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Various single‐pill combinations (SPCs) have been introduced to improve drug compliance and clinical efficacy. However, there is a lack of real‐world evidence regarding the effectiveness of these SPCs for hypertension. This study evaluated the real‐world clinical efficacy and safety of amlodipine/losartan‐based SPC therapies in patients with hypertension in a real‐world setting. A total of 15 538 patients treated with amlodipine/losartan‐based SPCs [amlodipine + losartan (AL), amlodipine + losartan + rosuvastatin (ALR), and amlodipine + losartan + chlorthalidone (ALC)] were selected from the database of three tertiary hospitals in Korea. The efficacy endpoints were target blood pressure (BP) and low‐density lipoprotein cholesterol (LDL‐C) achievement rates. Safety was evaluated based on laboratory parameters. Drug adherence was defined as the proportion of medication days covered (PDC). The target BP attainment rate was above 90% and was similar among the three groups. Although many patients in the AL and ALC groups took statins, the target LDL‐C attainment rate was significantly higher in the ALR group than in the AL and ALC groups. Safety endpoints were not significantly different among the groups, except serum uric acid level and incidence rate of new‐onset hyperuricemia, which were significantly lower in the AL and ALR groups than in the ALC group. The PDC was > 90% in all groups. In the real‐world hypertensive patients, amlodipine/losartan‐based SPC therapy demonstrated good target BP achievement rates. Especially, rosuvastatin‐combination SPC showed better target LDL‐C goal achievement rate compared to the other SPCs. All three amlodipine/losartan‐based SPC had excellent drug adherence.

Background: Metabolic syndrome (MetS) is closely associated with the aging process. However, changes in metabolic conditions and cardiac function that occur in middle aged population remain unclear. We evaluated longitudinal changes in metabolic parameters and cardiac function during a 3-year period in subjects with suspected MetS.Methods: We studied 191 participants with suspected MetS at baseline and after 3 years. Anthropometric parameters, including waist circumference (WC), and metabolic parameters, including fasting blood glucose and lipid profile were measured. Conventional echocardiography with two-dimensional speckle tracking was performed.Results: Mean age was 56.2±4.4 years, and there were 97 women (50.8%). Men had increased WC and triglycerides (TG) (WC 91.2±6.8 cm vs. 84.0±8.0 cm, P

Objective The Korean Society of Lipid and Atherosclerosis (KSoLA) has published the Dyslipidemia Fact Sheets in Korea 2020 to provide an overview of magnitude and management status of dyslipidemia and their recent trends therein. Methods The Fact Sheets were based on the analyses of Korean adults aged 20 years or older of the 2007-2018 Korea National Health and Nutrition Examination Survey (KNHANES) and the 2002-2018 National Health Insurance Big Data (NHI-BD). Results Between 2007 and 2018, the crude prevalence of hypercholesterolemia increased from 9.0% to 20.7%. During the same period, its management rate also improved yet remained unsatisfactory. In 2018, the prevalence of dyslipidemia was 45.6% in men and 31.3% in women, which increased with older age and presence of metabolic abnormalities. Indeed, the number of people diagnosed with dyslipidemia has increased nearly 8-fold from 1.5 million in 2002 to 11.6 million in 2018; alongside, the number of people receiving pharmacological treatment for dyslipidemia has also risen. Of the 7.7 million people treated for dyslipidemia in 2018, statin accounted for the majority (91.8%) of lipid-lowering drug prescriptions, followed by ezetimibe (14.6%), fibrate (8.5%), and omega-3 acid (5.9%). The most frequently used combination therapy was statin plus ezetimibe, accounting for 72% of dual therapy prescriptions. Conclusion Dyslipidemia continues to impose a substantial disease burden in Korea. Both healthcare practitioners and patients need to actively adopt guideline-recommended lifestyle modification and pharmacological treatment for comprehensive, timely, and sustained management.

Background/Aims: Useful biomarkers for metabolic syndrome have been insufficient. We investigated the performance of serum milk fat globule-EGF factor-8 (MFG-E8), the key mediator of inflammatory pathway, in diagnosis of metabolic syndrome. Methods: Subjects aged between 30 and 64 years were prospectively enrolled in the Seoul Metabolic Syndrome cohort. Serum MFG-E8 levels were measured at baseline. Results: A total of 556 subjects were included, comprising 279 women (50.2%) and 277 men (49.8%). Metabolic syndrome was diagnosed in 236 subjects (42.4%), and the mean MFG-E8 level of subjects with metabolic syndrome was significantly higher than that of subjects without metabolic syndrome (P

Although dual antiplatelet therapy is essential for patients who undergo percutaneous coronary interventions, the risk of bleeding remains an unsolved problem, and there is limited information on the potential relationship between genetic variants and major bleeding. We analyzed the correlations between four major single nucleotide polymorphisms (CYP2C19, ABCB1, PON1, and P2Y12 G52T polymorphisms) and clinical outcomes in 4489 patients from a prospective multicenter registry. The primary endpoint was major bleeding, defined as a Bleeding Academic Research Consortium ≥ 3 bleeding event. The allelic frequencies of ABCB1, PON1, and both individual and combined CYP2C19 variants did not differ significantly between patient groups with and without major bleeding. However, the allelic frequency of the P2Y12 variant differed significantly between the two groups. Focusing on the P2Y12 G52T variant, patients in the TT group had a significantly higher rate of major bleeding (6.4%; adjusted hazard ratio [HR] 2.51; 95% confidence interval [CI] 1.08–5.84; p = 0.033) than patients in the other groups (GG [2.9%] or GT [1.9%]). Therefore, the TT variant of the P2Y12 G52T polymorphism may be an independent predictor of major bleeding.Trial registration: NCT02707445 (https://clinicaltrials.gov/ct2/show/NCT02707445?term=02707445&draw=2&rank=1).

Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), neutrophil gelatinase-associated lipocalin (NGAL), and matrix metalloproteinase-9 (MMP-9) are inflammatory biomarkers involved in plaque destabilization resulting in acute coronary syndrome (ACS). This study aimed to investigate the diagnostic value of a combination of biomarkers to discriminate plaque ruptures in the setting of ACS. Eighty-five ACS patients with optical coherence tomography (OCT) images of the culprit plaque were included and categorized into two groups: ACS with plaque rupture (Rupture group, n = 42) or without plaque rupture (Non-rupture group, n = 43) verified by OCT. A discriminative model of plaque rupture using several biomarkers was developed and validated. The Rupture group had higher white blood cell (WBC) counts and peak creatine kinase-myocardial band (CK-MB) levels (13.39 vs. 2.69 ng/mL, p = 0.0016). sLOX-1 (227.9 vs. 51.7 pg/mL, p

Background: Identification of subclinical target organ damage (TOD) at early stage is important for the reduction in cardiovascular risk. This study was performed to assess the association between ...

Background The effect of chronic total occlusion (CTO) revascularization on survival remains controversial. Furthermore, data regarding outcome differences for CTO revascularization based on left ventricular systolic function (LVSF) are limited. The differential outcomes from CTO revascularization in patients with preserved LVSF (PLVSF) versus reduced LVSF (RLVSF) were assessed. Methods A total of 2,173 CTO patients were divided into either a PLVSF (n = 1661, Ejection fraction ≥ 50%) or RLVSF (n = 512, Results Patients with RLVSF had a mean 37% ejection fraction (EF) and 19% had EF p p = 0.0019], which was mainly driven by a reduction in cardiac death. The difference in survival probability was greater and became more pronounced over time in patients with RLVSF than with PLVSF (1-year, p = 0.197; 3-years, p = 0.048; 5-years, p = 0.036). Conclusions SCR was associated with better survival benefit than OMT regardless of LVSF. The benefit was greater and became more significant over time in patients with RLVSF versus PLVSF. Graphic abstract

Background Statin therapy reduces the risk of cardiovascular events across a broad spectrum of patients; however, it increases the risk of new-onset diabetes (NOD). Although the highest dose pitavastatin is considered to not be associated with NOD, there are limited data regarding the impact of long-term highest dose pitavastatin use on the development of NOD in patients at high risk of developing diabetes. Therefore, we prospectively compared the differences in the development of NOD between the lowest and the highest dose of pitavastatin in patients at high risk of developing diabetes during a 3-year follow-up. Methods This post hoc analysis of a prospective, single-blinded, randomized study compared the risk of NOD between the highest dose of pitavastatin (4 mg) and the lowest dose of pitavastatin (1 mg) over a 3-year follow-up in patients with acute coronary syndrome. Among 1044 patients of the original study, 667 patients at high risk of developing type 2 diabetes mellitus were in the subgroup analysis. The primary endpoint was a comparison of the differences in the cumulative incidence of NOD in the pitavastatin 1 mg and 4 mg groups during a 3-year follow-up. Results With propensity score matching, there were no significant differences in baseline demographic characteristics between the 2 groups. Incidence of NOD was similar between the pitavastatin 1 mg and 4 mg groups [12 of 289 patients (4.2%) and 8 of 289 patients (2.8%), respectively; p = 0.36]. In a prespecified analysis, there were no significant differences in NOD events according to sex, age, diagnosis, body mass index, glucose intolerance, or dyslipidemia. Conclusions Administration of highest-dose pitavastatin did not increase the risk of NOD in patients at high risk of developing diabetes during the 3-year follow-up. Moreover, various risk factors for NOD such as metabolic syndrome components, glucose intolerance, dyslipidemia, obesity, or hypertension did not affect the development of NOD during pitavastatin administration. Thus, the highest dose pitavastatin can be safely used in patients with metabolic syndrome who are at high risk of developing diabetes. Trial registration Clinical Trial registration information. URL: https://clinicaltrials.gov/ct2/show/NCT02545231. Unique identifier: NCT02545231

Background and aims Metabolic syndrome (MetS) is a cluster of multiple risk factors including central obesity that may lead to cardiac damage and cardiovascular events. We investigated whether visceral obesity induces cardiac structural and functional remodeling independently from central obesity and other risk factors in subjects with suspected MetS. Methods and results We studied 229 participants with suspected MetS. Visceral fat area (VFA) was measured by bioelectrical impedance analysis. Left ventricular (LV) mass index, early diastolic velocity of mitral annulus (e′), and LV global longitudinal strain (GLS) were measured by echocardiography. Subjects were categorized into high and low VFA group (VFAh and VFAl). MetS was more prevalent in the VFAh than in the VFAl (p = 0.004). The VFAh had a higher waist circumference (WC) than the VFAl (p Conclusions Visceral obesity assessed by VFA was well correlated with parameters of MetS. Visceral obesity, but not central obesity measured by WC, was independently associated with structural and functional cardiac remodeling in subjects with suspected MetS. It suggests that visceral obesity should be considered as an important risk factor for cardiac damage in dysmetabolic subjects. Trial registration NCT02077530 (date of registration: November 1, 2013).

Elderly patients treated with percutaneous coronary intervention (PCI) have a higher risk of both ischemic and bleeding complications than younger patients. However, few studies have reported how genetic information of elderly patients treated with PCI affects clinical outcomes. We investigated the impact of genetic variants on clinical outcomes in elderly patients. Correlations between single-nucleotide polymorphisms (CYP2C19 and P2Y12 receptor gene G52T polymorphism) and clinical outcomes were analyzed in 811 elderly patients (≥75 years of age) from a prospective multicenter registry. The primary endpoint was a composite of myocardial infarction and death. Secondary endpoints were an individual event of death, cardiac death, myocardial infarction, stent thrombosis, target lesion revascularization, stroke, and major bleeding (Bleeding Academic Research Consortium ≥3). Regarding CYP2C19, patients with poor metabolizers had a significantly higher risk for the primary endpoint (hazard ratio [HR] 2.43; 95% confidence interval [95% CI] 1.12-5.24; p=0.024) and secondary endpoints (death and cardiac death). Regarding P2Y12 G52T, the TT group had a significantly higher occurrence of major bleeding than the other groups (HR 3.87; 95% CI 1.41-10.68; p=0.009). In conclusion, poor metabolizers of CYP2C19 and TT groups of P2Y12 G52T may be significant predictors of poor clinical outcomes in elderly patients.

