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Soon Jun Hong,1,* Ki-Chul Sung,2,* Sang-Wook Lim,3 Seok-Yeon Kim,4 Weon Kim,5 Jinho Shin,6 Sungha Park,7 Hae-Young Kim,8 Moo-Yong Rhee9,10 On behalf of MH_APOLLO to read: HM_APOLLO1Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea; 2Department of Cardiology, Gangbuk Samsung Hospital, Sungkyunkwan University College of Medicine, Seoul, Republic of Korea; 3Cardiology Division, Cardiac Center, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea; 4Department of Cardiology, Seoul Medical Center, Seoul, Republic of Korea; 5Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul, Republic of Korea; 6Division of Cardiology, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea; 7Department of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 8Department of Health Policy and Management, College of Health Science & Department of Health Care Science, Graduate School, Korea University, Seoul, Republic of Korea; 9Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang-si, Gyeonggi, Republic of Korea; 10College of Medicine, Dongguk University, Gyeongju-si, Gyeongbuk, Republic of Korea*These authors contributed equally to this workCorrespondence: Moo-Yong RheeCardiovascular Center, Dongguk University Ilsan Hospital, 27 Dongguk-Ro, Ilsandong-Gu, Goyang-si, Gyeonggi-do 10326, Republic of KoreaTel +82 31 961 5775Fax +82 31 961 7786Email mooyong_rhee@dumc.or.krPurpose: We evaluated the dose-responsiveness, efficacy, and safety of low-dose triple antihypertensive combination therapies in patients with mild-to-moderate hypertension.Patients and Methods: After a 1 to 2-week placebo run-in period, 248 patients were randomized to the half-dose triple combination (amlodipine 2.5 mg + losartan 25 mg + chlorthalidone 6.25 mg), third-dose triple combination (amlodipine 1.67 mg + losartan 16.67 mg + chlorthalidone 4.17 mg), quarter-dose triple combination (amlodipine 1.25 mg + losartan 12.5 mg + chlorthalidone 3.13mg), amlodipine 10mg, amlodipine 5mg, losartan 100mg, and placebo groups for 8 weeks. The primary outcome was the mean change in systolic blood pressure (SBP) from baseline to week 8.Results: The placebo-corrected SBP reductions of the half-dose, third-dose, quarter-dose combination, amlodipine 10 mg, amlodipine 5 mg and losartan 100 mg treatments were − 17.2, − 19.5, − 14.9, − 18.5, − 11.3 and − 9.9 mmHg, respectively. The BP control and response rates were significantly higher in the half-dose, third-dose, and quarter-dose combination groups than in the placebo group (all p < 0.01). Despite no intergroup differences in study drug-related adverse events, ankle circumference increased significantly in the amlodipine group compared to those in the combination treatment groups. The quarter-dose combination, amlodipine 5 mg, and losartan 100 mg groups showed similar SBP reduction and BP response rates. The SBP reduction and BP response rate in the third-dose and half-dose combination groups were not significantly different from those in the amlodipine 10 mg group but superior to those in the losartan 100 mg group.Conclusion: Low-dose triple combination therapies could be effective as antihypertensive therapies.Trial Registration: ClinicalTrials.gov identifier NCT03897868.Keywords: hypertension, blood pressure, combination therapy, low-dose, amlodipine, losartan, chlorthalidone

