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BackgroundSinoatrial node dysfunction and atrial fibrillation (AF) often coexist, and each potentially initiates or perpetuates the other. Consequently, genetic risk factors for AF may be associated with sick sinus syndrome (SSS). This study evaluated clinical, sociodemographic, laboratory and genetic factors in predicting the SSS incidence by using a polygenic risk score (PRS) for AF, given the absence of a dedicated PRS for SSS.MethodsA total of 502 421 individuals aged 38–73 years across 22 centres from 2006 to 2010 were enrolled in the UK Biobank. After those with incomplete data, prior AF or valvular disease were excluded, 405 869 participants (median age 58.0 (IQR, 50.0–64.0) years; 213 684 (45.2%) male) were analysed. AF PRS categorised the participants into low (first quintile), intermediate (middle three quintiles) and high (fifth quintile) risks. SSS incidence was recorded, and associations were evaluated using Cox regression with sociodemographic, clinical, laboratory and genetic variables.ResultsDuring the median follow-up of 11.9 years, 769 SSS events occurred. Their incidence increased with age (HR 1.52, 95% CI 1.43 to 1.62 per 5 years), male sex (HR 1.39, 95% CI 1.03 to 1.88), prior myocardial infarction (HR 1.54, 95% CI 1.08 to 2.21) and hypertension (HR 1.21, 95% CI 1.02 to 1.42). The high-PRS and intermediate-PRS groups were related to 82% (HR 1.82, 95% CI 1.45 to 2.29) and 32% (HR 1.32, 95% CI 1.07 to 1.62) higher SSS risks, respectively. Cystatin C (HR 1.71, 95% CI 1.33 to 2.22) was also associated with the increased risk. The model’s C-index was 0.752 with sociodemographic and clinical variables, but it increased to 0.760 with genetic and biomarker data.ConclusionIn addition to sociodemographic and clinical risk factors, AF PRS and cystatin C were linked to the SSS incidence. Although their inclusion modestly improved prediction, these findings highlighted the potential of integrating genetic and biomarker information for comprehensive SSS risk assessments.

ContextMany studies have reported conflicting evidence on the association between weight change and mortality.ObjectiveWe investigated the association between weight change and subsequent all-cause mortality, using a large-scale, population-based cohort from the National Health Insurance System health checkup data between 2005 and 2015.MethodsA total of 11,524,763 subjects older than age 20 years were included. Weight was measured every 2 years and weight change over 4 years was divided into eight categories, from weight loss ≥15% to weight gain ≥20%, for every 5% of weight change. The hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were analyzed using multivariable Cox proportional hazard models compared with the stable weight group (weight change <5%) after adjusting for age, sex, smoking, drinking, exercise, diabetes mellitus, hypertension, dyslipidemia, cancer, and income.ResultsWeight loss was associated with increased mortality rates compared with weight gain; the group with weight loss ≥15% had the highest HR for all-cause mortality (HR, 2.598; 95% CI, 2.537 to 2.659). The HR for all-cause mortality in the ≥20% weight gain group was 1.784 (95% CI, 1.695 to 1.877). Across all body mass index (BMI) categories, weight loss ≥15% was associated with increased mortality rates and the highest mortality rates were found in the BMI ≥30 kg/m2 group (HR, 3.469; 95% CI, 2.236 to 5.381).ConclusionsWeight change over 4 years showed a reverse J-shaped all-cause mortality curve, independent of BMI status. Weight loss was associated with a greater risk of mortality than was weight gain.Weight change over 4 years showed a reverse J-shaped all-cause mortality curve independent of BMI status. Weight loss was associated with a greater risk of mortality than was weight gain.

