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).

Impacts of Pre-transplant Panel-Reactive Antibody on Post-transplantation Outcomes: A Study of Nationwide Heart Transplant Registry Data.

BACKGROUND AND OBJECTIVES: The number of sensitized heart failure patients on waiting lists for heart transplantation (HTx) is increasing. Using the Korean Organ Transplantation Registry (KOTRY), a nationwide multicenter database, we investigated the prevalence and clinical impact of calculated panel-reactive antibody (cPRA) in patients undergoing HTx. METHODS: We retrospectively reviewed 813 patients who underwent HTx between 2014 and 2021. Patients were grouped according to peak PRA level as group A: patients with cPRA ≤10% (n= 492); group B: patients with cPRA >10%, <50% (n=160); group C patients with cPRA ≥50% (n=161). Post-HTx outcomes were freedom from antibody-mediated rejection (AMR), acute cellular rejection, coronary allograft vasculopathy, and all-cause mortality. RESULTS: The median follow-up duration was 44 (19-72) months. Female sex, re-transplantation, and pre-HTx renal replacement therapy were independently associated with an increased risk of sensitization (cPRA ≥50%). Group C patients were more likely to have longer hospital stays and to use anti-thymocyte globulin as an induction agent compared to groups A and B. Significantly more patients in group C had positive flow cytometric crossmatch and had a higher incidence of preformed donor-specific antibody (DSA) compared to groups A and B. During follow-up, group C had a significantly higher rate of AMR, but the overall survival rate was comparable to that of groups A and B. In a subgroup analysis of group C, post-transplant survival was comparable despite higher preformed DSA in a desensitized group compared to the non-desensitized group. CONCLUSIONS: Patients with cPRA ≥50% had significantly higher incidence of preformed DSA and lower freedom from AMR, but post-HTx survival rates were similar to those with cPRA <50%. Our findings suggest that sensitized patients can attain comparable post-transplant survival to non-sensitized patients when treated with optimal desensitization treatment and therapeutic intervention.

Erratum: Correction of Figures in the Article "Angiotensin II Type 1 Receptor Blocker, Fimasartan, Reduces Vascular Smooth Muscle Cell Senescence by Inhibiting the CYR61 Signaling Pathway".

This corrects the article on p. 615 in vol. 49, PMID: 31074217.

Impact of Everolimus Initiation and Corticosteroid Weaning During Acute Phase After Heart Transplantation on Clinical Outcome: Data from the Korean Organ Transplant Registry (KOTRY).

The effect of changes in immunosuppressive therapy during the acute phase post-heart transplantation (HTx) on clinical outcomes remains unclear. This study aimed to investigate the effects of changes in immunosuppressive therapy by corticosteroid (CS) weaning and everolimus (EVR) initiation during the first year post-HTx on clinical outcomes. We analyzed 622 recipients registered in the Korean Organ Transplant Registry (KOTRY) between January 2014 and December 2021. The median age at HTx was 56 years (interquartile range [IQR], 45-62), and the median follow-up time was 3.9 years (IQR 2.0-5.1). The early EVR initiation within the first year post-HTx and maintenance during the follow-up is associated with reduced the risk of primary composite outcome (all-cause mortality or re-transplantation) (HR, 0.24; 95% CI 0.09-0.68; p < 0.001) and cardiac allograft vasculopathy (CAV) (HR, 0.39; 95% CI 0.19-0.79; p = 0.009) compared with EVR-free or EVR intermittent treatment regimen, regardless of CS weaning. However, the early EVR initiation tends to increase the risk of acute allograft rejection compared with EVR-free or EVR intermittent treatment.

SCORE and SCORE2 in East Asian Population: A Performance Comparison.