Moo-Yong Rhee,1 Cheol Ho Kim,2 Youngkeun Ahn,3 Joon-Han Shin,4 Seung Hwan Han,5 Hyun-Jae Kang,6 Soon Jun Hong,7 Hae-Young Kim8 1Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, Republic of Korea; 2Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 3Division of Cardiology, Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Republic of Korea; 4Department of Cardiology, Ajou University Medical Center, Suwon, Republic of Korea; 5Division of Cardiology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea; 6Department of Internal Medicine, Seoul National University Cardiovascular Center, Seoul National University Hospital, Seoul, Republic of Korea; 7Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Republic of Korea; 8Department of Health Policy and Management, College of Health Science & Department of Public Health Science, Graduate School, Korea University, Seoul, Republic of KoreaCorrespondence: Cheol Ho Kim Department of Internal MedicineSeoul National University Bundang Hospital, Seongnam, Republic of KoreaTel +82 31 787 7001Fax +82 31 787 4051Email cheolkim55@gmail.comPurpose: We evaluated the efficacy and safety of nebivolol and rosuvastatin combination treatment in patients with hypertension and hyperlipidemia.Patients and Methods: Eligible patients, after more than 4 weeks of therapeutic lifestyle change, were randomly assigned to three groups: 5 mg nebivolol plus 20 mg rosuvastatin (NEBI/RSV), 20 mg rosuvastatin (RSV), or 5 mg nebivolol (NEBI). Treatments lasted 8 weeks.Results: Efficacy was analyzed using data from 276 patients. Sitting systolic and diastolic blood pressures differed between the NEBI/RSV and RSV groups (LSmean difference = − 5.89 and − 5.99 mmHg; 95% confidence interval [CI] = − 9.88 to − 1.90 mmHg and − 8.13 to − 3.84 mmHg, respectively). Reductions in the two pressures did not differ between the NEB/RSV and NEB groups. The percent reduction in low-density lipoprotein (LDL) cholesterol differed between the NEBI/RSV and NEBI groups (LSmean difference = − 47.76%, 95% CI = − 52.69 to − 42.84%) but not between the NEBI/RSV and RSV groups. The blood pressure (BP) control rate was higher in the NEBI/RSV group than in the RVS group (51.09% vs 29.67%, p = 0.003). The LDL cholesterol goal achievement rate was higher in the NEBI/RSV group than in the NEBI group (85.87% vs 11.83%, p < 0.001). The incidence of adverse drug reactions in the NEBI/RSV, RSV, and NEBI groups was 8.51%, 7.45%, and 8.60%, respectively (p = 0.950).Conclusion: Nebivolol plus rosuvastatin treatment is effective in reducing BP and LDL cholesterol levels and is safe in patients with hypertension and hypercholesterolemia without the loss of BP or the LDL cholesterol-lowering effect of each drug.Trial Registration: CRIS registration number KCT0002148.Keywords: hypertension, hypercholesterolemia, nebivolol, rosuvastatin

Hong SJ, Sung KC, Lim SW, et al. Drug Des Devel Ther. 2020;14:5735–5746 Page 5735, the affiliation for Ki-Chul Sung should be “2Department of Cardiology, Kangbuk Samsung Hospital, Sungkyunkwan University College of Medicine, Seoul, Republic of Korea”. Page 5744, Acknowledgment section, 4th-6th lines, “....Hospital, Korea University College of Medicine), Ki- Chul Sung (Gangbuk Samsung Hospital, Sungkyunkwan University College of Medicine), Sang-Wook Lim (CHA.....” should read “......Hospital, Korea University College of Medicine), Ki- Chul Sung (Kangbuk Samsung Hospital, Sungkyunkwan University College of Medicine), Sang-Wook Lim (CHA......” The authors apologize for these errors. Read the original article

