The Efficacy and Tolerability of Irbesartan/Amlodipine Combination Therapy in Patients With Essential Hypertension Whose Blood Pressure Were not Controlled by Irbesartan Monotherapy.

PURPOSE: This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy. METHODS: Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP [MSSBP] ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography. FINDINGS: In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were -14.78 (12.35) mmHg, -21.47 (12.78) mmHg, and -8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were -13.30 (12.47) mmHg and -7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study. IMPLICATIONS: The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302).

Proposed diagnostic and prognostic markers of primary malignant hepatic vascular neoplasms.

INTRODUCTION: Primary malignant hepatic vascular tumors with various malignant potentials include epithelioid hemangioendothelioma (EHE) and angiosarcoma (AS), which may overlap pathologically. This study aimed to compare the pathological findings of hepatic EHE with those of AS, in association with patient outcomes. METHODS: Fifty-nine histologically confirmed patients with 34 EHE and 25 AS were admitted to a tertiary hospital from 2003 to 2020. Their EHE and AS pathological features were compared. Immunohistochemistry for CD31, ERG, CAMTA-1, TFE3, P53, and Ki-67 labeling was performed on paraffin-embedded blocks. Markers, along with histological findings, were analyzed for the purposes of diagnostic and prognostic significance by multivariate analysis. RESULTS: CAMTA-1 was 91.2% positive in EHE, but negative in AS (p = < 0.001). AS was significantly correlated to an aberrant p53 expression, high Ki-67 labeling, and high mitotic activity, compared to EHE (all, p = < 0.001). EHE can be classified as low grade (LG) and high grade (HG) using the prognostic values of mitotic activity and ki-67 labeling (sensitivity = 1, specificity = 1). Low grade-EHE showed significantly better overall survival than high grade-EHE (p = 0.020). CONCLUSIONS: Immunohistochemistry for CAMTA-1, P53, and Ki-67 labeling may help distinguish EHE and AS in histologically ambiguous cases, especially small biopsied tissue. Moreover, the combination of mitotic activity and Ki-67 labeling can be a prognostic factor for EHE with various clinical features.

Discordant PD-L1 results between 28-8 and 22C3 assays are associated with outcomes of gastric cancer patients treated with nivolumab plus chemotherapy.

BACKGROUND: We evaluated the concordance/discordance of PD-L1 staining results between the 28-8 and 22C3 assays and its impact on the efficacy outcomes of advanced gastric cancer patients treated with nivolumab plus chemotherapy. METHODS: This retrospective study involved 143 gastric cancer patients treated with first-line nivolumab plus chemotherapy whose PD-L1 results with both 28-8 and 22C3 assays were available. The concordance/discordance between these assays and the inter-observer variability were evaluated for PD-L1 combined positive score (CPS) positivity. Discordant PD-L1 results were analyzed regarding survival outcomes. RESULTS: The agreement rates and Cohen's kappa values between the 28-8 and 22C3 assays were 78.3% and 0.56 (for CPS ≥ 1), 81.8% and 0.60 (for CPS ≥ 5), and 88.8% and 0.66 (for CPS ≥ 10), respectively. Inter-observer variability, as represented by the intra-class correlation coefficient, was 0.89 and 0.88 for the 28-8 and 22C3 assays, respectively. With PD-L1 CPS ≥ 5 defined as positive, 35 (24.5%) and 82 (57.3%) had concordantly positive and negative results, respectively, between the 28-8 and 22C3 assays, whereas 26 (18.2%) had discordant results. Progression-free survival was shorter for those who exhibited negatively concordant PD-L1 results and discordant PD-L1 positivity between the 28-8 and 22C3 assays relative to those with positively concordant PD-L1 results (P = 0.013). CONCLUSION: PD-L1 assays by 28-8 and 22C3 showed suboptimal concordance, while inter-observer variability was not critical in advanced gastric cancer. Discordant PD-L1 results between 28-8 and 22C3 assays may be associated with unfavorable efficacy outcomes in patients treated with nivolumab plus chemotherapy.

Open-top Bessel beam two-photon light sheet microscopy for three-dimensional pathology.

