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.

Hypertrophic cardiomyopathy detection with artificial intelligence electrocardiography in international cohorts: an external validation study.

Aims: Recently, deep learning artificial intelligence (AI) models have been trained to detect cardiovascular conditions, including hypertrophic cardiomyopathy (HCM), from the 12-lead electrocardiogram (ECG). In this external validation study, we sought to assess the performance of an AI-ECG algorithm for detecting HCM in diverse international cohorts. Methods and results: A convolutional neural network-based AI-ECG algorithm was developed previously in a single-centre North American HCM cohort (Mayo Clinic). This algorithm was applied to the raw 12-lead ECG data of patients with HCM and non-HCM controls from three external cohorts (Bern, Switzerland; Oxford, UK; and Seoul, South Korea). The algorithm's ability to distinguish HCM vs. non-HCM status from the ECG alone was examined. A total of 773 patients with HCM and 3867 non-HCM controls were included across three sites in the merged external validation cohort. The HCM study sample comprised 54.6% East Asian, 43.2% White, and 2.2% Black patients. Median AI-ECG probabilities of HCM were 85% for patients with HCM and 0.3% for controls (P < 0.001). Overall, the AI-ECG algorithm had an area under the receiver operating characteristic curve (AUC) of 0.922 [95% confidence interval (CI) 0.910-0.934], with diagnostic accuracy 86.9%, sensitivity 82.8%, and specificity 87.7% for HCM detection. In age- and sex-matched analysis (case-control ratio 1:2), the AUC was 0.921 (95% CI 0.909-0.934) with accuracy 88.5%, sensitivity 82.8%, and specificity 90.4%. Conclusion: The AI-ECG algorithm determined HCM status from the 12-lead ECG with high accuracy in diverse international cohorts, providing evidence for external validity. The value of this algorithm in improving HCM detection in clinical practice and screening settings requires prospective evaluation.

Risk of Heart Disease in Patients With Amputation: A Nationwide Cohort Study in South Korea.

BACKGROUND: Amputation confers disabilities upon patients and is linked to substantial morbidity and death attributed to heart disease. While some studies have focused on traumatic amputees in veterans, few studies have focused on traumatic amputees within the general population. Therefore, the present study aimed to assess the risk of heart disease in patients with traumatic amputation with disability within the general population using a large-scale nationwide population-based cohort. METHODS AND RESULTS: We used data from the Korean National Health Insurance System. A total of 22 950 participants with amputation were selected with 1:3 age, sex-matched controls between 2010 and 2018. We used Cox proportional hazard models to calculate the risk of myocardial infarction, heart failure, and atrial fibrillation among amputees. Participants with amputation had a higher risk of myocardial infarction (adjusted hazard ratio [aHR], 1.30 [95% CI, 1.14-1.47]), heart failure (aHR, 1.27 [95% CI, 1.17-1.38]), and atrial fibrillation (aHR, 1.17 [95% CI, 1.03-1.33]). The risks of myocardial infarction and heart failure were further increased by the presence of disability (aHR, 1.43 [95% CI, 1.04-1.95]; and aHR, 1.38 [95% CI, 1.13-1.67], respectively). CONCLUSIONS: We demonstrate an increased risk of myocardial infarction, heart failure, and atrial fibrillation among individuals with amputation, and the risk further increased in those with disabilities. Clinicians should pay attention to the increased risk for heart disease in patients with amputation.

Increased Risk of Myocardial Infarction, Heart Failure, and Atrial Fibrillation After Spinal Cord Injury.