Namyi Gu,1,2 Joo-Youn Cho,3 Kwang-Hee Shin,4 In-Jin Jang,3 Moo-Yong Rhee2,5 1Department of Clinical Pharmacology and Therapeutics, 2Clinical Trial Center, Dongguk University College of Medicine and Ilsan Hospital, Goyang, 3Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 4Pharmacotherapy & Translational Research Lab., College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, 5Cardiovascular Center, Dongguk University College of Medicine and Ilsan Hospital, Goyang, Republic of Korea Abstract: A low sodium diet enhances the hemodynamic effect of renin–angiotensin system blockers. It was suggested that the substrates of P-glycoprotein or cytochrome P450 3A4 were reduced on a high sodium diet. This study aimed to investigate the influence of high sodium diet on the pharmacokinetics and pharmacodynamics of fimasartan, which is a substrate of cytochrome P450 3A4 but not P-glycoprotein. The study design was a two-diet, two-period, two-sequence, randomized, open-label, and crossover with 1-week washout for diet. Eligible subjects were fed with either low sodium (50 mEq/day) diet or high sodium diet (300 mEq/day) for 7 days in the first hospitalization period and the other diet in the second period. On the seventh morning of each period, subjects received a single dose of fimasartan 60 mg in a fasted state. The serial plasma concentrations of fimasartan, serum aldosterone concentration (SAC), and plasma renin activity (PRA) were measured for pharmacokinetic–pharmacodynamic analysis. Sixteen subjects completed the study satisfying the compliance test for diets. Although the mean systemic exposure of fimasartan is slightly (≈10%) decreased on a high sodium diet, the difference was not statistically or clinically significant (P>0.05). The SAC and PRA after fimasartan administration were highly dependent on their baseline levels. The dietary sodium content influenced the baseline of SAC and PRA, but did not influence the ratio change of SAC and PRA after fimasartan treatment. The ratio change of SAC after fimasartan treatment was correlated to the systemic exposure of fimasartan (P0.05). In conclusion, the pharmacokinetics of fimasartan and ratio changes of SAC and PRA after fimasartan treatment were not significantly influenced by dietary sodium content. Keywords: aldosterone, renin activity, angiotensin receptor blocker, aldosterone, renin, cytochrome P450 3A4, P-glycoprotein, healthy, sodium diet

Moo-Yong Rhee,1 Sang Hong Baek,2 Weon Kim,3 Chang Gyu Park,4 Seung Woo Park,5 Byung-Hee Oh,6 Sang-Hyun Kim,7 Jae-Joong Kim,8 Joon-Han Shin,9 Byung-Su Yoo,10 Se-Joong Rim,11 Jong-Won Ha,12 Joon Hyung Doh,13 Youngkeun Ahn,14 Jei Keon Chae,15 Jeong Bae Park,16 Soon-Kil Kim,17 Cheol Ho Kim18 1Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, 2Catholic University of Korea, Seoul St Mary’s Hospital, Seoul, 3Cardiovascular Department of Internal Medicine, Kyung Hee University Medical Center, Seoul, 4Division of Cardiology, Guro Hospital, Korea University College of Medicine, Seoul, 5Division of Cardiology, Samsung Medical Center, Seoul, 6Department of Internal Medicine, Seoul National University Hospital, Seoul, 7Division of Cardiology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, 8Division of Cardiology, Asan Medical Center, Seoul, 9Division of Cardiology, Ajou University Hospital, Suwon, 10Division of Cardiology, Wonju Severance Christian Hospital, Wonju, 11Division of Cardiology, GangNam Severance Hospital, Seoul, 12Division of Cardiology, Severance Hospital, Seoul, 13Division of Cardiology, Inje University Ilsan Hospital, Goyang, 14Department of Cardiology, Chonnam National University Hospital, Gwangju, 15Chonbuk National University Hospital, Jeonju, 16Department of Cardiology, Cheil General Hospital, Dankook University College of Medicine, Seoul, 17Department of Cardiology, Hanyang University Guri Hospital, Guri, 18Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea Background: The study reported here compared the blood pressure (BP)-lowering efficacy of fimasartan alone with that of fimasartan/hydrochlorothiazide (HCTZ) combination in patients whose BP goal was not achieved after 4 weeks of treatment with once-daily fimasartan 60 mg.Methods: Patients with sitting diastolic blood pressure (siDBP) ≥90 mmHg with 4 weeks of once-daily