What is known and objective Pre-treatment of clopidogrel 600 mg is better than 300 mg loading for reducing periprocedural myocardial infarction (PMI). We aimed to evaluate pre-treatment methods for preventing PMI among patients undergoing conventional coronary angiography (CAG) for stable angina pectoris. Materials and methods The study analyzed 402 patients who underwent percutaneous coronary intervention (PCI) during 2010 - 2011 at three Korean hospitals. Clopidogrel-naive patients received routine maintenance therapy (75 mg/day for ≥ 5 days) and were randomly assigned to a 300-mg reload (RL) or only the maintenance dose (MD). Patients who received a loading dose (LD; 600 mg at 2 - 24 hours before the procedure) were entered into a non-randomized group. Results After excluding patients who showed an abnormal creatinine kinase myocardial band (CK-MB) level, the study included 233 patients in the LD group, 85 patients in the RL group and 84 patients in the MD group. The LD group had a significantly higher rate of PMI (LD: 21, RL: 3, MD: 0 cases; p = 0.007) and a significant increase in the mean CK-MB levels after 8 hours (p = 0.016) and 24 h (p = 0.01). However, there was no difference in PMI between the RL and MD groups. Furthermore, no significant differences between the three groups were observed in the P2Y12 reaction unit (PRU) values (p = 0.57). Albeit not significantly, the LD group had a higher rate of moderate-to-severe GUSTO bleeding within 7 days. What is new and conclusion Clopidogrel maintenance is better than 600-mg loading for preventing PMI, and the RL protocol did not further prevent PMI. .

PURPOSE: To evaluate the feasibility of coronary iodine concentration (CIC) by using spectral CT in the assessment of the outcome of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). MATERIALS AND METHODS: In total, 50 consecutive patients underwent preprocedural coronary CT angiography with spectral CT prior to their staged PCI for CTO between June 2017 and July 2018. Iodine density maps, referred to as iodine-no-water maps throughout, with spectral CT provided the CIC at proximal CTO (CTO-CIC). Depending on the outcome of PCI, all CTO lesions were divided into two groups: failed PCI and successful PCI. The receiver operating characteristic curve was used to determine the cutoff values of CTO-CIC in the assessment of the outcome of PCI for CTO. RESULTS: Of the 50 CTO lesions in 50 patients, 34 (68%) and 16 (32%) were assigned to the successful PCI and failed PCI groups, respectively. The mean CTO-CIC was significantly less in the failed PCI group than in the successful PCI group (1.3 mg/mL ± 0.9 [standard deviation] vs 5.2 mg/mL ± 2.5; P < .001). A low CTO-CIC (≤ 2.5 mg/mL) predicted failed PCI with 87% sensitivity, 79% specificity, 79% positive predictive value, and 90% negative predictive value. At multivariable analysis, the low CTO-CIC was significantly associated with the failed PCI (odds ratio, 27.0; 95% confidence interval: 4.9, 147.6; P < .0001). CONCLUSION: The CTO-CIC determined by using spectral CT may be useful in the assessment of the outcome of staged PCI for CTO. See also the commentary by Rubinshtein and Blankstein in this issue. © RSNA, 2020

Background The current guidelines recommend both repeat stenting and drug-coated balloons (DCB) for in-stent restenosis (ISR) lesions, if technically feasible. However, real-world clinical data on the interventional strategies in patients with left main bifurcation (LMB)-ISR have not been elucidated. Methods Seventy-five patients with LMB-ISR, who underwent percutaneous coronary intervention (PCI) between January 2009 and July 2015, were retrospectively reviewed for the present study (repeat drug eluting stent [DES] implantation [n = 51], DCB angioplasty [n = 24]). Results Analysis of the baseline characteristics showed that the patients in the DCB group had a lower incidence of non-ST segment elevation myocardial infarction/ST segment elevation myocardial infarction at the index PCI (8.3% vs. 25.5%; p = 0.12), higher low-density lipoprotein-cholesterol level (92.9 mg/dL vs. 81.7 mg/dL; p = 0.09), and more “stent-in-stent” lesions (25% vs. 7.8%; p = 0.07) than those in the DES group. A smaller post-procedural minimal target lesion lumen diameter was also noted in the DCB group than in the DES group (2.71 mm vs. 2.85 mm; p = 0.03). The cumulative incidence rates of major adverse cardiac events (MACEs) were similar between both groups (median follow-up duration, 868 days; MACE rate, 25% in the DCB group vs. 25.5% in the DES group; p = 0.96). The multivariate Cox regression analysis indicated that the true bifurcation of ISR was an independent risk predictor of MACEs (hazard ratio, 4.62; 95% confidence interval, 1.572–13.561; p Conclusions DES and DCB showed comparable long-term clinical results in patients with LMB-ISR lesions.