BACKGROUND: Heart diseases are a growing concern for the spinal cord injury (SCI) population. OBJECTIVES: This study aims to compare the incidence of heart diseases between SCI survivors and the general non-SCI population. METHODS: We identified 5,083 SCI survivors and 1:3 age- and sex-matched non-SCI controls. Study outcomes were myocardial infarction (MI), heart failure (HF), and atrial fibrillation (AF). The cohort was followed up from the index date (diagnosis date for SCI or corresponding date for matched controls) until 2019. RESULTS: SCI survivors showed a higher risk for MI (adjusted HR [aHR]: 2.41; 95% CI: 1.93-3.00), HF (aHR: 2.24; 95% CI: 1.95-2.56), and AF (aHR: 1.84; 95% CI: 1.49-2.28) compared to controls. The risks were further increased for those who were registered in the National Disability Registry within 1 year from the index date (SCI survivors with disability): SCI survivors with severe disability had the highest risks of MI (aHR: 3.74; 95% CI: 2.43-5.76), HF (aHR: 3.96; 95% CI: 3.05-5.14), and AF (aHR: 3.32; 95% CI: 2.18-5.05). Cervical and lumbar SCI survivors had an increased risk of heart disease regardless of disability compared to matched controls; these risks were slightly higher in those with disability. Thoracic SCI survivors with disability had significantly increased risk of heart disease compared to matched controls. CONCLUSIONS: SCI survivors at all levels were at significantly greater risk for heart disease than non-SCI controls, particularly those with severe disability. Clinicians must be aware of the importance of heart disease in SCI survivors.

Impact of clonal haematopoiesis on atherosclerotic cardiovascular disease according to low-density lipoprotein cholesterol levels in general population.

AIMS: Clonal haematopoiesis of indeterminate potential (CHIP), defined as a clonal expansion of age-related recurrent somatic mutations, has recently emerged as a novel cardiovascular risk factor. However, the precise role of CHIP in the development of atherosclerotic cardiovascular disease (ASCVD) remains unclear. METHODS AND RESULTS: Among 4300 asymptomatic Korean participants aged 40-79 years, we investigated the risk of ASCVD by CHIP and the interplay between CHIP and conventional risk factors in ASCVD development. Additionally, we assessed changes in coronary arteries based on the presence of CHIP using coronary computed tomography angiography (CCTA). CHIP was present in 363 participants (8.4%), and its prevalence increased with age. Commonly mutated genes were DNMT3A, TET2, and ASXL1, in order. During the follow-up (median 4.7 years), 18 ASCVD cases (5.0%) were observed in CHIP carriers vs. 62 (1.6%) in non-carriers (P < 0.001), indicating an elevated risk of ASCVD associated with CHIP [adjusted hazard ratio (HR) 2.49; 95% confidence interval (CI) 1.45-4.29; P < 0.001]. Notably, with high levels of LDL cholesterol, CHIP enhanced the risk of ASCVD (adjusted HR 6.20; 95% CI 3.14-12.23; P < 0.001), demonstrating synergism between CHIP and LDL cholesterol levels (S-index 4.94; 95% CI 1.08-22.53; P = 0.039). Serial CCTAs confirmed that CHIP, in conjunction with high LDL cholesterol levels, had a significant early impact on coronary arteries, revealing new measurable coronary atherosclerosis, mainly with unstable plaque, in proximal lesions. CONCLUSION: The presence of CHIP was significantly associated with the risk of ASCVD, promoting the early stage of atherosclerosis through synergy with high LDL cholesterol in the general population.

In this cohort study of 4300 asymptomatic community-dwelling Korean adults, we demonstrated a detailed interplay between clonal haematopoiesis of indeterminate potential (CHIP) and conventional risk factors in the development of atherosclerotic cardiovascular disease (ASCVD).The presence of CHIP significantly increased the risk of ASCVD in the general population, displaying a notable synergistic effect with high levels of LDL cholesterol.Analyses of serial coronary computed tomography angiography scans revealed that CHIP, in conjunction with high LDL cholesterol levels, may contribute to the promotion of 'early' stage in coronary atherosclerosis, providing new insights into CHIP-associated atherosclerosis in the primary prevention.

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.

Smoking Behavior Change and the Risk of Heart Failure in Patients With Type 2 Diabetes: Nationwide Retrospective Cohort Study.