Nondestructive pathology based on three-dimensional (3D) optical microscopy holds promise as a complement to traditional destructive hematoxylin and eosin (H&E) stained slide-based pathology by providing cellular information in high throughput manner. However, conventional techniques provided superficial information only due to shallow imaging depths. Herein, we developed open-top two-photon light sheet microscopy (OT-TP-LSM) for intraoperative 3D pathology. An extended depth of field two-photon excitation light sheet was generated by scanning a nondiffractive Bessel beam, and selective planar imaging was conducted with cameras at 400 frames/s max during the lateral translation of tissue specimens. Intrinsic second harmonic generation was collected for additional extracellular matrix (ECM) visualization. OT-TP-LSM was tested in various human cancer specimens including skin, pancreas, and prostate. High imaging depths were achieved owing to long excitation wavelengths and long wavelength fluorophores. 3D visualization of both cells and ECM enhanced the ability of cancer detection. Furthermore, an unsupervised deep learning network was employed for the style transfer of OT-TP-LSM images to virtual H&E images. The virtual H&E images exhibited comparable histological characteristics to real ones. OT-TP-LSM may have the potential for histopathological examination in surgical and biopsy applications by rapidly providing 3D information.

Characterization of lymphocyte-rich hepatocellular carcinoma and the prognostic role of tertiary lymphoid structures.

BACKGROUND & AIMS: Lymphocyte-rich hepatocellular carcinoma (LR-HCC) is largely unknown and a rare subtype of HCC with immune-rich stroma. Tertiary lymphoid structures (TLS), frequently observed in LR-HCC, are known to be prognostically significant in various malignancies; however, their significance in HCC remains unevaluated. METHODS: Clinicopathologic data of 191 cases of surgically resected conventional HCC (C-HCC, n = 160) and LR-HCC (n = 31) were retrieved. Immunohistochemistry, multiplex immunofluorescence staining, RNA sequencing and proteomic analysis were conducted. Differences between the subtypes were statistically evaluated. RESULTS: LR-HCC was significantly correlated to larger tumour size, higher Edmondson-Steiner grade, presence of TLS and higher CD3-, CD8- and FOXP3-positive T cell, high PD-1 and PD-L1 expression (p < .001 for all) compared to C-HCC. Patients with LR-HCC exhibited significantly better overall survival (OS) (p = .044) and recurrence-free survival (RFS) (p = .025) than C-HCC. LR-HCC demonstrated TLS signatures with significantly higher proteomic-based immune scores in 14 of 17 types of tumour-infiltrating immune cells. Furthermore, C-HCC with secondary follicles, the most mature form of TLS, exhibited significantly better OS (p = .031) and RFS (p = .033) than those without. Across the global proteome, LR-HCC was well-differentiated from C-HCC and a map of protein-protein interactions between tumour-infiltrating lymphocytes and HCC in tumour microenvironment was completed. CONCLUSION: LR-HCC is clinicopathologically and molecularly distinct and shows better prognosis compared to C-HCC. Also, the presence of secondary follicle can be an important prognostic marker for better prognosis in both LR-HCC and C-HCC.

Unusual or Uncommon Histology of Gastric Cancer.

This review comprehensively examines the diverse spectrum of gastric cancers, focusing on unusual or uncommon histology that presents significant diagnostic and therapeutic challenges. While the predominant form, tubular adenocarcinoma, is well-characterized, this review focuses on lesser-known variants, including papillary adenocarcinoma, micropapillary carcinoma, adenosquamous carcinoma, squamous cell carcinoma (SCC), hepatoid adenocarcinoma, gastric choriocarcinoma, gastric carcinoma with lymphoid stroma, carcinosarcoma, gastroblastoma, parietal cell carcinoma, oncocytic adenocarcinoma, Paneth cell carcinoma, gastric adenocarcinoma of the fundic gland type, undifferentiated carcinoma, and extremely well-differentiated adenocarcinoma. Although these diseases have different nomenclatures characterized by distinct histopathological features, these phenotypes often overlap, making it difficult to draw clear boundaries. Furthermore, the number of cases was limited, and the unique histopathological nature and potential pathogenic mechanisms were not well defined. This review highlights the importance of understanding these rare variants for accurate diagnosis, effective treatment planning, and improving patient outcomes. This review emphasizes the need for ongoing research and case studies to enhance our knowledge of these uncommon forms of gastric cancer, which will ultimately contribute to more effective treatments and better prognostic assessments. This review aimed to broaden the pathological narrative by acknowledging and addressing the intricacies of all cancer types, regardless of their rarity, to advance patient care and improve prognosis.