Background: Systematic COronary Risk Evaluation 2 (SCORE2) and SCORE2-Older Persons (OP) models have been proposed as new cardiovascular risk evaluation tools. Objectives: This study evaluated the performance of SCORE/SCORE-OP and SCORE2/SCORE2-OP in the East Asian population by using population-based cohort data from the National Health Insurance Service (NHIS) Health Screening Cohort of Korea. Methods: A total of 324,384 NHIS examinees from 2004 to 2005 were divided into 5 age groups: 40-49 years, 50-59 years, 60-69 years,70-79 years, and more than 80 years. The examinees had their predicted cardiovascular disease risks calculated by using SCORE, SCORE2, SCORE-OP, and SCORE2-OP models. The low-risk model was applied on the basis of the cohort's observed event rates. The observed and predicted cardiovascular risks were compared. Results: A total of 324,384 subjects were included (mean age 51.4 ± 7.3 years; women, 37.9% for the SCORE/SCORE2 group and mean age 73.0 ± 2.8 years; women, 47.5% for the SCORE/SCORE2-OP group). Over a median follow-up of 9 years, cardiovascular events occurred in 15.0% and 28.9% in SCORE/SCORE2 and SCORE/SCORE2-OP groups, respectively. The SCORE/SCORE-OP model underestimated cardiovascular disease risk in young men (aged 40-49 years) and women (aged 40-59 years) and overestimated it in older age groups. In contrast, SCORE2/SCORE2-OP invariably overestimated the risk in all age groups and sexes. SCORE2/SCORE2-OP showed no improvement in Harrell's concordance index (C-index) compared with SCORE/SCORE-OP. Calibration plots favored SCORE2 over SCORE but not SCORE2-OP over SCORE-OP. Conclusions: Both SCORE2/SCORE2-OP and SCORE/SCORE-OP overestimated cardiovascular disease risk with low performance. SCORE2/SCORE2-OP showed slight improvement over older versions, but modifications are necessary for the East Asian population.

Association Between Orthostatic Hypertension and Frailty Among Older Patients With Hypertension.

BACKGROUND: Frailty frequently coexists with hypertension in older patients. We aimed to evaluate the association between frailty and positional change in blood pressure, especially orthostatic hypertension. METHODS: Participants were recruited from 12 University hospitals in South Korea. Using a digital device, trained research nurses measured blood pressure in the supine and standing positions. Physical frailty was evaluated using the Korean version of the FRAIL questionnaire, gait speed, and handgrip strength. Orthostatic hypertension was defined as a ≥20-mm Hg increase in systolic blood pressure within 3 minutes of standing and upright systolic blood pressure of ≥140 mm Hg. RESULTS: We analyzed the data of 2065 participants who had been enrolled until December 31, 2022. The mean age was 73.2±5.6 years, and 52.0% were female. The mean blood pressure was 137.1±14.9/75.1±9.7 mm Hg. Among the participants, 1886 (91.3%) showed normal response after standing, but 94 (4.6%) had orthostatic hypertension, and 85 (4.1%) had orthostatic hypotension. Orthostatic hypertension was associated with female sex, obesity, cognitive function, physical frailty, and lower quality of life. In the multivariable analysis, body mass index and frailty status were independently associated with orthostatic hypertension. CONCLUSIONS: Orthostatic hypertension is associated with physical frailty, cognitive impairment, and low quality of life in older patients with hypertension. Therefore, evaluation of orthostatic blood pressure changes to confirm orthostatic hypertension or hypotension in frail older adults will serve as an important diagnostic procedure in vulnerable patients. Further studies are required to identify the underlying mechanisms of this association.

Developing a national surveillance system for stroke and acute myocardial infarction using claims data in the Republic of Korea: a retrospective study.

BACKGROUND: Limited information is available concerning the epidemiology of stroke and acute myocardial infarction (AMI) in the Republic of Korea. This study aimed to develop a national surveillance system to monitor the incidence of stroke and AMI using national claims data. METHODS: We developed and validated identification algorithms for stroke and AMI using claims data. This validation involved a 2-stage stratified sampling method with a review of medical records for sampled cases. The weighted positive predictive value (PPV) and negative predictive value (NPV) were calculated based on the sampling structure and the corresponding sampling rates. Incident cases and the incidence rates of stroke and AMI in the Republic of Korea were estimated by applying the algorithms and weighted PPV and NPV to the 2018 National Health Insurance Service claims data. RESULTS: In total, 2,200 cases (1,086 stroke cases and 1,114 AMI cases) were sampled from the 2018 claims database. The sensitivity and specificity of the algorithms were 94.3% and 88.6% for stroke and 97.9% and 90.1% for AMI, respectively. The estimated number of cases, including recurrent events, was 150,837 for stroke and 40,529 for AMI in 2018. The age- and sex-standardized incidence rate for stroke and AMI was 180.2 and 46.1 cases per 100,000 person-years, respectively, in 2018. CONCLUSION: This study demonstrates the feasibility of developing a national surveillance system based on claims data and identification algorithms for stroke and AMI to monitor their incidence rates.

