Accelerometer-derived physical activity and the risk of death, heart failure, and stroke in patients with atrial fibrillation: a prospective study from UK Biobank.

OBJECTIVE: Data on cardiovascular outcomes according to objectively measured physical activity (PA) in patients with atrial fibrillation (AF) are scarce. This study explored the associations between PA derived from wrist-worn accelerometers and the risk of death, incident heart failure (HF), and incident stroke in patients with AF. METHODS: From 37 990 patients with AF in UK Biobank, 2324 patients with accelerometer data were included. Weekly moderate-to-vigorous PA (MVPA) duration was computed from accelerometer data. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, incident HF, and incident stroke. Restricted cubic splines estimated the dose-response associations between MVPA duration and the outcomes. The adjusted HRs (aHRs) of the outcomes according to adherence to PA standard guidelines (performing MVPA≥150 min/week) were also evaluated. RESULTS: The mean age was 66.9±6.2 years and 64.9% were male. During a median follow-up of 6.7 years, there were 181 all-cause deaths, 62 cardiovascular deaths, 225 cases of incident HF, and 91 cases of incident stroke; the overall incidence rate per 1000 patient-years was 11.76, 4.03, 15.16 and 5.99, respectively. There was a linear inverse dose-response relationship between MVPA (≥108 min/week) and all-cause mortality. Performing MVPA for 105-590 min/week was associated with a lower risk of HF than those with no measurable MVPA. The risk of stroke and cardiovascular mortality was not associated with MVPA. Performing guideline-adherent MVPA was related to a 30% lower risk of all-cause mortality (aHR: 0.70 (0.50-0.98), p=0.04) and 33% lower risk of HF (aHR 0.67 (0.49-0.93), p=0.02). CONCLUSION: In patients with AF, accelerometer-derived PA data supports lower risks of all-cause mortality and HF according to a greater level of MVPA and adherence to PA guidelines. Regular MVPA should be encouraged in patients with AF as a part of integrated management.

Mildly Reduced Renal Function Is Associated With Increased Heart Failure Admissions in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: The association between renal dysfunction and cardiovascular outcomes has yet to be determined in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate whether mildly reduced renal function is associated with the prognosis in patients with HCM. METHODS: Patients with HCM were enrolled at two tertiary HCM centers. Patients who were on dialysis, or had a previous history of heart failure (HF) or stroke were excluded. Patients were categorized into 3 groups by estimated glomerular filtration rate (eGFR): stage I (eGFR ≥ 90 mL/min/1.73 m², n = 538), stage II (eGFR 60-89 mL/min/1.73 m², n = 953), and stage III-V (eGFR < 60 mL/min/1.73 m², n = 265). Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, hospitalization for HF (HHF), or stroke during median 4.0-year follow-up. Multivariable Cox regression model was used to adjust for covariates. RESULTS: Among 1,756 HCM patients (mean 61.0 ± 13.4 years; 68.1% men), patients with stage III-V renal function had a significantly higher risk of MACEs (adjusted hazard ratio [aHR], 2.71; 95% confidence interval [CI], 1.39-5.27; P = 0.003), which was largely driven by increased incidence of cardiovascular death and HHF compared to those with stage I renal function. Even in patients with stage II renal function, the risk of MACE (vs. stage I: aHR, 2.21' 95% CI, 1.23-3.96; P = 0.008) and HHF (vs. stage I: aHR, 2.62; 95% CI, 1.23-5.58; P = 0.012) was significantly increased. CONCLUSION: This real-world observation showed that even mildly reduced renal function (i.e., eGFR 60-89 mL/min/1.73 m²) in patients with HCM was associated with an increased risk of MACEs, especially for HHF.

Comparative cardiovascular outcomes in type 2 diabetes patients taking dapagliflozin versus empagliflozin: a nationwide population-based cohort study.

