Clinical Outcomes of Patients with Atrial Fibrillation who Survived from Bleeding Event: The Results from COOL-AF Thailand Registry.

BACKGROUND: Bleeding events are often reported among patients with atrial fibrillation (AF), irrespective of antithrombotic use. This study is to determine clinical outcomes of patients with AF who survived from bleeding event. METHODS: We analyzed data from COOL-AF (Cohort of Antithrombotic Use and Optimal International Normalized Ratio Levels in Patients with Atrial Fibrillation) Thailand registry. Outcomes of patients who experienced any bleeding were compared with patients who had never bleed. Time updated multivariate Cox-proportional hazard models were used to estimate the risk for clinical outcomes of patients with and without bleeding. RESULTS: Of total 3,405 patients (mean age: 67.8 ± 11.3 years; 41.9% female) in COOL-AF registry, 609 patients (17.9%) reported bleeding event occurs and 568 patients (93.3%) survived though hospital discharge. Patients who survived major bleeding (n = 126) were at increased risk for both death (adjusted hazard ratio [HR]: 4.44, 95% confidence interval [CI]: 2.91-6.75, p < 0.001) and stroke/systemic embolism (adjusted HR: 4.49, 95% CI: 2.19-9.24, p < 0.001). Minor bleeding also increased subsequent death (adjusted HR: 2.13, 95% CI: 1.56-2.90, p < 0.001). Up to 30% of patients who survived major bleeding and 6.3% of minor bleedings discontinued oral anticoagulation. Discontinuation was associated with very high death rate (42.1%), whereas patients who resumed oral anticoagulation after bleeding had lower mortality (10%). The most common causes of death in patients who survived a bleeding event were not related to cardiovascular causes nor bleeding. CONCLUSION: Patients with AF who have bleeding events have an increased risk for subsequent death and stroke and systemic embolism. These patients should be identified as vulnerable clinically complex patients and require a holistic approach to their AF management.

Efficacy and Safety of Combination Therapy with Low-Dose Rivaroxaban in Patients with Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: To review the evidence on the effectiveness and safety of low-dose-rivaroxaban 2.5 mg twice daily (LDR) in patients with coronary artery disease (CAD) and/or peripheral artery disease (PAD) taking antiplatelets. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs). Efficacy endpoints were cardiovascular events (CVEs), myocardial infarction, stroke, all-cause, and cardiovascular death. Any, major, fatal bleeding, and intracranial hemorrhage (ICH) were safety endpoints. Numbers needed to treat (NNT), and numbers needed to harm (NNH) were also calculated. Results: Seven RCTs were included with 45,836 patients: 34,276 with CAD and 11,560 with PAD. Overall, 4247 CVEs and 3082 bleedings were registered. LDR in association with either any antiplatelet drug or aspirin (ASA) alone reduced the risk of CVEs (hazard ratio [HR] 0.86, 95% confidence interval [95%CI] 0.78-0.94) and ischemic stroke (HR 0.68, 95%CI 0.55-0.84). LDR + ASA increased the risk of major bleeding (HR 1.71, 95%CI 1.38-2.11) but no excess of fatal bleeding or ICH was found. The NNT to prevent one CVE for LDR + ASA was 63 (43-103) and the NNH to cause major bleeding was 107 (77-193). Conclusions: The combination of LDR with either antiplatelet drugs or low-dose aspirin reduces CVEs and ischemic stroke in patients with CAD/PAD. There was an increased risk of major bleeding but no excess of fatal or ICH was found. LDR seems to have a favorable net clinical benefit compared to ASA treatment alone.

Cardiovascular Risk in Young Patients Diagnosed With Obstructive Sleep Apnea.