There are little direct comparative evidences of strategies between ≥50% and the absolute target goal of low-density lipoprotein cholesterol (LDL-C) level <55 mg/100 ml for the patients who underwent percutaneous coronary intervention (PCI). This study aimed to investigate the clinical impact of different strategies between 2 groups of patients who underwent PCI. A total of 3,104 patients with previous PCI were retrospectively enrolled from 2014 to 2020 at Yeungnam University Medical Center. The study population was stratified into 2 groups based on whether the LDL-C level was <55 mg/100 ml at the 1-year mark or not. Furthermore, the 50% reduction rate of LDL-C was also categorized based on whether it had decreased by ≥50% from the initial LDL-C level at the 1-year mark. The primary end point was 3-year major adverse cardiovascular events (MACEs) which were defined as a composite of cardiovascular death, nonfatal myocardial infarction, target lesion revascularization, hospitalization for heart failure, or nonfatal stroke. There was no significant difference between the LDL <55 mg/100 ml group and the LDL ≥55 mg/100 ml group in the risk of MACEs (hazard ratio 1.06, 95% confidence interval 0.81 to 1.38, p = 0.690) after propensity score matching. However, the group that achieved ≥50% reduction of LDL-C from baseline LDL-C level showed a significant reduction in the occurrence of MACEs in the subgroup of LDL-C level ≥55 mg/100 ml (hazard ratio 0.41, 95% confidence interval 0.19 to 0.89, p = 0.025) compared with the group with <50% reduction of LDL-C. In all patients, the achievement rate of target LDL-C <55 mg/100 ml and more than 50% reduction from baseline was 17.2%. In conclusion, guideline-directed management strategy of ≥50% reduction of LDL-C from the baseline will be needed to reduce the incidence of MACEs in patients with LDL-C ≥55 mg/100 ml who underwent PCI. Additional efforts to increase the target goal achievement rate of LDL-C are warranted.

Background Sodium‐glucose co‐transporter 2 (SGLT2) inhibitors have been demonstrated to decrease cardiovascular adverse events. However, there is little real‐world clinical evidence regarding a direct comparison between dapagliflozin and empagliflozin in patients with diabetes mellitus (DM). Hypothesis A difference in the cardiovascular efficancy of dapagliflozin versus empagliflozin in DM patients was anticipated, aiming to guide the optimal choice of SGLT2 inhibitors based on cardiovascular outcomes. Methods From 2014 to 2020, a total of 1549 patients with DM who were prescribed SGLT2 inhibitors such as dapagliflozin or empagliflozin were retrospectively enrolled. We categorized the study population into two groups: dapagliflozin (n = 981) and empagliflozin group (n = 568). The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of all‐cause death, myocardial infarction (MI), stroke, or hospitalization for heart failure (HF) over a 3‐year period. Results Propensity‐score matching was performed (537 patients in each group). The mean age and hemoglobin A1c were 58.2 ± 13.0 years and 8.4 ± 1.7%, respectively. There was no significant difference between the dapagliflozin and empagliflozin groups in the risk of MACE (3.7% vs. 4.8%, hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.73–2.35; p = 0.349). Furthermore, there were no differences between the two groups in secondary endpoints including all‐cause death, MI, stroke, and hospitalization for HF. Prior MI and history of HF were independent predictors of MACE. Conclusions Dapagliflozin and empagliflozin showed no significant difference of real‐world clinical cardiovascular outcomes in patients with DM over a 3‐year period. Further large randomized clinical trials will be warranted for better evaluation. Comparative study on dapagliflozin and empagliflozin showed similar 3‐year cardiovascular outcomes in patients with diabetes mellitus. DM, diabetes mellitus; MACE, major adverse cardiovascular events; PS, propensity‐score; SGLT2, sodium‐glucose co‐transporter 2.

