (HR 0.82; 95% CI, 0.51-1.32.), hemorrhagic stroke (HR 1.50; 95% CI, 0.58-3.82), MI (HR 1.14; 95% CI, 0.49-2.65), and CV mortality (HR 1.06; 95% CI, 0.61-1.85). The use of sitagliptin in recent ischemic stroke patients with T2DM and CKD was not associated with increased or decreased risk of adverse CV events.

Eur J Clin Invest 2010; 40 (12): 1094–1103 Abstract Background Coronary vasospasm (CVsp) has been reported to be an inflammatory disease, reflected by elevated high-sensitivity C-reactive protein (hs-CRP). We investigated the interactions among gender, age, hypertension and hs-CRP in patients with CVsp. Materials and methods We retrospectively examined 722 Taiwanese patients with or without CVsp during an 8-year period. None of the patients had obstructive coronary artery disease. Serum hs-CRP levels were examined in a subset of 375 patients to evaluate the interactions of hs-CRP with gender, age, smoking and hypertension in the development of CVsp. Results In women, only the highest hs-CRP tertile (> 3 mg L−1) was independently associated with CVsp. In men, age > 58 years and the highest hs-CRP tertile were independently associated with CVsp. In women, elevated risk was only demonstrated in patients ≤ 58 years of age with hs-CRP levels in the highest tertile. In men, a positively monotonic trend was demonstrated between hs-CRP levels and CVsp in those > 58 years of age. The odds ratios of CVsp in both women and men with hs-CRP in the highest tertile reduced from 6·01 to 1·48 and 6·35–2·69 respectively, if they had hypertension. Conclusion The relationship between hs-CRP and CVsp differed between men and women. Our findings that there is a non-threshold model in men and a threshold model in women provide evidence that more smokers in men (life-style) and age (induction time) contribute to the natural history of CVsp development. The negative effect of hypertension on CVsp suggests that the pathogenesis of CVsp differs from that of coronary atherosclerosis.

Background: Cardiac remodeling has been demonstrated in patients on hemodialysis and in predialysis patients with chronic kidney disease (CKD). Using functional echocardiographic parameters to study the association of hemodynamic status and predialysis CKD has not yet been established. Methods: From November 2007 to September 2008, ninety-six patients (50 men and 46 women) with different stages of CKD were enrolled consecutively to undergo echocardiography. Group 1 consisted of 27 patients with mild CKD (CKD stages 1 and 2) and group 2 consisted of 69 patients with moderate/severe CKD (CKD stages 3–5). Results: Higher values were observed for the products of serum calcium and phosphorus, serum phosphorus, and intact parathyroid hormone; lower values were observed for hematocrit and serum albumin in group 2 patients. Higher mitral E and A velocities, longer isovolumic relaxation time, more prevalence of moderate-to-severe left ventricular (LV) diastolic dysfunction and higher mitral E/Em value were noted in group 2 patients. Eccentric left ventricular hypertrophy (LVH) had effects on systolic contraction disturbance in group 2 patients. CKD severity without LVH had effects on LV filling pressure elevation and relaxation impairment. Among biochemical and echocardiographic parameters, mitral E/Em was most independently associated with a diagnosis of moderate/severe CKD (odds ratio = 1.29, P = 0.023) and it was the most predictive variable with sensitivity and specificity values for a cutoff value of ≥13 of 64% and 74%, respectively. Conclusions: CKD severity without LVH increased LV filling pressure and impaired LV relaxation. Mitral E/Em was significantly associated with moderate/severe CKD. (Echocardiography 2010;27:621-629)

High body mass index (BMI) is an established risk factor for coronary artery disease (CAD) in the general population. This relationship is less clear in CAD patients with different stages of chronic kidney disease (CKD) because many complications of CKD can cause malnutrition and low BMI. We studied the association of BMI and angiography-confirmed CAD in CKD patients.Thousand one hundred thirty-three patients admitted for coronary angiography was stratified by CKD classification. Demographic, clinical, hemodynamic, and angiographic findings were assessed. CKD patients (n = 980) were divided into angiographic CAD and non-CAD groups to compare traditional CAD risk factors. Patients with angiography-confirmed CAD (n = 496) were further analyzed for the association between BMI and CAD risk at different stages of CKD patients.Mean BMI was 27.4 +/- 4.1, 27.7 +/- 4.0, 25.9 +/- 3.5, 24.2 +/- 3.8, 23.2 +/- 3.0 and 23.8 +/- 4.2 kg/m for normal renal function, stage I, II, III, IV, and V CKD patients, respectively. Male, old age, presence of CKD, diabetes, hypertension, smoking, and higher cholesterol had significant association with angiographic CAD in the CKD sub-cohort. Obesity was not related to CAD in the CKD sub-cohort. Using WHO category for obesity, mild CKD patients were more likely to be overweight (62.8%) and obese (72%); meanwhile, most moderate and severe CKD patients were not obese (P0.05). Only 17.6% and 18.8% of moderate and severe CKD patients were obese (P0.05), by Taiwan classification.High BMI was not associated with angiographic CAD in CKD patients with angina.

