Iron Deficiency in Korean Patients With Heart Failure.

BACKGROUND: Although iron deficiency (ID) is an important and treatable risk factor for heart failure (HF), data on ID are scarce in Asian patients with HF. Therefore, we sought to determine the prevalence and clinical characteristics of ID in hospitalized Korean patients with HF. METHODS: In this prospective, multicenter cohort study, 461 patients with acute HF seen at five tertiary centers from January to November 2019 in Korea were enrolled. ID was defined as serum ferritin < 100 µg/L or ferritin 100-299 µg/L in combination with transferrin saturation < 20%. RESULTS: The patients' mean age was 67.6 ± 14.9 years, and 61.8% were male. Among total 461 patients, ID was present in 248 patients (53.8%). The prevalence of ID was significantly higher in women than in men (65.3% vs. 47.3%, P < 0.001). In a multivariable logistic regression analysis, the independent predictors of ID were female sex (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.47-3.30), valvular heart disease (OR, 2.10; 95% CI, 1.10-4.17), higher heart rate (OR, 1.10; 95% CI, 1.01-1.21), anemia (OR, 1.60; 95% CI, 1.07-2.40), and the use of clopidogrel (OR, 1.56; 95% CI, 1.00-2.45). Among women, the prevalence of ID did not significantly differ between younger and older women (< 65 years: 73.7% vs. ≥ 65 years: 63.0%, P = 0.222), those with low and high body mass index (BMI < 25 kg/m²: 66.2% vs. BMI ≥ 25 kg/m²: 69.6%, P = 0.703), or those with low and high natriuretic peptide (NP) levels (NP < median: 69.8% vs. NP ≥ median: 61.1%, P = 0.295). Only 0.2% patients with acute HF received intravenous iron supplementation in Korea. CONCLUSION: The prevalence of ID is high in hospitalized Korean patients with HF. Because ID cannot be diagnosed by clinical parameters, routine laboratory examinations are necessary to identify patients with ID. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04812873.

Neutrophil-to-lymphocyte ratio as a predictor of in-hospital complications and overall mortality in Takotsubo syndrome preceded by physical triggers.

BACKGROUND: Takotsubo syndrome (TTS) with physical triggers has worse short- and long-term clinical courses than those with emotional triggers. However, predictive factors associated with poor outcomes of TTS with physical triggers are unknown. METHODS: We included 231 patients identified as TTS preceded by physical triggers at two tertiary referral hospitals from 2010 to 2019. In-hospital complications (IHC)-a composite of malignant arrhythmia, need for mechanical circulatory support or mechanical ventilation, and in-hospital death-and overall mortality were retrospectively reviewed. The associations with clinical features were evaluated by multivariable logistic and Cox regression analyses. RESULTS: The mean age was 69.3 ± 11.6 years, and 85 (36.8%) were male. The in-hospital complications rate was 46.8%. During a median follow-up of 883 days, 96 (41.6%) had died, and overall mortality was 13.6% per patient-year. Higher neutrophil-to-lymphocyte ratio (NLR) was associated with a higher risk of IHC (area under the receiver operating characteristic curve = 0.73; positive and negative predictive value = 60.9% and 67.2% for NLR ≤ 12); odds ratio (OR) with 95% confidence interval (CI) was 1.03 (1.01-1.05), p = 0.010. Subsequently, higher NLR was also related to a greater risk of overall mortality; patients with high NLR (NLR > 12) exhibited poor long-term survival than those with low NLR (NLR ≤ 5): hazard ratio (95% CI), 3.70 (1.72-7.94) with p < 0.001. CONCLUSIONS: A high NLR at initial presentation is associated with an increased risk of IHC and overall mortality in TTS preceded by physical triggers. Given that the treatment of TTS is mainly supportive, intensive monitoring with careful follow-up would be warranted in patients with high NLR.

Mortality Prediction in Patients With or Without Heart Failure Using a Machine Learning Model.