BACKGROUND: Sodium-glucose co-transporter-2 inhibitors displayed cardiovascular benefits in type 2 diabetes mellitus in previous studies; however, there were some heterogeneities regarding respective cardiovascular outcomes within the class. Furthermore, their efficacies in Asians, females, and those with low cardiovascular risks were under-represented. Thus, we compared the cardiovascular outcomes between new users of dapagliflozin and empagliflozin in a broad range of patients with type 2 diabetes mellitus using a nationwide population-based real-world cohort from Korea. METHODS: Korean National Health Insurance registry data between May 2016 and December 2018 were extracted, and an active-comparator new-user design was applied. The primary outcome was a composite of heart failure (HF)-related events (i.e., hospitalization for HF and HF-related death), myocardial infarction, ischemic stroke, and cardiovascular death. The secondary outcomes were individual components of the primary outcome. RESULTS: A total of 366,031 new users of dapagliflozin or empagliflozin were identified. After 1:1 nearest-neighbor propensity score matching, 72,752 individuals (mean age approximately 56 years, 42% women) from each group were included in the final analysis, with a follow-up of 150,000 ~ person-years. Approximately 40% of the patients included in the study had type 2 diabetes mellitus as their sole cardiovascular risk factor, with no other risk factors. The risk of the primary outcome was not different significantly between dapagliflozin and empagliflozin users (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.855-1.006). The risks of secondary outcomes were also similar, with the exception of the risks of HF-related events (HR 0.84, 95% CI 0.714-0.989) and cardiovascular death (HR 0.76, 95% CI 0.618-0.921), which were significantly lower in the dapagliflozin users. CONCLUSIONS: This large-scale nationwide population-based real-world cohort study revealed no significant difference in composite cardiovascular outcomes between new users of dapagliflozin and empagliflozin. However, dapagliflozin might be associated with lower risks of hospitalization or death due to HF and cardiovascular death than empagliflozin in Asian patients with type 2 diabetes mellitus.

Predictive Value of Electromechanical Window for Risk of Fatal Ventricular Arrhythmia.

BACKGROUND: As an indicator of electro-mechanical coupling, electromechanical window (EMW) can be used to predict fatal ventricular arrhythmias. We investigated the additive effect of EMW on the prediction of fatal ventricular arrhythmias in high-risk patients. METHODS: We included patients who had implantable cardioverter-defibrillator (ICD) implanted for primary or secondary prevention. The event group was defined as those who received an appropriate ICD therapy. We acquired echocardiograms at ICD implantation and follow-up. The EMW was calculated as the difference between the interval from QRS onset to aortic valve closure and QT interval from the electrocardiogram embedded in the continuous wave doppler image. We evaluated the predictive value of EMW for predicting fatal ventricular arrhythmia. RESULTS: Of 245 patients (67.2 ± 12.8 years, 63.7% men), the event group was 20.0%. EMW at baseline (EMW-Baseline) and follow-up (EMW-FU) was significantly different between event and control groups. After adjustment, both EMW-Baseline (odds ratio [OR]adjust 1.02 [1.01-1.03], P = 0.004) and EMW-FU (ORadjust 1.06 [1.04-1.07], P < 0.001) remained as significant predictors for fatal arrhythmic events. Adding EMW-Baseline significantly improved the discriminating ability of the multivariable model including clinical variables (area under the curve [AUC] 0.77 [0.70-0.84] vs. AUC 0.72 [0.64-0.80], P = 0.004), while a univariable model using EMW-FU alone showed the best performance among models (AUC 0.87 [0.81-0.94], P = 0.060 against model with clinical variables; P = 0.030 against model with clinical variables and EMW-Baseline). CONCLUSION: The EMW could effectively predict severe ventricular arrhythmia in ICD implanted patients. This finding supports the importance of incorporating the electro-mechanical coupling index into the clinical practice for predicting future fatal arrhythmia events.

Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomised, open-label, multicentre trial.

BACKGROUND: Optimal antiplatelet monotherapy during the chronic maintenance period in patients who undergo coronary stenting is unknown. We aimed to compare head to head the efficacy and safety of aspirin and clopidogrel monotherapy in this population. METHODS: We did an investigator-initiated, prospective, randomised, open-label, multicentre trial at 37 study sites in South Korea. We enrolled patients aged at least 20 years who maintained dual antiplatelet therapy without clinical events for 6-18 months after percutaneous coronary intervention with drug-eluting stents (DES). We excluded patients with any ischaemic and major bleeding complications. Patients were randomly assigned (1:1) to receive a monotherapy agent of clopidogrel 75 mg once daily or aspirin 100 mg once daily for 24 months. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater, in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02044250. FINDINGS: Between March 26, 2014, and May 29, 2018, we enrolled 5530 patients. 5438 (98·3%) patients were randomly assigned to either the clopidogrel group (2710 [49·8%]) or to the aspirin group (2728 [50·2%]). Ascertainment of the primary endpoint was completed in 5338 (98·2%) patients. During 24-month follow-up, the primary outcome occurred in 152 (5·7%) patients in the clopidogrel group and 207 (7·7%) in the aspirin group (hazard ratio 0·73 [95% CI 0·59-0·90]; p=0·0035). INTERPRETATION: Clopidogrel monotherapy, compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention with DES significantly reduced the risk of the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and BARC bleeding type 3 or greater. In patients requiring indefinite antiplatelet monotherapy after percutaneous coronary intervention, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future adverse clinical events. FUNDING: ChongKunDang, SamJin, HanMi, DaeWoong, and the South Korea Ministry of Health and Welfare.