Background A positive noninvasive stress test result is often considered as a false-positive indicator of coronary artery disease (CAD) when coronary angiography reveals no hemodynamically significant CAD. Methods From January 2001 through December 2004, 5474 patients scheduled to undergo exercise electrocardiogram (ECG) [exercise ECG without imaging or exercise ECG with thallium-201 (201Tl) single photon emission tomography (SPECT)] or dipyridamole 201Tl tomography at our outpatient clinic because of chest oppressive sensation were included in this prospective study. Coronary angiography was performed when a noninvasive test result was positive for ischemia or when ischemic chest pain was suspected. Intracoronary methylergonovine testing was performed when spastic angina was suspected and coronary angiography showed no hemodynamically significant CAD. Results Noninvasive stress testing was positive in 113 (67%) patients with coronary spasm. Of the 53 patients who had positive exercise ECG (exercise ECG with or without imaging), ST depression was found in 50 patients and ST elevationin in 3 patients. Multivessel spasm was found in 6 (15%), 6 (15%), and 7 (21%) of the patients with a positive result on exercise ECG without imaging, exercise ECG with 201Tl SPECT, and dipyridamole 201Tl SPECT, respectively. There was no significant difference in the results of noninvasive stress testing and the number of vessels with coronary spasm (1-vessel spasm versus multivessel spasm) among these 3 noninvasive stress testing groups. Conclusion Intracoronary ergonovine testing induced coronary spasm in over 50% of patients who had suspected ischemic chest pain, a positive noninvasive stress test, and no hemodynamically significant CAD.

Background Limited information is available comparing the clinical characteristics and prognosis for patients with coronary vasospastic angina in the absence of hemodynamically significant coronary artery disease (CAD) (defined as >50% stenosis) versus patients with significant fixed CAD presenting with either stable angina pectoris (SAP) or acute coronary syndromes (ACS). Methods Patients who underwent cardiac catheterization for suspected ischemic heart disease between August 1999 and February 2003 were followed clinically. For patients without hemodynamically significant CAD, a provocation test for coronary vasospasm was undertaken using a step-wise dose of intracoronary ergonovine administration. Results A total of 1134 patients were enrolled in the final analysis and stratified into 4 diagnostically distinct groups: control group (n = 239; mild CAD without coronary vasospasm); vasospasm group (n = 284; coronary vasospastic angina pectoris without hemodynamically significant CAD); SAP group (n = 110; hemodynamically significant CAD with SAP); ACS group (n = 501; hemodynamically significant CAD with ACS). Comparison of these 4 groups revealed that the ACS patients were more likely to be male, current smokers, and have hypercholesterolemia. In addition, this group had a significantly higher incidence of typical angina pectoris, 3-vessel CAD, and lower left ventricular ejection fraction. Between-group comparison revealed that vasospasm patients had a significantly higher incidence of early morning angina pectoris. Multivariate analysis showed that current smoking was the most independent risk factor associated with the diagnosis of coronary vasospastic angina pectoris in patients without hemodynamically significant CAD. During a median follow-up period of 49 months, recurrent angina pectoris was noted in patients from the control (n = 6; 3%), SAP (n = 9; 8%), vasospasm (n = 30, 11%), and ACS groups (n = 92; 18%); with nonfatal myocardial infarction identified during follow-up in the SAP (n = 5; 5%), vasospasm (n = 3; 1%), and ACS groups (n = 37; 7%). In addition, 29 and 3 cardiac deaths occurred in the ACS and SAP groups, respectively, whereas there were no such mortalities in the control and vasospasm groups. Conclusions Early morning angina pectoris and cigarette smoking were the most common clinical characteristics in patients with coronary vasospasm. These patients had an excellent prognosis despite the possibility of recurrences of vasospastic angina pectoris.

Chronic kidney disease increases cardiovascular mortality in patients with predialysis kidney disease, in those on dialysis and in kidney transplant recipients. Structural and functional cardiac remodelling play a critical role in such cardiovascular mortality.1 LV structural remodelling such as diffuse interstitial fibrosis occurs in early chronic kidney disease and is associated with myocardial dysfunction.2 Among patients with chronic kidney disease, the prevalence of LV hypertrophy increases as renal function deteriorates.3 Its presence predicts future cardiovascular disease in this patient population.3 Several studies have shown that successful renal transplantation is associated with resolution of the LV hypertrophy.1 ,4 However, the association between LV remodelling after renal transplantation, and allograft outcome has not been fully explored. Thus, screening for cardiovascular benefits and complications is advocated for patients who have undergone renal transplantation. In this issue of Heart , An et al 5 report a retrospective analysis of cardiac function in long-term renal transplant recipients from two Korean medical centres in which transthoracic echocardiography was used to assess LV structure and function. They analysed 767 adult patients who underwent echocardiography before transplantation and at 1 week, 1 year and 5 years after transplantation. LV hypertrophy, defined as a LV mass index >95 g/m2 for women and >115 g/m2 for men, occurred in 71% (546/767) of these patients with chronic kidney disease before transplantation. The prevalence of LV hypertrophy decreased from 71% before transplantation to 66% at 1 year and to …