Background: Most risk prediction models are confined to specific medical conditions, thus limiting their application to general medical populations. Objectives: The MARKER-HF (Machine learning Assessment of RisK and EaRly mortality in Heart Failure) risk model was developed in heart failure (HF) patients. We assessed the ability of MARKER-HF to predict 1-year mortality in a large community-based hospital registry database including patients with and without HF. Methods: This study included 41,749 consecutive patients who underwent echocardiography in a tertiary referral hospital (4,640 patients with and 37,109 without HF). Patients without HF were further subdivided into those with (n = 22,946) and without cardiovascular disease (n = 14,163) and also into cohorts based on recent acute coronary syndrome or history of atrial fibrillation, chronic obstructive pulmonary disease, chronic kidney disease, diabetes mellitus, hypertension, or malignancy. Results: The median age of the 41,749 patients was 65 years, and 56.2% were male. The receiver operated area under the curves for MARKER-HF prediction of 1-year mortality of patients with HF was 0.729 (95% CI: 0.706-0.752) and for patients without HF was 0.770 (95% CI: 0.760-0.780). MARKER-HF prediction of mortality was consistent across subgroups with and without cardiovascular disease and in patients diagnosed with acute coronary syndrome, atrial fibrillation, chronic obstructive pulmonary disease, chronic kidney disease, diabetes mellitus, or hypertension. Patients with malignancy demonstrated higher mortality at a given MARKER-HF score than did patients in the other groups. Conclusions: MARKER-HF predicts mortality for patients with HF as well as for patients suffering from a variety of diseases.

Body Mass Index, Muscle Mass, and All-Cause Mortality in Patients With Acute Heart Failure: The Obesity Paradox Revisited.

Background and Objectives: Lower body mass index (BMI) is considered a poor prognostic factor in patients with heart failure (HF). We aimed to investigate the clinical impact of BMI on the risk of mortality in patients with acute HF (AHF) across various phenotypes. Methods: We retrospectively identified 4,146 registry patients with AHF and BMI data. The study population was categorized according to the WHO Asia-Pacific BMI classification: BMI <18.5 kg/m2 (underweight; n=418), BMI 18.5-23 kg/m2 (ideal; n=1,620), BMI 23-25 kg/m2 (overweight; n=828), BMI 25-30 kg/m2 (obesity I; n=1,047), and BMI ≥30 kg/m2 (obesity II; n=233). The risk of all-cause mortality was compared between these 5 groups. Results: During a median follow-up of 32 months, 1,732 patients (41.8%) died. Compared to patients with obesity II, those with overweight, ideal BMI or underweight status had a higher risk of mortality (overweight: hazard ratio [HR], 1.606; 95% confidence interval [CI], 1.016-2.539; p=0.042) (ideal BMI: HR, 1.744; 95% CI, 1.112-2.734; p=0.015) (underweight: HR, 2.729; 95% CI, 1.686-4.417; p<0.001). Higher risk of mortality among patients with lower BMI was observed regardless of age, sex, hypertension, diabetes, ischemic heart disease, atrial fibrillation, and HF phenotype. Furthermore, low muscle index (total muscle mass/height2), calculated using serum cystatin C data in a subset of 579 patients, was associated with higher mortality risk. Conclusions: A lower BMI is associated with a higher risk of mortality in patients with AHF. This obesity paradox is observed in AHF regardless of comorbidities and HF phenotype.

Lifestyle Modification in the Management of Metabolic Syndrome: Statement From Korean Society of CardioMetabolic Syndrome (KSCMS).

With the recent rapid increase in obesity worldwide, metabolic syndrome (MetS) has gained significant importance. MetS is a cluster of obesity-related cardiovascular risk factors including abdominal obesity, atherogenic dyslipidemia, high blood pressure and impaired glucose tolerance. MetS is highly prevalent and strongly associated with an increased risk of developing diabetes and cardiovascular disease, putting a great burden on human society. Therefore, it is very important to reduce MetS risk, which can improve patients' cardiovascular prognosis. The primary and most effective strategy to control each component of MetS is lifestyle change such as losing body weight, keeping regular exercise, adopting a healthy diet, quitting smoking and alcohol drinking in moderation. Many studies have shown that lifestyle modification has improved all components of MetS, and reduces the incidence of diabetes and cardiovascular disease. Here, the Korean Society of CardioMetabolic Syndrome has summarized specific and practical methods of lifestyle modification in the management of MetS in the healthcare field.

Left Atrial Strain as a Predictor of New-Onset Atrial Fibrillation in Patients With Heart Failure.