Characteristics According to Frailty Status Among Older Korean Patients With Hypertension.

BACKGROUND: As the prevalence of hypertension increases with age and the proportion of the older population is also on the rise, research on the characteristics of older hypertensive patients and the importance of frailty is necessary. This study aimed to identify clinical characteristics of older hypertension in Korea and to investigate these characteristics based on frailty status. METHODS: The HOW to Optimize eLDerly systolic BP (HOWOLD-BP) is a prospective, multicenter, open-label, randomized clinical trial that aims to compare intensive (target systolic blood pressure [SBP] ≤ 130 mmHg) with standard (target SBP ≤ 140 mmHg) treatment to reduce cardiovascular events in older hypertensive Korean patients aged ≥ 65 years. Data were analyzed through a screening assessment of 2,085 patients recruited from 11 university hospitals. Demographic, functional (physical and cognitive), medical history, laboratory data, quality of life, and medication history of antihypertensive drugs were assessed. RESULTS: The mean age was 73.2 years (standard deviation ± 5.60), and 48.0% (n = 1,001) were male. Prevalent conditions included dyslipidemia (66.5%), obesity (body mass index ≥ 25 kg/m², 53.6%), and diabetes (28.9%). Dizziness and orthostatic hypotension were self-reported by 1.6% (n = 33) and 1.2% (n = 24), respectively. The majority of patients were on two antihypertensive drugs (48.4%), while 27.5% (n = 574) and 20.8% (n = 433) were on 1 and 3 antihypertensive medications, respectively. Frail to pre-frail patients were older and also tended to have dependent instrumental activities of daily living, slower gait speed, weaker grip strength, lower quality of life, and lower cognitive function. The frail to pre-frail group reported more dizziness (2.6% vs. 1.2%, P < 0.001) and had concerning clinical factors, including lower glomerular filtration rate, more comorbidities such as diabetes, stroke, and a history of admission. Frail to pre-frail older hypertensive patients used slightly more antihypertensive medications than robust older hypertensive patients (1.95 vs. 2.06, P = 0.003). Pre-frail to frail patients often chose beta-blockers as a third medication over diuretics. CONCLUSION: This study described the general clinical characteristics of older hypertensive patients in Korea. Frail hypertensive patients face challenges in achieving positive clinical outcomes because of multifactorial causes: they are older, have more morbidities, decreased function, lower quality of life and cognitive function, and take more antihypertensive medications. Therefore, it is essential to comprehensively evaluate and monitor disease-related or drug-related adverse events more frequently during regular check-ups, which is necessary for pre-frail to frail older patients with hypertension. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0003787.

Management of Hypertension in the Asia-Pacific Region: A Structured Review.

This article reviews available evidence regarding hypertension management in the Asia-Pacific region, focussing on five research questions that deal with specific aspects: blood pressure (BP) control, guideline recommendations, role of renin-angiotensin-aldosterone system (RAAS) inhibitors in clinical practice, pharmacological management and real-world adherence to guideline recommendations. A PubMed search identified 2537 articles, of which 94 were considered relevant. Compared with Europeans, Asians have higher systolic/diastolic/mean arterial BP, with a stronger association between BP and stroke. Calcium channel blockers are the most-commonly prescribed monotherapy in Asia, with significant variability between countries in the rates of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin-receptor blockers (ARBs) and single-pill combination (SPC) use. In clinical practice, ARBs are used more commonly than ACEis, despite the absence of recommendation from guidelines and clinical evidence supporting the use of one class of drug over the other. Ideally, antihypertensive treatment should be tailored to the individual patient, but currently there are limited data on the characteristics of hypertension in Asia-Pacific individuals. Large outcome studies assessing RAAS inhibitor efficacy and safety in multi-national Asian populations are lacking. Among treated patients, BP control rates were ~ 35 to 40%; BP control in Asia-Pacific is suboptimal, and disproportionately so compared with Western nations. Strategies to improve the management of hypertension include wider access/availability of affordable treatments, particularly SPCs (which improve adherence), effective public health screening programs targeting patients to drive health-seeking behaviours, an increase in physician/patient awareness and early implementation of lifestyle changes. A unified Asia-Pacific guideline on hypertension management with pragmatic recommendations, particularly in resource-limited settings, is essential.