Serum levels of inflammatory markers (interleukin-6, monocyte chemoattractant protein-1, soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and C-reactive protein) were measured at baseline in serum samples from 189 patients who were admitted for coronary angiography because of suspected ischemic heart disease. Median duration of follow-up was 28 months. Patients in our sample were enrolled in 4 diagnostic groups: no hemodynamically significant coronary artery disease (CAD) and no coronary vasospasm (control group, n = 32), hemodynamically significant CAD and stable angina pectoris (SAP group, n = 34), coronary vasospastic angina pectoris without hemodynamically significant CAD (vasospasm group, n = 31), and acute coronary syndrome (ACS) and hemodynamically significant CAD (ACS group, n = 92). Overall, the level of serum inflammatory markers was highest in the ACS group and lowest in the control group, with intermediate values observed in the SAP and vasospasm groups, with the exception of soluble intercellular adhesion molecule-1, the level of which was highest in the vasospasm group. Multivariate analysis showed that log (interleukin-6) was independently associated with a diagnosis of coronary vasospastic angina pectoris in patients without hemodynamically significant CAD (odds ratio 8.48, p = 0.027). Patients in the ACS group had a significantly lower survival rate compared with the other 3 groups but without an independent predictor that could be identified in this patient cohort. Recurrent angina pectoris occurred with similar rates in the SAP, vasospasm, and ACS groups. The independent predictor for recurrent angina pectoris was treatment that did not include clopidogrel (odds ratio 3.88, p = 0.007). In conclusion, the results of this study suggest that inflammation can exist in coronary vasospasm without hemodynamically significant CAD.

Background Exercise-induced ST-segment elevation is a relatively uncommon problem and occurs more frequently in patients who have had a myocardial infarction. Data is limited on the characteristics of Taiwanese patients without prior myocardial infarction who develop exercise-induced ST-segment elevation. Methods and Results Exercise-induced ST-segment elevation developed in 9 of 6,147 consecutive patients without myocardial infarction who underwent treadmill exercise testing at out institution over a 4-year period. The clinical and angiographic characteristics of these patients were studied. Angiographically normal coronary arteries with coronary vasospasm were found in 5 patients, hemodynamically significant coronary stenosis was found in 3 patients, and coexisting spasm in angiographically normal coronary arteries combined with hemodynamically significant coronary stenosis in the different vessel was found in 1 patient. During a median follow-up of 71 months, 2 patients with coronary vasospasm developed recurrent angina after self-discontinuation of calcium antagonists and 2 patients (1 with coronary vasospasm and 1 with hemodynamically significant coronary stenosis) died of cardiac causes before arrival at the emergency department. Conclusion Coronary vasospasm was a more common underlying pathology of exercise-induced ST-segment elevation in this Taiwanese cohort. Coronary angiography ± intracoronary ergonovine provocation testing is necessary in these patients to identify the underlying pathology and appropriate treatment. (Circ J 2006; 70: 254 - 261)

We prospectively investigated the relation of high-sensitivity C-reactive protein (hs-CRP) to coronary vasospasm and no hemodynamically significant coronary artery disease (CAD) in a sample of 428 patients who underwent coronary angiography. These patients were assigned to 1 of 3 groups. The control group consisted of 66 patients who had no coronary vasospasm and no hemodynamically significant CAD. The vasospasm group consisted of 116 patients who had coronary vasospasm and no hemodynamically significant CAD. The acute coronary syndrome (ACS) group consisted of 246 patients who had ACS and hemodynamically significant CAD. Serum hs-CRP was measured immediately before coronary angiography. Patients were followed for subsequent cardiac events and mortality. Median hs-CRP levels in the control, vasospasm, and ACS groups were 1.0, 5.5, and 8.2 mg/L, respectively. The proportion of hs-CRP increased from the lowest to the highest tertile in the control, vasospasm, and ACS groups, respectively. In the control and vasospasm groups, multivariate analysis showed that hs-CRP was independently associated with a diagnosis of coronary vasospastic angina pectoris (odds ratio 68.74, 95% confidence interval 8.03 to 588.71, p0.001). During a median follow-up period of 26 months (range 0.4 to 48), 27 cardiac deaths occurred in the ACS group, whereas no cardiac death occurred in the control and vasospasm groups. In conclusion, serum hs-CRP level measured immediately before coronary angiography was an independent marker of coronary vasospasm in patients who had no hemodynamically significant CAD.