OBJECTIVES: This study sought to identify whether left atrial strain can predict new-onset atrial fibrillation (NOAF) in patients with heart failure (HF) and sinus rhythm. BACKGROUND: Both HF and atrial fibrillation have common risk factors, and HF is a risk factor for the development of atrial fibrillation and vice versa. METHODS: Among 4,312 consecutive patients with acute HF from 3 tertiary hospitals, 2,461 patients with sinus rhythm and peak atrial longitudinal strain (PALS) were included in the study. Reduced PALS was defined as PALS ≤18%, and the primary endpoint was 5-year NOAF. RESULTS: During a 5-year follow-up, 397 (16.1%) patients developed NOAF. Patients with reduced PALS had higher NOAF than their counterparts (18.2% vs. 12.7%; p < 0.001). After adjustment for significant covariates, we identified 6 independent predictors of NOAF, including age >70 years (hazard ratio [HR]: 1.50; 95% confidence interval [CI]: 1.12 to 2.00), hypertension (HR: 1.45; 95% CI: 1.10 to 1.91), left atrial volume index ≥40 ml/m2 (HR: 2.03; 95% CI: 1.48 to 2.77), PALS <18% (HR: 1.60; 95% CI: 1.18 to 2.17), HF with preserved ejection fraction (HR: 1.47; 95% CI: 1.11 to 1.95), and no beta-blocker prescription at discharge (HR: 1.48; 95% CI: 1.14 to 1.92). A weighted score based on these variables was used to create a composite score, HAS-BAP (H = hypertension; A = age; S = PALS; B = no beta-blocker prescription at discharge; A = atrial volume index; P = HF with preserved ejection fraction [range 0 to 6] with a median of 3 [interquartile range: 2 to 4]). The probability of NOAF increased with HAS-BAP score. CONCLUSIONS: In patients with HF and sinus rhythm, 16.1% developed NOAF, and PALS could be used to predict the risk for NOAF. The HAS-BAP score allows determination of the risk of NOAF. (Strain for Risk Assessment and Therapeutic Strategies in Patients With Acute Heart Failure [STRATS-AHF] Registry; NCT03513653).

Association of Plasma Marker of Oxidized Lipid with Histologic Plaque Instability in Patients with Peripheral Artery Disease.

BACKGROUND: The association between oxidized low-density lipoprotein (OxLDL) and plaque instability in coronary and carotid artery disease is well established. However, the association between OxLDL and the histologic changes of plaque in peripheral artery disease has not been clearly elucidated. This study aims to investigate the association between plasma OxLDL and histologic plaque instability in patients with peripheral artery disease. METHODS: Prospectively obtained plaques from 48 patients who underwent endovascular atherectomy (n = 20), surgical endarterectomy (n = 9), or bypass surgery (n = 19) for treatment of atherosclerotic femoropopliteal artery disease were evaluated for histologic fibrosis, sclerosis, calcification, necrosis, cholesterol cleft, and foamy macrophages using hematoxylin and eosin, oil red O, and immunohistochemical staining. Unstable plaques were defined as plaques that were positive for foamy macrophages and with lipid content of more than 10% of the total plaque area. Plasma OxLDL levels were measured using an enzyme-linked immunosorbent assay (Mercodia AB, Uppsala, Sweden). RESULTS: Of the 48 patients, 26 (54%) had unstable plaques. The unstable plaque group was younger, had fewer angiographic total occlusions, less calcification, and more CD68-positive and LOX-1-positive cells than the stable plaque group. Plasma OxLDL levels were significantly higher in the unstable plaque group than in the stable plaque group (57.4 ± 13.9 vs. 47.2 ± 13.6 U/L, P = 0.014). Multivariate analysis revealed that plasma OxLDL level, smoking, angiographic nontotal occlusion, and statin nonuse were independent predictors of unstable plaque. CONCLUSIONS: Among patients with peripheral artery disease, the histologic instability of femoropopliteal plaque was independently associated with high plasma OxLDL, smoking, nontotal occlusion, and statin nonuse. Further large-scale studies are necessary to evaluate the role of noninvasive OxLDL measurement for predicting plaque instability and future adverse vascular event.

Differential impact of smoking on cardiac or non-cardiac death according to age.