Protective effect of proton-pump inhibitor against gastrointestinal bleeding in patients receiving oral anticoagulants: A systematic review and meta-analysis.

AIMS: The evidence of a protective effect of proton-pump inhibitor (PPI) in oral anticoagulant (OAC)-treated patients against gastrointestinal bleeding (GIB) is still lacking. We conducted a meta-analysis to estimate the risk of GIB in patients with OAC and PPI cotherapy. METHODS: A systematic search of PubMed, EMBASE, Cochrane and Scopus databases was performed for studies reporting GIB risk in OAC and PPI cotherapy. Primary outcomes were total GIB and major GIB events. Pooled estimates of GIB risk were calculated by a random-effect meta-analysis and reported as odds ratios and 95% confidence interval. RESULTS: A total of 10 studies and 1 970 931 patients were included. OAC and PPI cotherapy were associated with a lower odds of total and major GIB; odds ratio (95% confidence interval) was 0.67 (0.62-0.74) for total and 0.68 (0.63-0.75) for major GIB, respectively. No differences in the GIB of PPI cotherapy were observed between Asians and non-Asians (P-for-difference, total GIB = .70, major GIB = .75, respectively). For all kinds of OAC except for edoxaban, PPI cotreatment was related to lower odds of GIB by 24-44%. The protective effect of PPI on total GIB was more significant in concurrent antiplatelets or nonsteroidal anti-inflammatory drug users and those with high bleeding risks: patients with previous GIB history, HAS-BLED ≥3 or underlying gastrointestinal diseases. CONCLUSION: In patients who receive OAC, PPI cotherapy is associated with a lower total and major GIB irrespective of ethnic group and OAC type, except for edoxaban. PPI cotherapy can be considered particularly in patients with high risk of GIB.

Age-specific association between invasively measured central blood pressure and left ventricular mass index.

Background: The impact of age on the association between central aortic hemodynamics and left ventricular (LV) remodeling has not been well elucidated. We compared the relationship between measurements of central blood pressure (CBP) and LV mass index (LVMI) according to their ages (<50 years versus ≥50 years). Methods: A total of 305 consecutive subjects (64.4 ± 10.9 years, 60.7% males) who underwent invasive coronary angiography (ICA) for the evaluation of coronary artery disease were prospectively enrolled. Just before ICA, CBP was measured at the aortic root using a pig-tail catheter, and CBP indices, including aortic systolic blood pressure (aSBP), aortic pulse pressure (aPP), aortic fractional pulse pressure (=aPP/mean aortic pressure), and aortic pulsatility index (=aPP/diastolic aortic pressure), were recorded. All subjects underwent transthoracic echocardiography, and LVMI was measured on the same day of ICA. Results: In simple linear correlation analyses, LVMI was associated with all CBP indices in subjects aged <50 years (n = 29) (P < .05 for each), but not in those aged ≥50 years (n = 276) (P > .05 for each). In the younger age group (≤50 years), multivariable analysis showed that aSBP (ß = 0.457, P= .021) and aPP (ß = 0.610, P= .006) had a significant association with LVMI after adjusting for possible confounding factors. The results remained consistent even when analyzed in a 1:1 propensity score-matched cohort. In conclusion, invasively measured aPP showed the closest association with LVMI in subjects aged <50 years, but not those aged ≥50 years. Conclusion: Aortic pulsatile hemodynamic status appears to have a greater effect on LV remodeling in younger people than in older people.

Physiological and Clinical Assessment of Resting Physiological Indexes.