Background Increased oxidative stress and impaired antioxidant defense are important mechanisms in the pathogenesis of diabetic myopathy. Alpha-lipoic acid (ALA) has been indicated as a weight-loss treatment in rodents and humans, but studies are limited. In the present study, we aimed to determine the influence of ALA, a potent biological antioxidant, on metabolic and growth processes in diabetic rat skeletal muscle. Methods Male 25-week-old type 2 diabetic rats (OLETF) were randomly divided into two groups, a control group (OLETF-C) and an ALA-treated group (OLETF-ALA) supplemented with 100 mg/kg ALA for 8 weeks. Age-matched, healthy, nondiabetic LETO (LETO-C) rats were used as controls. Results At 32 weeks of age, body weight was decreased by 6.8%, and the areas under the curve of IP-GTT, fasting glucose, and insulin were less in OLETF-ALA rats compared with OLETF-C rats. ALA significantly preserved muscle mass and enhanced muscle fiber cross-sectional area and fiber frequency percentage in the skeletal muscle of OLETF rats. Although the activation of myoD, myogenin, and myostatin in gastrocnemius muscle was significantly inhibited in OLETF-ALA rats relative to OLETF-C rats, there were no differences in the expression levels of muscle atrogin-1 and MuRF1 between the two groups. ALA treatment significantly increased the levels of phosphorylated 5′-AMPK, SIRT1, and PGC-1α, as well as the levels of phosphorylated AKT, mTOR, and p70S6 kinase in OLETF-ALA rats compared with OLETF-C rats. In contrast, the levels of phosphorylated p38 MAPK, IRS-1, and FOXO1 were decreased in OLETF-ALA rats compared with OLETF-C rats. Conclusions ALA treatment preserved mass in the gastrocnemius muscles of OLETF rats. ALA significantly upregulated the AMPK/SIRT1/PGC-1α and AKT/mTOR/p70S6K signaling pathways in OLETF rat skeletal muscle. Therefore, ALA may be a potential therapeutic intervention for skeletal muscle loss in animal models of insulin resistance.

This study aimed to determine the impact of dysglycemia on myocardial injury and cardiac dysfunction in acute myocardial infarctions (AMIs). From 2005 to 2016, a total of 1,593 patients with AMIs who underwent percutaneous coronary intervention were enrolled. The patients were classified into five groups according to the admission glucose level: ≤80, 81 to 140, 141 to 200, 201 to 260, and ≥261 mg/dL. The clinical and echocardiographic parameters and 30-day mortality were analyzed. The peak troponin I and white blood cell levels had a positive linear relationship to the admission glucose level. The left ventricular ejection fraction had an inverted U-shape trend, and the E/E' ratio was U-shaped based on euglycemia. The 30-day mortality also increased as the admission glucose increased, and the cut-off value for predicting the mortality was 202.5 mg/dL. Dysglycemia, especially hyperglycemia, appears to be associated with myocardial injury and could be another adjunctive parameter for predicting mortality in patients with AMIs.

Data on the clinical impact of beta-blockers (BBs) in patients with myocardial infarction (MI) who had non-reduced left ventricular ejection fraction (LVEF) after percutaneous coronary intervention are limited. From 2016 to 2020, we evaluated a cohort of 12,101 myocardial infarction patients with a non-reduced LVEF (≥40%) from the Korean Acute Myocardial Infarction Registry V. Patients were divided into two groups based on their BB (carvedilol, bisoprolol, or nebivolol) treatment at discharge: with beta-blocker treatment (BB,  = 9,468) and without beta-blocker treatment (non-BB,  = 2,633). The primary endpoint after discharge was the occurrence of patient-oriented composite endpoints (POCEs), including all-cause mortality, any MI, or any revascularization at 1-year follow-up. The median follow-up period was 353 days (interquartile range, 198-378 days). At 1-year follow-up, no significant differences were observed in the primary endpoint between the BB group and the non-BB group. Before propensity score (PS) matching, the POCE incidence was 3.1% in the BB group vs. 3.4% in the non-BB group [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.68-1.09,  = 0.225]. After PS matching, the POCE incidence remained similar between the two groups (3.7% vs. 3.4%, HR 1.01, 95% CI 0.76-1.35,  = 0.931). Individual outcomes, including all-cause mortality, myocardial infarction, and revascularization, also showed no significant differences between the two groups. Independent predictors of 1-year POCEs after discharge were age, chronic kidney disease, reduced LVEF, and multivessel disease. BB treatment in patients with acute MI and non-reduced LVEF was not associated with a significant reduction in cardiovascular outcomes at 1-year follow-up.