fimasartan 60 mg were randomly assigned to receive either once-daily fimasartan 60 mg/HCTZ 12.5 mg or fimasartan 60 mg for 4 weeks. After 4 weeks, the dose was increased from fimasartan 60 mg/HCTZ 12.5 mg to fimasartan 120 mg/HCTZ 12.5 mg or from fimasartan 60 mg to fimasartan 120 mg if siDBP was ≥90 mmHg.Results: Of the 263 randomized patients, 256 patients who had available efficacy data were analyzed. The fimasartan/HCTZ treatment group showed a greater reduction of siDBP compared to the fimasartan treatment group at Week 4 (6.88±8.10 mmHg vs 3.38±7.33, P=0.0008), and the effect persisted at Week 8 (8.67±9.39 mmHg vs 5.02±8.27 mmHg, P=0.0023). Reduction of sitting systolic BP in the fimasartan/HCTZ treatment group was also greater than that in the fimasartan treatment group (at Week 4, 10.50±13.76 mmHg vs 5.75±12.18 mmHg, P=0.0069 and, at Week 8, 13.45±15.15 mmHg vs 6.84±13.57 mmHg, P=0.0007). The proportion of patients who achieved a reduction of siDBP ≥10 mmHg from baseline and/or a mean siDBP

Objective: Accelerated atherosclerosis in inflammatory rheumatic diseases such as ankylosing spondylitis (AS) stands out among the leading causes of morbidity and mortality. We assessed the correlation between subclinical carotid atherosclerosis and its related clinical parameters in AS patients.Methods: Twenty-eight patients (23 males, 5 females) with AS and 27 sex- and age-matched controls were consecutively recruited to this study. We estimated the carotid intima-media thickness (IMT) and parameters related to arterial elastic properties, including the distensibility coefficient (DC), stiffness index (beta), and incremental elastic modulus (E(inc)) using high-resolution ultrasonography. Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) were measured using enzyme-linked immunosorbent assay (ELISA).Results: Carotid IMT values and arterial elastic parameters in AS patients showed no statistical significance compared to those of controls (0.57+/-0.07 vs 0.55+/-0.05, p=0.387 for IMT, 28.45+/-9.23 vs 31.93+/-9.52, p=0.175 for DC, 2.32+/-0.18 vs 2.29+/-0.15, p=0.559 for stiffness index (beta), and 0.14+/-0.05 vs 0.12+/-0.03, p=0.116 for E(inc)). The serum level of IL-6 in AS patients was significantly different compared with controls (p=0.001), but not in serum levels of TNF-alpha and MCP-1 (p=0.162, p=0.087, respectively). Carotid IMT and all arterial elastic parameters calculated in this study were not found to be associated with serum levels of TNF-alpha, IL-6, and MCP-1.Conclusion: This cross-sectional study showed that carotid IMT and parameters related with arterial elastic properties in young AS patients without clinically evident cardiovascular risk factors were not different from those of sex- and age-matched healthy controls. Serum levels of TNF-alpha, IL-6, and MCP-1 did not reflect the degree of carotid subclinical atherosclerosis. However, these findings should be confirmed further in a larger population. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the characteristics of out-of-office blood pressure (BP) measurements in patients with apparent treatment-resistant hypertension (aRH) enrolled from 15 tertiary care centers in South Korea. aRH was defined as having uncontrolled office BP ≥ 130/80 mmHg despite receiving three classes of antihypertensive medication or any level of BP despite receiving ≥4 classes of antihypertensive medication. Patients with complete data for office BP, 24-h ambulatory BP monitoring (ABPM), and home BP measurements at baseline were included. BP control status between ABPM and home BP measurements was compared. Out of 1457 patients, 823 meeting the enrollment criteria were included (mean age: 59.9 ± 13.6 years; 57.5% male patients). Among them, 7.2% had