BACKGROUND: Recently, resting pressure-derived indexes such as resting full-cycle ratio (RFR) and diastolic pressure ratio (dPR) have been introduced to assess the functional significance of epicardial coronary stenosis. The present study sought to investigate the agreement of RFR or dPR with other pressure-derived indexes (instantaneous wave-free ratio [iFR] or fractional flow reserve), the sensitivity of RFR or dPR for anatomic or hemodynamic stenosis severity, and the prognostic implications of RFR or dPR compared with iFR Methods: RFR and dPR were calculated from resting pressure tracings by an independent core laboratory in 1024 vessels (435 patients). The changes in resting physiological indexes according to diameter stenosis were compared among iFR, RFR, and dPR. Among 115 patients who underwent 13N-ammonia positron emission tomography, the changes in those indexes according to basal and hyperemic stenosis resistance and absolute hyperemic myocardial blood flow were compared. The association between resting physiological indexes and the risk of 2-year vessel-oriented composite outcomes (a composite of cardiac death, vessel-related myocardial infarction, and vessel-related ischemia-driven revascularization) was analyzed among 864 deferred vessels. RESULTS: Both RFR and dPR showed a significant correlation with iFR ( R=0.979, P<0.001 for RFR; and R=0.985, P<0.001 for dPR), which was higher than that with fractional flow reserve ( R=0.822, P<0.001; and R=0.819, P<0.001, respectively). RFR and dPR showed a very high agreement with iFR (C index, 0.987 and 0.993). Percent difference of iFR, RFR, and dPR according to the increase in anatomic and hemodynamic severity was almost identical. The diagnostic performance of iFR, RFR, and dPR was not different in the prediction of myocardial ischemia defined by both low hyperemic myocardial blood flow and low coronary flow reserve by 13N-ammonia positron emission tomography. All resting physiological indexes showed significant association with the risk of 2-year vessel-oriented composite outcomes (iFR per 0.1 increase: hazard ratio, 0.514 [95% CI, 0.370-0.715], P<0.001; RFR per 0.1 increase: hazard ratio, 0.524 [95% CI, 0.378-0.725], P<0.001; dPR per 0.1 increase: hazard ratio, 0.587 [95% CI, 0.436-0.791], P<0.001) in deferred vessels. CONCLUSIONS: All resting pressure-derived physiological indexes (iFR, RFR, and dPR) can be used as invasive tools to guide treatment strategy in patients with coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01621438.

Relevance of anatomical, plaque, and hemodynamic characteristics of non-obstructive coronary lesions in the prediction of risk for acute coronary syndrome.

OBJECTIVES: We explored the anatomical, plaque, and hemodynamic characteristics of high-risk non-obstructive coronary lesions that caused acute coronary syndrome (ACS). METHODS: From the EMERALD study which included ACS patients with available coronary CT angiography (CCTA) before the ACS, non-obstructive lesions (percent diameter stenosis < 50%) were selected. CCTA images were analyzed for lesion characteristics by independent CCTA and computational fluid dynamics core laboratories. The relative importance of each characteristic was assessed by information gain. RESULTS: Of the 132 lesions, 24 were the culprit for ACS. The culprit lesions showed a larger change in FFRCT across the lesion (ΔFFRCT) than non-culprit lesions (0.08 ± 0.07 vs 0.05 ± 0.05, p = 0.012). ΔFFRCT showed the highest information gain (0.051, 95% confidence interval [CI] 0.050-0.052), followed by low-attenuation plaque (0.028, 95% CI 0.027-0.029) and plaque volume (0.023, 95% CI 0.022-0.024). Lesions with higher ΔFFRCT or low-attenuation plaque showed an increased risk of ACS (hazard ratio [HR] 3.25, 95% CI 1.31-8.04, p = 0.010 for ΔFFRCT; HR 2.60, 95% CI 1.36-4.95, p = 0.004 for low-attenuation plaque). The prediction model including ΔFFRCT, low-attenuation plaque and plaque volume showed the highest ability in ACS prediction (AUC 0.725, 95% CI 0.724-0.727). CONCLUSION: Non-obstructive lesions with higher ΔFFRCT or low-attenuation plaque showed a higher risk of ACS. The integration of anatomical, plaque, and hemodynamic characteristics can improve the noninvasive prediction of ACS risk in non-obstructive lesions. KEY POINTS: • Change in FFR CT across the lesion (ΔFFR CT ) was the most important predictor of ACS risk in non-obstructive lesions. • Non-obstructive lesions with higher ΔFFR CT or low-attenuation plaque were associated with a higher risk of ACS. • The integration of anatomical, plaque, and hemodynamic characteristics can improve the noninvasive prediction of ACS risk.

Clinical Outcome of Lesions With Discordant Results Among Different Invasive Physiologic Indices　- Resting Distal Coronary to Aortic Pressure Ratio, Resting Full-Cycle Ratio, Diastolic Pressure Ratio, Instantaneous Wave-Free Ratio, and Fractional Flow Reserve.

