BACKGROUND AND OBJECTIVES:De-differentiation and proliferation of smooth muscle cells (SMCs), triggered by pro-atherogenic factors or endothelial damage, contribute to progressive vascular remodeling. However, biomarkers reflecting the SMC phenotypic changes indicative of vulnerable plaques remain unavailable. METHODS:We characterized mRNA and protein expression of interleukin-12 receptor beta 2 subunit (IL-12Rβ2) in human aortic SMCs and human carotid arteries with atherosclerotic lesions by quantitative real-time polymerase chain reaction, immunoblotting, flow cytometry, and immunohistochemistry. Functional roles of IL-12Rβ2 were evaluated by siRNA-mediated knockdown in synthetic SMCs and a rat carotid balloon injury model. A capture enzyme-linked immunosorbent assay (ELISA) was developed to measure circulating IL-12Rβ2 levels in plasma from patients with acute coronary syndromes. RESULTS:The IL-12Rβ2 protein is about 2-fold higher in the thickened carotid arteries from patients with atherosclerosis than in normal arteries. The in vitro studies demonstrate that IL-12Rβ2 expression is induced in synthetic SMCs by interferon (IFN)-γ stimulation. The knockdown of IL-12Rβ2 significantly reduces proliferation, migration, and monocyte adhesion in synthetic SMCs and inhibits neointimal thickening in a rat carotid balloon injury model. IL-12Rβ2 is detected in SMC-derived extracellular vesicles (EVs) circulating in plasma from acute myocardial infarction (AMI) patients and is successfully quantified using a capture ELISA employing anti-PDGFRβ antibody as an SMC-specific marker. CONCLUSIONS:IL-12Rβ2, selectively induced in synthetic SMCs by IFN-γ, is released via EVs into blood in AMI patients, representing a novel biomarker to detect vulnerable atherosclerotic plaques through the newly-developed ELISA system.
BACKGROUND AND OBJECTIVES:Thermal energy-based catheter ablation techniques, including cryoballoon ablation (CBA) and radiofrequency ablation (RFA), are widely utilized for rhythm control in patients with atrial fibrillation. However, direct comparisons of CBA and RFA using real-world data are limited. This study aims to evaluate the short- and long-term outcomes of CBA and RFA. METHODS:A total of 4,868 patients who underwent procedures between January 2018 and July 2022 were selected from the Korean CBA Registry and a multicenter RFA cohort. The primary outcome was the atrial tachyarrhythmia recurrence. To reduce selection bias, 1:1 propensity score matching (PSM) was performed, yielding 1,843 patients in each group. RESULTS:After PSM, RFA demonstrated significantly lower recurrence rates compared with CBA at both 1 year (20.9% vs. 27.9%; hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.61-0.79) and 3 years (31.9% vs. 35.2%; HR, 0.72; 95% CI, 0.65-0.81). In multivariable Cox regression analysis, RFA was independently associated with lower recurrence risk, with a 30% relative risk reduction at 1 year (HR, 0.70; 95% CI, 0.61-0.80) and a 27% relative risk reduction at 3 years (HR, 0.73; 95% CI, 0.65-0.81). When cavotricuspid isthmus (CTI) ablation was performed in addition to pulmonary vein isolation (PVI), recurrence rates were comparable between RFA and CBA. CONCLUSIONS:In this large, multicenter real-world cohort, RFA consistently demonstrated more favorable short- and long-term outcomes than CBA, even after PSM and multivariable adjustment. However, outcomes were comparable when CTI ablation was additionally performed, underscoring the importance of procedural strategies beyond PVI.
BACKGROUND AND OBJECTIVES:Cognitive impairment frequently complicates heart failure (HF) and is linked to poor self-care, reduced treatment adherence, and worse clinical outcomes. Cardiac rehabilitation (CR), centered on structured exercise training, may improve cognitive function, but current evidence is inconsistent. We systematically evaluated the effects of CR on cognitive function in patients with HF. METHODS:A systematic search was conducted to identify randomized controlled trials and observational studies assessing cognitive outcomes in HF patients undergoing CR. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used and heterogeneity was assessed using the I² statistic. Prespecified and exploratory subgroup analyses were conducted to explore potential sources of heterogeneity. The primary outcome was the change in global cognitive function. RESULTS:Eleven studies involving 1,580 participants were included in the systematic review. Ten were eligible for quantitative analyses. Two pre-post CR studies (n=66) showed improved cognitive scores following CR (SMD=0.56; 95% CI, 0.21-0.91; p=0.002). In 6 CR versus non-CR studies (n=876), CR was associated with improved cognition (SMD=0.53; 95% CI, 0.09-0.97; p=0.02), with substantial heterogeneity (I²=83%). Sensitivity analyses suggested heterogeneity was influenced by methodological quality. Exploratory analyses indicated cognitive benefit was more apparent in stable chronic HF and among patients with baseline cognitive impairment. Three studies (n=190) found no significant additional benefit from beyond adjunctive therapies beyond standard CR (SMD=-0.26, 95% CI, -1.43-0.91, p=0.67). CONCLUSIONS:CR is associated with improvements in global cognitive function in patients with HF and may contribute to both physical and cognitive health in HF management.