Electrocardiography score based on the Minnesota code classification system predicts cardiovascular mortality in an asymptomatic low-risk population.

BACKGROUND: The use of a single abnormal finding on electrocardiography (ECG) is not recommended for stratifying the risk of cardiovascular (CV) events in low-risk general populations because of its low discriminative power. However, the value of a scoring system containing multiple abnormal ECG findings for predicting CV death has not been sufficiently evaluated. METHODS: In a prospective community-based cohort study, 8417 participants without atherosclerotic CV diseases (ASCVDs) and any related symptoms were followed for 18 years. The standard 12-lead ECGs were recorded at baseline and the ECG findings were categorized using the Minnesota code classification. CV deaths were defined as death from myocardial infarction (MI), chronic ischemic heart disease, heart failure, fatal arrhythmia, cerebrovascular event, pulmonary thromboembolism, peripheral vascular disease and sudden cardiac arrest and identified using the Korean National Statistical Office (KOSTAT) database. RESULTS: In a multivariate Cox proportional hazard (CPH) model, major and minor ST-T wave abnormalities, atrial fibrillation (AF), Q waves in the anterior leads, the lack of Q waves in the posterior leads, high amplitudes of the left and right precordial leads, left axis deviation and sinus tachycardia were associated with higher risks of CV deaths. The ECG score consisted of these findings showed modest predictive values represented by C-statistics that ranged from 0.632 to 760 during the follow-up and performed better in the early follow-up period. The ECG score independently predicted CV death after adjustment for relevant covariates in a multivariate model, and improved the predictive performance of the 10-year ASCVD risk estimator and a model of conventional risk factors including age, diabetes and current smoking. The combined ECG score (Harrell's C-index: 0.852, 95% confidence interval [CI], 0.828-0.876) composed of the ECG score and the conventional risk factors outperformed the 10-year ASCVD risk estimator (Harrell's C-index: 0.806; 95% CI, 0.780-0.833) and the model of the conventional risk factors (Harrell's C-index: 0.841, 95% CI, 0.817-0.865) and exhibited an excellent goodness of fit between the predicted and observed probabilities of CV death. CONCLUSIONS: The ECG score could be useful to predict CV death independently and may add value to the conventional CV risk estimators regarding the risk stratification of CV death in asymptomatic low-risk general populations.

The ECG score based on the Minnesota code classification can independently predict CV death and significantly improve the predictive power of the conventional CV risk estimators in asymptomatic low-risk general population.The combined ECG score comprised the ECG score, age and the presence of diabetes and current smoking predicted CV mortality more accurately than the conventional SV risk estimators.ECG may still be a viable CV risk stratification tool for population-based health screening projects.

Clinicopathologic features and prognostic value of claudin 18.2 overexpression in patients with resectable gastric cancer.

Claudin 18.2 has emerged as a promising therapeutic target in gastric cancer based on phase 3 studies. However, clinicopathologic features associated with claudin 18.2 overexpression have not been comprehensively studied specifically for patients with resectable gastric cancer. This retrospective study included 299 patients with stage I-III resectable gastric cancer who underwent curative surgical resection. Possible associations between claudin 18.2 overexpression (moderate-to-strong expression in ≥ 75% by the 43-14A clone) and clinicopathologic features and survival outcomes were analyzed. There were 90 (30.1%), 96 (32.1%), and 113 (37.8%) patients with stage I, II, and III disease, respectively. Claudin 18.2 overexpression was noted in 139 out of 299 patients (46.5%). Claudin 18.2 overexpression was associated with a younger age, a lower invasion depth limited to the mucosa/submucosa, and less frequent lymphovascular invasion. Claudin 18.2 overexpression was also associated with Borrmann type 4 among patients with advanced gastric cancer and the diffuse histological type. Claudin 18.2 overexpression was not an independent factor for survival outcomes. In conclusion, claudin 18.2 was overexpressed in almost half of resectable gastric cancer patients. Claudin 18.2 overexpression was associated with some clinicopathological characteristics, but was not an independent prognostic factor in a localized setting.

