Privacy-Preserving Federated Model Predicting Bipolar Transition in Patients With Depression: Prediction Model Development Study.

BACKGROUND: Mood disorder has emerged as a serious concern for public health; in particular, bipolar disorder has a less favorable prognosis than depression. Although prompt recognition of depression conversion to bipolar disorder is needed, early prediction is challenging due to overlapping symptoms. Recently, there have been attempts to develop a prediction model by using federated learning. Federated learning in medical fields is a method for training multi-institutional machine learning models without patient-level data sharing. OBJECTIVE: This study aims to develop and validate a federated, differentially private multi-institutional bipolar transition prediction model. METHODS: This retrospective study enrolled patients diagnosed with the first depressive episode at 5 tertiary hospitals in South Korea. We developed models for predicting bipolar transition by using data from 17,631 patients in 4 institutions. Further, we used data from 4541 patients for external validation from 1 institution. We created standardized pipelines to extract large-scale clinical features from the 4 institutions without any code modification. Moreover, we performed feature selection in a federated environment for computational efficiency and applied differential privacy to gradient updates. Finally, we compared the federated and the 4 local models developed with each hospital's data on internal and external validation data sets. RESULTS: In the internal data set, 279 out of 17,631 patients showed bipolar disorder transition. In the external data set, 39 out of 4541 patients showed bipolar disorder transition. The average performance of the federated model in the internal test (area under the curve [AUC] 0.726) and external validation (AUC 0.719) data sets was higher than that of the other locally developed models (AUC 0.642-0.707 and AUC 0.642-0.699, respectively). In the federated model, classifications were driven by several predictors such as the Charlson index (low scores were associated with bipolar transition, which may be due to younger age), severe depression, anxiolytics, young age, and visiting months (the bipolar transition was associated with seasonality, especially during the spring and summer months). CONCLUSIONS: We developed and validated a differentially private federated model by using distributed multi-institutional psychiatric data with standardized pipelines in a real-world environment. The federated model performed better than models using local data only.

Impact of pitavastatin on new-onset diabetes mellitus compared to atorvastatin and rosuvastatin: a distributed network analysis of 10 real-world databases.

BACKGROUND: Statin treatment increases the risk of new-onset diabetes mellitus (NODM); however, data directly comparing the risk of NODM among individual statins is limited. We compared the risk of NODM between patients using pitavastatin and atorvastatin or rosuvastatin using reliable, large-scale data. METHODS: Data of electronic health records from ten hospitals converted to the Observational Medical Outcomes Partnership Common Data Model (n = 14,605,368 patients) were used to identify new users of pitavastatin, atorvastatin, or rosuvastatin (atorvastatin + rosuvastatin) for ≥ 180 days without a previous history of diabetes or HbA1c level ≥ 5.7%. We conducted a cohort study using Cox regression analysis to examine the hazard ratio (HR) of NODM after propensity score matching (PSM) and then performed an aggregate meta-analysis of the HR. RESULTS: After 1:2 PSM, 10,238 new pitavastatin users (15,998 person-years of follow-up) and 18,605 atorvastatin + rosuvastatin users (33,477 person-years of follow-up) were pooled from 10 databases. The meta-analysis of the HRs demonstrated that pitavastatin resulted in a significantly reduced risk of NODM than atorvastatin + rosuvastatin (HR 0.72; 95% CI 0.59-0.87). In sub-analysis, pitavastatin was associated with a lower risk of NODM than atorvastatin or rosuvastatin after 1:1 PSM (HR 0.69; CI 0.54-0.88 and HR 0.74; CI 0.55-0.99, respectively). A consistently low risk of NODM in pitavastatin users was observed when compared with low-to-moderate-intensity atorvastatin + rosuvastatin users (HR 0.78; CI 0.62-0.98). CONCLUSIONS: In this retrospective, multicenter active-comparator, new-user, cohort study, pitavastatin reduced the risk of NODM compared with atorvastatin or rosuvastatin.

Long-term proton pump inhibitor use and risk of osteoporosis and hip fractures: A nationwide population-based and multicenter cohort study using a common data model.