Tobacco smoking causes cardiovascular diseases, lung disease, and various cancers. Understanding the population-based characteristics associated with smoking and the cause of death is important to improve survival. This study sought to evaluate the differential impact of smoking on cardiac or non-cardiac death according to age. Data from 514,866 healthy adults who underwent national health screening in South Korea were analyzed. The participants were divided into three groups: never-smoker, ex-smoker or current smoker according to the smoking status. The incidence rates and hazard ratios (HRs) of cardiac or non-cardiac deaths according to smoking status and age groups during the 10-year follow-up were calculated to evaluate the differential risk of smoking. Over the follow-up period, 6,192 and 24,443 cardiac and non-cardiac deaths had occurred, respectively. The estimated incidence rate of cardiac and non-cardiac death gradually increased in older age groups and was higher in current smokers and ex-smokers than that in never-smokers among all age groups. After adjustment of covariates, the HRs for cardiac death of current smokers compared to never-smokers were the highest in individuals in their 40's (1.82; 95% CI, 1.45-2.28); this gradually decreased to 0.96 (95% CI, 0.67-1.38) in individuals >80 years. In contrast, the HRs for non-cardiac death peaked in individuals in their 50's, (HR 1.69, 95% CI 1.57-1.82) and was sustained in those >80 years (HR 1.40, 95% CI 1.17-1.69). Ex-smokers did not show elevated risk of cardiac death compared to never-smokers in any age group, whereas they showed significantly higher risk of non-cardiac death in their 60's and 70's (HR, 1.29; 95% CI, 1.19-1.39; HR 1.22, 95% CI, 1.12-1.32, respectively). Acute myocardial infarction and lung cancer showed patterns similar to those of cardiac and non-cardiac death, respectively. Smoking was associated with higher relative risk of cardiac death in the middle-aged group and non-cardiac death in the older age group. Ex-smokers in the older age group had elevated risk of non-cardiac death. To prevent early cardiac death and late non-cardiac death, smoking cessation should be emphasized as early as possible.

Fimasartan for Remodeling after Myocardial Infarction.

An angiotensin receptor blocker (ARB) mitigates cardiac remodeling after myocardial infarction (MI). Here, we investigated the effect of fimasartan, a new ARB, on cardiac remodeling after MI. Sprague⁻Dawley rats were assigned into 3 groups: surgery only (sham group, n = 7), MI without (MI-only group, n = 13), and MI with fimasartan treatment (MI + Fima group, n = 16). MI was induced by the permanent ligation of the left anterior descending artery. Treatment with fimasartan (10 mg/kg) was initiated 24 h after MI and continued for 7 weeks. Rats in the MI + Fima group had a higher mean ejection fraction (66.3 ± 12.5% vs. 51.3 ± 14.8%, P = 0.002) and lower left ventricular end-diastolic diameter (9.14 ± 1.11 mm vs. 9.91 ± 1.43 mm, P = 0.045) than those in the MI-only group at 7 weeks after MI. The infarct size was lower in the MI + Fima than in the MI group (P < 0.05). A microarray analysis revealed that the expression of genes related to the lipid metabolism and mitochondrial membrane ion transporters were upregulated, and those involved in fibrosis and inflammation were downregulated by fimasartan. Fimasartan attenuates cardiac remodeling and dysfunction in rats after MI and may prevent the progression to heart failure after MI.

Clinical and Computed Tomography Angiographic Predictors of Coronary Lesions That Later Progressed to Chronic Total Occlusion.