Eligibility and Cost-Utility Analysis of Dapagliflozin in Patients with Heart Failure Across the Whole Spectrum of Ejection Fraction in South Korea.

BACKGROUND: The DAPA-HF and DELIVER trials demonstrated the clinical benefits of dapagliflozin in heart failure (HF) patients across the entire ejection fraction (EF) spectrum. However, further investigation is needed for the real-world application of dapagliflozin in HF patients. This study examines the proportion of real-world HF patients eligible for dapagliflozin and evaluates the cost-effectiveness of adding dapagliflozin to current HF therapy. METHODS: Data from the nationwide prospective registry, the Korean Acute Heart Failure (KorAHF) registry, were used to determine dapagliflozin eligibility based on the enrollment criteria of the DAPA-HF/DELIVER trials. A cost-utility analysis was conducted using a Markov model to assess the cost-effectiveness of dapagliflozin by comparing it to the standard of care. RESULTS: Out of 5178 KorAHF patients, 48.7% met the enrollment criteria of the DAPA-HF/DELIVER trials, while 89.5% met the label criteria (US Food and Drug Administration, European Medicines Agency, and Korean Ministry of Food and Drug Safety). Eligibility was highest among HF patients with preserved EF (55.3% vs. HF with mildly reduced EF and HF with reduced EF 46.4%). Dapagliflozin proved to be cost-effective, with an incremental cost-effectiveness ratio (ICER) of 4557 US dollar (US$) per quality-adjusted life year, which falls below the US$18,182 willingness-to-pay threshold. The cost-effectiveness benefit was more pronounced in patients with a left ventricular EF (LVEF) ≤ 40% (ICER US$3279 for LVEF ≤ 40% vs. US$8383 for LVEF > 40%). CONCLUSIONS: Discrepancies in dapagliflozin eligibility were observed between real-world data and clinical trial results. The addition of dapagliflozin to HF therapy proved to be highly cost-effective across the entire EF spectrum.

Association of epicardial adipose tissue with metabolic risk factors on cardiovascular outcomes: serial coronary computed tomography angiography study.

BACKGROUND/AIMS: Epicardial adipose tissue (EAT) shares pathophysiological properties with other visceral fats and potentially triggers local inflammation. However, the association of EAT with cardiovascular disease (CVD) is still debatable. The study aimed to observe the changes and associations in EAT and risk factors over time, as well as to investigate whether EAT was associated with CVD. METHODS: A total of 762 participants from Seoul National University Hospital (SNUH) and SNUH Gangnam Center were included in this study. EAT was measured using coronary computed tomography angiography. RESULTS: Baseline EAT level was positively associated with body mass index (BMI), calcium score, atherosclerotic cardiovascular disease (ASCVD) 10-year risk score, glucose, triglycerides (TG)/high-density lipoprotein (HDL), but not with total cholesterol, low-density lipoprotein (LDL). At follow-up, EAT levels increased in all groups, with low EAT groups demonstrating a significant increase in EAT per year. Change in EAT was associated with a change in BMI, TG/HDL, and glucose, while changes in LDL, calcium score, and ASCVD 10-year risk score were not associated. Although calcium score and ASCVD 10-year risk score were associated with CVD events, baseline information of EAT, baseline EAT/body surface area, or EAT change was not available. CONCLUSION: Metabolic risks, e.g., BMI, TG/HDL, and glucose, were associated with EAT change per year, whereas classical CVD risks, e.g., LDL, calcium score, and ASCVD 10-year risk score, were not. The actual CVD event was not associated with EAT volume, warranting future studies combining qualitative assessments with quantitative ones.

Real-World Eligibility and Cost-Effectiveness Analysis of Empagliflozin for Heart Failure in Korea.

BACKGROUND: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. METHODS: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). RESULTS: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). CONCLUSION: There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843.

Feasibility and Effectiveness of a Ring-Type Blood Pressure Measurement Device Compared With 24-Hour Ambulatory Blood Pressure Monitoring Device.