BACKGROUND: In older adults, obstructive sleep apnea (OSA) has been associated with several cardiovascular complications. Whether young patients diagnosed with OSA also are at higher risk of developing subsequent cardiovascular disease is uncertain. We aimed to estimate the risk of developing an incident cardiovascular event among young patients diagnosed with OSA. METHODS AND RESULTS: We linked nationwide Danish health registries to identify a cohort of patients aged ≤50 years with OSA using data from 2010 through 2018. Cases without OSA from the general population were matched as controls (1:5). The main outcome was any cardiovascular event (including hypertension, diabetes, atrial fibrillation, ischemic heart disease, ischemic stroke, heart failure, and venous thromboembolism). All-cause mortality was a secondary outcome. The study included 20 240 patients aged ≤50 years with OSA (19.6% female; mean±SD age 39.9±7.7 years) and 80 314 controls. After 5-year follow-up, 31.8% of the patients with OSA developed any cardiovascular event compared with 16.5% of the controls, with a corresponding relative risk (RR) of 1.96 (95% CI, 1.90-2.02). At 5-year follow-up, 27.3% of patients with OSA developed incident hypertension compared with 15.0% of the controls (RR, 1.84 [95% CI, 1.78-1.90]). Incident diabetes occurred in 6.8% of the patients with OSA and 1.4% of controls (RR, 5.05 [95% CI, 4.60-5.54]). CONCLUSIONS: Similar to older adults, young adults with OSA demonstrate increased risk of developing cardiovascular events. To prevent cardiovascular disease progression, accumulation of cardiovascular risk factors, and mortality, risk stratification and prevention strategies should be considered for these patients.

Effect of combination pioglitazone with sodium-glucose cotransporter-2 inhibitors or glucagon-like peptide-1 receptor agonists on outcomes in type 2 diabetes: A systematic review, meta-analysis, and real-world study from an international federated database.

AIMS: To evaluate the efficacy and cardiovascular outcomes of combination pioglitazone with either a glucagon-like peptide-1 receptor agonist (GLP-1RA) or a sodium-glucose cotransporter-2 (SGLT2) inhibitor in individuals with type 2 diabetes (T2D) by conducting a systematic review, meta-analysis, and analysis of a large international real-world database. METHODS: We searched MEDLINE, SCOPUS and Web of Science to identify relevant articles for inclusion (PROSPERO [CRD: 42023483126]). Nineteen studies assessing pioglitazone + SGLT2 inhibitors or GLP-1RAs versus controls were identified, 16 of which were randomized controlled trials. Risk of bias was assessed using Cochrane-endorsed tools and quality of evidence was assessed using GRADE. We additionally performed a retrospective cohort study of all individuals aged 18 years or over with T2D, using the TriNetX platform. We included propensity-score-matched individuals who were treated for at least 1 year with pioglitazone and a GLP-1RA or pioglitazone and an SGLT2 inhibitor, compared against GLP-1RA and SGLT2 inhibitor monotherapy. Outcomes were all-cause mortality, heart failure, chronic kidney disease and composite stroke and transient ischaemic attack. RESULTS: The average follow-up in the included studies ranged from 24 to 52 weeks. Combination of pioglitazone with a GLP-1RA reduced glycated haemoglobin (HbA1c) and weight greater than in controls: mean differences -1% (95% confidence interval [CI] -1.27, -0.74) and -1.19 kg (95% CI -1.80, -0.58), respectively. There was no statistically significant difference in systolic blood pressure (SBP) or mortality between groups: mean difference - 1.56 mmHg (95% CI -4.48, 1.35; p = 0.30) and relative risk (RR) 0.29 (95% CI 0.07-1.15; p = 0.08), respectively. Combination of pioglitazone with SGLT2 inhibitors reduced HbA1c, weight and SBP to a greater extent than control treatment: mean differences -0.48% (95% CI -0.67, -0.28), -2.3 kg (95% CI -2.72, -1.88) and -2.4 mmHg (95% CI -4.1, -0.7; p = 0.01), respectively. There was no statistically significant difference in mortality between groups (RR 1.81, 95% CI 0.30-10.97; p = 0.52). The included trials demonstrated a reduction in risk of heart failure with combination treatment. Similarly, from the real-world database (n = 25 230 identified), pioglitazone and SGLT2 inhibitor combination therapy was associated with reduced risk of heart failure compared to monotherapy alone (hazard ratio 0.50, 95% CI 0.38-0.65; p < 0.001). CONCLUSION: Both our systematic review/meta-analysis and the real-world dataset show that combination of pioglitazone with either GLP-1RAs or SGLT2 inhibitors is associated with increased weight loss and reduced risk of heart failure compared with monotherapy.