BACKGROUND AND OBJECTIVES:The (pro)renin receptor [(P)RR] plays an important role in physiological processes through an angiotensin II (Ang-II) independent pathway. Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for atherosclerotic cardiovascular disease. Its clearance depends on binding to the low-density lipoprotein receptor (LDLR), which is regulated by proprotein convertase subtilisin/kexin type 9 (PCSK9) and sterol regulatory elements binding protein 2 (SREBP2). This study aimed to explore whether (P)RR regulates LDL-C metabolism and exacerbated atherosclerosis via an Ang-II independent pathway. METHODS:Apolipoprotein E-knockout mice were fed with a high-fat diet, treated with losartan and received prorenin injection for 8 weeks. Hep G2 cells were incubated with prorenin, small interfering RNA or plasmid for (P)RR, inhibitors of pathway in vitro. In the population study, individuals were divided into two groups based on their plasma renin activity (PRA). Clinical characteristics and LDL-C levels were collected and compared. RESULTS:The mice in the prorenin group exhibited higher liver and plasma levels of LDL-C and a larger aortic plaque area. The (P)RR upregulated the mRNA and protein expression of SREBP2 and PCSK9, while downregulating LDLR expression. Silencing (P)RR or treatment with SREBP2 and/or PCSK9 inhibitor reversed the reduction in LDLR and reduced SREBP2 and PCSK9 expression. Consistent with these findings, participants with higher PRA had significantly higher plasma LDL-C levels in the population study. CONCLUSIONS:(P)RR regulates LDL-C metabolism and promotes atherosclerosis progression via the SREBP2/PCSK9/LDLR pathway. Targeting (P)RR may represent a promising approach to counteract atherosclerosis by lowering LDL-C.
BACKGROUND AND OBJECTIVES:In South Korea and other countries operating national health insurance, claims data are used to estimate the burden of acute myocardial infarction (AMI) and stroke. However, most previous studies relied on diagnostic claim codes and did not distinguish first-ever from recurrent events. To estimate nationwide trends in the incidence and fatality of AMI and stroke using validated claims-based algorithms that distinguish first-ever from recurrent events. METHODS:We analyzed National Health Insurance Service (NHIS) claims data covering the entire Korean population from 2002 to 2023. The period from 2002-2010 served as a washout period, and annual incidence and case-fatality rates were estimated for 2011-2023. AMI (ICD-10: I21-I23) and stroke (ICD-10: I60-I61, I63-I64) events were identified from hospitalization episodes using diagnostic, procedure, imaging, and mortality codes. Crude and age-standardized rates were calculated. RESULTS:Between 2011 and 2023, AMI events increased from 22,395 to 34,768, including 1,472 to 3,373 recurrent cases. Stroke events rose from 99,837 to 113,098, including 16,925 to 22,813 recurrent cases. Crude incidence increased for AMI (44.7 to 68.0 per 100,000 person-years) and stroke (199.2 to 221.1), whereas age-standardized incidence increased slightly for AMI (35.7 to 37.1) but declined markedly for stroke (158.3 to 113.2). AMI fatality rates remained stable, whereas stroke fatality rates declined initially but rose modestly in recent years. CONCLUSIONS:By linking NHIS claims with mortality statistics and applying validated algorithms, this study demonstrates that reliable national monitoring of AMI and stroke incidence and fatality is feasible without extensive hospital-based registries or active surveillance systems.