BACKGROUND: Heart failure (HF) is one of the most common initial manifestations of cardiovascular disease in patients with type 2 diabetes. Although smoking is an independent risk factor for HF, there is a lack of data for the incidence of HF according to changes in smoking behaviors in patients with type 2 diabetes. OBJECTIVE: We aimed to examine the association between interval changes in smoking behavior and the risk of HF among patients with type 2 diabetes. METHODS: We conducted a retrospective cohort study using the National Health Insurance Service database. We identified 365,352 current smokers with type 2 diabetes who had 2 consecutive health screenings (2009-2012) and followed them until December 31, 2018, for the incident HF. Based on smoking behavior changes between 2 consecutive health screenings, participants were categorized into quitter, reducer I (≥50% reduction) and II (<50% reduction), sustainer (reference group), and increaser groups. RESULTS: During a median follow-up of 5.1 (IQR 4.0-6.1) years, there were 13,879 HF cases (7.8 per 1000 person-years). Compared to sustainers, smoking cessation was associated with lower risks of HF (adjusted hazard ratio [aHR] 0.90, 95% CI0.86-0.95), whereas increasers showed higher risks of HF than sustainers; heavy smokers who increased their level of smoking had a higher risk of HF (aHR 1.13, 95% CI 1.04-1.24). In the case of reducers, the risk of HF was not reduced but rather increased slightly (reducer I: aHR 1.14, 95% CI 1.08-1.21; reducer II: aHR 1.03, 95% CI 0.98-1.09). Consistent results were noted for subgroup analyses including type 2 diabetes severity, age, and sex. CONCLUSIONS: Smoking cessation was associated with a lower risk of HF among patients with type 2 diabetes, while increasing smoking amount was associated with a higher risk for HF than in those sustaining their smoking amount. There was no benefit from reduction in smoking amount.

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.

Clonal haematopoiesis of indeterminate potential and atrial fibrillation: an east Asian cohort study.

BACKGROUND AND AIMS: Both clonal haematopoiesis of indeterminate potential (CHIP) and atrial fibrillation (AF) are age-related conditions. This study investigated the potential role of CHIP in the development and progression of AF. METHODS: Deep-targeted sequencing of 24 CHIP mutations (a mean depth of coverage = 1000×) was performed in 1004 patients with AF and 3341 non-AF healthy subjects. Variant allele fraction ≥ 2.0% indicated the presence of CHIP mutations. The association between CHIP and AF was evaluated by the comparison of (i) the prevalence of CHIP mutations between AF and non-AF subjects and (ii) clinical characteristics discriminated by CHIP mutations within AF patients. Furthermore, the risk of clinical outcomes-the composite of heart failure, ischaemic stroke, or death-according to the presence of CHIP mutations in AF was investigated from the UK Biobank cohort. RESULTS: The mean age was 67.6 ± 6.9 vs. 58.5 ± 6.5 years in AF (paroxysmal, 39.0%; persistent, 61.0%) and non-AF cohorts, respectively. CHIP mutations with a variant allele fraction of ≥2.0% were found in 237 (23.6%) AF patients (DNMT3A, 13.5%; TET2, 6.6%; and ASXL1, 1.5%) and were more prevalent than non-AF subjects [356 (10.7%); P < .001] across the age. After multivariable adjustment (age, sex, smoking, body mass index, diabetes, and hypertension), CHIP mutations were 1.4-fold higher in AF [adjusted odds ratio (OR) 1.38; 95% confidence interval 1.10-1.74, P < .01]. The ORs of CHIP mutations were the highest in the long-standing persistent AF (adjusted OR 1.50; 95% confidence interval 1.14-1.99, P = .004) followed by persistent (adjusted OR 1.44) and paroxysmal (adjusted OR 1.33) AF. In gene-specific analyses, TET2 somatic mutation presented the highest association with AF (adjusted OR 1.65; 95% confidence interval 1.05-2.60, P = .030). AF patients with CHIP mutations were older and had a higher prevalence of diabetes, a longer AF duration, a higher E/E', and a more severely enlarged left atrium than those without CHIP mutations (all P < .05). In UK Biobank analysis of 21 286 AF subjects (1297 with CHIP and 19 989 without CHIP), the CHIP mutation in AF is associated with a 1.32-fold higher risk of a composite clinical event (heart failure, ischaemic stroke, or death). CONCLUSIONS: CHIP mutations, primarily DNMT3A or TET2, are more prevalent in patients with AF than non-AF subjects whilst their presence is associated with a more progressive nature of AF and unfavourable clinical outcomes.