Artificial intelligence-enhanced electrocardiogram analysis for identifying cardiac autonomic neuropathy in patients with diabetes.

AIM: To develop and employ machine learning (ML) algorithms to analyse electrocardiograms (ECGs) for the diagnosis of cardiac autonomic neuropathy (CAN). MATERIALS AND METHODS: We used motif and discord extraction techniques, alongside long short-term memory networks, to analyse 12-lead, 10-s ECG tracings to detect CAN in patients with diabetes. The performance of these methods with the support vector machine classification model was evaluated using 10-fold cross validation with the following metrics: accuracy, precision, recall, F1 score, and area under the receiver-operating characteristic curve (AUC). RESULTS: Among 205 patients (mean age 54 ± 17 years, 54% female), 100 were diagnosed with CAN, including 38 with definite or severe CAN (dsCAN) and 62 with early CAN (eCAN). The best model performance for dsCAN classification was achieved using both motifs and discords, with an accuracy of 0.92, an F1 score of 0.92, a recall at 0.94, a precision of 0.91, and an excellent AUC of 0.93 (95% confidence interval [CI] 0.91-0.94). For the detection of any stage of CAN, the approach combining motifs and discords yielded the best results, with an accuracy of 0.65, F1 score of 0.68, a recall of 0.75, a precision of 0.68, and an AUC of 0.68 (95% CI 0.54-0.81). CONCLUSION: Our study highlights the potential of using ML techniques, particularly motifs and discords, to effectively detect dsCAN in patients with diabetes. This approach could be applied in large-scale screening of CAN, particularly to identify definite/severe CAN where cardiovascular risk factor modification may be initiated.

Ischaemic stroke in women with atrial fibrillation: temporal trends and clinical implications.

BACKGROUND AND AIMS: Female sex has been linked with higher risk of ischaemic stroke (IS) in atrial fibrillation (AF), but no prior study has examined temporal trends in the IS risk associated with female sex. METHODS: The registry-linkage Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study included all patients with AF in Finland from 2007 to 2018. Ischaemic stroke rates and rate ratios were computed. RESULTS: Overall, 229 565 patients with new-onset AF were identified (50.0% women; mean age 72.7 years). The crude IS incidence was higher in women than in men across the entire study period (21.1 vs. 14.9 events per 1000 patient-years, P < .001), and the incidence decreased both in men and women. In 2007-08, female sex was independently associated with a 20%-30% higher IS rate in the adjusted analyses, but this association attenuated and became statistically non-significant by the end of the observation period. Similar trends were observed when time with and without oral anticoagulant (OAC) treatment was analysed, as well as when only time without OAC use was considered. The decrease in IS rate was driven by patients with high IS risk, whereas in patients with low or moderate IS risk, female sex was not associated with a higher IS rate. CONCLUSIONS: The association between female sex and IS rate has decreased and become non-significant over the course of the study period from 2007 to 2018, suggesting that female sex could be omitted as a factor when estimating expected IS rates and the need for OAC therapy in patients with AF.

Patterns of comorbidities in patients with atrial fibrillation and impact on management and long-term prognosis: an analysis from the Prospective Global GLORIA-AF Registry.

