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Atrial fibrillation (AF) is the most common sustained arrhythmia, causing a 2‐fold increase in mortality and a 5‐fold increase in stroke. The Asian population is rapidly aging, and in 2050, the estimated population with AF will reach 72 million, of whom 2.9 million may suffer from AF‐associated stroke. Therefore, stroke prevention in AF is an urgent issue in Asia. Many innovative advances in the management of AF‐associated stroke have emerged recently, including new scoring systems for predicting stroke and bleeding risks, the development of non‐vitamin K antagonist oral anticoagulants (NOACs), knowledge of their special benefits in Asians, and new techniques. The Asia Pacific Heart Rhythm Society (APHRS) aimed to update the available information, and appointed the Practice Guideline sub‐committee to write a consensus statement regarding stroke prevention in AF. The Practice Guidelines sub‐committee members comprehensively reviewed updated information on stroke prevention in AF, emphasizing data on NOACs from the Asia Pacific region, and summarized them in this 2017 Consensus of the Asia Pacific Heart Rhythm Society on Stroke Prevention in AF. This consensus includes details of the updated recommendations, along with their background and rationale, focusing on data from the Asia Pacific region. We hope this consensus can be a practical tool for cardiologists, neurologists, geriatricians, and general practitioners in this region. We fully realize that there are gaps, unaddressed questions, and many areas of uncertainty and debate in the current knowledge of AF, and the physician׳s decision remains the most important factor in the management of AF.

Despite the availability of effective pharmacological treatments to aid the control of blood pressure, the global rate of uncontrolled blood pressure remains high. As such, further measures are required to improve blood pressure control. Recently, several national and international guidelines for the management of hypertension have been published. These aim to provide easily accessible information for healthcare professionals and patients to aid the diagnosis and treatment of hypertension. In this review, we have compared new and current guidelines from the American and International Societies of Hypertension; the American Heart Association, American College of Cardiology and the US Center for Disease Control and Prevention; the panel appointed to the Eighth Joint National Committee; the European Societies of Hypertension and Cardiology; the French Society of Hypertension; the Canadian Hypertension Education Program; the National Institute for Health and Clinical Excellence (UK); the Taiwan Society of Cardiology and the Chinese Hypertension League. We have identified consensus opinion regarding best practises for the management of hypertension and have highlighted any discrepancies between the recommendations. In general there is good agreement between the guidelines, however, in some areas, such as target blood pressure ranges for the elderly, further trials are required to provide sufficient high-quality evidence to form the basis of recommendations.

Although the incidence of venous thromboembolism (VTE) in Asian populations is lower than in Western countries, the overall burden of VTE in Asia has been considerably underestimated. Factors that may explain the lower prevalence of VTE in Asian populations relative to Western populations include the limited availability of epidemiological data in Asia, ethnic differences in the genetic predisposition to VTE, underdiagnoses, low awareness toward thrombotic disease, and possibly less symptomatic VTE in Asian patients. The clinical assessment, diagnostic testing, and therapeutic considerations for VTE are, in general, the same in Asian populations as they are in Western populations. The management of VTE is based upon balancing the treatment benefits against the risk of bleeding. This is an especially important consideration for Asian populations because of increased risk of intracranial hemorrhage with vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants have shown advantages over current treatment modalities with respect to bleeding outcomes in major phase 3 clinical trials, including in Asian populations. Although anticoagulant therapy has been shown to reduce the risk of postoperative VTE in Western populations, VTE prophylaxis is not administered routinely in Asian countries. Despite advances in the management of VTE, data in Asian populations on the incidence, prevalence, recurrence, risk factors, and management of bleeding complications are limited and there is need for increased awareness. To that end, this review summarizes the available data on the epidemiology, risk stratification, diagnosis, and treatment considerations in the management of VTE in Asia.