BACKGROUND: We evaluated the 2-year clinical outcomes of deferred lesions with discordant results between resting and hyperemic pressure-derived physiologic indices, including resting distal to aortic coronary pressure (resting Pd/Pa), instantaneous wave-free ratio (iFR), resting full-cycle ratio (RFR), diastolic pressure ratio (dPR), and fractional flow reserve (FFR).Methods and Results:The 2-year clinical outcomes of 1,024 vessels (435 patients) with available resting Pd/Pa, iFR, RFR, dPR, and FFR data were analyzed according to a 4-group classification using known cutoff values (resting Pd/Pa ≤0.92, iFR/RFR/dPR ≤0.89, and FFR ≤0.80): Group 1 (concordant normal), Group 2 (high resting index and low FFR), Group 3 (low resting index and high FFR), and Group 4 (concordance abnormal). The primary outcome was vessel-oriented composite outcomes (VOCO) in deferred vessels at 2 years. In the comparison of VOCO risk among 4 groups classified according to FFR and 4 resting physiologic indices, Group 4 consistently showed a significantly higher risk of VOCO than Group 1. Comparison of VOCO risk among 4 groups classified according to iFR and other resting physiologic indices also showed the same results. The presence of discordance, either between hyperemic and resting indices or among resting indices, was not an independent predictor for VOCO. CONCLUSIONS: Discordant results between resting physiologic indices and FFR and among the resting indices were not associated with increased risk of VOCO in deferred lesions.

Prognostic Impact of ß-Blocker Dose After Acute Myocardial Infarction.

BACKGROUND: The differential prognostic impact of ß-blocker dose after acute myocardial infarction (AMI) has been under debate. The current study sought to compare clinical outcome after AMI according to ß-blocker dose using the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH). Methods and Results: Of the total population of 13,104 consecutive AMI patients enrolled in the KAMIR-NIH, the current study analyzed 11,909 patients. These patients were classified into 3 groups (no ß-blocker; low-dose [<25% of target dose]; and high-dose [≥25% of target dose]). The primary outcome was cardiac death at 1 year. Compared with the no ß-blocker group, both the low-dose and high-dose groups had significantly lower risk of cardiac death (HR, 0.435; 95% CI: 0.363-0.521, P<0.001; HR, 0.519; 95% CI: 0.350-0.772, P=0.001, respectively). The risk of cardiac death, however, was similar between the high- and low-dose groups (HR, 1.194; 95% CI: 0.789-1.808, P=0.402). On multivariable adjustment and inverse probability weighted analysis, the result was the same. CONCLUSIONS: The use of ß-blockers in post-AMI patients had significant survival benefit compared with no use of ß-blockers. There was no significant additional benefit of high-dose ß-blockers compared with low-dose ß-blockers, however, in terms of 1-year risk of cardiac death.

Efficacy and safety of dual antiplatelet therapy after coronary stenting in patients with chronic kidney disease.

BACKGROUND: We compared efficacy and safety of short- (3 or 6 months) versus long-term (≥12 months) dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation, according to the presence of chronic kidney disease (CKD). METHODS: Patient-level pooled analysis was performed with 7242 patients (87.2% with 2nd generation DES) from 5 randomized controlled trials. RESULTS: In both CKD (1273 patients) and non-CKD (5969 patients) population, the rates of patient-oriented composite outcomes at 1-year (POCO, all-cause death, any myocardial infarction [MI], stroke and TIMI major bleeding) were not different between the short- and long-term DAPT (hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.76-1.86, P=.449 in CKD population; HR 1.14, 95% CI 0.83-1.56, P=.434 in non-CKD population). The rates of coronary thrombotic events (any MI and definite/probable stent thrombosis) also did not differ between short- and long-term DAPT in either CKD or non-CKD population. As for bleeding events, long-term DAPT increased the TIMI major bleeding (HR 2.91, 95% CI 1.31-6.48, P=.009) in non-CKD population. The similar trend was observed with long-term DAPT in CKD population. But it did not reach statistical significance (HR 3.15, 95% CI 0.64-15.63, P=.160). CONCLUSIONS: The rates of POCO and coronary thrombotic events were significantly higher in patients with CKD compared with those without CKD, which were not affected by short- or long-term DAPT. Higher bleeding incidence by long-term DAPT was only observed in non-CKD patients but not in CKD patients. Further large scale studies are warranted to confirm our findings.

Randomized Prospective Comparison of Everolimus-Eluting vs. Sirolimus-Eluting Stents in Patients Undergoing Percutaneous Coronary Intervention　- 3-Year Clinical Outcomes of the EXCELLENT Randomized Trial.