Anhydrous Alum Inhibits α-MSH-Induced Melanogenesis by Down-Regulating MITF via Dual Modulation of CREB and ERK.

Melanogenesis, the intricate process of melanin synthesis, is central to skin pigmentation and photoprotection and is regulated by various signaling pathways and transcription factors. To develop potential skin-whitening agents, we used B16F1 melanoma cells to investigate the inhibitory effects of anhydrous alum on melanogenesis and its underlying molecular mechanisms. Anhydrous alum (KAl(SO4)2) with high purity (>99%), which is generated through the heat-treatment of hydrated alum (KAl(SO4)2·12H2O) at 400 °C, potentiates a significant reduction in melanin content without cytotoxicity. Anhydrous alum downregulates the master regulator of melanogenesis, microphthalmia-associated transcription factor (MITF), which targets key genes involved in melanogenesis, thereby inhibiting α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis. Phosphorylation of the cAMP response element-binding protein, which acts as a co-activator of MITF gene expression, is attenuated by anhydrous alum, resulting in compromised MITF transcription. Notably, anhydrous alum promoted extracellular signal-regulated kinase phosphorylation, leading to the impaired nuclear localization of MITF. Overall, these results demonstrated the generation and mode of action of anhydrous alum in B16F1 cells, which constitutes a promising option for cosmetic or therapeutic use.

Efficacy and safety of standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg in primary hypertension: A randomized, double-blind, active-controlled, multicenter phase 3 trial.

The authors evaluated the efficacy, safety, and characteristics of patients who respond well to standard dose triple combination therapy including chlorthalidone 25 mg with telmisartan 80 mg plus amlodipine 5 mg in hypertensive patients. This is a multicenter, double-blind, active-controlled, phase 3, randomized trial. Patients are randomized to triple combination (telmisartan 40 mg/amlodipine 5 mg/chlorthalidone 12.5 mg, TEL/AML/CHTD group) or dual combination (telmisartan 40 mg/amlodipine 5 mg, TEL/AML group) treatment and then dose up titration to TEL 80/AML5/CHTD25mg and TEL80/AML5, respectively. The primary endpoint is the change of mean sitting systolic blood pressure (MSSBP) at week 8. A Target BP achievement rate, a response rate, and the safety endpoints are also evaluated. Total 374 patients (mean age = 60.9 ± 10.7 years, male = 78.3%) were randomized to the study. The baseline MSSBPs/diastolic BPs were 149.9 ± 12.2/88.5 ± 10.4 mm Hg. After 8 weeks treatment, the change of MSSBPs at week 8 are -19.1 ± 14.9 mm Hg (TEL/AML/CHTD) and -11.4 ± 14.7 mm Hg (TEL/AML) (p < .0001). The achievement rates of target BP (53.8% vs. 37.8%, p = .0017) and responder rate (54.8% vs. 35.6%, p = .0001) at week 8 were significantly higher in TEL/AML/CHTD. There are no serious adverse event and no one discontinued medication due to adverse event. Among the TEL 80/AML5/CHTD25mg treatment group, patients of female or age ≥ 65 years old showed higher rate of target BP achievement than relatively young male. (61.4 vs. 46.8%, p = .042) Our study showed standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg is efficacious and safe in treatment of primary hypertension. Target BP achievement with triple therapy would be facilitated in female or old age.

Clinical and life style factors related to the nighttime blood pressure, nighttime dipping and their phenotypes in Korean hypertensive patients.