Hypertension‐related death is the leading cause of mortality worldwide, making blood pressure (BP) control an important issue. Salt substitute is a non‐pharmaceutical strategy to improve hypertension control. The goal of this study was to evaluate the effect of salt substitute on BP and cardiovascular disease. The authors searched the Cochrane Library and PubMed databases through March 2022, and assessed the risk‐of‐bias for included studies by the Cochrane risk‐of‐bias tool. Twenty‐three randomized controlled trials with 32073 patients were included in our systematic review. A meta‐analysis with random effects was performed to analyze the effects of salt substitute on systolic and diastolic BP, 24‐h urinary sodium and potassium, and cardiovascular and all‐cause mortality. In the random‐effects model, participants consuming salt substitute showed significant reduction in systolic BP (mean difference (MD) −4.80 mmHg, 95% confidence interval (CI) −6.12 to −3.48, P < 0.0001) and diastolic BP (MD −1.48 mmHg, 95% CI −2.06 to −0.90, P < 0.0001) compared with participants consuming normal salt. In the urine electrolyte analysis, the salt substitute group had significant reduction in 24‐h urine sodium (MD −22.96 mmol/24‐h, P = 0.0001) and significant elevation in 24‐h urine potassium (MD 14.41 mmol/24‐h, P < 0.0001). Of the five studies with mortality outcome data, salt substitute significantly reduced all‐cause mortality (hazard ratio 0.88, P = 0.0003). In conclusion, our analyses showed that salt substitute has a strong effect on lowering BP and reducing all‐cause mortality. By modifying the daily diet with salt substitute, the authors can improve BP control by using this non‐pharmaceutical management.

Left ventricular dysfunction is a known risk factor for morbidity and mortality in hemodialysis patients. The prognostic value of left ventricular global longitudinal strain (LV GLS) among those with preserved left ventricular ejection fraction (LVEF) remains uncertain. Subjects with end-stage renal disease initiated hemodialysis at Taipei Veteran General Hospital between 2015 and 2018 were registered. All participants received annually echocardiographic studies thereafter. Left ventricular end-systolic volume (LVESV), end-diastolic volume (LVEDV) and internal diameter in systole (LVIDs), LVEF, and LV GLS were measured. A LV GLS of > – 15.9% was defined as reduced LV GLS. Clinical outcomes of mortality and hospitalization for heart failure (HHF) were followed. A total of 319 patients with preserved LVEF (66.3 ± 15.1 years, 48.6% men) were recruited in the study. Subjects with reduced LV GLS had more coronary artery disease (CAD), higher LVESV and LVIDs, but were similar in age, gender, co-morbidities, biochemistries and other echocardiographic parameters as the counterpart. Both CAD [(odds ratio (OR) and 95% confidence intervals (CIs): 1.669, 1.023–2.724], and LVESV (OR per-1 mL and 95% CIs: 1.073, 1.004–1.146) were independent determinants of reduced LV GLS. Kaplan-Meier analysis indicated that patients with reduced LV GLS had a significantly lower event-free survival rate compared to those with preserved GLS. The multivariate Cox regression analysis further demonstrated LV GLS as a significant predictor of adverse clinical events (hazard ratio per-1% and 95% CIs: 1.055, 1.002–1.110) after accounting for age, gender, and diabetes. Among the hemodialysis patients with preserved LVEF, LV GLS but not the conventional left ventricular functional indices were associated with long-term mortality and HHF. CAD could be a modifiable risk factor among the subjects with reduced LV GLS.

The variability of blood pressure (BPV) has been suggested as a clinical indicator for cognitive dysfunction, yet the results from clinical studies are variable. This study investigated the relationship between BPV and the risk of cognitive decline or dementia. Bibliographic databases, including PubMed, Scopus, and Embase, were searched systematically for longitudinal cohort studies with BPV measurements and neuropsychological examinations or dementia diagnosis. A traditional meta‐analysis with subgroup analysis, and a further dose‐response meta‐analysis were conducted. Twenty cohort studies with 7 924 168 persons were included in this review. The results showed that a higher systolic BPV (SBPV), when measured with the coefficient of variation (SBP‐CV) or standard deviation (SBP‐SD), was associated with a higher risk of all‐cause dementia diagnosis but not incidence of cognitive decline on neuropsychological examinations. In subgroup analysis, the effect was more prominent when using BPV of shorter timeframes, during shorter follow‐ups, or among the elderly aged more than 65 years. No dose‐response relationship could be found. Our study suggested possible positive associations between SBPV and the risk of dementia. Further studies are required to validate these findings.