BACKGROUND: Everolimus-eluting stents (EES) have equivalent short-term angiographic and clinical outcomes to sirolimus-eluting stents (SES), but EES may be superior to SES with regard to long-term clinical safety. We report the 3-year clinical outcomes of EES and SES from the prospective EXCELLENT Randomized Trial (NCT00698607).Methods and Results:We randomly assigned 1,443 patients undergoing percutaneous coronary intervention 3:1 to receive EES and SES, respectively. We investigated endpoints including target lesion failure (TLF) and individual clinical outcomes including stent thrombosis (ST) at 3 years. For EES and SES, the TLF rate was 4.82% and 4.12% (risk ratio [RR], 1.16, 95% CI: 0.65-2.06, P=0.62), respectively. Results were similar in other efficacy endpoints including target lesion revascularization. For safety endpoints, rate of all-cause death was significantly lower for EES (1.67%) than SES (3.57%; RR, 0.46; 95% CI: 0.23-0.94, P=0.03), while the incidence of cardiac death or myocardial infarction was numerically lower in EES. On 1-year landmark analysis, rates of all-cause death and major adverse cardiovascular events were significantly lower for EES than SES. Definite or probable ST was numerically 3-fold higher for SES (1.37%) compared with EES (0.46%). CONCLUSIONS: EES and SES had similar efficacy with regard to 3-year outcomes in the EXCELLENT trial, while delayed safety events all trended to favor EES.

Effects of Statin Intensity on Clinical Outcome in Acute Myocardial Infarction Patients.

BACKGROUND: There has been debate regarding the added benefit of high-intensity statins compared with low-moderate-intensity statins, especially in patients with acute myocardial infarction (AMI).Methods and Results:The Korea Acute Myocardial Infarction Registry-National Institutes of Health consecutively enrolled 13,104 AMI patients. Of these, a total of 12,182 patients, who completed 1-year follow-up, were included in this study, and all patients were classified into 3 groups (no statin; low-moderate-intensity statin; and high-intensity statin). The primary outcome was major adverse cardiac event (MACE) including cardiac death, non-fatal MI, and repeat revascularization at 1 year. Both low-moderate-intensity and high-intensity statin significantly reduced low-density lipoprotein cholesterol (LDL-C; all P<0.001). Compared with the no statin group, both statin groups had significantly lower risk of MACE (low-moderate intensity: HR, 0.506; 95% CI: 0.413-0.619, P<0.001; high intensity: HR, 0.464; 95% CI: 0.352-0.611, P<0.001). The risk of MACE, however, was similar between the low-moderate- and high-intensity statin groups (HR, 0.917; 95% CI: 0.760-1.107, P=0.368). Multivariable adjustment, propensity score matching, and inverse probability weighted analysis also produced the same results. CONCLUSIONS: When adequate LDL-C level is achieved, patients on a low-moderate-intensity statin dose have similar cardiovascular outcomes to those on high-intensity statins.

Cirrhosis is a risk factor for atrial fibrillation: A nationwide, population-based study.

BACKGROUND & AIMS: Information is lacking regarding whether cirrhosis is associated with atrial fibrillation development. We aimed to investigate the incidence and clinical significance of atrial fibrillation in cirrhotic patients. METHODS: Cirrhotic patients (n=3596; mean age, 54.7±12.3 years; male, 72.5%) without previous atrial fibrillation were selected from the Korean National Health Insurance Service National Sample Cohort database between 2004 and 2008. Age- and sex-matched controls (n=17 980) were randomly sampled in a 5:1 ratio from non-cirrhotic individuals. Both cohorts were followed up for incident atrial fibrillation and death until 2013. RESULTS: During 9 years of follow-up, atrial fibrillation was newly detected in 113 (3.1%) cirrhosis patients and 385 (2.1%) controls (incidence: 3.48 and 2.16 per 1000 person-years respectively). Cirrhotic patients were at higher risk for atrial fibrillation development compared to controls (hazard ratio, 1.46; 95% confidence interval, 1.18-1.80) after multivariate adjustment. On subgroup analysis, cirrhosis increased the risk for atrial fibrillation, especially in younger (age younger than 65 years) men without comorbidities (CHA2 DS2 -VASc score, 0). Cirrhotic patients showed increased overall mortality compared to controls (hazard ratio, 4.80; 95% confidence interval, 4.47-5.15) as well as increased cardiovascular mortality (hazard ratio, 1.37; 95% confidence interval, 1.07-1.75). However, there was no significant association between development of atrial fibrillation and increased mortality in cirrhosis patients (P=.188 and .260). CONCLUSIONS: Cirrhosis was an independent risk factor for atrial fibrillation development, especially in younger, otherwise healthy men, stressing the importance of cardiac assessment in cirrhotic patients. Meanwhile, atrial fibrillation development in cirrhosis patients was not associated with increased mortality.

Association between Cumulative Metabolic Risk Exposure and Cardiovascular Disease: A Nationwide Cohort of Over 3.6 Million Young Adults.