BACKGROUND: Clinical complexity, as the interaction between ageing, frailty, multimorbidity and polypharmacy, is an increasing concern in patients with AF. There remains uncertainty regarding how combinations of comorbidities influence management and prognosis of patients with atrial fibrillation (AF). We aimed to identify phenotypes of AF patients according to comorbidities and to assess associations between comorbidity patterns, drug use and risk of major outcomes. METHODS: From the prospective GLORIA-AF Registry, we performed a latent class analysis based on 18 diseases, encompassing cardiovascular, metabolic, respiratory and other conditions; we then analysed the association between phenotypes of patients and (i) treatments received and (ii) the risk of major outcomes. Primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). Secondary exploratory outcomes were also analysed. RESULTS: 32,560 AF patients (mean age 70.0 ± 10.5 years, 45.4% females) were included. We identified 6 phenotypes: (i) low complexity (39.2% of patients); (ii) cardiovascular (CV) risk factors (28.2%); (iii) atherosclerotic (10.2%); (iv) thromboembolic (8.1%); (v) cardiometabolic (7.6%) and (vi) high complexity (6.6%). Higher use of oral anticoagulants was found in more complex groups, with highest magnitude observed for the cardiometabolic and high complexity phenotypes (odds ratio and 95% confidence interval CI): 1.76 [1.49-2.09] and 1.57 [1.35-1.81], respectively); similar results were observed for beta-blockers and verapamil or diltiazem. We found higher risk of the primary outcome in all phenotypes, except the CV risk factor one, with highest risk observed for the cardiometabolic and high complexity groups (hazard ratio and 95%CI: 1.37 [1.13-1.67] and 1.47 [1.24-1.75], respectively). CONCLUSIONS: Comorbidities influence management and long-term prognosis of patients with AF. Patients with complex phenotypes may require comprehensive and holistic approaches to improve their prognosis.

Adverse Events and Clinical Correlates in Asian Patients with Atrial Fibrillation and Diabetes Mellitus: A Report from Asia Pacific Heart Rhythm Society Atrial Fibrillation Registry.

Aims. To evaluate the adverse events (and its clinical correlates) in a large prospective cohort of Asian patients with atrial fibrillation (AF) and diabetes mellitus (DM). Material and Methods. We recruited patients with atrial fibrillation (AF) from the Asia-Pacific Heart Rhythm Society (APHRS) AF Registry and included those for whom the diabetic mellitus (DM) status was known. We used Cox-regression analysis to assess the 1-year risk of all-cause death, thromboembolic events, acute coronary syndrome, heart failure and major bleeding. Results. Of 4058 patients (mean age 68.5 ± 11.8 years; 34.4% females) considered for this analysis, 999 (24.6%) had DM (age 71 ± 11 years, 36.4% females). Patients with DM had higher mean CHA2DS2-VASc (2.3 ± 1.6 vs. 4.0 ± 1.5, p < 0.001) and HAS-BLED (1.3 ± 1.0 vs. 1.7 ± 1.1, p < 0.001) risk scores and were less treated with rhythm control strategies compared to patients without DM (18.7% vs. 22.0%). After 1-year of follow-up, patients with DM had higher incidence of all-cause death (4.9% vs. 2.3%, p < 0.001), cardiovascular death (1.3% vs. 0.4%, p = 0.003), and major bleeding (1.8% vs. 0.9%, p = 0.002) compared to those without DM. On Cox regression analysis, adjusted for age, sex, heart failure, coronary and peripheral artery diseases and previous thromboembolic event, DM was independently associated with a higher risk of all-cause death (HR 1.48, 95% CI 1.00-2.19), cardiovascular death (HR 2.33, 95% CI 1.01-5.40), and major bleeding (HR 1.91, 95% 1.01-3.60). On interaction analysis, the impact of DM in determining the risk of all-cause death was greater in young than in older patients (p int = 0.010). Conclusions. Given the high rates of adverse outcomes in these Asian AF patients with DM, efforts to optimize the management approach of these high-risk patients in a holistic or integrated care approach are needed.

The association of appendicular lean mass and grip strength with low-density lipoprotein, very low-density lipoprotein, and high-density lipoprotein particle diameter: a Mendelian randomization study of the UK Biobank cohort.