J-shaped association between LDL cholesterol and cardiovascular events: A longitudinal primary prevention cohort of over 2.4 million people nationwide.

INTRODUCTION: Low-density lipoprotein (LDL) cholesterol-lowering treatment is beneficial for the secondary or primary prevention of high-risk atherosclerotic cardiovascular disease (ASCVD). However, the prognostic implications of low LDL cholesterol levels in patients without previous ASCVD and without statin use remain elusive. METHODS: From a nationwide cohort, 2,432,471 participants without previous ASCVD or statin use were included. For myocardial infarction (MI) and ischemic stroke (IS), participants were followed-up from 2009 to 2018. They were stratified according to 10-year ASCVD risk (<5 %, 5 %-<7.5 %, 7.5 %-<20 %, and ≥20 %) and LDL cholesterol level (<70, 70-99, 100-129, 130-159, 160-189, and ≥190 mg/dL). RESULTS: The relationship between LDL cholesterol levels and ASCVD events exhibited a J-shaped curve for both MI and IS. After classification according to the ASCVD risk, this J-shaped relationship was consistently observed for the composite of MI and IS. Participants with an LDL cholesterol level <70 mg/dL showed a higher MI risk than those with a level of 70-99 mg/dL or 100-129 mg/dL in the low-ASCVD risk group. The J-shaped curve between LDL cholesterol levels and MI risk was attenuated across ASCVD risk groups. For IS, participants with an LDL cholesterol level <70 mg/dL demonstrated increased risks compared with those with a level of 70-99 mg/dL, 100-129 mg/dL, or 130-159 mg/dL in the borderline, intermediate, and high ASCVD risk groups, respectively. In contrast, a linear association was observed in participants taking statins. Interestingly, a J-shaped association was observed between LDL cholesterol and high-sensitivity C-reactive protein (hs-CRP) levels; the mean hs-CRP level and the proportion of individuals with increased hs-CRP levels were relatively high among individuals with an LDL cholesterol level <70 mg/dL. CONCLUSIONS: Although high LDL cholesterol levels increase the risk of ASCVD, low LDL cholesterol levels do not warrant safety from ASCVD. Therefore, individuals with low LDL cholesterol levels should be carefully monitored.

Age-dependent association of metabolic dyslipidemia with clinical expression of hypertrophic cardiomyopathy.

BACKGROUND: Previous studies have shown that the clinical expression of hypertrophic cardiomyopathy (HCM) can be determined by obesity and metabolic syndrome. The present study aimed to investigate the association between triglyceride and high-density lipoprotein cholesterol (HDLC) level, the two dyslipidemia-related components of metabolic syndrome, and the incidence of HCM. We also explored an age-dependent association between them. METHODS: Individuals without previous HCM diagnosis who underwent a designated national health examination in 2009 were recruited. Individuals who used lipid-lowering medications within 1-year of the baseline were excluded. The outcome of interest was a newly diagnosed HCM. RESULTS: Our cohort consisted of 8,652,709 individuals (mean 46 years, 55.6% men). During the median 9.3 years of follow-up, 5932 (0.07%) individuals were newly diagnosed with HCM. There was a gradual increase in the incidence of HCM towards higher triglyceride and lower HDL-C levels (log-rank p < 0.001). When stratified by age, the incidence of HCM was highest in individuals aged ≥65 years, followed by those aged 40-64 and 20-39 years (0.22% vs. 0.07% vs. 0.03%, log-rank p < 0.001). In individuals aged 20-39 years, a higher triglyceride level was associated with a higher incidence of HCM (i.e., ≥200 vs. <100 mg/dL: adjusted hazard ratio 2.28, 95% confidence interval 1.89-2.75), whereas there was no significant association in older groups (p-for-interaction<0.001). Similarly, a lower HDL-C level was associated with a higher incidence of HCM, particularly in individuals aged 20-39 years (p-for-interaction = 0.001). CONCLUSIONS: High triglyceride and low HDL-C levels are associated with a higher incidence of HCM, particularly in young individuals.