BACKGROUND AND AIM: Association between protonpump inhibitors (PPIs) and osteoporosis, hip fractures has not been fully elucidated. We aimed to evaluate the relationship between PPIs use and the risk of osteoporosis and hip fractures in the databases converted to a common data model (CDM) and to compare the results across the databases. METHODS: This was a population-based, propensity-matched, retrospective cohort study that included patients aged ≥ 50 years who were prescribed with PPIs for over 180 days. We compared the incidence of osteoporosis and hip fractures between new PPI user and new user of other drugs using the Cox proportional hazards model and performed meta-analysis in the electronic health record (EHR) databases. RESULTS: In the Korean National Health Insurance Service (NHIS)-CDM database, long-term PPI users had greater risk of osteoporosis [PPIs vs non-PPIs groups, 28.42/1000 person-years vs 19.29/1000 person-years; hazard ratio (HR), 1.62; 95% confidence interval (CI), 1.22-2.15; P = 0.001]. The meta-analytic results of six EHR databases also showed similar result (pooled HR, 1.57; 95% CI, 1.28-1.92). In the analysis of hip fracture, PPI use was not significantly associated with a hip fracture in the NHIS-CDM database (PPI vs non-PPI groups, 3.09/1000 person-years vs 2.26/1000 person-years; HR, 1.45; 95% CI, 0.74-2.80; P = 0.27). However, in the meta-analysis of four EHR databases, the risk of hip fractures was higher in PPI users (pooled HR, 1.82; 95% CI, 1.04-3.19). CONCLUSIONS: Long-term PPI was significantly associated with osteoporosis; however, the results of hip fractures were inconsistent. Further study based on better data quality may be needed.

Association between proton pump inhibitor use and gastric cancer: a population-based cohort study using two different types of nationwide databases in Korea.

OBJECTIVE: The association between proton pump inhibitor (PPI) use and gastric cancer related to Helicobacter pylori eradication has not been fully investigated in geographical regions with high risk of gastric cancer. We aimed to evaluate the association between PPIs and gastric cancer in Korea. DESIGN: This study analysed the original and common data model versions of the Korean National Health Insurance Service database from 2002 to 2013. We compared the incidence rates of gastric cancer after 1-year drug exposure, between new users of PPIs and other drugs excluding PPIs, by Cox proportional hazards model. We also analysed the incidence of gastric cancer among PPI users after H. pylori eradication. RESULTS: The analysis included 11 741 patients in matched PPI and non-PPI cohorts after large-scale propensity score matching. During a median follow-up of 4.3 years, PPI use was associated with a 2.37-fold increased incidence of gastric cancer (PPI≥30 days vs non-PPI; 118/51 813 person-years vs 40/49 729 person-years; HR 2.37, 95% CI 1.56 to 3.68, p=0.001). The incidence rates of gastric cancer showed an increasing trend parallel to the duration of PPI use. In H. pylori-eradicated subjects, the incidence of gastric cancer was significantly associated with PPI use over 180 days compared with the non-PPI group (PPI≥180 days vs non-PPI; 30/12 470 person-years vs 9/7814 person-years; HR 2.22, 95% CI 1.05 to 4.67, p=0.036). CONCLUSION: PPI use was associated with gastric cancer, regardless of H. pylori eradication status. Long-term PPIs should be used with caution in high-risk regions for gastric cancer.

Clinical impact of statin therapy on vasospastic angina: data from a Korea nation-wide cohort study.

The effect of statin therapy on reducing adverse cardiovascular events in vasospastic angina (VSA) has been inconsistent. Therefore, we investigated the association between statin therapy and adverse cardiovascular events in a large, prospective VSA cohort. The Variant Angina Korea registry consecutively enrolled 2960 patients suspected VSA. Among them, we included 1713 patients who were diagnosed with VSA based on coronary provocation test. We divided the patients into the statin (n = 744) and no-statin group (n = 914) according to the medication prescribed at discharge. The primary outcome was a composite of cardiac death, acute coronary syndrome, and new-onset life-threatening arrhythmia during a 3-year follow-up period. The primary outcome occurred in 32 patients (4.3%) in the statin and 28 patients (3.1%) in the no-statin group. In Kaplan-Meier analysis before and after propensity score matching, there was no significant difference in the cumulative incidence of primary outcomes between both groups. Multivariate Cox regression analysis demonstrated that the focal type of VSA was independent predictor of primary outcomes, but statin therapy was not. Furthermore, the lack of benefit of statin therapy for primary outcomes was consistently observed across the statin intensity and spasm characteristics. In conclusion, the present study demonstrated that statin therapy did not reduce adverse cardiovascular events in patients with VSA.

Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin-Receptor Blockers in Heart Failure With Chronic Kidney Disease　- Propensity Score Matching Analysis.

BACKGROUND: Whether angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) exert beneficial effects in patients with concomitant heart failure (HF) and chronic kidney disease (CKD) remains uncertain. In this study, the effects of ACEI and ARB on long-term clinical outcomes in such patients were investigated.Methods and Results:Study data were obtained from a multicenter cohort that included patients hospitalized for HF. A total of 1,601 patients with both HF and CKD were classified according to prescription of ACEI or ARB at discharge. The mortality rate was 19.0% in the ACEI/ARB treatment group (n=943) and 33.6% in the no ACEI/ARB treatment group (n=658) during follow-up. The ACEI/ARB treatment group had a significantly higher cumulative death-free survival rate than the no ACEI/ARB treatment group. Cox regression analysis showed that using ACEI or ARB was independently associated with reduced risk of all-cause death after adjusting for confounding factors. The beneficial effects of ACEI or ARB were retained after propensity score matching. CONCLUSIONS: Prescription of an ACEI or ARB at discharge was associated with reduction in all-cause mortality in patients with acute HF and CKD. Clinicians need to be aware of the prognostic value and consider prescribing ACEI or ARB to high-risk patients.

Efficacy of IntraCoronary Erythropoietin Delivery BEfore Reperfusion-Gauging Infarct Size in Patients with Acute ST-segment Elevation Myocardial Infarction (ICEBERG).

Previous clinical studies have shown inconsistent results regarding the effect of erythropoietin in ST-segment elevation myocardial infarction (STEMI). This study investigated whether directed intracoronary infusion of darbepoetin-α into ischemic myocardium before reperfusion would reduce infarct size or post-infarct remodeling in STEMI patients.Eighty STEMI patients received one of the following treatments simultaneously with the first balloon inflation: intracoronary darbepoetin-α 300 µg (n = 40) or saline (n = 40), administered via the over-the-wire balloon system. The primary endpoint was infarct size estimated by serial cardiac enzyme levels after procedure. The secondary endpoints were (1) infarct size and proportion of salvaged myocardium measured with cardiac magnetic resonance (CMR) at baseline; (2) post-infarct remodeling (PIR), defined as an increase in left ventricular end-diastolic volume more than 20% at 4 months compared to the baseline on CMR; and (3) composite cardiovascular endpoints assessed at 4 months.The peak CK-MB [median 270.0 (interquartile range 139.8-356.3) versus 231.5 (131.0-408.5) ng/mL, P = 0.55] and troponin-I [128.5 (63.5-227.8) versus 109.0 (43.8-220.0) ng/mL, P = 0.52) ] did not differ between the darbepoetin-α and control group. Fifty-seven patients completed the baseline and 4-month follow-up CMR. There were no differences in infarct size [30.6 (18.1-49.8) versus 31.5 (22.5-47.3) cm3, P = 0.91), proportion of salvaged myocardium [26.7% (15.9-42.6%) versus 35.8% (22.4-48.8%), P = 0.12) or PIR (8.0% versus 6.7%, P = 0.62) between the two groups. Composite cardiovascular outcomes did not differ between the two groups.In conclusion, administration of intracoronary darbepoetin-α before reperfusion did not reduce infarct size or post-infarct remodeling in STEMI patients.

Real-World Risk of Gastrointestinal Bleeding for Direct Oral Anticoagulants and Warfarin Users: A Distributed Network Analysis Using a Common Data Model.