BACKGROUND AND OBJECTIVES The Sapien 3 (S3) valve has not been compared to the Sapien XT (SXT) valve in Korea. We compared procedural and clinical outcomes between the 2 devices. METHODS A total of 189 patients who underwent transcatheter aortic valve replacement (TAVR) with S3 (n=95) or SXT (n=94) valve was analyzed. The primary endpoint was cardiovascular mortality at 1 year. The median follow-up duration was 438 days. RESULTS The Society of Thoracic Surgeons score was similar between the 2 groups. The device success rate (90.4% vs. 97.9%; p=0.028) was higher in the S3 than in the SXT. The S3 showed significantly fewer cases of moderate or severe paravalvular leakage (PVL) (16.7% vs. 0.0%; p=0.001) than the SXT. However, effective orifice area (EOA) (2.07±0.61 vs. 1.70±0.49 cm²; p

Background As body fat composition and metabolism differ between men and women, we evaluated sex-related differences in the association among epicardial adipose tissue (EAT), secretome profile, and myocardial function of subjects with suspected metabolic syndrome. Methods We evaluated 277 participants (men, n = 140; 56.1 ± 4.7 years) who underwent conventional echocardiography and two-dimensional speckle tracking from the Seoul Metabolic Syndrome cohort. EAT was measured from the right ventricular free wall perpendicular to the aortic annulus at end systole. Global longitudinal strain (GLS) was obtained from 18 apical segments. Apolipoprotein A1, apolipoprotein B, adiponectin, and high-sensitivity C-reactive protein (hs-CRP) levels were measured using immunoturbidimetry assay. Results Mean age, body mass index, and hs-CRP level did not differ by sex. Waist circumference, fasting blood glucose level, and triglyceride/high-density lipoprotein cholesterol ratio were higher, and apolipoprotein AI and adiponectin levels were lower in men. No significant difference in mean EAT thickness was found (7.02 ± 1.81 vs. 7.13 ± 1.70 mm, p = 0.613). Men had a higher left ventricular (LV) mass index and lower GLS. EAT thickness was associated with hs-CRP level in men alone (ß = 0.206, p = 0.015). LV mass index (ß = 2.311, p = 0.037) and function represented by e′ (ß = − 0.279, p = 0.001) and GLS (ß = − 0.332, p Conclusions In middle-aged subjects with suspected metabolic syndrome, EAT was associated with inflammation represented by hs-CRP level, LV mass, and subclinical myocardial dysfunction only in men, suggesting that the inflammatory activity of EAT induced myocardial remodeling and dysfunction in middle-aged subjects but was attenuated in women. Trial registration NCT02077530 (date of registration: November 1, 2013)

Clopidogrel is the mainstay for antiplatelet treatment after percutaneous coronary intervention (PCI). The relationship of platelet reactivity and genetic polymorphism with clinical outcomes with newer-generation drug-eluting stents is unclear. We analysed 4,587 patients for the most powerful single-nucleotide polymorphisms (CYP2C19, CYP2C9, ABCB1, PON1, and P2Y12) related to on-treatment platelet reactivity (OPR). The optimal cut-off value of high OPR for major adverse thrombotic events was 266. CYP2C19 was significantly associated with high OPR and the number of CYP2C19*R (*2 or *3) alleles was proportional to the increased risk of high OPR. Death, myocardial infarction (MI), stroke, stent thrombosis, and bleeding events were assessed during a 1-year follow-up period. Primary endpoints were death and non-fatal MI. The cumulative 1-year incidence of death and stent thrombosis was significantly higher in patients with CYP2C19*2/*2, CYP2C19*2/*3, and CYP2C19*3/*3 (Group 3) than in patients with CYP2C19*1/*1 (Group 1). Multivariate Cox proportional hazard model showed that cardiac death risk was significantly higher in Group 3 than in Group 1 (hazard ratio 2.69, 95% confidence interval 1.154–6.263, p = 0.022). No association was reported between bleeding and OPR. Thus, CYP2C19 may exert a significant impact on the prognosis of PCI patients even in the era of newer-generation drug-eluting stents.

A novel tissue engineering strategy using 3D bio-print technology has become a promising therapeutic method for acute myocardial infarction (AMI) in an animal model. However, the application of 3D bio-printed tissue remains limited due to poor graft survival. Therefore, it is a scientific priority to enhance graft survival by precisely adjusting the 3D environment of encapsulated cells. In this study, novel transplantable 3D cardiac mesh (cMesh) tissue with a porous mesh structure was presented using human cardiomyocytes, human cardiac fibroblasts, and gelatin-methacryloyl-collagen hydrogel. Cardiomyocytes and cardiac fibroblasts were well spreaded. The cardiomyocytes were connected with a gap junction channel in bio-printed cMesh and a 3D cardiac patch with an aggregated structure. Porous cMesh demonstrated structural advantages by increased phosphorylation of mTOR, AKT, and ERK signals associated with cell survival. Transplanted cMesh in rats with AMI improved long-term graft survival, vessel formation, and stabilization, reduced fibrosis, increased left ventricle thickness, and enhanced cardiac function. Our results suggest that porous cMesh provides structural advantages and a positive therapeutic effect in an AMI animal model.

Background: Previous studies have shown conflicting results on the benefits of deferred stenting (DS) in infarct size and the incidence of microvascular obstruction in patients with ST elevation myocardial infarction (STEMI). However, effect of DS on left ventricular (LV) function was not known. We aimed to evaluate whether DS improve LV function and relevant clinical outcomes after STEMI, using follow-up data from the INNOVATION study (NCT02324348). Methods: In total, 114 patients were randomly assigned to DS group or immediate stenting (IS) group at a 1:1 ratio. LV functional remodeling indices and MACE (major adverse cardiac events: a composite of death, non-fatal MI, unplanned target vessel revascularization, or hospitalization due to heart failure) were compared between DS and IS groups. Results: Serial echocardiographic analyses were completed in 89 subjects (78%). There were no significant changes in LV volume in either group. While LV ejection fraction and wall motion score index (WMSI) improved in both groups during follow-up, the increments were not statistically different between the 2 groups (4.3 ± 8.2 vs 3.2 ± 7.1, P = .504 for ΔLV ejection fraction; –0.16 ± 0.25 vs –0.16 ± 0.25, P = .99 for ΔWMSI). However, E/e′’ was decreased and e′ was increased only in the DS group (–3.31 ± 5.60 vs –0.46 ± 3.10, P = .005 for ΔE/e′; 0.77 ± 1.71 vs –0.22 ± 1.64, P = .009 for Δe′). The incidence of major adverse cardiac events was numerically lower in the DS group than in the IS group without a statistical significance at 1-year follow-up. Conclusions: Routine DS improved LV diastolic function but not systolic function compared with IS in patients with STEMI.