Sacubitril/valsartan and the risk of incident dementia in heart failure: a nationwide propensity-matched cohort study.

BACKGROUND: Sacubitril acts to inhibit neprilysin and as neprilysin is involved in amyloid-beta degradation in the central nervous system, and there is concern that sacubitril/valsartan may increase the risk of dementia. We aimed to compare the risk of incident dementia associated with sacubitril/valsartan and angiotensin II receptor blockers (ARBs). METHODS: Patients with heart failure with reduced ejection fraction treated with either sacubitril/valsartan or ARB, identified from the Korean National Health Insurance Service database, were matched in a 1:2 ratio using propensity scores (6789 on sacubitril/valsartan and 13,578 on ARBs) and followed up for incident dementia. RESULTS: During a mean follow-up of 2.5 years, 526 (2.6%) patients were newly diagnosed with dementia: Alzheimer dementia in 282, vascular dementia in 8, and other dementia in 236. There was no significant difference in the risk of overall dementia (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.70-1.01), Alzheimer dementia (HR 0.85, 95% CI 0.67-1.10), vascular dementia (HR 0.98, 95% CI 0.23-4.11), and all other dementias (HR 0.81, 95% CI 0.62-1.07) between sacubitril/valsartan users and ARB users. These results were consistent regardless of initial sacubitril/valsartan dose and subgroups including old age, previous mild cognitive impairment, previous stroke, and concomitant antiplatelet or anticoagulation. Sensitivity analysis with a 1-year lag period for dementia assessment confirmed the main analysis. Meanwhile, risk of incident stroke was lower in sacubitril/valsartan users compared to ARBs users. CONCLUSIONS: In a nationwide propensity-matched cohort of patients with heart failure, sacubitril/valsartan was not associated with an increased risk of incident dementia compared to ARBs. Sacubitril/valsartan and the risk of incident dementia in heart failure. ARB, angiotensin II receptor blocker; ARNI, angiotensin receptor neprilysin inhibitor.

The effect of non-optimal lipids on the progression of coronary artery calcification in statin-naïve young adults: results from KOICA registry.

Background: Despite the importance of attaining optimal lipid levels from a young age to secure long-term cardiovascular health, the detailed impact of non-optimal lipid levels in young adults on coronary artery calcification (CAC) is not fully explored. We sought to investigate the risk of CAC progression as per lipid profiles and to demonstrate lipid optimality in young adults. Methods: From the KOrea Initiative on Coronary Artery calcification (KOICA) registry that was established in six large volume healthcare centers in Korea, 2,940 statin-naïve participants aged 20-45 years who underwent serial coronary calcium scans for routine health check-ups between 2002 and 2017 were included. The study outcome was CAC progression, which was assessed by the square root method. The risk of CAC progression was analyzed according to the lipid optimality and each lipid parameter. Results: In this retrospective cohort (mean age, 41.3 years; men 82.4%), 477 participants (16.2%) had an optimal lipid profile, defined as triglycerides <150 mg/dl, LDL cholesterol <100 mg/dl, and HDL cholesterol >60 mg/dl. During follow-up (median, 39.7 months), CAC progression was observed in 434 participants (14.8%), and more frequent in the non-optimal lipid group (16.5% vs. 5.7%; p < 0.001). Non-optimal lipids independently increased the risk of CAC progression [adjusted hazard ratio (aHR), 1.97; p = 0.025], in a dose-dependent manner. Even in relatively low-risk participants with an initial calcium score of zero (aHR, 2.13; p = 0.014), in their 20 s or 30 s (aHR 2.15; p = 0.041), and without other risk factors (aHR 1.45; p = 0.038), similar results were demonstrable. High triglycerides had the greatest impact on CAC progression in this young adult population. Conclusion: Non-optimal lipid levels were significantly associated with the risk of CAC progression in young adults, even at low-risk. Screening and intervention for non-optimal lipid levels, particularly triglycerides, from an early age might be of clinical value.