BACKGROUNDS AND OBJECTIVES: This study aimed to evaluate the applicability and precision of a ring-type cuffless blood pressure (BP) measurement device, CART-I Plus, compared to conventional 24-hour ambulatory BP monitoring (ABPM). METHODS: Forty patients were recruited, and 33 participants were included in the final analysis. Each participant wore both CART-I Plus and ABPM devices on the same arm for approximately 24 hours. BP estimation from CART-I Plus, derived from photoplethysmography (PPG) signals, were compared with the corresponding ABPM measurements. RESULTS: The CART-I Plus recorded systolic blood pressure (SBP)/diastolic blood pressure (DBP) values of 131.4±14.1/81.1±12.0, 132.7±13.9/81.9±11.9, and 128.7±14.6/79.3±12.2 mmHg for 24-hour, daytime, and nighttime periods respectively, compared to ABPM values of 129.7±11.7/84.4±11.2, 131.9±11.6/86.3±11.1, and 124.5±13.6/80.0±12.2 mmHg. Mean differences in SBP/DBP between the two devices were 1.74±6.69/-3.24±6.51 mmHg, 0.75±7.44/-4.41±7.42 mmHg, and 4.15±6.15/-0.67±5.23 mmHg for 24-hour, daytime, and nighttime periods respectively. Strong correlations were also observed between the devices, with r=0.725 and r=0.750 for transitions in SBP and DBP from daytime to nighttime, respectively (both p<0.001). CONCLUSIONS: The CART-I Plus device, with its unique ring-type design, shows promising accuracy in BP estimation and offers a potential avenue for continuous BP monitoring in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06084065.

Sex differences in the applicability of Western cardiovascular disease risk prediction equations in the Asian population.

AIMS: Cardiovascular diseases (CVDs) are the most common cause of death, but they can be effectively managed through appropriate prevention and treatment. An important aspect in preventing CVDs is assessing each individual's comprehensive risk profile, for which various risk engines have been developed. The important keys to CVD risk engines are high reliability and accuracy, which show differences in predictability depending on disease status or race. Framingham risk score (FRS) and the atherosclerotic cardiovascular disease risk equations (ASCVD) were applied to the Korean population to assess their suitability. METHODS: A retrospective cohort study was conducted using National Health Insurance Corporation sample cohort from 2003 to 2015. The enrolled participants over 30 years of age and without CVD followed-up for 10 years. We compared the prediction performance of FRS and ASCVD and calculated the relative importance of each covariate. RESULTS: The AUCs of FRS (men: 0.750; women: 0.748) were higher than those of ASCVD (men: 0.718; women: 0.727) for both sexes (Delong test P <0.01). Goodness of fits (GOF) were poor for all models (Chi-square P < 0.001), especially, underestimation of the risk was pronounced in women. When the men's coefficients were applied to women's data, AUC (0.748; Delong test P<0.01) and the GOF (chi-square P = 0.746) were notably improved in FRS. Hypertension was found to be the most influential variable for CVD, and this is one of the reasons why FRS, having the highest relative weight to blood pressure, showed better performance. CONCLUSION: When applying existing tools to Korean women, there was a noticeable underestimation. To accurately predict the risk of CVD, it was more appropriate to use FRS with men's coefficient in women. Moreover, hypertension was found to be a main risk factor for CVD.

Sex differences in clinical characteristics and long-term outcome in patients with heart failure: data from the KorAHF registry.

BACKGROUND/AIMS: Sex differences in the prognosis of heart failure (HF) have yielded inconsistent results, and data from Asian populations are even rare. This study aimed to investigate sex differences in clinical characteristics and long-term prognosis among Korean patients with HF. METHODS: A total of 5,625 Korean patients hospitalized for acute HF were analyzed using a prospective multi-center registry database. Baseline clinical characteristics and long-term outcomes including HF readmission and death were compared between sexes. RESULTS: Women were older than men and had worse symptoms with higher N-terminal pro B-type natriuretic peptide levels. Women had a significantly higher proportion of HF with preserved ejection fraction (HFpEF). There were no significant differences in in-hospital mortality and rate of guideline-directed medical therapies in men and women. During median follow- up of 3.4 years, cardiovascular death (adjusted hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.07-1.78; p = 0.014), and composite outcomes of death and HF readmission (adjusted HR, 1.13; 95% CI, 1.01-1.27; p = 0.030) were significantly higher in men than women. When evaluating heart failure with reduced ejection fraction (HFrEF) and HFpEF separately, men were an independent risk factor of cardiovascular death in patients with HFrEF. Clinical outcome was not different between sexes in HFpEF. CONCLUSION: In the Korean multi-center registry, despite having better clinical characteristics, men exhibited a higher risk of all-cause mortality and readmission for HF. The main cause of these disparities was the higher cardiovascular mortality rate observed in men compared to women with HFrEF.