Background: No large-scale study has compared the clinical and angiographic predictors of cardiovascular events in patients with left main bifurcation (LMB) and non-LMB stenting after second-generation DES implantation. Herein, we investigated differential clinical and angiographic factors for predicting outcomes in LMB versus non-LMB stenting. Methods: A total of 2648 patients with bifurcation lesions treated with second-generation DESs from the retrospective patient cohort were divided into an LMB group (n = 935) and a non-LMB group (n = 1713). The primary outcome was the 7-year incidence of target lesion failure (TLF), defined as the composite of cardiac death, myocardial infarction, and target lesion revascularization. Results: The incidence of TLF was 9.8%. Those in the LMB group were associated with a higher risk of TLF (14.2% versus 7.5%, p &lt, 0.001) than those in the non-LMB group. Regarding the LMB group, independent predictors of TLF were chronic kidney disease (CKD), reduced left ventricular ejection fraction (LVEF), and two-stenting. Regarding the non-LMB group, CKD, reduced LVEF, old age, diabetes, and small diameter of the main vessel stent were independent predictors of TLF. Conclusions: The two-stent strategy could potentially increase TLF for the LMB lesions, and achieving the maximal diameter of the main vessel stent could result in better clinical outcomes for non-LMB lesions.

Background The beneficial effects of angiotensin II type 1 receptor blockers (ARBs) on atherosclerosis have been demonstrated in numerous studies. We investigated the effects of fimasartan on reducing neointimal formation and systemic inflammation after carotid artery (CA) injury in Apolipoprotein E knockout (ApoE KO) mice. Methods ApoE KO mice were randomly allocated to Group I (without CA injury), Group II (without CA injury + Fimasartan), Group III (CA injury), and Group IV (CA injury + Fimasartan). Fimasartan was orally administered everyday starting 3 days before iatrogenic left CA injury. Results At 28 days, neointimal hyperplasia and the inflammatory cytokines including TNFα, IL-6, ICAM, and MMP-9 in the peripheral blood were significantly reduced in Groups II and IV compared to Groups I and III, respectively. All fimasartan-administered groups revealed significant increases of CD4+CD25+Foxp3+ regulatory T (Treg) cells with increased plasma levels of IL-10 and TGFβ. In addition, increased CD8+ T cells by fimasartan were correlated with reduced smooth muscle cell (SMC) proliferation in the neointima in Groups II and IV. Furthermore, the populations of Treg and CD8+ T cells in total splenocytes were increased in Groups II and IV compared to Groups I and III, respectively. The enlargement of spleens due to CA injury in the Group III was attenuated by fimasartan, as shown in the Group IV. These data indicate that fimasartan significantly reduced SMC proliferation in neointima and increased Treg cells in ApoE KO CA injury mice. Conclusions This study suggests fimasartan could be an efficient strategy for reduction of atherosclerotic progression, with a decrease in immune response and systemic inflammation. Electronic supplementary material The online version of this article (10.1186/s10020-019-0095-0) contains supplementary material, which is available to authorized users.

Administration of black raspberry (Rubus occidentalis) is known to improve vascular endothelial function in patients at a high risk for cardiovascular (CV) disease. We investigated short-term effects of black raspberry on circulating endothelial progenitor cells (EPCs) and arterial stiffness in patients with metabolic syndrome. Patients with metabolic syndrome (n = 51) were prospectively randomized into the black raspberry group (n = 26, 750 mg/day) and placebo group (n = 25) during the 12-week follow-up. Central blood pressure, augmentation index, and EPCs, such as CD34/KDR(+), CD34/CD117(+), and CD34/CD133(+), were measured at baseline and at 12-week follow-up. Radial augmentation indexes were significantly decreased in the black raspberry group compared to the placebo group (-5% ± 10% vs. 3% ± 14%, P

Objective Black raspberry (Rubus occidentalis) is known for improving vascular function. However, there has been no study evaluating its effects on 24-h systolic and diastolic blood pressure in prehypertensive patients. The aim of this study was to examine those effects. Methods Patients with prehypertension (N = 45) were prospectively randomized into a moderate-dose black raspberry group (n = 15, 1500 mg/d), a high-dose black raspberry group (n = 15, 2500 mg/d), or a placebo group (n = 15) during an 8-wk follow-up period. Raspberries were consumed in the form of a dried powder extract that was fashioned into capsules. The capsules contained 187.5 and 312.5 mg of raspberry powder, which was equivalent to 1500 and 2500 mg raspberries. Ambulatory 24-h blood pressure (BP); central BP; pulse-wave velocity; abdominal visceral fat; serum renin; angiotensin-converting enzyme; and inflammatory cytokines such as interleukin-6, tumor necrosis factor-α, C-reactive protein, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and plasminogen activator inhibitor-1 were measured at baseline and at 8-wk follow-up. Results High-dose black raspberry significantly reduced 24-h systolic blood pressure (SBP; 3.3 ± 10 mm Hg versus –6.7 ± 11.8 mm Hg; P

Aim: Although arterial stiffness has been associated with the development of atherosclerosis, the role of brachial-ankle pulse wave velocity (baPWV) for diagnosing composite coronary and carotid atherosclerosis has not been completely elucidated. Method: We enrolled 773 asymptomatic individuals who were referred from 25 public health centers in Seoul and who underwent carotid ultrasonography and coronary computed tomography. Noninvasive hemodynamic parameters, including baPWV, were also measured. Composite coronary and carotid atherosclerosis was defined as follows: 1) coronary artery calcium (CAC) score ≥ 100, 2) coronary artery stenosis (CAS) ≥ 50% of diameter stenosis, 3) carotid intima medial thickness (CIMT) ≥ 0.9 mm, or 4) presence of carotid artery plaque (CAP). Results: The incidence of composite coronary and carotid atherosclerosis was 28.2%. Coronary atherosclerosis (CAC and CAS) was significantly associated with carotid atherosclerosis (CIMT and CAP). Subjects with higher baPWV (highest quartile) had a higher prevalence of composite coronary and carotid atherosclerosis (p < .001). Although multivariate analysis failed to show baPWV as an independent predictor for composite atherosclerosis, baPWV had moderate diagnostic power to detect a subject with more than two positive subclinical atherosclerosis exams [area under the curve (AUC), 0.692]. Conclusion: baPWV was associated with the composite coronary and carotid atherosclerotic burden in a community-based asymptomatic population.