Association between office visit intervals and long-term cardiovascular risk in hypertensive patients.

Hypertension is a chronic disease that requires long-term follow-up in many patients, however, optimal visit intervals are not well-established. This study aimed to evaluate the incidences of major cardiovascular events (MACEs) according to visit intervals. We analyzed data from 9894 hypertensive patients in the Korean Hypertension Cohort, which enrolled and followed up 11,043 patients for over 10 years. Participants were classified into five groups based on their median visit intervals (MVIs) during the 4-year period and MACEs were compared among the groups. The patients were divided into clinically relevant MVIs of one (1013; 10%), two (1299; 13%), three (2732; 28%), four (2355; 24%), and six months (2515; 25%). The median follow-up period was 5 years (range: 1745 ± 293 days). The longer visit interval groups did not have an increased cumulative incidence of MACE (12.9%, 11.8%, 6.7%, 5.9%, and 4%, respectively). In the Cox proportional hazards model, those in the longer MVI group had a smaller hazard ratio (HR) for MACEs or all-cause death: 1.77 (95% confidence interval [CI], 1.45-2.17), 1.7 (95% CI: 1.41-2.05), 0.90 (95% CI: 0.74-1.09) and 0.64 (95% CI: 0.52-0.79), respectively (Reference MVI group of 75-104 days). In conclusion, a follow-up visits with a longer interval of 3-6 months was not associated with an increased risk of MACE or all-cause death in hypertensive patients. Therefore, once medication adjustment is stabilized, a longer interval of 3-6 months is reasonable, reducing medical expenses without increasing the risk of cardiovascular outcomes.

Clonal hematopoiesis as a novel risk factor for type 2 diabetes mellitus in patients with hypercholesterolemia.

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) is associated with atherosclerosis and cardiovascular disease. It has been suggested that CHIP may be related to diabetes, so we investigated the association between CHIP and new-onset type 2 diabetes. Methods: This study included 4,047 subjects aged >=40 years without diabetes. To detect CHIP, targeted gene sequencing of genomic DNA from peripheral blood cells was performed. The incidence of new-onset type 2 diabetes during the follow-up period was evaluated. Results: Of the total subjects, 635 (15.7%) had CHIP. During the median follow-up of 5.1 years, the incidence of new-onset diabetes was significantly higher in CHIP carriers than in subjects without CHIP (11.8% vs. 9.1%, p = 0.039). In a univariate analysis, CHIP significantly increased the risk of new-onset diabetes (HR 1.32, 95% CI 1.02-1.70, p = 0.034), but in a multivariate analysis, it was not significant. The CHIP-related risk of new onset diabetes differed according to LDL cholesterol level. In the hyper-LDL cholesterolemia group, CHIP significantly increased the risk of diabetes (HR 1.64, 95% CI 1.09-2.47, p = 0.018), but it did not increase the risk in the non-hyper-LDL cholesterolemia group. The subjects with CHIP and hyper-LDL-cholesterolemia had approximately twice the risk of diabetes than subjects without CHIP and with low LDL cholesterol (HR 2.05, 95% CI 1.40-3.00, p < 0.001). Conclusion: The presence of CHIP was a significant risk factor for new-onset type 2 diabetes, especially in subjects with high LDL cholesterol. These results show the synergism between CHIP and high LDL cholesterol as a high-risk factor for diabetes.

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.

Deep learning-based prediction for significant coronary artery stenosis on coronary computed tomography angiography in asymptomatic populations.