This study aimed to develop a new set of screening criteria that is easily applicable and highly sensitive for the detection of patients at high risk of Fabry disease (FD) among hypertrophic cardiomyopathy (HCM) patients. We prospectively studied 273 consecutive unrelated patients who were referred to HCM clinic for unknown left ventricular hypertrophy. Among the 273 patients, we selected 65 high-risk patients who fulfilled at least one of our newly proposed screening criteria. All 273 patients were assayed for plasma α-galactosidase A (α-GAL A) activity. The new screening criteria were: (1) atypical HCM, (2) history or presence of documented arrhythmia, (3) short PR interval defined as <120 ms on electrocardiogram, and (4) symptoms of autonomic dysfunction. From this screening study, three unrelated patients (4.6%; 2 females and 1 male) were newly diagnosed with FD using α-GAL A activity and mutation analysis of the GLA gene. Using the screening method based on the newly proposed criteria, the prevalence of FD in our HCM population was 4.6% if at least one criterion was met and 18.8% if ⩾3 criteria were met. Therefore, our proposed criteria are easily applicable and highly sensitive for classifying patients at high risk of FD from HCM patients.

Hemorheologic indices are known to be related to vascular complications in variable clinical settings. However, little is known about the associations between hemorheologic parameters and acute myocardial infarction (AMI) in type 2 diabetes mellitus (T2DM). The purpose of this study was to demonstrate the changes of hemorheologic environment inside of blood using hemorheologic parameters, especially the elongation index (EI) and critical shear stress (CSS) in diabetics with versus without AMI. A total of 195 patients with T2DM were enrolled. Patients were divided into the study group with AMI (AMI+, n=77) and control group (AMI-, n=118) who had no history of coronary artery disease. Hemorheologic parameters such as EI and CSS were measured and compared between the two groups. The EI was lower (30.44%±1.77% in AMI+ and 31.47%±1.48% in AMI-, P<0.001) but the level of CSS was higher (316.13±108.20 mPa in AMI+ and 286.80±85.34 mPa in AMI-, P=0.040) in the AMI+. The CSS was significantly related to the erythrocyte sedimentation rate (R²=0.497, P<0.001) and use of dipeptidyl peptidase-4 inhibitors (R²=0.574, P=0.048). Diabetics with AMI resulted in adverse hemorheologic changes with lower EI and higher CSS compared to diabetic subjects without AMI. Evaluation of the hemorheologic parameters may provide valuable supplementary information for managing patients with AMI and T2DM.

This study aimed to investigate the characteristics of out-of-office blood pressure (BP) measurements in patients with apparent treatment-resistant hypertension (aRH) enrolled from 15 tertiary care centers in South Korea. aRH was defined as having uncontrolled office BP ≥ 130/80 mmHg despite receiving three classes of antihypertensive medication or any level of BP despite receiving ≥4 classes of antihypertensive medication. Patients with complete data for office BP, 24-h ambulatory BP monitoring (ABPM), and home BP measurements at baseline were included. BP control status between ABPM and home BP measurements was compared. Out of 1457 patients, 823 meeting the enrollment criteria were included (mean age: 59.9 ± 13.6 years; 57.5% male patients). Among them, 7.2% had controlled BP, 8.7% had whitecoat uncontrolled hypertension, 15.1% had masked uncontrolled hypertension, and 69% had sustained hypertension, as measured through baseline ABPM. Additionally, 43% of patients with controlled BP based on home BP measurement had nocturnal hypertension. Relying solely on home BP measurement may result in misclassifying 70% of patients as having either controlled BP or whitecoat uncontrolled BP. This study reaffirms the circadian pattern of resistant hypertension, characterized by a higher prevalence of non-dipping and rising patterns, even in patients with BP controlled based on ABPM. Considering the persistent difference between home BP measurement and ABPM, even at a lower home BP threshold, integrating both measurements into the management of aRH is advisable.