AIMS: Since lifetime accumulation of cardiovascular risk factors is getting important, early identification and management of risk factors are emphasised. The global prevalence of metabolic syndrome (MetS), a constellation of these risk factors, is increasing, particularly among young adults. We aimed to investigate the association between cumulative exposure to metabolic risk and cardiovascular disease (CVD) in young adults. METHODS: In this nationwide population-based cohort, we analysed 3,688,787 young adults (<40 years) with two biennial National Health Screening examinations from 2009 to 2012. Participants were categorised into MetS-free, MetS-developed, MetS-recovered, or MetS-persistent group, based on MetS presence at each examination. The endpoint was new CVD development, including myocardial infarction (MI), and ischaemic stroke. RESULTS: During follow-up (median, 7.7 years), CVD occurred in 19,219 individuals (0.5%). CVD incidence rates were 0.58, 1.17, 1.20, and 1.83 (1,000 person-year) in the MetS-free, MetS-developed, MetS-recovered, and MetS-persistent groups, respectively. CVD risk was proportionally associated with cumulative metabolic risk exposure, with a maximum 2-fold increase in the MetS-persistent group (aHR 1.94, 95% CI 1.84-2.04), and followed by the MetS-recovered and MetS-developed groups with similar risks. Among the MetS components, persistent exposure to elevated blood pressure (BP) had the greatest association with CVD risk (aHR 1.69, 95% CI 1.63-1.76). This tendency was consistent in the analyses of the risk of MI and ischaemic stroke. CONCLUSIONS: CVD risk increased in an exposure-dependent manner among young adults. Efforts to optimise cardiometabolic profile, particularly BP, even after the establishment of MetS, might help promote long-term cardiovascular prognosis.

In this large-scale nationwide cohort comprising 3,688,787 asymptomatic young adults under 40 years, we showed that the long-term risk of cardiovascular disease (CVD) increased in proportion with cumulative exposure to metabolic risk, as assessed by the temporal changes in metabolic syndrome (MetS) status, with blood pressure (BP) demonstrating the greatest impact. The risk of CVD exhibited a gradual increase in accordance with cumulative metabolic risk exposure, with a 2-fold increment in the MetS-persistent group. Among the MetS components, persistent exposure to elevated BP had the most profound impact to increase the risk of CVD, and the optimisation of BP levels might be helpful to promote long-term cardiovascular health in young adults.

Neuroticism and the Risk of Atrial Fibrillation: An Observational Epidemiologic and Mendelian Randomization Study.

Background: The association between neuroticism and atrial fibrillation (AF) remains unknown. Objectives: This study aimed to assess the epidemiological and causal relationships between neuroticism and AF. Methods: Individuals without AF history were selected From the UK Biobank nationwide prospective cohort study. Participants were divided into 2 groups (high and low) based on the median summary score from a self-questionnaire of 12 neurotic behavior domains. The 10-year AF risk was compared between the neuroticism score groups using inverse probability of treatment weighting. The causal relationship between neuroticism and AF was evaluated using a 2-sample summary-level Mendelian randomization with the inverse variance-weighted method. Results: Of 394,834 participants (mean age 56.3 ± 8.1 years, 45.9% male), AF occurred in 23,509 (6.0%) during a 10-year follow-up. The risk of incident AF significantly increased in the high neuroticism score group (score ≥4) (inverse probability of treatment weighting-adjusted HR: 1.05; 95% CI: 1.02-1.09; P = 0.005) compared with the low neuroticism group. In the subgroup analysis, younger age, lower body mass index, or nonsmoker/ex-smoker participants were particularly susceptible to increased AF risk due to high neuroticism scores. A Mendelian randomization analysis showed a significant causal relationship between an increase in neuroticism score and increased risk of AF (OR by inverse variance-weighted method 1.06; 95% CI: 1.02-1.11; P = 0.007) without evidence of reverse causality. Conclusions: There was a significant longitudinal and causal relationship between neuroticism and AF. An integrated care including active mental health screening and management may benefit in high-risk populations.

Machine Learning-Based Discrimination of Cardiovascular Outcomes in Patients With Hypertrophic Cardiomyopathy.