Background: Although coronary computed tomography angiography (CCTA) is currently utilized as the frontline test to accurately diagnose coronary artery disease (CAD) in clinical practice, there are still debates regarding its use as a screening tool for the asymptomatic population. Using deep learning (DL), we sought to develop a prediction model for significant coronary artery stenosis on CCTA and identify the individuals who would benefit from undergoing CCTA among apparently healthy asymptomatic adults. Methods: We retrospectively reviewed 11,180 individuals who underwent CCTA as part of routine health check-ups between 2012 and 2019. The main outcome was the presence of coronary artery stenosis of ≥70% on CCTA. We developed a prediction model using machine learning (ML), including DL. Its performance was compared with pretest probabilities, including the pooled cohort equation (PCE), CAD consortium, and updated Diamond-Forrester (UDF) scores. Results: In the cohort of 11,180 apparently healthy asymptomatic individuals (mean age 56.1 years; men 69.8%), 516 (4.6%) presented with significant coronary artery stenosis on CCTA. Among the ML methods employed, a neural network with multi-task learning (19 selected features), one of the DL methods, was selected due to its superior performance, with an area under the curve (AUC) of 0.782 and a high diagnostic accuracy of 71.6%. Our DL-based model demonstrated a better prediction than the PCE (AUC, 0.719), CAD consortium score (AUC, 0.696), and UDF score (AUC, 0.705). Age, sex, HbA1c, and HDL cholesterol were highly ranked features. Personal education and monthly income levels were also included as important features of the model. Conclusion: We successfully developed the neural network with multi-task learning for the detection of CCTA-derived stenosis of ≥70% in asymptomatic populations. Our findings suggest that this model may provide more precise indications for the use of CCTA as a screening tool to identify individuals at a higher risk, even in asymptomatic populations, in clinical practice.

The role of retinal vessel geometry as an indicator of systemic arterial stiffness assessed by cardio-ankle vascular index.

Objective: To determine whether retinal vessel geometry is associated with systemic arterial stiffness, as determined by the cardio-ankle vascular index (CAVI). Methods: This single-center retrospective cross-sectional study included 407 eyes of 407 subjects who underwent routine health exams, including CAVI and fundus photography. Retinal vessel geometry was measured using a computer-assisted program (Singapore "I" Vessel Assessment). Subjects were classified into two groups based on CAVI values: high CAVI (≥9) or low CAVI (<9). The main outcome measures included the association of retinal vessel geometry and CAVI value evaluated using multivariable logistic regression models. Results: Three hundred forty-three subjects (343, 84.3%) were in the low CAVI group, and 64 (15.7%) subjects were in the high CAVI group. Multivariable logistic linear regression analyses adjusted for age, sex, body mass index, smoking status, mean arterial pressure, and the presence of hypertension, diabetes mellitus, and dyslipidemia showed a significant association between high CAVI values and the following retinal vessel geometry parameters: central retinal arteriolar equivalent caliber (CRAE; adjusted odds ratio [AOR], 0.95; 95% confidence interval [CI], 0.89-1.00; P = 0.043), fractal dimension of arteriolar network (FDa; AOR, 4.21 × 10-4; 95% CI, 2.32 × 10-7-0.77; P = 0.042), and arteriolar branching angle (BAa; AOR, 0.96; 95% CI, 0.93-0.99; P = 0.007). Conclusions: Increased systemic arterial stiffness had a significant association with retinal vessel geometry related to arterial narrowing (CRAE), less branching complexity of the arterial tree (FDa), and acute arteriolar bifurcation (BAa).

Aspirin vs Clopidogrel for Long-term Maintenance After Coronary Stenting in Patients With Diabetes: A Post Hoc Analysis of the HOST-EXAM Trial.