Background/Aims: Early studies on direct oral anticoagulants (DOACs) reported a higher risk of gastrointestinal bleeding (GIB) compared with warfarin; however, recent studies have reported a reduced risk. Therefore, this study was designed to evaluate the risk of GIB in users of DOAC and warfarin. Methods: Using a common data model, we investigated the comparative risk of GIB in subjects from eight hospitals who were newly prescribed DOACs or warfarin. We excluded subjects who had a prior history of GIB or had been prescribed both medications. After propensity score matching, we analyzed 3,347 matched pairs of new DOAC and new warfarin users. Results: The risk of GIB in new DOAC users was comparable to that in new warfarin users (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.65 to 1.40; p=0.808). New DOAC users had a similar risk of GIB to new warfarin users among older patients >65 years (HR, 1.00; 95% CI, 0.69 to 1.52; p=0.997) and in older patients >75 years (HR, 1.21; 95% CI, 0.68 to 2.10; p=0.509). In addition, the risk of GIB was not significantly different between two groups according to sex. We also found that the risk of GIB in DOAC users was 26% lower in edoxaban or apixaban subgroups compared to rivaroxaban or dabigatran subgroups (HR, 0.74; 95% CI, 0.69 to 1.00; p=0.049). Conclusions: In real-world practice, the risk of GIB in new DOAC users is comparable to that in new warfarin users. In DOAC users, the risk of GIB was lower in edoxaban or apixaban subgroups than rivaroxaban or dabigatran subgroups.

Percutaneous coronary intervention versus medical therapy in stable angina: a matched cohort study.

OBJECTIVE: It is uncertain whether percutaneous coronary intervention (PCI) in addition to optimal medical therapy (OMT) can reduce adverse clinical events in the long term as compared with OMT alone in patients with pure stable angina. METHODS: We enrolled patients from 2006 to 2010 using the Korean national insurance data. 58 742 patients with pure stable angina with no history of myocardial infarction (MI) nor PCI were candidate, and finally, 5673 patients in the PCI plus OMT group and 5673 in the OMT alone group were selected with 1:1 propensity matching. They were followed up for 9.3 years. RESULTS: Primary endpoint, a composite of MI, stroke and cardiac death rate was significantly higher in the PCI group than in the OMT group, 13.5/1000 vs 11.5/1000 person-year with HR of 1.18 (95% CI 1.06 to 1.32, p=0.003). Individual event rate of MI and cardiac death rate was higher in the PCI group than in the OMT group at 9.3 years, 2.9 vs 2.1 (HR 1.38, 95% CI 1.09 to 1.7, p=0.009) and 4.8 vs 3.4/1000 person-year (HR 1.40, 95% CI 1.16 to 1.69, p=0.001), respectively. Revascularisation and total death occurred more in the PCI group as compared with the OMT group, 30.3 vs 8.2 (HR 3.64, 95% CI 3.27 to 4.05, p<0.001) and 13.5 vs 10.6/1000 person-year (HR 1.23, 95% CI 1.12 to 1.40, p<0.001), respectively. In subgroup analysis, the same trend of more event in the PCI group was detected. CONCLUSIONS: PCI plus OMT was associated with higher rate of primary endpoint of MI, stroke, cardiac death as compared with OMT alone in patients with pure stable angina at 9.3-year follow-up in large population.

Diagnostic performance of angiography-derived fractional flow reserve compared to pressure wire-derived fractional flow reserve: Rationale and design of MPFFR pivotal trial.

BACKGROUND: Cardiovascular disease remains the leading cause of death and the use of percutaneous coronary intervention (PCI) is steadily increasing. Current guidelines advocate the use of the fractional flow reserve (FFR) to assess coronary stenosis and treatment strategies; however, invasive FFR has some limitations. Angiography-derived FFR is a potential alternative for calculating FFR from two-dimensional (2D) angiographic images, thereby reducing invasiveness and complications. A novel artificial intelligence (AI)-based angiography-derived FFR, named "MPFFR," offers automated operator-independent hemodynamic calculations; this phase 3 trial aims to validate its diagnostic performance against 2D-quantitative coronary angiography (QCA). METHODS AND ANALYSIS: This pivotal MPFFR trial is a prospective, multicenter, single-blind study. This trial involves patients with coronary artery disease (CAD) from eight cardiovascular centers. Invasive FFR will be performed according to standard guidelines and defined as the reference standard. Angiography-derived FFR will be computed using a proprietary method and 2D-QCA will be performed using validated software. The primary endpoint is the area under the curve for identifying physiologically significant coronary stenosis (FFR ≤0.80), with secondary endpoints including diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and correlations between angiography-derived and invasive FFR. This study is designed to demonstrate the superiority of angiography-derived FFR over 2D-QCA and is powered to achieve this with a sample size of 240 patients. Medipixel Inc. supports the trial and is not involved in the data analysis or management.