Statins are mainstay anti-lipidaemic treatments for preventing cardiovascular diseases but also known to increase coronary artery calcification (CAC). However, underlying relationship between statin and CAC is still unclear. This study explored the mediating role of five statin-related biochemical factors [i.e., low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, glucose, and high sensitivity C-reactive protein levels]. Seoul Metabolic Syndrome cohort study includes 1370 participants suspected of metabolic syndrome. For causal mediation analysis, the dataset for 2016 including 847 participants with coronary computed tomography without any missing value were analysed using the Mediation package in R software. This study identified a causal mediation mechanism of HDL-cholesterol among the five biochemical factors. It implied that statin treatment increases the HDL-cholesterol level, leading to decreasing the probability of CAC score > 0. Estimated values of interest in HDL-cholesterol mediation were (1) average causal mediation effect, -0.011 with 95% CI [-0.025, -0.003], (2) average direct effect, 0.143 with 95% CI [0.074, 0.219], and total effect, 0.132 with 95% CI [0.063, 0.209]. Its mediation effect was maintained regardless of statin intensity. Sensitivity analysis also provided a robustness of the results under potential existence of a confounder between HDL-cholesterol and CAC. This study suggests a potential causal pathway between statin and CAC (the positive association of statin on CAC) through HDL-cholesterol as an inhibitor.

Background There have been limited data on the impact of hyperuricemia on long-term clinical outcomes after percutaneous coronary intervention (PCI) for in-stent restenosis (ISR). Methods From January 2009 to July 2015, 317 patients who underwent repeat PCI for ISR were divided into two groups: patients with normal serum uric acid (UA) levels (normal UA group) and patients with higher serum UA levels (higher UA group). The higher UA group included patients with serum UA levels > 6.8 mg/dL or patients who were taking anti-hyperuricemic medication. Results During a median follow-up period of 1088 days, the cumulative incidence rates of major adverse event (MAE), including a composite of all-cause death, non-fatal myocardial infarction, and any revascularization, were similar between the two groups (higher UA 36.4% vs. normal UA 29.9%, p = 0.389, log-rank p = 0.367). Follow-up angiographic data showed similar outcomes of late lumen loss (0.8 ± 0.9 mm vs. 0.8 ± 1.1 mm, p = 0.895) and binary restenosis rate (28.1% vs. 34.7%, p = 0.622). Multivariate Cox regression analysis indicated higher levels of low-density lipoprotein cholesterol (hazard ratio [HR] 1.011, 95% confidence interval [CI] 1.003–1.019, p = 0.006) and lower left ventricular ejection fraction (HR 0.972, 95% CI 0.948–0.996, p = 0.022), but not UA levels, to be the independent risk predictors of MAE. Conclusion Hyperuricemia is not associated with poor clinical outcomes after repeat PCI for ISR lesions. Electronic supplementary material The online version of this article (10.1186/s12872-018-0840-2) contains supplementary material, which is available to authorized users.

Current ACC/AHA guidelines recommend high-dose statin therapy after coronary stenting, especially in diabetic patients; however, pitavastatin 4 mg or pitavastatin 1 mg are frequently used after coronary stenting in Asia, even in patients with acute coronary syndrome. We compared the effects of highest-dose and lowest-dose pitavastatin therapy on coronary neointimal hyperplasia at 12-month follow-up in diabetic patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) using optical coherence tomography. A total of 72 diabetic patients with NSTE-ACS were randomized to lowest-dose pitavastatin [1 mg (n = 36)] or highest-dose pitavastatin [4 mg (n = 36)] after everolimus-eluting stent implantation. The primary endpoint was to compare the normalized neointimal volume at 12-month follow-up. Normalized neointimal volume was significantly lower in the pitavastatin 4 mg group (4.00 ± 2.80 vs. 8.24 ± 2.83 mm3/mm, p

Background:Although the relationship between physical activity and arterial stiffness has been shown in healthy persons, it remains controversial in obese persons.Methods:From January 2014 to September 2014, we evaluated 795 obese subjects from 25 public health centers in Seoul, Korea. We compared physical activity and brachial-ankle pulse wave velocity (baPWV) between obese subjects with metabolic syndrome (MetS) (MO) and obese subjects without MetS (NMO).Results:The MO group had more men, higher body mass index (BMI), higher fasting glucose level, lower high-density lipoprotein-cholesterol level, and higher triglyceride level. The mean physical activity levels were similar between the 2 groups. baPWV was higher in the MO group than the NMO group. MO group showed positive correlation between baPWV and physical activity (Ptrend = 0.04). Interestingly, baPWV was significantly higher in the MO group than in the NMO group in subjects with moderate and vigorous physical activity (1403.4 cm/sec vs 1349 cm/sec [95% CI 21.4 to 87.4], P < .05). Multivariate regression analysis demonstrated that brachial-ankle pulse wave velocity was apparently associated with age, BMI, blood pressure, and glucose level.Conclusions:In a community-based population, baPWV was higher in obese MetS group compared with obese non-MetS group. Physical activity showed different association with baPWV depending on metabolic status.