Importance: Selecting the optimal antiplatelet agent in patients who have received percutaneous coronary intervention is especially important in those with diabetes due to the heightened risk of ischemic events in this population. Studies on the efficacy and safety of clopidogrel vs aspirin for long-term maintenance after percutaneous coronary intervention in patients with diabetes are lacking. Objective: To investigate cardiovascular outcomes with clopidogrel vs aspirin in patients with and without diabetes. Design, Setting, and Participants: This was a post hoc analysis of the HOST-EXAM randomized clinical trial, an investigator-initiated, prospective, randomized, open-label, multicenter trial performed at 37 centers in Korea. Patients who received dual antiplatelet therapy without clinical events for 6 to 18 months after percutaneous coronary intervention with drug-eluting stents were enrolled from March 2014 to May 2018 with follow-up at 6, 12, 18, and 24 months. All 5438 patients in the original trial were included in this analysis, which was conducted from June to October 2021. Interventions and Exposures: Enrolled patients were randomized 1:1 to clopidogrel or aspirin monotherapy. Subgroup analyses were performed by the presence of diabetes. Main Outcomes and Measures: The main outcome was primary composite end point of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and major bleeding (Bleeding Academic Research Consortium type 3 or 5) at 24-month follow-up. Results: Of 5438 patients (mean [SD] age, 63.5 [10.7] years; 1384 [25.5%] female), 1860 (34.2%) had diabetes (925 in the clopidogrel arm and 935 in the aspirin arm), and 5338 (98.2%) completed follow-up. The rate of the primary composite end point was significantly lower in the clopidogrel group compared to the aspirin group in patients with diabetes (6.3% vs 9.2%; hazard ratio [HR], 0.69; 95% CI, 0.49-0.96; P = .03; absolute risk difference [ARD], 2.7%; number needed to treat [NNT], 37) and without diabetes (5.3% vs 7.0%; HR, 0.76; 95% CI, 0.58-1.00; P = .046; ARD, 1.6%, NNT, 63; P for interaction = .65). The presence of diabetes was not associated with a difference in benefit observed with clopidogrel monotherapy over aspirin for the thrombotic composite end point (HR, 0.68; 95% CI, 0.45-1.04 for patients with diabetes vs HR, 0.68; 95% CI, 0.49-0.93 for those without; P for interaction = .99) and any bleeding with Bleeding Academic Research Consortium 2, 3, or 5 (HR, 0.65; 95% CI, 0.39-1.09 for patients with diabetes vs HR, 0.74; 95% CI, 0.48-1.13 for those without; P for interaction = .71). Conclusion and Relevance: In this study, clopidogrel monotherapy was associated with a lower rate of the primary composite end point compared to aspirin monotherapy as long-term maintenance therapy after dual antiplatelet therapy for coronary stenting in both patients with and without diabetes. Clopidogrel might thus be considered rather than aspirin in patients who have undergone coronary stenting and successfully completed dual antiplatelet therapy, regardless of diabetes status. Trial Registration: ClinicalTrials.gov Identifier: NCT02044250.

Impact of coronary artery revascularization on long-term outcome in hypertrophic cardiomyopathy patients: a nationwide population-based cohort study.

Limited data are available on the long-term outcomes in patients with hypertrophic cardiomyopathy (HCM) patients with significant coronary artery disease (CAD) requiring revascularization. We investigated the risk of cardiovascular outcomes in HCM patients who underwent coronary revascularization compared to the control group without HCM. HCM patients aged ≥ 20 years were enrolled from the Korean National Health Insurance Database. Information on the diagnosis and previous medical history was obtained from the claims data. Cardiovascular outcomes were identified during 8-year after coronary revascularization in HCM patients (HCM group) and matched controls without HCM (non-HCM control group). A total of 431 patients in the HCM group and 1968 in the non-HCM control group were analyzed. The risk of all-cause death, cardiovascular death, sudden cardiac death (SCD), ischemic stroke, and hospitalization due to heart failure was significantly higher in the HCM group than in the non-HCM group, with prominent risk increase of cardiovascular death (adjusted hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.63-3.15, P < 0.001) and ischemic stroke (adjusted HR 2.38, 95% CI 1.55-3.64, P < 0.001). Beyond 1-year after revascularization, the HCM group still had a significantly higher risk of cardiovascular death, SCD, and ventricular fibrillation/tachycardia compared to the non-HCM group. Mortality and major cardiovascular outcomes occurred more frequently in HCM patients with significant CAD requiring revascularization, compared to the matched non-HCM control group. Active and regular surveillance for concomitant risk factors and relevant intervention are warranted in HCM patients at increased risk for CAD.