BackgroundThe bleeding risk profile of patients with atrial fibrillation (AF) may change over time, and the increment of HAS-BLED score is perceived to result in discontinuations of oral anticoagulants (OACs).ObjectivesTo investigate the changes of HAS-BLED scores of AF patients initially with a low bleeding risk. The associations between continuation or discontinuation of OACs and clinical outcomes after patients’ bleeding risk profile worsened (ie HAS-BLED increased) were studied.MethodsThe present study used Taiwan nationwide health insurance research database. From year 2000 to 2015, a total of 24,990 AF patients aged ≥ 20 years with a CHA2DS2-VASc score  ≥ 1 (males) or  ≥ 2 (females) having an HAS-BLED score of 0–2 who were treated with OACs were identified and followed up for changes of the HAS-BLED scores. Patients who did not refill OACs within 90 days after their HAS-BLED scores increased to  ≥ 3 were defined as discontinuations of OACs. The risks of clinical outcomes were compared between patients who continued or stopped OACs once their HAS-BLED scores increased to  ≥ 3.ResultsMean HAS-BLED score of study population increased from 1.54 to 3.33. At end of 1 year, 5,229 (20.9%) patients had an increment of their HAS-BLED scores to  ≥ 3, mainly due to newly diagnosed hypertension, stroke, bleeding, and concomitant drug therapies. Among 4777 patients who consistently had an HAS-BLED score  ≥ 3, 1,062 (22.2%) stopped their use of OACs. Patients who kept on OACs (n = 3715; 77.8%) even after their HAS-BLED scores increased to ≥ 3 were associated with a lower risk of ischemic stroke (aHR 0.60, 95%CI 0.53–0.69), major bleeding (aHR 0.78, 95%CI 0.67–0.91), all-cause mortality (aHR 0.88, 95%CI 0.79–0.97), and any adverse events (aHR 0.75, 95%CI 0.68–0.82) adjusted for age, sex, heart failure, and HAS-BLED score. These results were consistent among the cohorts after propensity matching.ConclusionsFor patients whose HAS-BLED scores increased to ≥ 3, the continuation of OACs was associated with better clinical outcomes. An increased HAS-BLED score in anticoagulated AF patients may not be the only reason to withhold OACs, but reminds physicians to correct modifiable bleeding risk factors and follow up patients more closely.Associations between Continuation or Discontinuation of Oral Anticoagulants and Risks of Clinical Outcomes after HAS-BLED Scores IncreasedAF atrial fibrillation; aHR adjusted hazard ratio; ICH intra-cranial hemorrhage; OACs oral anticoagulants