Comparison of Finasteride and Dutasteride on Risk of Prostate Cancer in Patients with Benign Prostatic Hyperplasia: A Pooled Analysis of 15 Real-world Databases.

PURPOSE: Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2 form of 5-alpha-reductase, whereas dutasteride blocks both type 1 and 2 forms of the enzyme. Previous studies suggest the possibility that dutasteride may be superior to finasteride in preventing prostate cancer. We directly compared the effects of finasteride and dutasteride on the risk of prostate cancer in patients with BPH using a pooled analysis of 15 real-world databases. MATERIALS AND METHODS: We conducted a multicenter, cohort study of new-users of finasteride and dutasteride. We include patients who were prescribed 5 mg finasteride or dutasteride for the first time to treat BPH and had at least 180 days of prescription. We excluded patients with a history of prostate cancer or a prostate-specific antigen level ≥ 4 ng/mL before the study drug prescription. Cox regression analysis was performed to examine the hazard ratio (HR) for prostate cancer after propensity score (PS) matching. RESULTS: A total of 8,284 patients of new-users of finasteride and 8,670 patients of new-users of dutasteride were included across the 15 databases. In the overall population, compared to dutasteride, finasteride was associated with a lower risk of prostate cancer in both on-treatment and intent-to-treat time-at-risk periods. After 1:1 PS matching, 4,897 patients using finasteride and 4,897 patients using dutasteride were enrolled in the present study. No significant differences were observed for risk of prostate cancer between finasteride and dutasteride both on-treatment (HR=0.66, 95% confidence interval [CI]: 0.44-1.00; p=0.051) and intent-to-treat time-at-risk periods (HR=0.87, 95% CI: 0.67-1.14; p=0.310). CONCLUSIONS: Using real-world databases, the present study demonstrated that dutasteride was not associated with a lower risk of prostate cancer than finasteride in patients with BPH.

Biodegradable Polymer Versus Polymer-Free Ultrathin Sirolimus-Eluting Stents: Analysis of the Stent Arm Registry From the HOST-IDEA Randomized Trial.

BACKGROUND: The efficacy and safety of each third-generation drug-eluting stent with ultrathin struts and advanced polymer technology remain unclear. We investigated the clinical outcomes of percutaneous coronary intervention using the Coroflex ISAR polymer-free sirolimus-eluting stent (SES) or Orsiro biodegradable polymer SES. METHODS: The HOST-IDEA trial (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Coronary Intervention With Next-Generation Drug-Eluting Stent Platforms and Abbreviated Dual Antiplatelet Therapy), initially designed with a 2×2 factorial approach, sought to randomize patients undergoing percutaneous coronary intervention based on dual antiplatelet therapy duration (3 versus 12 months) and stent type (Coroflex ISAR versus Orsiro). Despite randomizing 2013 patients for dual antiplatelet therapy duration, the stent arm transitioned to a registry format during the trial. Among these, 328 individuals (16.3%) were randomized for Coroflex ISAR or Orsiro SES, while 1685 (83.7%) underwent percutaneous coronary intervention without stent-type randomization. In this study, the Coroflex ISAR (n=559) and Orsiro groups (n=1449) were matched using a propensity score. The prespecified primary end point was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization at 12 months. RESULTS: The baseline patient and procedural characteristics were well balanced between the Coroflex ISAR and Orsiro groups after propensity score matching (n=559, each group). The Coroflex ISAR group was significantly associated with a higher rate of target lesion failure, mainly driven by clinically driven target lesion revascularization, compared with the Orsiro group (3.4% versus 1.1%; hazard ratio, 3.21 [95% CI, 1.28-8.05]; P=0.01). A higher risk of target lesion failure in the Coroflex ISAR group was consistently observed across various subgroups. The rates of any bleeding (hazard ratio, 0.85 [95% CI, 0.51-1.40]; P=0.52) and major bleeding (hazard ratio, 1.58 [95% CI, 0.61-4.08]; P=0.34) were comparable between the 2 groups. CONCLUSIONS: In this propensity score-matched analysis of the stent arm registry from the HOST-IDEA trial, the Orsiro SES was associated with significantly better outcomes in terms of 1-year target lesion failure, mainly driven by clinically driven target lesion revascularization, than the Coroflex ISAR SES. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02601157.