Aims: Reduced muscle mass and reduced strength are frequently associated with both alterations in blood lipids and poorer cardiometabolic outcomes in epidemiological studies; however, a causal association cannot be determined from such observations. Two-sample Mendelian randomization (MR) was applied to assess the association of genetically determined appendicular lean mass (ALM) and handgrip strength (HGS) with serum lipid particle diameter. Methods and results: Mendelian randomization was implemented using summary-level data from the largest genome-wide association studies on ALM (n = 450 243), HGS (n = 223 315), and lipoprotein [low-density lipoprotein (LDL), very LDL (VLDL), and high-density lipoprotein (HDL)] particle diameters (n = 115 078). Inverse variance-weighted (IVW) method was used to calculate the causal estimates. Weighted median-based method, MR-Egger, and leave-one-out method were applied as sensitivity analysis. Greater ALM had a statistically significant positive effect on HDL particle diameter (MR-Egger: ß = 0.055, SE = 0.031, P = 0.081; IVW: ß = 0.068, SE = 0.014, P < 0.001) and a statistically significant negative effect on VLDL particle diameter (MR-Egger: ß = -0.114, SE = 0.039, P = 0.003; IVW: ß = -0.081, SE = 0.017, P < 0.001). Similarly, greater HGS had a statistically significant positive effect on HDL particle diameter (MR-Egger: ß = 0.433, SE = 0.184, P = 0.019; IVW: ß = 0.121, SE = 0.052, P = 0.021) and a statistically significant negative effect on VLDL particle diameter (MR-Egger: ß = -0.416, SE = 0.163, P = 0.011; IVW: ß = -0.122, SE = 0.046, P = 0.009). There was no statistically significant effect of either ALM or HGS on LDL particle diameter. Conclusion: There were potentially causal associations between both increasing ALM and HGS and increasing HDL particle size and decreasing VLDL particle size. These causal associations may offer possibilities for interventions aimed at improving cardiovascular disease risk profile.

The effect of hypertension on cerebrovascular carbon dioxide reactivity in atrial fibrillation patients.

Atrial fibrillation (AF) and hypertension (HTN) are both associated with impaired cerebrovascular carbon dioxide reactivity (CVRCO2), an indicator of cerebral vasodilatory reserve. We hypothesised that CVRCO2 would be lower in patients with both AF and HTN (AF + HTN) compared to normotensive AF patients, due to an additive effect of AF and HTN on CVRCO2. Forty AF (68 ± 9 years) and fifty-seven AF + HTN (68 ± 8 years) patients underwent transcranial Doppler ultrasound measurement of middle cerebral artery blood velocity (MCA Vm) during stepped increases and decreases in end-tidal carbon dioxide (PETCO2). A cerebrovascular conductance index (CVCi) was calculated as the ratio of MCA Vm and mean arterial pressure (MAP). CVRCO2 was determined from the linear slope for MCA Vm and MCA CVCi vs PETCO2. Baseline MAP was higher in AF + HTN than AF (107 ± 9 vs. 98 ± 9 mmHg, respectively; p < 0.001), while MCA Vm was not different (AF + HTN:49.6 [44.1-69.0]; AF:51.7 [45.2-63.3] cm.s-1; p = 0.075), and CVCi was lower in AF + HTN (0.46 [0.42-0.57] vs. 0.54 [0.44-0.63] cm.s-1.mmHg-1; p < 0.001). MCA Vm CVRCO2 was not different (AF + HTN: 1.70 [1.47-2.19]; AF 1.74 [1.54-2.52] cm/s/mmHg-2; p = 0.221), while CVCi CVRCO2 was 13% lower in AF + HTN (0.013 ± 0.004 vs 0.015 ± 0.005 cm.s-1.mmHg-1; p = 0.047). Our results demonstrate blunted cerebral vasodilatory reserve (determined as MCA CVCi CVRCO2) in AF + HTN compared to AF alone. This may implicate HTN as a driver of further cerebrovascular dysfunction in AF that may be important for the development of AF-related cerebrovascular events and downstream cognitive decline. We demonstrated reduced cerebrovascular CO2 responsiveness in atrial fibrillation with hypertension (AF+HTN) vs. atrial fibrillation (AF). Furthermore, AF per se (as opposed to normal sinus rhythm) predicts reduced cerebrovascular CO2 responsiveness. Our findings suggest additional cerebrovascular dysfunction in AF+HTN vs. AF.