We compared a standard antihypertensive losartan treatment with a pharmacogenomics-guided rostafuroxin treatment in never-treated Caucasian and Chinese patients with primary hypertension. Rostafuroxin is a digitoxigenin derivative that selectively disrupts the binding to the cSrc-SH2 domain of mutant α-adducin and of the ouabain-activated Na-K pump at 10–11 M. Of 902 patients screened, 172 were enrolled in Italy and 107 in Taiwan. After stratification for country and genetic background, patients were randomized to rostafuroxin or losartan, being the difference in the fall in office systolic blood pressure (OSBP) after 2-month treatment the primary endpoint. Three pharmacogenomic profiles (P) were examined, considering: P1, adding to the gene variants included in the subsequent P2, the variants detected by post-hoc analysis of a previous trial; P2, variants of genes encoding enzymes for endogenous ouabain (EO) synthesis (LSS and HSD3B1), EO transport (MDR1/ABCB1), adducin (ADD1 and ADD3); P3, variants of the LSS gene only. In Caucasians, the group differences (rostafuroxin 50 μg minus losartan 50 mg in OSBP mmHg) were significant both in P2 adjusted for genetic heterogeneity (P2a) and P3 LSS rs2254524 AA [9.8 (0.6–19.0), P = 0.038 and 13.4 (25.4–2.5), P = 0.031, respectively]. In human H295R cells transfected with LSS A and LSS C variants, the EO production was greater in the former (P = 0.038); this difference was abolished by rostafuroxin at 10–11 M. Chinese patients had a similar drop in OSBP to Caucasians with losartan but no change in OSBP with rostafuroxin. These results show that genetics may guide drug treatment for primary hypertension in Caucasians.

To investigate the impact on outcomes of changing treatment guideline recommendations by comparing the proportion of patients with atrial fibrillation (AF) recommended oral anticoagulants (OACs) under the 2011 and 2014 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. We used the “National Health Insurance Research Database” in Taiwan, which included 354,649 patients with AF from January 1, 1996 through December 31, 2011. Patients with a CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score of 2 or more and a CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65-74 years, female sex category) score of 2 or more were considered to have a definitive indication for receiving OACs according to the 2011 and 2014 ACC/AHA guidelines, respectively. The percentages of patients with AF recommended OACs increased from 69.3% (n=245,598) under the 2011 guideline to 86.7% (n=307,640) under the new 2014 guidelines, an increment of 17.5% (95% CI, 17.4-17.6). Most women with AF (94.1%) and patients older than 65 years (97.2%) would receive OACs on the basis of the 2014 guidelines. Among patients previously not being recommended OACs in older guidelines, OAC use under the new guidelines was associated with a lower risk of adverse outcomes (ischemic stroke or intracranial hemorrhage or bleeding requiring blood transfusion or mortality) with an adjusted hazard ratio of 0.89 (95% CI, 0.85-0.94). In this nationwide cohort study, use of the 2014 guidelines led more patients with AF to receive OACs for stroke prevention, and this increased OAC use was associated with better outcomes. Better efforts to implement guidelines would lead to improved outcomes for patients with AF.

Background: It remains debatable whether statin increases the risk of intracerebral hemorrhage (ICH) in poststroke patients. Methods: We systematically searched PubMed, EMBASE, and CENTRAL for randomized controlled trials. Trial sequential analysis (TSA) was conducted to assess the reliability and conclusiveness of the available evidence in the meta-analysis. To evaluate the overall effectiveness, the net composite endpoints were derived by totaling ischemic stroke, hemorrhagic stroke, transient ischemic attack (TIA), myocardial infarction, and cardiovascular mortality. Results: A total of 17 trials with 11,576 subjects with previous ischemic stroke, TIA, or ICH were included, in which statin therapy increased the risk of hemorrhagic stroke (risk ratio [RR], 1.42; 95% confidence interval [CI], 1.07–1.87), but reduced the risk of ischemic stroke (RR, 0.85; 95% CI, 0.75–0.95). For the net composite endpoints, statin therapy was associated with a 17% risk reduction (95% CI, 12–21%; number needed to treat = 6). With a control event rate 2% and RR increase 40%, the TSA suggested a conclusive signal of an increased risk of hemorrhagic stroke in stroke survivors taking statin. However, with the sensitivity analysis by changing assumptions, the conclusions about hemorrhagic stroke risk were less robust. Conclusions: Statin therapy in poststroke patients increased the risk of hemorrhagic stroke but effectively reduced ischemic stroke risk. Weighing the benefits and potential harms, statin has an overall beneficial effect in patients with previous stroke or TIA. However, more studies are required to investigate the conclusiveness of the increased hemorrhagic stroke risk revealed in our study.