Proton pump inhibitors and chronic kidney disease risk: a comparative study with histamine-2 receptor antagonists.

This observational study explored the association between proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) use and the risk of chronic kidney disease (CKD). Using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) and six-hospital electronic health record (EHR) databases, CKD incidence was analyzed among PPI and H2RA users. Propensity score matching was used to balance baseline characteristics, with 1,869 subjects each in the PPI and H2RA groups from the NHIS-NSC, and 5,967 in EHR databases. CKD incidence was similar for both groups (5.72/1000 person-years vs. 7.57/1000 person-years; HR = 0.68; 95% CI, 0.35-1.30). A meta-analysis of the EHR databases showed no significant increased CKD risk associated with PPI use (HR = 1.03, 95% CI: 0.87-1.23). These results suggest PPI use may not increase CKD risk compared to H2RA use, but the potential role of PPI-induced CKD needs further research. Clinicians should consider this when prescribing long-term PPI therapy.

Risks of long-term use of proton pump inhibitor on ischemic vascular events: A distributed network analysis of 5 real-world observational Korean databases using a common data model.

BACKGROUND: Proton pump inhibitors (PPIs) are frequently prescribed drugs. However, it has been suggested that they are associated with an increased risk of ischemic vascular events (IVE) including stroke, although the data are inconsistent. AIMS: We investigated the association between PPIs use and IVE in five observational Korean databases using a common data model (CDM). METHODS: This study included patient-based retrospective, observational cohort data of subjects aged over 18 years between January 1, 2004, and December 31, 2020, from five medical centers as part of the Observational Medical Outcomes Partnership (OMOP) CDM. Subjects who were included in both cohorts or had a previous history of ischemic stroke were excluded. After propensity matching, 8007 propensity-matched pairs between the PPIs and H2 receptor antagonist (H2RA) users were included in this study. RESULTS: In the 1:1 propensity score matching with 8007 in each group, long-term PPIs use (⩾365 days) was not associated with ischemic stroke (odds ratio (OR) = 1.05, 95% confidence interval (CI) 0.71-1.56; I2 = 57%), ischemic stroke and transient ischemic attack (OR = 1.02, 95% CI 0.71-1.48; I2 = 53%), and net adverse clinical events (OR = 1.08, 95% CI 0.83-1.40; I2 = 47%) compared with H2RAs users. CONCLUSIONS: Our analysis in a large dataset found no evidence that long-term use of PPIs was associated with an increased risk of ischemic stroke.

Long-term mortality and cardiovascular events of seven angiotensin receptor blockers in hypertensive patients: Analysis of a national real-world database: A retrospective cohort study.

Background and Aims: Although many angiotensin receptor blockers (ARBs) are widely used, comparative data regarding their impact on clinical outcomes are limited. We aimed to compare the clinical effectiveness of seven ARBs on long-term cardiovascular outcomes in Korean patients with hypertension. Methods: Using the Korean National Health Insurance Service database, the data of 780,785 patients with hypertension without cardiovascular disease (CVD) who initiated ARB treatment (candesartan, fimasartan, irbesartan, losartan, olmesartan, telmisartan, or valsartan) in 2014 and underwent this treatment for more than 6 months, were analyzed. Cox-regression analysis was performed using Losartan as a comparator, as it was the most widely used drug, by adjusting age, sex, diabetes, dyslipidemia, smoking, alcohol drinking, exercise, body mass index, systolic blood pressure, albuminuria, estimated glomerular filtration rate, and concomitant medications. The occurrence of mortality and the rate of major adverse cardiovascular events (MACEs) of the six ARBs was compared with that of losartan. Results: The median follow-up duration was 5.94 (interquartile range, 5.87-5.97) years. In the crude analysis of all-cause mortality and MACEs, fimasartan exhibited the lowest event rates. In the Cox-regression analysis with adjustment, there was no significant difference in all-cause mortality among ARBs. The risk of MACEs with ARBs was similar to that with losartan, although the risks with irbesartan (hazard ratio [HR], 1.079; 95% confidence interval [CI], 1.033-1.127; p = 0.007) and candesartan (HR: 1.066; 95% CI, 1.028-1.106; p = 0.015) were slightly higher. Conclusion: In a Korean population of patients with hypertension without CVD, six different ARBs showed similar efficacy to losartan in terms of long-term mortality and MACEs. Further well-designed prospective studies are required to confirm our findings.

Stent coated with antibody against vascular endothelial-cadherin captures endothelial progenitor cells, accelerates re-endothelialization, and reduces neointimal formation.

OBJECTIVE: In contrast to CD34, vascular endothelial-cadherin (VE-cadherin) is exclusively expressed on the late endothelial progenitor cells (EPC) whereas not on the early or myeloid EPC. Thus, VE-cadherin could be an ideal target surface molecule to capture circulating late EPC. In the present study, we evaluated whether anti-VE-cadherin antibody-coated stents (VE-cad stents) might accelerate endothelial recovery and reduce neointimal formation through the ability of capturing EPC. METHODS AND RESULTS: The stainless steel stents were coated with rabbit polyclonal anti-human VE-cadherin antibodies and exposed to EPC for 30 minutes in vitro. The number of EPC that adhered to the surface of VE-cad stents was significantly higher than bare metal stents (BMS) in vitro, which was obliterated by pretreatment of VE-cad stent with soluble VE-cadherin proteins. We deployed VE-cad stents and BMS in the rabbit right and left iliac arteries, respectively. At 48 hours after stent deployment in vivo, CD-31-positive endothelial cells adhered to VE-cad stent significantly more than to BMS. At 3 days, scanning electron microscopy showed that over 90% surface of VE-cad stents was covered with endothelial cells, which was significantly different from BMS. At 42 days, neointimal area that was filled with smooth muscle cells positive for actin or calponin was significantly smaller in VE-cad stents than in BMS by histological analysis (0.95±0.22 versus 1.34±0.43 mm(2), respectively, P=0.02). Immuno-histochemical analysis revealed that infiltration of inflammatory cells was not significantly different between 2 stents. CONCLUSIONS: VE-cad stents captured EPC successfully in vitro, accelerated endothelial recovery on stent, and eventually reduced neointimal formation in vivo.

Choroidal vascularity index of patients with coronary artery disease.

We investigated the changes in subfoveal choroidal thickness and choroidal vascularity index (CVI) and their relationship with the severity of coronary artery stenosis in patients with cardiovascular risk factors and symptoms suggestive of coronary artery disease (CAD). Ninety patients who underwent coronary angiography (CAG) for evaluation of their coronary artery status and cardiac symptoms were included. Forty-two patients showed no evidence of CAD; 31 patients had one to two vessel disease; and 17 had a triple vessel disease. There were no significant differences in the subfoveal choroidal thickness among the three groups; however, the CVI in the triple vessel disease group was lower than those in the other groups. The CVI values were good predictors of the presence of triple-vessel disease (p = 0.020). Multivariate logistic regression analysis results revealed that male sex (odds ratio 5.4, p = 0.049), hypertension (odds ratio 4.9, p = 0.017), and CVI (%, odds ratio 0.8, p = 0.016) were significant factors associated with the presence of triple vessel disease. Although CVI may not be a sensitive marker for detecting early changes in the coronary artery, it may be helpful in indicating severe CAD.

Long-term use of proton-pump inhibitor on Alzheimer's disease: a real-world distributed network analysis of six observational Korean databases using a Common Data Model.