For Debate: The 2023 European Society of Hypertension guidelines - cause for concern.

Originally, the beta-blockers were equally ranked alongside the other antihypertensive drug classes. Things changed when two major long-term randomized controlled trials, ASCOT-BPLA and LIFE showed that the patients receiving the beta-blockers based regimes suffered 25-30% more strokes than those receiving a calcium channel blocker based regime or an angiotensin receptor blocker based regime. The inferiority of the beta-blockers at stroke prevention was not due to differences in blood pressure control during the follow-up period in both trials. The 2023 European Society of Hypertension (ESH) guidelines still argue in favour of beta-blockers that their clinical inferiority was simply to lesser blood pressure reduction rather than class effect. The analysis argues that the return of beta-blockers as a first-line option for the management of uncomplicated hypertension by the ESH is a cause for concern and should be reconsidered.

Risk of diabetic retinopathy and diabetic macular oedema with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in type 2 diabetes: a real-world data study from a global federated database.

AIMS/HYPOTHESIS: A protective role of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP1-ra) in the development of diabetic retinopathy and diabetic macular oedema has been described in some recent studies, which may extend beyond glycaemic control. We aimed to review the clinical impact of SGLT2i and GLP1-ra therapy on the risk of diabetic retinopathy and diabetic macular oedema in individuals with type 2 diabetes taking insulin. METHODS: This is a retrospective cohort analysis of approximately two million people with type 2 diabetes receiving insulin across 97 healthcare organisations using a global federated health research network (TriNetX, Cambridge, USA). Two intervention cohorts (SGLT2i + insulin, n=176,409; GLP1-ra + insulin, n=207,034) were compared against a control cohort (insulin with no SGLT2i/GLP1-ra, n=1,922,312). Kaplan-Meier survival analysis was performed and estimated HRs were reported for each outcome. Propensity score was used to 1:1 match for age, sex, ischaemic heart disease, hypertension, microvascular complications, chronic kidney disease, HbA1c, BMI and use of pioglitazone, lipid modifying agents, antilipemic agents, ACE inhibitors, angiotensin II inhibitors and metformin. A sub-analysis comparing the two intervention cohorts was also performed. RESULTS: SGLT2i with insulin was associated with a reduced HR (95% CI) for diabetic macular oedema compared with the control cohort (0.835; 0.780, 0.893), while GLP1-ra with insulin demonstrated a lack of signal with no statistical significance to the HR (1.013; 0.960, 1.069). SGLT2i with insulin was not associated with a clinically significant increase in the risk of developing diabetic retinopathy (1.076; 1.027, 1.127), while GLP1-ra with insulin increased diabetic retinopathy risk (1.308; 1.261, 1.357). Compared with SGLT2i with insulin, GLP1-ra with insulin was associated with higher risk of diabetic retinopathy (1.205; 1.153, 1.259) and diabetic macular oedema (1.130; 1.056, 1.208). CONCLUSIONS/INTERPRETATION: Our study suggests that the combination of SGLT2i and insulin is associated with lower risk of developing diabetic macular oedema. However, the use of GLP1-ra was associated with an increased risk of diabetic retinopathy in individuals with type 2 diabetes also taking insulin. A comparative analysis showed favourable outcomes with SGLT2i and insulin in the development of diabetic macular oedema and diabetic retinopathy. RCTs using dedicated  retinal imaging are required to determine the causal relationship with these therapies.

Sarcopenia is linked to higher levels of B-type natriuretic peptide and its N-terminal fragment in heart failure: a systematic review and meta-analysis.