This study compared adenosine-associated pleiotropic effects of the 2 P2YBoth ticagrelor and prasugrel have potent antiplatelet effects. However, only ticagrelor inhibits cellular uptake of adenosine.Using a randomized, crossover design with 10-week follow-up ticagrelor or prasugrel was administered to type 2 diabetic patients with non-ST-segment elevation acute coronary syndrome requiring stent implantation. A total of 62 patients underwent randomization in a 1:1 ratio to receive ticagrelor or prasugrel for 5 weeks followed by a direct cross over to the alternative treatment for 5 additional weeks. Brachial artery flow-mediated dilation, inflammatory markers, and number of circulating EPCs were compared.Improvement in brachial artery flow-mediated dilation was greater in the ticagrelor group (0.15 ± 0.19 mm vs. -0.03 ± 0.18 mm; p 0.001). Moreover, ticagrelor compared with prasugrel decreased interleukin 6 (-0.58 ± 0.43 pg/ml vs. -0.05 ± 0.24 pg/ml; p 0.001), tumor necrosis factor alpha (-5.62 ± 4.40 pg/ml vs. -0.42 ± 2.64 pg/ml; p 0.001), and increased adiponectin (2.31 ± 2.00 μg/ml vs. 0.08 ± 1.50 μg/ml; p 0.001) during 10-week follow-up. Other inflammatory cytokines like high-sensitivity C-reactive protein and soluble vascular cell adhesion molecule-1 were decreased in both groups. Ticagrelor compared with prasugrel significantly increased absolute numbers of circulating EPCs CD34+/KDR+ (42.5 ± 37.8 per μl vs. -28.2 ± 23.7 per μl; p 0.001), CD34+/CD117+ (51.9 ± 77.2 per μl vs. -66.3 ± 45.2 per μl; p 0.001), and CD34+/CD133+ (55.2 ± 69.2 per μl vs. -28.0 ± 34.1 per μl; p 0.001).Compared with prasugrel, ticagrelor significantly decreased inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha and increased circulating EPCs, contributing to improved arterial endothelial function in diabetic non-ST-segment elevation acute coronary syndrome patients. Thus, data support that pleiotropic effects of ticagrelor beyond its potent antiplatelet effects could contribute to additional clinical benefits. (Comparison of Ticagrelor vs. Prasugrel on Inflammation, Arterial Stiffness, Endothelial Function, and Circulating Endothelial Progenitor Cells in Diabetic Patients With Non-ST Elevation Acute Coronary Syndrome [NSTE-ACS] Requiring Coronary Stenting; NCT02487732).

Background Arterial stiffness has been suggested as a valuable predictor of coronary artery stenosis (CAS). However, little data are available on aortic stiffness and CAS in patients who have previously undergone percutaneous coronary artery intervention (PCI). The aim of this study was to investigate the association of arterial stiffness to CAS in patients with a history of PCI and those without a history of PCI. Methods We retrospectively studied 1093 consecutive patients who had undergone coronary angiography (CAG). Arterial stiffness was determined by brachial-ankle pulse wave velocity (baPWV) measured prior to CAG. Results In patients without a history of PCI, baPWV significantly increased in patients with CAS compared to that in patients without CAS (p

Background Although it has been demonstrated that visceral adipose tissue content and serum levels of adiponectin are associated with metabolic syndrome, their predictive potential for the development of metabolic syndrome remains to be elucidated. Methods We studied 1,130 participants of the Seoul Metabolic Syndrome cohort. A total of 337 subjects without metabolic syndrome underwent the follow-up evaluation and finally analyzed. Visceral fat area (VFA) was measured using dual bioelectrical impedance analysis. We compared the 1-year incidence rate of metabolic syndrome among four different groups: Group 1 (high adiponectin level and low VFA), Group 2 (low adiponectin level and low VFA), Group 3 (high adiponectin level and high VFA) and Group 4 (low adiponectin level and high VFA). Results Median follow-up duration was 17 months. Cut-off points of adiponectin level and VFA for metabolic syndrome were 7.34 ng/ml and 84 cm2 for men, and 12.55 and 58 cm2 ng/ml for women, respectively. The incidence of metabolic syndrome was the highest in Group 4 (Group 1; 16.47%, Group 2; 22.08%, Group 3; 25%, and Group 4; 46.15%, p

Black raspberry (Rubus occidentalis) has been known for its anti-inflammatory and anti-oxidant effects. However, short-term effects of black raspberry on lipid profiles and vascular endothelial function have not been investigated in patients with metabolic syndrome. Patients with metabolic syndrome (n = 77) were prospectively randomized into a group with black raspberry (n = 39, 750 mg/day) and a placebo group (n = 38) during a 12-week follow-up. Lipid profiles, brachial artery flow-mediated dilatation (baFMD), and inflammatory cytokines such as IL-6, TNF-α, C-reactive protein, adiponectin, sICAM-1, and sVCAM-1 were measured at the baseline and at the 12-week follow-up. Decreases from the baseline in the total cholesterol level (-22.8 ± 30.4 mg/dL vs. -1.9 ± 31.8 mg/dL, p

Background— The aim of this study was to assess whether deferred stenting (DS) reduces infarct size and microvascular obstruction (MVO) compared with immediate stenting (IS) in primary percutaneous coronary intervention for ST-segment–elevation myocardial infarction. Methods and Results— From February 2013 to August 2015, 114 patients (mean age: 69 years) were randomized into the following 2 groups: DS with an intention to stent 3 to 7 days later or IS after primary reperfusion in 2 centers. The primary and secondary end points were infarct size and the incidence of MVO, respectively, assessed by cardiac magnetic resonance imaging at 30 days after primary reperfusion. The median time to the second procedure in the DS was 72.8 hours. Six patients in the DS group were crossed over to the IS group because of progression of dissection or safety concerns after randomization. In the intention-to-treat analysis, DS did not significantly reduce infarct size (15.0% versus 19.4%; P =0.112) and the incidence of MVO (42.6% versus 57.4%; P =0.196), compared with IS. However, in anterior wall myocardial infarction, infarct size (16.1% versus 22.7%; P =0.017) and the incidence of MVO (43.8% versus 70.3%; P =0.047) were significantly reduced in the DS group. There was no urgent revascularization event during deferral period. Conclusions— A routine DS did not significantly reduce infarct size and MVO compared with IS, although it was safe. The beneficial effect of DS in patients with anterior myocardial infarction should be confirmed by larger randomized studies. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02324348.