BACKGROUND: Non-dipping or reverse dipping patterns are known to be associated with adverse cardiovascular prognosis among the general population and clinical cohort. Few large sized studies have explored factors including sleep duration and sleep quality related to nighttime blood pressure (BP) and nocturnal dipping patterns. METHODS: Among 5,360 patients enrolled  in Korean multicenter nationwide prospective Registry of ambulatory BP monitoring (KORABP), 981 subjects with complete data on sleep duration, sleep quality assessed using a 4-point Likert scale, and clinical variables were included in the analysis. Phenotypes of nighttime BP pattern were categorized as extreme dipper, dipper, non-dipper, and reverse dipper. Hypertension was defined as a 24-h ambulatory BPs were 130/80 mmHg or higher. RESULTS: Among 981 subjects, 221 were normotensive, 359 were untreated hypertensive, and 401 were treated hypertensive. Age of the participants were 53.87 ± 14.02 years and 47.1% were female. In overall patients, sleep duration was 431.99 ± 107.61 min, and one to four points of sleep quality were observed in 15.5%, 30.0%, 30.4%, and 24.2%, respectively. Of the 760 hypertensive patients, extreme dipper, dipper, non-dipper, and reverse dipper were observed in 58 (7.63%), 277 (36.45%), 325 (42.76%), and 100 (13.16%), respectively. In multiple linear regression analysis, sleep duration (ß = 0.0105, p < 0.001) and sleep quality (ß = -0.8093, p < 0.001) were associated with nighttime systolic BP and sleep quality was associated with extent of nighttime systolic BP dipping (ß = 0.7622, p < 0.001) in hypertensive patients. In addition, sleep quality showed positive association with dipper pattern (odds ratio [OR] = 1.16, 95% confidence interval [CI] = 1.03-1.30) and showed negative association with reverse dipper pattern (OR = 0.73, 95% CI = 0.62-0.86) in multiple logistic regression analyses. CONCLUSION: When adjusted covariates, less sleep duration and poor sleep quality were positively associated with nighttime systolic BP. Additionally, sleep quality was the independent associated factor for dipper and reverse dipper phenotypes. The study also found that male sex, low estimated glomerular filtration rate, high ambulatory BP, low office BP, and poor sleep quality were associated with blunted nighttime SBP dipping.

Direct comparison of an automated oscillometric device with an electronic auscultatory device for epidemiologic survey to evaluate the prevalence of hypertension.

Mercury-free sphygmomanometers are gradually replacing the traditional sphygmomanometers in clinical settings and epidemiological surveys for measuring blood pressure (BP) due to mercury toxicity. No direct comparative studies have evaluated BP differences and statistical errors of automated oscillometric devices (ODs) against electronic auscultatory devices (ADs) for epidemiologic surveys. Herein, we evaluated the validity of ODs for the Korea National Health and Nutrition Examination Survey (KNHANES) using the Universal Standard for BP device validation through a direct comparison with ADs as the reference standard. Four trained observers performed validation on 278 volunteers aged ≥ 19 years with a standardized BP measurement protocol. Agreement between the BP measurements recorded with an OD against those recorded with an AD was assessed by Lin's concordance correlation coefficient (CCC) and Bland-Altman's limits of agreement. To evaluate the agreement for BP classification, weighted kappa values were estimated. To explore the factors associated with BP measurement differences between the 2 devices, multiple linear regression analysis was performed. The average BP differences (OD-AD) were 2.6 ±â€…6.2 mm Hg for systolic BP (SBP) and -5.1 ±â€…5.6 mm Hg for diastolic BP (DBP). Lin's CCCs were 0.927 and 0.768 for the overall SBP and DBP, respectively. The cumulative percentage of absolute errors ≤10 mm Hg was 88.1% for SBP and 81.3% for DBP. The weighted kappa value for the Joint National Committee 7 BP classification was 0.75 (95% confidence interval: 0.68-0.81). An OD overestimated the prevalence of SBP (0.3%, P = .0222) and underestimated the prevalence of DBP (1.8%, P < .0001). Multivariate analysis to identify the risk factors for BP difference revealed the arm circumference (AC) to be negatively associated with BP difference. Male sex was positively associated, while age was negatively associated with SBP difference. OD-DBP was positively associated with DBP difference and negatively associated for DBP absolute error. ODs met the accuracy requirements of the Universal Standard criteria against ADs for SBP but not for DBP. Thus, the DBP values may be underestimated by ODs in the KNHANES.

Impact of a screening protocol for blood pressure level for hypertension in the Korean community health survey.