AIMS: Sarcopenia is linked to impaired physical function and exercise tolerance. The aim of this systematic review and meta-analysis was to examine the association of sarcopenia and low appendicular skeletal muscle (ASM) with biomarkers of cardiac function, B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP), in patients with heart failure (HF). METHODS AND RESULTS: From inception until May 2023, a systematic literature search of observational studies was undertaken utilizing the PubMed, Web of Science, Scopus, and Cochrane Library databases. A meta-analysis employing a random-effects model was used to compute the pooled effects (CRD42023418465). Overall, 16 studies were included in this systematic review and meta-analysis. Our main analysis showed that sarcopenia in HF was linked to significantly higher levels of BNP (MD: 87.76, 95% CI 20.74-154.78, I2 = 61%, P = 0.01) and NT-proBNP (MD: 947.45, 95% CI 98.97-1795.93, I2 = 35%, P = 0.03). Similarly, low ASM was associated with significantly higher levels of BNP (MD: 118.95, 95% CI 46.91-191.00, I2 = 93%, P < 0.01) and NT-proBNP (MD: 672.01, 95% CI 383.72-960.30, I2 = 2%, P < 0.01). The quality of the included cohort studies was considered moderate, using the binary AXIS checklist and the Cochrane Tool to Assess the Risk of Bias in Cohort Studies. CONCLUSIONS: In patients with HF, sarcopenia and reduced ASM are associated with considerably higher plasma levels of BNP and NT-proBNP. Future research is required to investigate whether sarcopenia may express dysregulated biomarkers of cardiac function.

Effect of physical activity on incident atrial fibrillation in individuals with varying duration of diabetes: a nationwide population study.

BACKGROUND: Diabetes mellitus (DM) duration affects incident atrial fibrillation (AF) risk; the effect of physical activity on mitigating AF risk related to varying DM duration remains unknown. We assessed the effect of physical activity on incident AF in patients with DM with respect to known DM duration. METHODS: Patients with type 2 DM who underwent the Korean National Health Insurance Service health examination in 2015-2016 were grouped by DM duration: new onset and < 5, 5-9, and ≥ 10 years. Physical activity was classified into four levels: 0, < 500, 500-999, 1,000-1,499, and ≥ 1,500 metabolic equivalent task (MET)-min/week, with the primary outcome being new-onset AF. RESULTS: The study enrolled 2,392,486 patients (aged 59.3 ± 12.0 years, 39.8% female) with an average follow-up of 3.9 ± 0.8 years and mean DM duration of 5.3 ± 5.1 years. Greater physical activity was associated with a lower AF risk. Lowering of incident AF risk varied with different amounts of physical activity in relation to known DM duration. Among patients with new-onset DM, DM duration < 5 years and 5-9 years and 1,000-1,499 MET-min/week exhibited the lowest AF risk. Physical activity ≥ 1,500 MET-min/week was associated with the lowest incident AF risk in patients with DM duration ≥ 10 years (by 15%), followed DM duration of 5-9 years (12%) and < 5 years (9%) (p-for-interaction = 0.002). CONCLUSIONS: Longer DM duration was associated with a high risk of incident AF, while increased physical activity generally reduced AF risk. Engaging in > 1,500 MET-min/week was associated with the greatest AF risk reduction in patients with longer DM duration, highlighting the potential benefits of higher activity levels for AF prevention.