Background: Dementia has a crucial impact on the quality of life of elderly patients and their caregivers. Proton-pump inhibitors (PPIs) are the most frequently prescribed treatment, but they have been shown to be associated with dementia. The data are inconsistent, however. Objective: To investigate the association between PPIs use and Alzheimer's disease (AD) or all-cause dementia in six observational Korean databases using a Common Data Model (CDM) and to perform a distributed network analysis. Methods: Subjects aged over 18 years between 1 January 2004 and 31 December 2020. Among 7,293,565 subjects from 6 cohorts, 41,670 patients met the eligibility criteria. A total of 2206 patients who were included in both cohorts or with a history of dementia were excluded. After propensity matching, 5699 propensity-matched pairs between the PPIs and histamine-2 receptor antagonist (H2RA) users were included in this study. The primary outcome was the incidence of AD at least 365 days after drug exposure. The secondary outcome was the incidence of all-cause dementia at least 365 days after drug exposure. Results: In the 1:1 propensity score matching, the risk of AD or all-cause dementia was not significantly different between the PPIs and H2RA groups in all six databases. In the distributed network analysis, the long-term PPI users (⩾365 days) were unassociated with AD [hazard ratio (HR) = 0.92, 95% confidence interval (CI) = 0.68-1.23; I 2 = 0%] and all-cause dementia (HR =1.04, 95% CI = 0.82-1.31; I 2 = 0%) compared with H2RA users. Conclusion: In the distributed network analysis of six Korean hospital databases using Observational Medical Outcomes Partnership (OMOP)-CDM data, the long-term use of PPI was not associated with a statistically significantly increased risk of AD or all-cause dementia. Therefore, we suggest that physicians should not avoid these medications because of concern about dementia risk.

Lifestyle Modification in the Management of Metabolic Syndrome: Statement From Korean Society of CardioMetabolic Syndrome (KSCMS).

With the recent rapid increase in obesity worldwide, metabolic syndrome (MetS) has gained significant importance. MetS is a cluster of obesity-related cardiovascular risk factors including abdominal obesity, atherogenic dyslipidemia, high blood pressure and impaired glucose tolerance. MetS is highly prevalent and strongly associated with an increased risk of developing diabetes and cardiovascular disease, putting a great burden on human society. Therefore, it is very important to reduce MetS risk, which can improve patients' cardiovascular prognosis. The primary and most effective strategy to control each component of MetS is lifestyle change such as losing body weight, keeping regular exercise, adopting a healthy diet, quitting smoking and alcohol drinking in moderation. Many studies have shown that lifestyle modification has improved all components of MetS, and reduces the incidence of diabetes and cardiovascular disease. Here, the Korean Society of CardioMetabolic Syndrome has summarized specific and practical methods of lifestyle modification in the management of MetS in the healthcare field.

Nitrates vs. Other Types of Vasodilators and Clinical Outcomes in Patients with Vasospastic Angina: A Propensity Score-Matched Analysis.

Although vasodilators are widely used in patients with vasospastic angina (VA), few studies have compared the long-term prognostic effects of different types of vasodilators. We investigated the long-term effects of vasodilators on clinical outcomes in VA patients according to the type of vasodilator used. Study data were obtained from a prospective multicenter registry that included patients who had symptoms suggestive of VA. Patients were classified into two groups according to use of nitrates (n = 239) or other vasodilators (n = 809) at discharge. The composite clinical events rate, including acute coronary syndrome (ACS), cardiac death, new-onset arrhythmia (including ventricular tachycardia and ventricular fibrillation), and atrioventricular block, was significantly higher in the nitrates group (5.3% vs. 2.2%, p = 0.026) during one year of follow-up. Specifically, the prevalence of ACS was significantly more frequent in the nitrates group (4.3% vs. 1.5%, p = 0.024). After propensity score matching, the adverse effects of nitrates remained. In addition, the use of nitrates at discharge was independently associated with a 2.69-fold increased risk of ACS in VA patients. In conclusion, using nitrates as a vasodilator at discharge can increase the adverse clinical outcomes in VA patients at one year of follow-up. Clinicians need to be aware of the prognostic value and consider prescribing other vasodilators.