Background: Current risk stratification strategies for patients with hypertrophic cardiomyopathy (HCM) are limited to traditional methodologies. Objectives: The authors aimed to establish machine learning (ML)-based models to discriminate major cardiovascular events in patients with HCM. Methods: We enrolled consecutive HCM patients from 2 tertiary referral centers and used 25 clinical and echocardiographic features to discriminate major adverse cardiovascular events (MACE), including all-cause death, admission for heart failure (HF-adm), and stroke. The best model was selected for each outcome using the area under the receiver operating characteristic curve (AUROC) with 20-fold cross-validation. After testing in the external validation cohort, the relative importance of features in discriminating each outcome was determined using the SHapley Additive exPlanations (SHAP) method. Results: In total, 2,111 patients with HCM (age 61.4 ± 13.6 years; 67.6% men) were analyzed. During the median 4.0 years of follow-up, MACE occurred in 341 patients (16.2%). Among the 4 ML models, the logistic regression model achieved the best AUROC of 0.800 (95% CI: 0.760-0.841) for MACE, 0.789 (95% CI: 0.736-0.841) for all-cause death, 0.798 (95% CI: 0.736-0.860) for HF-adm, and 0.807 (95% CI: 0.754-0.859) for stroke. The discriminant ability of the logistic regression model remained excellent when applied to the external validation cohort for MACE (AUROC = 0.768), all-cause death (AUROC = 0.750), and HF-adm (AUROC = 0.806). The SHAP analysis identified left atrial diameter and hypertension as important variables for all outcomes of interest. Conclusions: The proposed ML models incorporating various phenotypes from patients with HCM accurately discriminated adverse cardiovascular events and provided variables with high importance for each outcome.

Differing Efficacy of Dapagliflozin Versus Empagliflozin on the Risk of Incident Atrial Fibrillation in Patients With Type 2 Diabetes: A Real-World Observation Using a Nationwide, Population-Based Cohort.

BACKGROUND: Meta-analyses of large clinical trials investigating SGLT2 (sodium-glucose cotransporter-2) inhibitors have suggested their protective effects against atrial fibrillation in patients with type 2 diabetes. However, the results were predominantly driven from trials involving dapagliflozin. METHODS AND RESULTS: We used a nationwide, population-based cohort of patients with type 2 diabetes who initiated either dapagliflozin or empagliflozin between May 2016 and December 2018. An active-comparator, new-user design was used, and the 2 groups of patients were matched using propensity scores. The primary outcome was incident nonvalvular atrial fibrillation, which was analyzed using both the main intention-to-treat and sensitivity analysis that censored patients who skipped their medications for ≥30 days. Men ≥55 years of age and women ≥60 years of age with ≥1 traditional risk factor or those with established cardiovascular disease were categorized as high cardiovascular risk group. Patients not included in the high-risk group were categorized as low risk. After 1:1 propensity-score matching, a total of 137 928 patients (mean age, 55 years; 58% men) were included and followed up for 2.2±0.6 years. The risk of incident atrial fibrillation was significantly lower in the dapagliflozin group in both the main (hazard ratio [HR], 0.885 [95% CI, 0.789-0.992]) and sensitivity analyses (HR, 0.835 [95% CI, 0.719-0.970]). Notably, this was consistent in both the low and high cardiovascular risk groups. There was no effect modification by age, sex, body mass index, duration of diabetes, or renal function. CONCLUSIONS: This real-world, population-based study demonstrates that patients with type 2 diabetes using dapagliflozin may have a lower risk of developing nonvalvular atrial fibrillation than those using empagliflozin.

Association of Fibrate use with clinical expression of hypertrophic cardiomyopathy.

AIMS: An association between obesity, metabolic abnormalities and clinical hypertrophic cardiomyopathy (HCM) expression has been reported. We investigated whether managing dyslipidaemia with fibrates could affect the clinical expression of HCM. METHODS: We screened patients who used fibrates between 2010 and 2017 from a nationwide database. After excluding patients with a history of HCM, we identified fibrate-user group (n = 412 823). We then constructed a 1:1 matched cohort of fibrate-naïve participants (n = 412 823). After a 1 year lag period, we identified the incident HCM cases for the following 5 years. RESULTS: During a median follow-up period of 3.96 years, we identified 454 incident clinical HCM cases. After adjusting for covariates, fibrate use was associated with a lower risk of clinical HCM expression [hazard ratio (HR) 95% confidence interval (CI): 0.763 (0.630-0.924)]. In subgroup analyses, fibrate use was associated with a reduced risk of clinical HCM expression in patients with a body mass index ≥25 kg/m2 and those with abdominal obesity [HR (95% CI): 0.719 (0.553-0.934) and 0.655 (0.492-0.872)], but not in those without obesity. Fibrate use was also associated with lower risks of incident clinical HCM in patients with triglyceride levels ≥150 mg/dL and those with metabolic syndrome [HR (95% CI): 0.741 (0.591-0.929) and 0.750 (0.609-0.923)], but not in their counterparts. Regarding lifestyle behaviours, fibrate use appeared to provide more prognostic benefits in patients who currently smoked, consumed alcohol or did not engage in regular physical activities. CONCLUSION: The use of fibrates is associated with a lower incidence of clinical HCM expression. This association was also more prominent in those with obesity, unhealthy metabolic profiles and poor lifestyle behaviours.