OBJECTIVES: This study aimed to investigate clinical and coronary computed tomographic angiography (CTA) characteristics of lesions that progressed to chronic total occlusion (CTO). BACKGROUND: CTO is one of the most common reasons for referral to coronary artery bypass surgery. Prediction and adequate early management for future CTO lesions may be beneficial. METHODS: The study evaluated patients with at least 1 vessel with a diameter stenosis of ≥70% on invasive coronary angiography (ICA) who underwent previous coronary CTA >12 months before ICA, from 2006 to 2015. The study compared the baseline clinical and coronary CTA characteristics of the patients with future CTO lesions with those of the patients with future non-CTO lesions (patient-level analysis) and compared coronary CTA findings between the future CTO lesion with the most stenotic non-CTO lesion in each CTO patient (lesion-level analysis). RESULTS: Among the 216 patients, 32 (14.8%) had a CTO lesion on ICA. In patient-level analysis, no significant differences in clinical characteristics were found, whereas the coronary CTA culprit lesions of the CTO group had a smaller minimal lumen diameter (MLD) with more adverse plaque characteristics. In lesion-level analysis, future CTO lesions had a smaller MLD, a smaller reference segment diameter (RD), and longer lesion length. These lesions were more likely to be noncalcified plaques with a noneccentric cross-sectional distribution, and had a higher remodeling index, lower mean plaque attenuation (MPA), and more napkin-ring signs. In multivariate analysis and receiver-operating characteristic curve analysis, MLD of <2.0 mm, RD of <3.2 mm, and MPA of <50 Hounsfield units were independent predictors of future CTO lesions. The risk of CTO development in lesions with triple risk factors was 14-fold higher than that of the lesions with no risk factors. CONCLUSIONS: Lesions that progressed to CTO had more severe baseline coronary CTA features than non-CTO lesions. A small MLD, small RD, and low MPA were independent predictors of progression to CTO.

Effect of tailored use of tirofiban in patients with Non-ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention: a randomized controlled trial.

BACKGROUND: We conducted a randomized controlled trial to investigate whether an additional platelet inhibition with tirofiban would reduce the extent of myocardial damage and prevent periprocedural myonecrosis in patients with Non-ST-elevation acute coronary syndrome (NSTE-ACS) with a high residual platelet activity (HPR). METHODS: Patients with an HPR, defined as P2Y12 reaction unit (PRU) > 230, were randomly assigned to group A (tirofiban treatment, n = 30) or C1 (n = 30) and patients without an HPR to C2 (n = 78). Periprocedural myocardial damage was assessed using the area under the curve (AUC) of serial cardiac enzyme levels from the time of the procedure to post-36 h. Periprocedural myonecrosis incidence was evaluated. RESULTS: The troponin I AUC was not different between the groups (197.2 [41.5395.7], 37.9 [8.9313.9], 121.3 [43.7481.8] h∙ng/mL; p = 0.088). The results did not change when the baseline levels were adjusted (365.3 [279.5, 451.1], 293.0 [207.1, 379.0], and 298.0 [244.7, 351.3] h∙ng/mL; p = 0.487). The rate of periprocedural myonecrosis was also not different between the groups (53.0% vs. 50.0% vs. 33.3%, p = 0.092). The CK-MB isoenzyme analysis showed similar results. No difference in complications was noted. CONCLUSION: Additional tirofiban administration was not beneficial to patients with NSTE-ACS even with an HPR. TRIAL REGISTRATION: Clinical trial no. NCT03114995 , registered 11 April, 2017, retrospectively.

Need for Systematic Efforts to Modify Health-Related Behaviors After Acute Myocardial Infarction in Korea.

BACKGROUND: Modification of health-related behaviors may improve clinical outcomes after acute myocardial infarction (AMI), but the need for systematic efforts to modify such behaviors and the estimated effect have not been investigated, especially in Asian populations. The aim of the study was to investigate changes in smoking and physical activity after AMI and their associations with death and recurrent revascularization. Methods and Results: Using the Korean National Insurance Health Service database, we included 13,452 patients with AMI in 2011, who were stable until 1.5 years on average after onset. Patients were grouped according to their smoking status and physical activity before and after AMI. After AMI, 44.6% of smokers continued smoking and only 11.0% of inactive patients increased their physical activity to a sufficient level. The 'smoker/smoker' group and 'non-smoker/smoker' group showed higher mortality (hazard ratio (HR): 1.566, 95% confidence interval (CI): 1.192-2.035; HR: 1.785, 95% CI: 1.061-2.815, respectively). On the other hand, the 'active/active' group and 'inactive/active' group showed less mortality (HR: 0.625, 95% CI: 0.460-0.832; HR: 0.681, 95% CI: 0.438-1.009, respectively) and the 'inactive/active' group showed less recurrent revascularization (HR: 0.761, 95% CI: 0.599-0.952). CONCLUSIONS: Smoking cessation and maintaining sufficient physical activity after AMI remain challenging for many Korean patients, and are associated with higher rates of mortality and recurrent revascularization. Systematic nationwide efforts such as cardiac rehabilitation (CR) to change health-related behaviors after AMI are required in Korea.