PURPOSE: A community program is an efficient model for improving the management of chronic diseases such as hypertension, diabetes, and dyslipidemia. A specific blood pressure (BP) measurement protocol was developed for community settings in which BP was measured by the interviewer at the interviewee's home. MATERIALS AND METHODS: In the 2018 Korean Community Health Survey, BP was measured twice at a five-minute interval after a five-minute resting period at the beginning of the survey. In 2019, BP was measured at the end of the survey after a two-minute rest and was obtained as three measurements at one-minute intervals. As factors related to BP level, stressful stimuli within 30 min before BP measurement such as smoking, caffeine, and/or exercise; duration of rest; and survey year were analysed. RESULTS: The mean age of participants was 55.2 years, and females accounted for 55.4% of the participants (n = 399,838). Stressful stimuli were observed in 21.9% of the participants in 2018 (n = 188,440) and 11.3% in 2019 (n = 211,398). Duration of rest was 0 min (2.1%), two minutes (55.0%), and five minutes (47.9%). When adjusted for age, sex, body mass index, antihypertensive medication, the arm of measurement, survey year (beta= -4.092), stressful stimuli (beta = 0.834), and resting time (beta = -1.296 per one minute of rest) were significant factors for mean systolic BP. A two-minute rest was not a significant factor in mean BP. The differences in adjusted mean systolic BPs were significant for rest times of five minutes vs. two minutes (3.1 mmHg, p < 0.0001), for stressful stimuli (0.8 mmHg, p < 0.0001), and for survey year (127.8 ± 0.2 mmHg vs. 122.2 ± 0.3 mmHg for 2018 vs. 2019, p < 0.0001). CONCLUSION: For the community-based home visit survey, avoidance of stressful stimuli, five-minute rest, and allocation of BP measurement in the last part of the survey was useful for obtaining a stable BP level.

A Long-Term Incidence of Heart Failure and Predictors Following Newly Developed Acute Myocardial Infarction: A 10 Years Retrospective Cohort Study with Korean National Health Insurance Data.

Heart failure (HF) is the major mechanism of mortality in acute myocardial infarction (AMI) during early or intermediate post-AMI period. But heart failure is one of the most common long-term complications of AMI. Applied the retrospective cohort study design with nation representative population data, this study traced the incidence of late-onset heart failure since 1 year after newly developed acute myocardial infarction and assessed its risk factors. Methods and Results: Using the Korea National Health Insurance database, 18,328 newly developed AMI patients aged 40 years or older and first hospitalized in 2010 for 3 days or more, were set up as baseline cohort (12,403). The incidence rate of AMI per 100,000 persons was 79.8 overall, and 49.6 for women and 112.3 for men. A total of 2010 (1073 men, 937 women) were newly developed with HF during 6 years following post AMI. Cumulative incidences of HF per 1000 AMI patients for a year at each time period were 37.4 in initial hospitalization, 32.3 in 1 year after discharge, and 8.9 in 1-6 years. The overall and age-specific incidence rates of HF were higher in women than men. For late-onset HF, female, medical aid, pre-existing hypertension, severity of AMI, duration of hospital stay during index admission, reperfusion treatment, and drug prescription pattern including diuretics, affected the occurrence of late-onset HF. Conclusion: With respect to late-onset HF following AMI, appropriate management including hypertension and medical aid program in addition to quality improvement of AMI treatment are required to reduce the risk of late-onset heart failure.

Disparities in Mortality and Cardiovascular Events by Income and Blood Pressure Levels Among Patients With Hypertension in South Korea.

Background Socioeconomic status is associated with differences in risk factors of cardiovascular disease and increased risks of cardiovascular disease and mortality. However, it is unclear whether an association exists between cardiovascular disease and income, a common measure of socioeconomic status, among patients with hypertension. Methods and Results This population-based longitudinal study comprised 479 359 patients aged ≥19 years diagnosed with essential hypertension. Participants were categorized by income and blood pressure levels. Primary end point was all-cause and cardiovascular mortality and secondary end points were cardiovascular events, a composite of cardiovascular death, myocardial infarction, and stroke. Low income was significantly associated with high all-cause (hazard ratio [HR], 1.26; 95% CI, 1.23-1.29, lowest versus highest income) and cardiovascular mortality (HR, 1.31; 95% CI, 1.25-1.38) as well as cardiovascular events (HR, 1.07; 95% CI, 1.05-1.10) in patients with hypertension after adjusting for age, sex, systolic blood pressure, body mass index, smoking status, alcohol consumption, physical activity, fasting glucose, total cholesterol, and the use of aspirin or statins. In each blood pressure category, low-income levels were associated with high all-cause and cardiovascular mortality and cardiovascular events. The excess risks of all-cause and cardiovascular mortality and cardiovascular events associated with uncontrolled blood pressure were more prominent in the lowest income group. Conclusions Low income and uncontrolled blood pressure are associated with increased all-cause and cardiovascular mortality and cardiovascular events in patients with hypertension. These findings suggest that income is an important aspect of social determinants of health that has an impact on cardiovascular outcomes in the care of hypertension.

Antihypertensive Drugs and the Risk of Cancer: A Nationwide Cohort Study.

We sought to assess the association between common antihypertensive drugs and the risk of incident cancer in treated hypertensive patients. Using the Korean National Health Insurance Service database, the risk of cancer incidence was analyzed in patients with hypertension who were initially free of cancer and used the following antihypertensive drug classes: Angiotensin-converting enzyme inhibitors (ACEIs); angiotensin receptor blockers (ARBs); beta blockers (BBs); calcium channel blockers (CCBs); and diuretics. During a median follow-up of 8.6 years, there were 4513 (6.4%) overall cancer incidences from an initial 70,549 individuals taking antihypertensive drugs. ARB use was associated with a decreased risk for overall cancer in a crude model (hazard ratio (HR): 0.744, 95% confidence interval (CI): 0.696-0.794) and a fully adjusted model (HR: 0.833, 95% CI: 0.775-0.896) compared with individuals not taking ARBs. Other antihypertensive drugs, including ACEIs, CCBs, BBs, and diuretics, did not show significant associations with incident cancer overall. The long-term use of ARBs was significantly associated with a reduced risk of incident cancer over time. The users of common antihypertensive medications were not associated with an increased risk of cancer overall compared to users of other classes of antihypertensive drugs. ARB use was independently associated with a decreased risk of cancer overall compared to other antihypertensive drugs.

Regional differences in office and self-measured home heart rates in Asian hypertensive patients: AsiaBP@Home study.

Increased heart rate is a predictor of cardiovascular disease, heart failure, and all-cause mortality. In those with high heart rates, interventions for heart rate reduction have been associated with reductions in coronary events. Asia is a diverse continent, and the prevalences of hypertension and cardiovascular disease differ among its countries. The present analysis of AsiaBP@Home study data investigated differences among resting heart rates (RHRs) in 1443 hypertensive patients from three Asian regions: East Asia (N = 595), Southeast Asia (N = 680), and South Asia (N = 168). This is the first study to investigate self-measured RHR values in different Asian countries/regions using the same validated home BP monitoring device (Omron HEM-7130-AP/HEM-7131-E). Subjects in South Asia had higher RHR values compared with the other two regions, and the regional tendency found in RHR values was different from that found in BP values. Even after adjusting for age, sex, BMI, habitual alcohol consumption, current smoking habit, shift worker, hyperlipidemia, diabetes, chronic kidney disease, history of heart failure, and beta-blocker use, both office and home RHR values in South Asia were the highest among Asia (mean values ± SE of office: East Asia [E] 75.2 ± 1.5 bpm, Southeast Asia [Se] 76.7 ± 1.5 bpm, South Asia [S] 81.9 ± 1.4 bpm; home morning: [E] 69.0 ± 1.2 bpm, [Se] 72.9 ± 1.2 bpm, [S] 74.9 ± 1.1 bpm; home evening: [E] 74.6 ± 1.2 bpm, [Se] 78.3 ± 1.2 bpm, [S] 83.8 ± 1.1 bpm). Given what is known about the impact of RHR on heart disease, our findings suggest the possible benefit of regionally tailored clinical strategies for cardiovascular disease prevention.

Effect of angiotensin receptor blockers on the development of cancer: A nationwide cohort study in korea.