BACKGROUND AND OBJECTIVES:The optimal P2Y12 inhibitor for patients with acute myocardial infarction and renal impairment (AMI-RI) remains unclear, particularly in East Asian populations. This study compared the real-world effectiveness and safety of initial ticagrelor versus clopidogrel therapy in Korean patients with AMI-RI. METHODS:We analyzed 7,590 patients with AMI-RI (estimated glomerular filtration rate [eGFR] <90 mL/min/1.73 m²) from a nationwide multicenter registry. Of these, 3,793 received ticagrelor and 3,797 received clopidogrel as initial P2Y12 therapy. The primary efficacy endpoint was major adverse cardiac and cerebrovascular events (MACCEs), and the primary safety endpoint was clinically significant bleeding. Propensity score matching (PSM) was performed to adjust for baseline differences. RESULTS:At 1 year, after PSM (n=1,869 per group), no significant differences were observed between ticagrelor and clopidogrel in the primary efficacy endpoint (MACCE; hazard ratio [HR], 0.810; p=0.212) or clinically significant bleeding (HR, 1.056; p=0.795). Renal function-stratified analyses showed consistent outcomes across eGFR categories, with no significant differences in MACCE after adjustment. During follow-up, a substantial proportion of patients initially treated with ticagrelor switched to clopidogrel, whereas most patients in the clopidogrel group maintained their initial therapy. CONCLUSIONS:Among Korean patients with AMI-RI, most clopidogrel users continued therapy, whereas many ticagrelor users switched during the 1-year follow-up. After propensity score adjustment, no statistically significant differences in ischemic or clinically significant bleeding outcomes were observed between the initial ticagrelor and clopidogrel strategies. These findings should be interpreted as inconclusive rather than indicative of equivalence.
Peripheral artery disease (PAD) and chronic limb-threatening ischemia (CLTI) impose an increasing global burden. Although procedural success exceeds 90%, 1-year amputation rates remain >20%, highlighting a disconnect between technical success and clinical benefit. PAD is commonly treated as a uniform atherosclerotic condition; however, distinct biological phenotypes drive heterogeneous outcomes and require individualized management. Diabetes mellitus and chronic kidney disease (CKD), present in >70% of patients with CLTI, promote divergent pathological mechanisms. Diabetes is characterized by intimal inflammation, endothelial dysfunction, and microangiopathy, whereas CKD is dominated by medial calcification due to disordered mineral metabolism, limiting the reliability of the ankle-brachial index. Diabetes-CKD coexistence, observed in 35-50% of cases, produces combined occlusive and rigid vascular features and carries a disproportionately high risk of poor wound healing, major amputation, and early mortality-a burden that current lesion-centric approaches consistently fail to adequately address. This review integrates mechanistic insights, diagnostic considerations, and clinical evidence supporting phenotype-based management. We propose a practical framework that aligns phenotype recognition with targeted strategies: endovascular intervention with metabolic optimization for diabetes-predominant PAD, calcium-modifying approaches or bypass surgery for CKD-predominant PAD, and early prognostic counseling with palliative integration for combined phenotypes. This limb-first paradigm reframes revascularization as a biologically informed intervention and provides evidence-based pathways to improve outcomes in contemporary CLTI care.
BACKGROUND AND OBJECTIVES:Limited data on the comparative efficacy and safety of potent P2Y₁₂ inhibitors versus clopidogrel in patients with acute myocardial infarction (AMI) stratified by bleeding risk. This study evaluated the differential prognostic impact of potent P2Y₁₂ inhibitors in patients with AMI by bleeding risk. METHODS:From the nationwide pooled registry of the Korea Acute Myocardial Infarction Registry, 1,144 propensity score-matched pairs with high bleeding risk (HBR) and 6,181 matched pairs with non-HBR were selected according to use of potent P2Y₁₂ inhibitors or clopidogrel. The primary efficacy outcome was 3-year major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, MI, repeat revascularization, stent thrombosis, or ischemic cerebrovascular accident. The primary safety outcome was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. RESULTS:In HBR patients, the risk of MACCE was comparable between potent P2Y₁₂ inhibitors and clopidogrel (28.1% vs. 28.9%, adjusted hazard ratio [aHR], 1.00; 95% confidence interval [CI], 0.82-1.22; p=0.996). Conversely, non-HBR patients showed significantly lower risk of MACCE with potent P2Y₁₂ inhibitors (10.3% vs. 13.3%, aHR, 0.78; 95% CI, 0.69-0.88; p<0.004; p for interaction=0.016). Potent P2Y₁₂ inhibitors were associated with higher risk of bleeding in both HBR (12.4% vs. 7.6%, aHR, 1.67; 95% CI, 1.18-2.36; p=0.004) and non-HBR patients (6.5% vs. 4.3%, aHR, 1.66; 95% CI, 1.38-1.99; p<0.001; p for interaction=0.790). CONCLUSIONS:Potent P2Y₁₂ inhibitors were associated with a lower risk of MACCE only in AMI patients with non-HBR. Regardless of underlying bleeding risk, potent P2Y₁₂ inhibitors were associated with increased bleeding risk than clopidogrel.