Adipose-derived stem cell (ADSC) transplantation has been proposed to improve cardiac function and acute myocardial infarction (AMI). Recently, cell sheet technology has been investigated for its potential applicability in cardiac injury. However, a detailed comparison of the functional recovery in the injured myocardium between cell sheets and conventional cell injection has not been adequately examined. ADSCs were isolated from the inguinal fat tissue of ICR mice. Three groups of AMI induction only (sham), intramyocardial injection of ADSCs (imADSC), and ADSC sheet transplantation (shADSC) were compared by using rat AMI models. Engraftment of ADSCs was better sustained through 28 days in the shADSC group compared with the imADSC group. Ejection fraction was improved in both imADSC and shADSC groups compared with the sham group. Ventricular wall thickness in the infarct zone was higher in the shADSC group compared with both imADSC and sham groups. Growth factor and cytokine expression in the implanted heart tissue were higher in the shADSC group compared with both imADSC and sham groups. Furthermore, only the shADSC group showed donor-derived vessels at the peri-infarct zone. Taken together, these results indicate that, although shADSC resulted in a similar improvement in left ventricular systolic function, it significantly promoted cellular engraftment and upregulated growth factor and cytokine expression, and, ultimately, attenuated adverse cardiac remodeling in rat AMI models compared with imADSC.

BACKGROUND The optimal antithrombotic regimen in patients with atrial fibrillation (AF) undergoing drug-eluting stent (DES) implantation for complex coronary artery disease is unclear. We compared the net clinical outcomes of triple antithrombotic therapy (TAT; aspirin, thienopyridine, and warfarin) and dual antiplatelet therapy (DAPT; aspirin and thienopyridine) in AF patients who had undergone DES implantation. METHODS A total of 367 patients were enrolled and analyzed retrospectively; 131 patients (35.7%) received TAT and 236 patients (64.3%) received DAPT. DAPT and warfarin were maintained for a minimum of 12 and 24 months, respectively. The primary endpoint was the 2-year net clinical outcomes, a composite of major bleeding and major adverse cardiac and cerebral events (MACCE). Propensity score-matching analysis was carried out in 99 patient pairs. RESULTS The 2-year net clinical outcomes of the TAT group were worse than those of the DAPT group (34.3 vs. 21.1%, P=0.006), which was mainly due to the higher incidence of major bleeding (16.7 vs. 4.6%, P

BACKGROUND Aberrant expression of microRNAs is associated with neointimal hyperplasia (NIH) in type 2 diabetes. We prospectively compared the effects of pioglitazone on coronary NIH and changes in microRNAs according to NIH status in type 2 diabetic patients during 9-month follow-up. METHODS AND RESULTS Type 2 diabetic patients were randomly assigned to the pioglitazone (n=36) or control groups (n=36) after coronary stenting. Primary endpoint was the comparison of changes in neointimal volume on OCT and in the level of circulating microRNA-17,-24,-92a,-126 and -145 during 9-month follow-up. Secondary endpoint was the comparison of changes in brachial artery flow-mediated dilation and inflammatory markers such as IL-6, TNF-α, hsCRP, adiponectin, sICAM-1, and sVCAM-1 between the 2 groups. Neointimal volume was significantly lower in the pioglitazone group (25.02±17.78 mm(3)vs. 55.10±30.01 mm(3), P

Revascularization of chronic total occlusion in coronary artery is known to be associated with symptomatic improvement and long-term survival benefit. However, there has been a paucity of data about survival benefit of revascularization of chronic total occlusion in coronary artery according to

Over the past decade, stem cell therapy has been extensively studied for clinical application for heart diseases. Among various stem cells, adipose tissue-derived stem cell (ADSC) is still an attractive stem cell resource due to its abundance and easy accessibility. In vitro studies showed the multipotent differentiation potentials of ADSC, even differentiation into cardiomyocytes. Many pre-clinical animal studies have also demonstrated promising therapeutic results of ADSC. Furthermore, there were several clinical trials showing the positive results in acute myocardial infarction using ADSC. The present article covers the brief introduction, the suggested therapeutic mechanisms, application methods including cell dose and delivery, and human clinical trials of ADSC for myocardial regeneration.

Although both ticagrelor and prasugrel have shown potent anti-platelet effects, only ticagrelor inhibits cellular uptake of adenosine. We therefore compared adenosine associated pleiotropic effects such as systemic inflammation, vascular function, and circulating endothelial progenitor cells between

Intramyocardial injection of adipose-derived stem cells (ASC) with other cell types in acute myocardial infarction (AMI) animal models has consistently shown promising clinical regenerative capacities. We investigated the effects of intramyocardial injections of mouse ASC (mASC) with mouse endothelial cells (mEC) on left ventricular function and generation of pericardial fat in AMI rats. AMI rat models were created by ligating left anterior descending coronary artery and were randomly assigned into four groups: control (n = 10), mASC (n = 10), mEC (n = 10) and mASC+mEC (n = 10) via direct intramyocardial injections, and each rat received 1x10(6) cells around three peri-infarct areas. Echocardiography and cardiac positron emission tomography (PET) were compared at baseline and on 28 days after AMI. Changes in left ventricular ejection fraction measured by PET, increased significantly in mASC and mASC+mEC groups compared to mEC and control groups. Furthermore, significant decreases in fibrosis were confirmed after sacrifice on 28 days in mASC and mASC + mEC groups. Successful cell engraftment was confirmed by positive Y-Chromosome staining in the transplantation region. Pericardial fat increased significantly in mASC and mASC+mEC groups compared to control group, and pericardial fat was shown to originate from the AMI rat. mASC group expressed higher adiponectin and lower leptin levels in plasma than control group. In addition, pericardial fat from AMI rats demonstrated increased phospho-AMPK levels and reduced phospho-ACC levels. Intramyocardial mASC transplantation after AMI in rats increased pericardial fat, which might play a protective role in the recovery of myocardial function after ischemic myocardial damage.