The potential cancer risk associated with long-term exposure to angiotensin receptor blockers (ARBs) is still unclear. We assessed the risk of incident cancer among hypertensive patients who were treated with ARBs compared with patients exposed to angiotensin-converting enzyme inhibitors (ACEIs), which are known to have a neutral effect on cancer development. Using the Korean National Health Insurance Service database, we analyzed the data of patients diagnosed with essential hypertension from January 2005 to December 2012 who were aged ≥40 years, initially free of cancer, and were prescribed either ACEI or ARB (n = 293,962). Cox proportional hazard model adjusted for covariates was used to evaluate the risk of incident cancer. During a mean follow-up of 10 years, 24,610 incident cancers were observed. ARB use was associated with a decreased risk of overall cancer compared with ACEI use (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.72-0.80). Similar results were obtained for lung (HR 0.73, 95% CI 0.64-0.82), hepatic (HR 0.56, 95% CI 0.48-0.65), and gastric cancers (HR 0.74, 95% CI 0.66-0.83). Regardless of the subgroup, greater reduction of cancer risk was seen among patients treated with ARB than that among patients treated with ACEIs. Particularly, the decreased risk of cancer among ARB users was more prominent among males and heavy drinkers (interaction P < .005). Dose-response analyses demonstrated a gradual decrease in risk with prolonged ARB therapy than that with ACEI use. In conclusion, ARB use was associated with a decreased risk of overall cancer and several site-specific cancers.

The feasibility of polypill for cardiovascular disease prevention in Asian Population.

Polypill is a fixed-dose combination of medications with proven benefits for the prevention of cardiovascular disease (CVD). Its role in CVD prevention has been extensively debated since the inception of this concept in 2003. There are two major kinds of polypills in clinical studies. The first is polypill that combines multiple low-dose medications for controlling only one CVD risk factor (such as high blood pressure or high serum cholesterol). These "single-purpose" polypills were mostly developed from original producers and have higher cost. The polypill that combines 3-4 pharmaceutical components, each with potential to reduce one major cardiovascular risk factors is "multi-purpose" or "cardiovascular" polypill. Using data from various clinical trials and from meta-analysis, Wald and Law claimed that this "cardiovascular" polypill when administered to every individual older than 55 years could reduce the incidence of CVD by more than 80%. Several short and intermediate to long-term studies with different cardiovascular polypills in phase II and III trials showed that they could provide better adherence, equivalent, or better risk factor control and quality of life among users as compared to usual care. One recently published randomized controlled clinical trial demonstrated the effectiveness and safety of a four-component polypill for both primary and secondary CVD prevention with acceptable number needed to treat (NNT) to prevent one major cardiovascular event. Considering the slow achievement of CVD prevention in many poor- and middle-income Asian countries and also the need to further improve compliance of antihypertensive and lipid lowering medications in many high-income Asian countries, the concept of "cardiovascular polypill" could be very useful. With further support from ongoing polypill cardiovascular outcome trials, polypill could be the foundation of the population-based strategies for CVD prevention.

Positive association of alcohol consumption with incidence of hypertension in adults aged 40 years and over: Use of repeated alcohol consumption measurements.

BACKGROUND & AIMS: Managing alcohol consumption may be an effective way of preventing hypertension, which is an important modifiable risk factor for cardiovascular diseases. However, there is little evidence on the temporal relationship between alcohol consumption and incidence of hypertension. We investigated the prospective association between repeated measures of alcohol consumption and hypertension incidence among Korean adults aged 40 and over. METHODS: This study included a total of 4989 participants that were not taking antihypertensive drugs and had normal blood pressure (BP) (systolic < 140 mmHg and diastolic < 90 mmHg). We used three measures of alcohol consumption (baseline, most recent, and average) as exposures and compared the three approaches. Using a modified Poisson regression model with a robust error estimator, we estimated incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for hypertension. RESULTS: Over a total of 17,689 person-years (average 3.5 years of follow-up), 574 incident cases of hypertension were identified. In multivariable models, consuming ≥30 ml/d of alcohol was associated with a risk of hypertension among men (IRR = 1.72, 95% CI = 1.20-2.48, p trend = 0.017 for baseline alcohol consumption; IRR = 1.69, 95% CI = 1.23-2.33, p trend = 0.005 for the most recent alcohol consumption; IRR = 1.49, 95% CI = 1.09-2.03, p trend = 0.014 for average alcohol consumption). After additional adjustment for baseline BP the positive association remained only when the most recent alcohol consumption measure was used. There was no significant association between alcohol consumption and hypertension among women, and no interaction effect between alcohol consumption and baseline BP levels on incidence of hypertension (all p interaction > 0.05) existed. CONCLUSIONS: Alcohol consumption, especially consuming ≥30 ml/d, may be positively linked with incidence risk of hypertension among men.