Relation between secondhand smoke exposure and cardiovascular risk factors in never smokers.

OBJECTIVE: Secondhand smoke exposure (SHSE) in nonsmokers has been associated with premature cardiovascular mortality and ischemic heart disease. We conducted a cross-sectional, population-based study evaluating the relationship between SHSE, measured by subjective and objective methods, and conventional cardiovascular risks such as blood pressure, lipid profiles, and fasting glucose. METHODS: We extracted information on 7376 healthy adults who had never smoked, for whom there were available urine cotinine levels, from the Korea National Health and Nutrition Examination Survey 2008-2011. SHSE was defined using self-report questionnaires and urine cotinine levels. The main outcomes included SBP and DBP, serum lipid profiles, and fasting glucose. RESULTS: The mean age of the study population was 45.4 ±â€Š0.4 years and 75.2% were women. Self-reported SHSE had no significant association with study outcomes except for DBP, which had marginally positive relationships (P = 0.060). Unadjusted analysis showed higher cotinine levels were associated with lower SBP, total cholesterol, LDL cholesterol, and triglyceride. All associations lost statistical significance after multivariable adjustment. Fasting glucose had a positive relationship with urine cotinine in quartiles but not with logarithm-transformed cotinine. CONCLUSION: Although SHSE is associated with increased risk of cardiovascular mortality and morbidity, we did not find any consistent relationship among SHSE and blood pressure, lipid, or fasting glucose levels in this cross-sectional study. Using objective measurements of urine cotinine did not alter this relationship. Further long-term prospective studies are needed to evaluate the effect of SHSE as a cardiovascular risk factor.

Long-Term Prognostic Value of Late Gadolinium-Enhanced Magnetic Resonance Imaging in Patients With and Without Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Grafting.

The value of late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI) for the prediction of functional recovery after surgical revascularization has been previously established. However, the impact of LGE-MRI on the long-term prognosis after coronary artery bypass grafting (CABG) remains incompletely understood. Therefore, we aimed to evaluate the long-term prognostic value of LGE-MRI, based on the presence or absence of left ventricular (LV) dysfunction, in patients with coronary artery disease undergoing CABG. One hundred forty-six consecutive patients underwent cine- and LGE-MRI before CABG. Adverse cardiac events included cardiac death, nonfatal myocardial infarction, heart failure, and unstable angina. A 3-year landmark analysis of the primary end point was also performed for patients surviving beyond 3 years after CABG. During a median follow-up of 9.4 years, 44 patients (30%) experienced adverse cardiac events. Although a LV ejection fraction <50% was associated only with adverse cardiac events at 3 years after CABG, LGE was associated with a worse outcome both at and beyond 3 years after CABG. In the overall study population, LGE presence (adjusted hazard ratio [HR] 2.58; p = 0.027), score (adjusted HR 1.06; p <0.001), and extent (adjusted HR 1.08; p <0.001) were independent predictors of adverse cardiac events. Moreover, in both the LV ejection fraction <50% and ≥50% groups, the LGE extent was an independent predictor of adverse cardiac events. In conclusion, our qualitative and quantitative analyses of LGE-MRI provide long-term prognostic information after surgical revascularization. The LGE extent was a strong predictor of adverse cardiac events, independent of the LV function.

Cigarette Smoking Does Not Enhance Clopidogrel Responsiveness After Adjusting VerifyNow P2Y12 Reaction Unit for the Influence of Hemoglobin Level.

OBJECTIVES: The authors performed this analysis to examine whether the enhanced clopidogrel responsiveness in current smokers is maintained after adjusting the influence of hemoglobin on VerifyNow P2Y12 reaction unit (PRU). BACKGROUND: PRU is consistently reported to be lower in current smokers. However, PRU has a significant inverse relationship with hemoglobin level, and smokers have higher hemoglobin levels. Because the association between PRU and hemoglobin is likely to be an in vitro phenomenon, we hypothesized that the observed difference in PRU between nonsmokers and current smokers is the result of confounding effect of hemoglobin rather than true difference in platelet reactivity. METHODS: Three cohorts were combined for the analysis (SNUBH [Seoul National University Bundang Hospital], n = 459; CILON-T [influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation], n = 715; HOST-ASSURE [Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen], n = 1,357). The final combined cohort consisted of 1,314 patients who underwent percutaneous coronary intervention and had VerifyNow P2Y12 assay results. General linear model (analysis of covariance) was used to control the effect of hemoglobin on PRU. RESULTS: A significant inverse correlation was observed between PRU and hemoglobin (r = -0.389; p < 0.001). Current smokers showed a significantly higher hemoglobin level (13.5 ± 1.6 vs. 14.4 ± 1.5; p < 0.001) but lower PRU level (230.1 ± 90.7 vs. 212.2 ± 83.6; p < 0.001). After adjusting the influence of hemoglobin on PRU, there was no difference in PRU between nonsmokers and current smokers (224.1 [95% confidence interval: 218.7 to 229.5] vs. 225.3 [95% confidence interval: 217.2 to 233.3]; p = 0.813). CONCLUSIONS: The observed difference in PRU between nonsmokers and current smokers is largely attributable to the difference in hemoglobin level. Enhanced clopidogrel responsiveness in cigarette smokers is not confirmed in this study and the concept of the smokers' paradox needs further validation.

The effects of erythropoiesis stimulating therapy for anemia in chronic heart failure: A meta-analysis of randomized clinical trials.

BACKGROUND: Although anemia is common in chronic heart failure (CHF), the use of erythropoiesis stimulating agents (ESAs) in CHF patients remains controversial. In this meta-analysis, we sought to clarify the efficacy and safety of ESAs in anemic patients with CHF. METHODS: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, the U.S. National Institutes of Health registry of clinical trials. We included 13 randomized clinical trials (RCTs) in the meta-analysis. The co-primary outcome was all-cause mortality and rehospitalization. The safety analysis outcome was thromboembolic events. RESULTS: Preliminary analysis showed that ESA-treatment did not have any effect for all-cause mortality and rehospitalization. However, we revealed a significant small-study bias, and used the trim-and-fill method to reduce this bias. The summary effect of ESA-treatment was insignificant for all-cause mortality (risk ratio [RR] 0.91, 95% confidence interval [CI] 0.59-1.42, p=0.69) and for rehospitalization (RR 0.91, 95% CI 0.67-1.23, p=0.53). Regarding symptoms, ESA-treatment improved dyspnea (NYHA grade improvement: 1.63, 95% CI 0.65-2.62, p<0.001) and quality-of-life measured by subjective questionnaires. However, in safety analysis, ESAs increased the over-all risk for thromboembolic events (RR 1.28, 95% CI 1.03-1.58, p=0.026), however, no specific increase was observed in severe thromboembolic events. Subgroup analysis showed no difference in ESA-treatment according to the type of ESAs (darbepoetin vs. erythropoietin) and between studies of different follow-up durations (<6months or ≥6months). CONCLUSION: Among CHF patients with anemia, ESA-treatment has a neutral effect on all-cause mortality and rehospitalization and improves symptoms, but has harmful effects on thromboembolic events.

Impact of smoking status on clinical outcomes after successful chronic total occlusion intervention: Korean national registry of CTO intervention.

OBJECTIVES: We sought to evaluate the effect of cigarette smoking on long-term outcomes after successful percutaneous coronary intervention for chronic total occlusion (CTO) lesions. BACKGROUND: Cigarette smoking promotes the progression of atherosclerosis but enhances the antiplatelet effect of clopidogrel. METHODS: The Korea National Registry of CTO Intervention included 2,167 patients with CTO lesions from 26 centers who were successfully revascularized with drug-eluting stents from 2007 to 2009. Thrombotic events were defined as the composite of cardiac death, nonfatal myocardial infarction, and stent thrombosis. RESULTS: Current-smokers had more favorable baseline characteristics such as a younger age and lower prevalence of hypertension and diabetes mellitus. At 1 year, current-smokers had a significantly lower thrombotic event rate (1.1% vs. 2.7%, P = 0.034), but a significantly higher target vessel revascularization (TVR) rate (7.2% vs. 4.2%, P = 0.017) compared with never-smokers. After adjustment, current-smoking was independently associated with a 72% decreased risk for thrombotic events, and 73% increased risk for TVR. CONCLUSIONS: In patients with a revascularized CTO lesion, cigarette smoking is associated with fewer thrombotic events but with a higher incidence of TVR. Patients with CTO may benefit from smoking cessation to reduce TVR in conjunction with the use of new more potent antiplatelet agents whose effect is independent of cigarette smoking to improve thrombotic events. © 2015 Wiley Periodicals, Inc.

The prognostic value of arterial blood gas analysis in high-risk acute heart failure patients: an analysis of the Korean Heart Failure (KorHF) registry.

AIMS: In acute heart failure (AHF) patients, pulmonary oedema and low tissue perfusion may lead to changes in the acid-base balance, which may be associated with worse outcomes. METHODS AND RESULTS: In this prospective nationwide cohort study from 24 academic hospitals, arterial blood gas (ABG) was measured in 1982 AHF patients at hospital admission. Acidosis was defined as pH <7.36, and alkalosis as pH >7.44. Mortality was stratified according to ABG results. Overall, 19% had acidosis, 37% had normal pH, and 44% had alkalosis. The most common type of acidosis was the mixed type (42%) followed by metabolic acidosis (40%), and the most common type of alkalosis was respiratory alkalosis (58%). At 12 months' follow-up 304 patients (15%) died. Patients with acidosis had higher mortality (acidosis 19.5%, neutral pH 13.7%, alkalosis 14.9%; P = 0.007). In the Cox proportional-hazards regression model, acidosis was a significant predictor of mortality (hazard ratio 1.93; 95% confidence intervals 1.27-2.93) along with N-terminal pro-brain type natriuretic peptide (NT-proBNP), among others. In contrast, alkalosis was not associated with increased mortality. pH had an incremental prognostic value over NT-proBNP (net reclassification improvement 30%; P < 0.001), and ABG analysis identified extra patients at increased risk for mortality among patients with an NT-proBNP level less than the median (12-month mortality 17.5% vs. 9.9%; P = 0.009). CONCLUSION: In high-risk AHF patients, the most common acid-base imbalance is respiratory alkalosis. Acidosis is observed in every fifth patient and is a significant predictor of mortality. pH provides an additional prognostic value and may be used to optimize risk stratification in high-risk AHF patients.

Prevalence of cigarette smoking among adult cancer survivors in Korea.

PURPOSE: Cigarette smoking is associated not only with increased risk of cancer incidence, but also influences prognosis, and the quality of life of the cancer survivors. Thus, smoking cessation after cancer diagnosis is necessary. However, smoking behavior among Korean cancer-survivors is yet unknown. MATERIALS AND METHODS: We investigated the smoking status of 23770 adults, aged 18 years or older, who participated in the Health Interview Survey of the Korea National Health and Nutrition Examination Survey from 2007 to 2010. Data on the cancer diagnosis and smoking history were obtained from an interview conducted by trained personals. "Cancer-survivor" was defined as anyone who has been diagnosed with cancer by a physician regardless of time duration since diagnosis. Smoking status was classified into "never-smoker", "former-smoker", and "current-smoker". Former-smoker was further divided into "cessation before diagnosis" and "cessation after diagnosis". RESULTS: Overall, 2.1% of Korean adults were cancer-survivors. The smoking rate of Korean cancer-survivors was lower than that of non-cancer controls (7.8±1.3% vs. 26.4±0.4%, p<0.001). However, 53.4% of the cancer-survivors continued to smoke after their cancer diagnosis. In multivariate analysis, male gender [odds ratio (OR), 6.34; 95% confidence interval (CI), 2.62-15.31], middle-aged group (OR, 2.74; 95% CI, 1.12-6.72), the lowest income (OR, 4.10; 95% CI, 1.19-14.15), living with smoking family member(s) (OR, 5.49; 95% CI, 2.42-12.48), and the poor self-perceived health status (OR, 2.78; 95% CI, 1.01-7.71) were independently associated with persistent smoking among Korean cancer-survivors. CONCLUSION: The smoking rate among Korean cancer survivors is low. However, the smoking cessation rate after the cancer diagnosis is also low. This mandates comprehensive and systematic intervention for smoking cessation among cancer-survivors.