Risk of Death and Cardiovascular Events in Asian Patients With Atrial Fibrillation and Chronic Obstructive Pulmonary Disease: A Report From the Prospective APHRS Registry.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of adverse events in patients with atrial fibrillation (AF); however, few data are available on this topic in Asian populations. METHODS AND RESULTS: Prospective observational study conducted on patients with AF enrolled in the Asia-Pacific Heart Rhythm Society (APHRS) AF Registry. The diagnosis of COPD was based on data reported in the case report form by the investigators. Cox-regression models were used to assess the 1-year risk of a primary composite outcome of all-cause death, thromboembolic events, acute coronary syndrome, and heart failure. Analysis on single outcomes and cardiovascular death was also performed. Interaction analysis was used to assess the risk of composite outcome and all-cause death in different subgroups. The study included 4094 patients with AF (mean±SD age 68.5±12 years, 34.6% female), of whom 112 (2.7%) had COPD. Patients with COPD showed a higher incidence of the primary composite outcome (25.1% versus 6.3%, P<0.001), all-cause death (14.9% versus 2.6%, P<0.001), cardiovascular death (2.0% versus 0.6%, P<0.001), and heart failure (8.3% versus 6.0%, P<0.001). On multiple Cox-regression analysis, COPD was associated with a higher risk of the primary composite outcome (hazard ratio [HR], 3.17 [95% CI, 2.05-4.90]), all-cause death (HR, 3.59 [95% CI, 2.04-6.30]), and heart failure (HR, 3.32 [95% CI, 1.56-7.03]); no statistically significant differences were found for other outcomes. The association between COPD and mortality was significantly modified by the use of beta blockers (Pint=0.018). CONCLUSIONS: In Asian patients with AF, COPD is associated with worse prognosis. In patients with AF and COPD, the use of beta blockers was associated with a lower mortality. REGISTRATION INFORMATION: clinicaltrials.gov Identifier: NCT04807049.

Oral anticoagulation therapy initiation in patients with atrial fibrillation in relation to world region of origin: a register-based nationwide study.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia and results in a high risk of stroke. The number of immigrants is increasing globally, but little is known about potential differences in AF care across migrant populations. AIM: To investigate if initiation of oral anticoagulation therapy (OAC) differs for patients with incident AF in relation to country of origin. METHODS: A nationwide register-based study covering 1999-2017. AF was defined as a first-time diagnosis of AF and a high risk of stroke. Stroke risk was defined according to guidelines from the European Society of Cardiology (ESC). Poisson regression adjusted for sex, age, socioeconomic position and comorbidity was made to compute incidence rate ratios (IRR) for initiation of OAC. RESULTS: The AF population included 254 586 individuals of Danish origin, 6673 of Western origin and 3757 of non-Western origin. Overall, OAC was initiated within -30/+90 days relative to the AF diagnosis in 50.3% of individuals of Danish origin initiated OAC, 49.6% of Western origin and 44.5% of non-Western origin. Immigrants from non-Western countries had significantly lower adjusted IRR of initiating OAC according to all ESC guidelines compared with patients of Danish origin. The adjusted IRRs ranged from 0.73 (95% CI: 0.66 to 0.80) following the launch of the 2010 ESC guideline to 0.89 (95% CI: 0.82 to 0.97) following the launch of the 2001 ESC guideline. CONCLUSION: Patients with AF with a high risk of stroke of non-Western origin have persistently experienced a lower chance of initiating OAC compared with patients of Danish origin during the last decades.

The optimal antithrombotic strategy for post-stroke patients with atrial fibrillation and extracranial artery stenosis-a nationwide cohort study.

BACKGROUND: In post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies. METHODS: This study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone. RESULTS: The risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052-1.158, p < 0.001). For patients with ECAS, when compared to AP only, non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551, 95% CI 0.454-0.669), the composite of ischaemic stroke/major bleeding (aHR 0.626, 95% CI 0.529-0.741) and the composite of ischaemic stroke/ICH (aHR 0.577, 95% CI 0.478-0.697), with non-significant difference for major bleeding and ICH. When compared to AP only, warfarin monotherapy was associated with higher risks of major bleeding (aHR 1.521, 95% CI 1.231-1.880), ICH (aHR 2.045, 95% CI 1.329-3.148), and the composite of ischaemic stroke and major bleeding. With combination of AP plus warfarin, there was an increase in ischaemic stroke, major bleeding, and the composite outcomes, when compared to AP only. NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination of AP-OAC) were associated with negative NCB. CONCLUSIONS: For post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy.