Angiotensin Receptor-neprilysin Inhibitor Versus Renin-angiotensin System Inhibitor for Dementia Risk in Patients With Heart Failure.

ABSTRACT: The authors report the impact of angiotensin receptor-neprilysin inhibitor (ARNI) versus renin-angiotensin system inhibitor (RASI) on the management and outcomes in dementia among heart failure (HF) patients as obtained from the real-life nationwide registry. In this study, HF patients between January 1, 2017 and December 31, 2019 were divided into 2 groups, including subjects receiving RASI and ARNI. The incidence rate of dementia was calculated with the unit of 1000 person-years. Cox proportional hazard model was applied for the examination of the hazard ratio, and also presented with 95% confidence interval. Between 2017 and 2019, RASI and ARNI cohorts contain 18,154 subjects. After adjusting with age, sex, comorbidities, and medications, ARNI cohort had a lower risk of dementia (adjusted hazard ratio = 0.83; 95% confidence interval = 0.72, 0.95) than RASI cohort. The authors concluded that use of ARNI was associated with a lower risk of new-onset dementia in patients with HF.

Association of Heart Failure Patients With and Without Sacubitril-Valsartan Use With Incident Cancer Risk.

ABSTRACT: This study was to evaluate the association between heart failure (HF) patients with and without sacubitril-valsartan use with incident cancer risk. This study consisted of 18,072 patients receiving sacubitril-valsartan and 18,072 control group participants. In the Fine and Gray model, which extends the standard Cox proportional hazards regression model, we estimated the relative risk of developing cancer between the sacubitril-valsartan cohort and the non-sacubitril-valsartan cohort by using subhazard ratios (SHRs) and 95% confidence intervals (CIs). The incidence rates of cancer were 12.02 per 1000 person-years for the sacubitril-valsartan cohort and 23.31 per 1000 person-years for the non-sacubitril-valsartan cohort. Patients receiving sacubitril-valsartan had a significantly lower risk of developing cancer with an adjusted SHR of 0.60 (0.51, 0.71). Sacubitril-valsartan users were less to be associated with the development of cancer.

Comparisons of HATCH, HAVOC and CHA2DS2-VASc scores for all-cause mortality prediction in atrial fibrillation: a real-world evidence study.

OBJECTIVE: This study focused on the predictive ability of the 3 scores for all-cause mortality in 6444 patients with atrial fibrillation (AF). METHODS: To assess the predictive accuracy of risk of death modelled by HATCH, HAVOC and CHA2DS2-VASc scores, the area under the curve of receiver operating characteristics (AUROC) was applied. RESULTS: Over follow-up time, the cumulative incidence of death was clearly associated with the three scores (log-rank test, p<0.001). The AUROC for the HATCH (0.6618) was significantly higher than HAVOC Score (0.5733) and CHA2DS2-VAScs Score (0.6423). CONCLUSIONS: HATCH score has better ability in predicting mortality in comparison to other two scores in patients with AF.

Weekend versus weekday hospitalization and clinical outcomes in atrial fibrillation patients with and without stroke.

PURPOSE: The relation between hospitalization timing and risk of clinical outcomes among patients with atrial fibrillation (AF) with and without stroke remained undetermined. METHODS: Rehospitalization due to AF, cardiovascular (CV) death and all-cause mortality were the outcomes of interest in this study. Multivariable Cox proportional hazard model was applied to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). RESULTS: While considering patients with AF hospitalized during weekdays without stroke as the reference group, patients with AF hospitalized during weekends with stroke had the risk of AF rehospitalization, CV death and all-cause death by 1.48 (95% CI 1.44 to 1.51), 1.77 (95% CI 1.71 to 1.83) and 1.17 (95% CI 1.15 to 1.19) times, respectively. CONCLUSION: Patients with AF hospitalized during weekends with stroke had the worst clinical outcomes.

Using progression in adapted diabetes complications severity index score to predict erectile dysfunction in men affected by type 2 diabetes mellitus.

OBJECTIVE: This study is on the use of the adapted Diabetes Complications Severity Index (aDCSI) for erectile dysfunction (ED) risk stratification in male patients with type 2 diabetes mellitus (DM). METHODS: This is a retrospective study with records obtained from Taiwan's National Health Insurance Research Database. Adjusted HRs (aHRs) were estimated by multivariate Cox proportional hazards models with 95% confidence intervals (CIs).. RESULTS: A population of 84 288 eligible male patients with type 2 DM were included. Compared with change in aDCSI score of 0.0-0.5 per year, the aHRs and the corresponding 95% CIs for other changes in aDCSI scores are summarised as follows: 1.10 (0.90 to 1.34) for change in aDCSI score of 0.5-1.0 per year; 4.44 (3.47 to 5.69) for change in aDCSI score of 1.0-2.0 per year; and 10.9 (7.47 to 15.9) for change in aDCSI score of >2.0 per year.. CONCLUSIONS: Progression in aDCSI score might be used for ED risk stratification in men affected by type 2 DM.

Comparisons of HATCH, HAVOC and CHA2DS2-VASc scores for all-cause mortality prediction in atrial fibrillation: a real-world evidence study.

OBJECTIVE: This study focused on the predictive ability of the 3 scores for all-cause mortality in 6444 patients with atrial fibrillation (AF). METHODS: To assess the predictive accuracy of risk of death modelled by HATCH, HAVOC and CHA2DS2-VASc scores, the area under the curve of receiver operating characteristics (AUROC) was applied. RESULTS: Over follow-up time, the cumulative incidence of death was clearly associated with the three scores (log-rank test, p<0.001). The AUROC for the HATCH (0.6618) was significantly higher than HAVOC Score (0.5733) and CHA2DS2-VAScs Score (0.6423). CONCLUSIONS: HATCH score has better ability in predicting mortality in comparison to other two scores in patients with AF.

Beta blocker versus ivabradine for cardiovascular outcomes among patients with atrial fibrillation.

PURPOSE: We conducted a retrospective observational study using Taiwanese insurance records to examine the association between beta blocker (BB)/ ivabradine (IVA) and cardiovascular (CV) outcomes in patients with atrial fibrillation (AF). METHODS: A total of 1884 AF subjects were enrolled. The propensity score-matching technique was applied to estimate the effect of IVA by accounting for the covariates. The CV outcomes included hospitalisation/rehospitalisation due to acute myocardial infarction, heart failure (HF), haemorrhagic stroke, ischaemic stroke, CV death and all-cause death. Univariate and multivariate Cox proportional hazards regression models were used to estimate crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: IVA users were found to have a higher risk of HF requiring admission (adjusted HR=2.01; 95% CI 1.67 to 2.42), and all cause death (adjusted HR=1.47; 95% CI 1.11 to 1.94) after adjusting for age, sex, comorbidities and medications. CONCLUSION: Concerning adverse clinical events, IVA might not be appropriate for patients with AF.

Real-world observational study of assessment of CHA2DS2-VASc, C2HEST and HAVOC scores for atrial fibrillation among patients with rheumatological disorders: a nationwide analysis.

PURPOSE: This is a nationwide-based retrospective study aiming to compare the three different scoring systems (CHA2DS2-VASc, C2HEST and HAVOC scores) in the prediction of atrial fibrillation (AF) in patients with rheumatological disease. METHODS: We used the Fine and Gray model to estimate the risk of AF (subhazard ratio and 95% CI). The predictive accuracy and discriminatory ability of the predictive model were evaluated by receiver operating characteristic (ROC) curve. RESULTS: Among the three predictive models, the model using CHA2DS2-VASc score had the better discriminative ability with an ROC of 0.79. The model with C2HEST score had an ROC of 0.78. The discriminative ability of the HAVOC score was 0.77, estimated by ROC. CONCLUSION: We concluded the CHA2DS2-VASc score has better performance in predicting AF compared with C2HEST score or HAVOC score.

A Comparison of Atrial Fibrillation Incidence Among Physicians and the General Population.

The aim of this study is to explore the association of atrial fibrillation (AF) among physicians in Taiwan.We used Cox proportional hazards models to estimate the incidence rate and the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) to determine the risk of AF in the physician study cohort relative to the comparison cohort.A total of 22,479 physicians and 22,479 matched controls for comparison were included in the study. The Cox proportional hazard regression model revealed that male physician was associated with a trend toward increased risk of AF than nonphysician after adjusting for potential confounders (aHR, 1.05; 95% CI: 1.00-1.11). In age-specific analysis, male physicians aged ≤ 45 years showed the stronger association with AF (aHR, 1.33; 95% CI: 1.22-1.45). Further stratification with medical categories, surgeons had a significantly higher risk of AF than nonphysicians group (aHR, 1.28; 95% CI: 1.18-1.39).We reported a pivotal study that showed possible relation between physician specialists and AF in the large cohort.

Protective effects of luteolin against oxidative stress and mitochondrial dysfunction in endothelial cells.

BACKGROUND AND AIMS: Luteolin is a common flavonoid that is abundantly present in various edible plants, it is known to exhibit beneficial effects on cardiovascular system. However, the mechanisms which underlie the protective effects of luteolin on endothelial cell damage caused by oxidative stress remains unclear. The purpose of this study is to test the hypothesis which states that luteolin protects against H2O2-induced oxidative stress via modulating ROS-mediated P38 MAPK/NF-κB and calcium-evoked mitochondrial apoptotic signalling pathways. METHODS AND RESULTS: Human umbilical vein endothelial cells (HUVECs) were pretreated with luteolin prior to being stimulated by 600 µM H2O2 for another 24 h. The expression of native and phosphorylated-P38, IκB, NF-κB, native eNOS, phosphorylated-eNOS, iNOS and several apoptosis-related proteins were analyzed by Western blot. In addition, intracellular calcium was determined by fura-2 AM and mitochondrial membrane potential was examined by using JC1. Using the data gathered, we found indications that H2O2 induced P38 MAPK/NF-κB activation. H2O2 downregulated the expression of eNOS and upregulated iNOS, which in turn contribute to an elevated NO generation and protein nitrosylation. However, pretreatment with luteolin markedly reversed all of these alterations dose-dependently. Additionally, an intracellular calcium rise and subsequent mitochondrial membrane potential collapse, P53 phosphorylation, reduced BcL-2/Bax ratio in the mitochondrial membrane, release cytochrome c from mitochondria, leading to the subsequent activation of caspase 3 activation by H2O2 were all markedly suppressed in the presence of luteolin. CONCLUSION: Results from this study may provide the possible molecular mechanisms underlying cardiovascular protective effects of luteolin.

Comparison of CHA2DS2-VASc and C2HEST scores for predicting the incidence of atrial fibrillation among patients with end-stage renal disease.

PURPOSE: The authors have studied assessment of CHA2DS2-VASc score versus C2HEST score in atrial fibrillation risk prediction in end-stage renal disease patients. METHODS: The authors conducted this study by Longitudinal Health Insurance Database 2000. The authors totally enrolled 4,601 end-stage renal disease patients. The predictive capability of atrial fibrillation by using CHA2DS2-VASc and C2HEST score was estimated by area under the receiver operating characteristic curve (AUROC). RESULTS: The AUROC for CHA2DS2-VASc score in predicting atrial fibrillation events was 0.5786, and AUROC for C2HEST score for atrial fibrillation prediction was 0.5983. CONCLUSION: Both scores yield almost identical AUROC values implying no difference in predictive power. Further work is warranted to verify the prognostic value of the current scores.

Association of irritable bowel syndrome in patients with atrial fibrillation: a nationwide population-based investigation.

OBJECTIVE: We seek to characterize the association between atrial fibrillation and irritable bowel syndrome. METHODS: We identify 11,642 cases (atrial fibrillation) and 46,487 sex-, age-, and index year-matched controls (non-atrial fibrillation) from Longitudinal Health Insurance Database. Kaplan-Meier, Cox proportional hazards regression methods and competing risk analysis methods were used to assess the association of atrial fibrillation with outcome of irritable bowel syndrome. RESULTS: After adjustment for gender, age, comorbidities and medications, patients with atrial fibrillation had a significant higher risk (adjusted hazard ratio = 1.12, p < 0.01) to develop irritable bowel syndrome than patients without atrial fibrillation. Compared to participants without atrial fibrillation, those with atrial fibrillation had 1.13-fold (p < 0.05) and 1.11-fold (p < 0.05) risk of irritable bowel syndrome in female and male subgroup, respectively. Among subjects aged ≥65 years, those with AF had 1.11-fold risk of irritable bowel syndrome than non-AF cohort (P < 0.01). Among participants with any one of the comorbidities, those with atrial fibrillation had 1.10-fold risk of irritable bowel syndrome than non-atrial fibrillation cohort (p < 0.05). CONCLUSION: We report that the presence of atrial fibrillation is associated with greater incidence of irritable bowel syndrome and the association is stronger among female gender, age 65 years or above, and with comorbidities.

A Retrospective Study of Suicide Attempts in Patients With Pulmonary Hypertension.

BACKGROUND: To investigate whether pulmonary hypertension and suicide attempts are correlated. METHODS: This study enrolled 7,727 pulmonary hypertension patients and 7,727 comparison subjects. The multivariate Cox proportional hazard model was used to calculate the adjusted hazard ratios (HRs) after adjustment for variables that were associated with suicide attempts in univariate model. RESULTS: After adjustment for variables which were associated with suicide attempt, pulmonary hypertension patients had significantly higher adjusted HRs (95% confidence interval[CI]) of 2.08 (1.85, 2.34) for a suicide attempt. CONCLUSIONS: We found that pulmonary hypertension was associated with a higher risk of suicide attempt.

A nationwide cohort study of the role of CHADS2 score in predicting lower extremity amputation and death among patients with peripheral arterial occlusive disease.

OBJECTIVES: The current study aimed to explore whether the CHADS2 score was predictive of lower extremity amputation (LEA) and death in people with peripheral arterial occlusive disease (PAOD). METHODS: This nationwide cohort came from Taiwan, with 16,888 PAOD patients, from 2000 through 2011, extracted from the Longitudinal Health Insurance Database 2000. Cox proportional hazard regression models were employed to identify the LEA and mortality risk according to CHADS2 score. The discriminatory properties of the score in predicting the outcomes were quantified by the area under the receiver operating characteristic curve (AUROC) and the Cox C-index. RESULTS: The AUROC of the CHADS2 score in predicting LEA and death were 0.75 (95% CI = 0.73-0.77) and 0.70 (95% CI = 0.69-0.71), respectively. The CHADS2 score had an acceptable stratification capacity for LEA (C-index = 0.79) and death (C-index = 0.76) based on Cox-regression analysis. CONCLUSIONS: This study correlates the CHADS2 score with risk of developing LEA and death in patients with PAOD. The acceptable discriminative power of the score diversifies its predictive role in this population.

A novel atrial fibrillation prediction model for Chinese subjects: a nationwide cohort investigation of 682 237 study participants with random forest model.

AIMS: We aimed to construct a random forest model to predict atrial fibrillation (AF) in Chinese population. METHODS AND RESULTS: This study was comprised of 682 237 subjects with or without AF. Each subject had 19 features that included the subjects' age, gender, underlying diseases, CHA2DS2-VASc score, and follow-up period. The data were split into train and test sets at an approximate 9:1 ratio: 614 013 data points were placed into the train set and 68 224 data points were placed into the test set. In this study, weighted average F1, precision, and recall values were used to measure prediction model performance. The F1, precision, and recall values were calculated across the train set, the test set, and all data. The area under receiving operating characteristic (ROC) curve was also used to evaluate the performance of the prediction model. The prediction model achieved a k-fold cross-validation accuracy of 0.979 (k = 10). In the test set, the prediction model achieved an F1 value of 0.968, precision value of 0.958, and recall value of 0.979. The area under ROC curve of the model was 0.948 (95% confidence interval 0.947-0.949). This model was validated with a separate dataset. CONCLUSIONS: This study showed a novel AF risk prediction scheme for Chinese individuals with random forest model methodology.

Oral administration of alcalase potato protein hydrolysate-APPH attenuates high fat diet-induced cardiac complications via TGF-ß/GSN axis in aging rats.

Consumption of high fat diet (HFD) is associated with increased cardiovascular risk factors among elderly people. Aging and obesity induced-cardiac remodeling includes hypertrophy and fibrosis. Gelsolin (GSN) induces cardiac hypertrophy and TGF-ß, a key cytokine, which induces fibrosis. The relationship between TGF-ß and GSN in aging induced cardiac remodeling is still unknown. We evaluated the expressions of TGF-ß and GSN in HFD fed 22 months old aging SD rats, followed by the administration of either probucol or alcalase potato protein hydrolysate (APPH). Western blotting and Masson trichrome staining showed that APPH (45 and 75 mg/kg/day) and probucol (500 mg/kg/day) treatments significantly reduced the aging and HFD-induced hypertrophy and fibrosis. Echocardiograph showed that the performance of the hearts was improved in APPH, and probucol treated HFD aging rats. Serum from all rats was collected and H9c2 cells were cultured with collected serums separately. The GSN dependent hypertrophy was inhibited with an exogenous TGF-ß in H9c2 cells cultured in HFD+ APPH treated serum. Thus, we propose that along with its role in cardiac fibrosis, TGF-ß also acts as an upstream activator of GSN dependent hypertrophy. Hence, TGF-ß in serum could be a promising therapeutic target for cardiac remodeling in aging and/or obese subjects.

CHA2DS2-VASc score for ischaemic stroke risk stratification in patients with chronic obstructive pulmonary disease with and without atrial fibrillation: a nationwide cohort study.