Differential effect of left ventricular unloading according to the aetiology of cardiogenic shock.

AIMS: Evidence for the effectiveness of left ventricular (LV) unloading in patients who received venoaterial extracorporeal membrane oxygenation (VA-ECMO) for acute myocardial infarction (AMI) or non-AMI induced cardiogenic shock (CS) is limited. The aim of the present study was to compare the effect of LV unloading in AMI-induced and non-AMI-induced CS. METHODS AND RESULTS: This is a single-centre retrospective observational study of patients with CS undergoing VA-ECMO from January 2011 to March 2019. Patients were classified as AMI-induced and non-AMI-induced CS. The association of LV unloading with 90-day mortality in both groups was analysed using Cox proportional hazard regression analysis. RESULTS: Of the 128 CS patients, 71 (55.5%) patients received VA-ECMO due to AMI-induced CS, and the remaining 57 (44.5%) received VA-ECMO due to non-AMI-induced CS. The modality of LV unloading was predominantly with IABP (94.5%). In the AMI-induced CS group, LV unloading did not reduce 90-day mortality (adjusted hazard ratio 1.96, 95% confidence interval 0.90-4.27, P = 0.089). However, in the non-AMI-induced CS group, LV unloading combined with VA-ECMO significantly reduced 90-day mortality (adjusted hazard ratio 0.37, 95% confidence interval 0.14-0.96, P = 0.041; P for interaction = 0.029) as compared with those who received VA-ECMO alone. CONCLUSIONS: LV unloading with VA-ECMO may reduce 90-day mortality compared with VA-ECMO alone in patients with non-AMI-induced CS, but not in AMI-induced CS.

Lifestyle management of hypertension: International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension.

Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools.

Metformin treatment is associated with improved survival in diabetic patients hospitalized with acute heart failure: A prospective observational study using the Korean acute heart failure registry data.

AIMS: Although the hypothesis that metformin is beneficial for patients with diabetes and heart failure (HF) has been steadily raised, there is limited data on metformin use in patients with acute HF. We analyzed the association of metformin on all-cause mortality in hospitalized patients with type 2 diabetes and acute HF. METHODS: The Korean Acute Heart Failure registry prospectively enrolled patients hospitalized for acute HF from 2011 to 2014. Among this cohort, we analyzed patients with diabetes with baseline estimated glomerular filtration rate (eGFR) of 30 ml/min/1.73 m2 or more. We analyzed the all-cause mortality and re-hospitalization for HF within 1 year after discharge. Inverse probability treatment weighting method was used to adjust baseline differences on metformin treatment. RESULTS: The study analyzed data from 1,309 patients with HF and diabetes (mean age 69 years, 56 % male). Among them, 613 (47 %) patients were on metformin at admission. During the median follow-up period of 11 months, 132 (19 %) and 74 (12 %) patients not receiving and receiving metformin treatment died, respectively. The mortality rate was lower in metformin users than in non-users (hazard ratio 0.616 [0.464-0.819] P<0.001). After adjustment, metformin was significantly associated with a lower risk for the mortality (hazard ratio 0.677 [0.495-0.928] P=0.015). In subgroup analyses, this association remains significant irrespective of baseline kidney function (eGFR <60 or ≥60 ml/min/1.73 m2, P-for-interaction=0.176) or left ventricular ejection fraction (<40 %, 40-49 %, or ≥50 %, P-for-interaction=0.224). CONCLUSIONS: Metformin treatment at the time of admission was associated with a lower risk for 1-year mortality in patients with diabetes, hospitalized for acute HF.