Aims: We conducted this nationwide cohort study to identify the performance of CHA2DS2-VASc score for ischaemic stroke risk stratification in chronic obstructive pulmonary disease (COPD) patients whether they had comorbid atrial fibrillation (AF) or not. Methods and results: Using the longitudinal health insurance database 2000, patients aged ≥20 years with newly diagnosed COPD from 2000 to 2011 with at least three claims for outpatient and/or hospitalization visits were identified. A total of 1492 COPD patients with AF and 50 343 COPD patients without AF were included in this study. We calculated the CHA2DS2-VASc score-specific incidence density rates of ischaemic stroke with person-years in each cohort. Cox models were conducted to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of ischaemic stroke risk in COPD patients with and without concomitant AF. The predictive performance of CHA2DS2-VASc score with regard to ischaemic stroke events was assessed using area under the receiver operating characteristic curve (C-statistic). COPD patients with a higher CHA2DS2-VASc score were more likely to develop ischaemic stroke whether or not AF was present. Moreover, the C-statistics of CHA2DS2-VASc score in predicting ischaemic stroke in COPD patients with and without AF were 0.58 (95% CI = 0.55-0.62) and 0.71(95% CI = 0.70-0.72), respectively. Conclusions: Our study is the first to show that the performance of CHA2DS2-VASc score in predicting ischaemic stroke is better for COPD patients without AF than for COPD patients with AF.

Aplastic Anemia and Risk of Incident Atrial Fibrillation　- A Nationwide Cohort Study.

BACKGROUND: This retrospective cohort study sought to follow up patients with aplastic anemia (AA) to evaluate their risk of developing atrial fibrillation (AF).Methods and Results:From the National Health Insurance Research Database of Taiwan, this study identified an AA cohort (n=3,921), a general population cohort (n=17,617,843) and a propensity score-matched none AA cohort (PSM non-AA cohort in brief, n=15,684) in 2000-2010. By the end of 2011, the incident AF was higher in the AA cohort than in the general population and PSM non-AA cohorts (8.94 vs. 1.14 and 6.47 per 1,000 person-years, respectively). The adjusted hazards ratio of AF for the AA cohort was 2.12 (95% confidence interval 1.46-3.08) compared with the PSM non-AA cohort, after controlling for covariates. However, after further controlling for the competing risk of death, adjusted subhazard ratio was 1.21 (95% CI 0.97-1.50). Among those who developed AF, the AA cohort had a higher mortality rate (83.7 vs. 51.1 per 100), but a lower rate of incident stroke (26.0 vs. 41.5 per 100), compared with the PSM non-AA cohort. CONCLUSIONS: Patients with AA could have an elevated risk for AF. The mortality risk increased further for those who develop AF.

Use of CHA2DS2-VASc Score to Predict New-Onset Atrial Fibrillation in Chronic Obstructive Pulmonary Disease Patients　- Large-Scale Longitudinal Study.

BACKGROUND: The aim of this study was to assess the accuracy of CHA2DS2-VASc score in predicting new-onset atrial fibrillation (AF) in patients with chronic obstructive pulmonary disease (COPD).Methods and Results:A total of 50,430 COPD patients were enrolled in this study. The area under the receiver operating characteristic curve (AUC) and the Cox model c-statistic were used to assess the association between new-onset AF risk and CHA2DS2-VASc score in COPD patients. After adjustment for comorbidities other than the components of CHA2DS2-VASc score, risk of new-onset AF in COPD patients increased from 1.24 (95% confidence interval (CI): 1.01-1.52) for a score of 1, to 2.15 (95% CI: 1.62-2.86) for score ≥6 (trend test, P<0.001), compared with CHA2DS2-VASc score 0. The AUC for CHA2DS2-VASc score in predicting new-onset AF in COPD patients was 0.69 (95% CI: 0.68-0.70). The c-statistic of Cox model in predicting incident AF was 0.73. CONCLUSIONS: Risk of new-onset AF in COPD patients increased with increasing CHA2DS2-VASc score. The predictive ability of the score was moderate. CHA2DS2-VASc score might be used as a screening tool for AF in COPD patients.

Hemorrhoid is associated with increased risk of peripheral artery occlusive disease: A nationwide cohort study.

BACKGROUND: This study was conducted to evaluate the association between hemorrhoid and risk of incident peripheral artery occlusive disease (PAOD). METHODS: Using the Taiwanese Longitudinal Health Insurance Database 2000, we compared the incident PAOD risk between the hemorrhoid and the non-hemorrhoid cohorts. Both of these cohorts were followed up from the index date until the date of PAOD diagnosis, withdrawal from the National Health Insurance program, or the end of 2011. RESULTS: The mean follow-up period was 6.82 (standard deviation [SD], 3.22) and 6.70 (SD, 3.23) years in the hemorrhoid and non-hemorrhoid cohorts, respectively. The plot of the Kaplan-Meier analysis showed that, by the end of the 12-year follow-up period, the cumulative incidence of PAOD was significantly higher for the hemorrhoid cohort than for the non-hemorrhoid cohort (log-rank test: P < 0.001). CONCLUSIONS: A significantly increased PAOD risk in patients with hemorrhoids was found in this nationwide cohort study.