controlled BP, 8.7% had whitecoat uncontrolled hypertension, 15.1% had masked uncontrolled hypertension, and 69% had sustained hypertension, as measured through baseline ABPM. Additionally, 43% of patients with controlled BP based on home BP measurement had nocturnal hypertension. Relying solely on home BP measurement may result in misclassifying 70% of patients as having either controlled BP or whitecoat uncontrolled BP. This study reaffirms the circadian pattern of resistant hypertension, characterized by a higher prevalence of non-dipping and rising patterns, even in patients with BP controlled based on ABPM. Considering the persistent difference between home BP measurement and ABPM, even at a lower home BP threshold, integrating both measurements into the management of aRH is advisable., Competing Interests: Compliance with ethical standards. Conflict of interest: JS have nothing to declare. CJL received lecture honoraria from Novartis, Hanmi Pharmaceutical, Yuhan, Boryung Pharmaceutical, and Daiichi Sankyo. DHK received honoraria from Viatris, Organon, Boryoung, Hanmi, Daewoong, Celltrion, Daiichi Sankyo, and Chong Kun Dang and a research grant from Daewoong Pharmaceutical. SYK received honoraria from Norvatis, Amgen Korea, BMS Korea, Bayer Korea, Viatris, Boryoung, Hanmi, Menarini, JW Pharmaceutical, Inno N, Dongkook, Yuhan, Chong Kun Dang, GC Biopharma, and Daewon. JHP received honoraria from Viatris, Jeil, Boryoung, Daewoong, Hanmi, Yuhan, Chong Kun Dang, BMS. ICK received honoraria from Abbott, Novartis, Yuhan, Viatris, Organon, Boryoung, Hanmi, Daewoong, Celltrion, Servier, Daiichi Sankyo, Chong Kun Dang, and Daewon. JHL received honoraria from Daewoong Pharmaceutical, Handok Pharmaceuticals, Novartis, Chong Kun Dang Pharmaceutical Corp, Menarini Korea, Samjin Pharmaceuticals Co. Ltd, Daiichi Sankyo Korea, Hanmi Pharmaceutical, Yuhan Corporation, Boryung Pharmaceutical, Bayer. HYL received honoraria from Viatris, Organon, Boryoung, Hanmi, Daewoong, Donga, Celltrion, Servier, Daiichi Sankyo, Chong Kun Dang, and Daewon, and a research grant from Daiichi Sankyo. HYL also received consultation fee from Skylab. JWC received honoraria from Bayer, Astrazeneca, Organon, Hanmi, Yuhan, Daewoong, Chong Kun Dang, JW, Boryoung, GC Corp, Donga, Handok, Ildong, Jeil, Daewon, Ahn-gook, Samjin, Daiichi Sankyo, Otsuka, Mitsubishi Tanabe, Hyundai, Kuhnil, Bukwang and Aju. JWC also received research grants from Handok, Daewon, Boryung, GC Corp, Addpharma, and Kyung Dong. SHI received honoraria from Boryoung, Daewoong, Donga, Celltrion, Servier, Daiichi Sankyo, and Menarini, and a research grant from Daiichi Sankyo. SHI has received consultation fee from Skylab. JS received honoraria from Boryoung, Daiichi Sankyo, Chong Kun Dang, and Inno-N and consultaion fee from Skylab and Inbody. SP received honoraria from Viatris, Organon, Boryoung, Hanmi, Daewoong, Donga, Celltrion, Servier, Daiichi Sankyo, Chong Kun Dang, and Daewon, and a research grant from Daiichi Sankyo. SP has received consultation fee from Skylab. Also, SP has received stock option from Mediwhale. Others have nothing to declare., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Importance: Antiplatelet monotherapy in the chronic maintenance period for patients with high bleeding risk (HBR) and those who have undergone complex percutaneous coronary intervention (PCI) has not yet been explored., Objective: To compare clopidogrel vs aspirin monotherapy in patients with HBR and/or PCI complexity., Design, Setting, and Participants: This post hoc analysis of the multicenter HOST-EXAM Extended study, an open-label trial conducted across 37 sites in South Korea, enrolled patients from 2014 to 2018 with up to 5.9 years of follow-up. The analysis was conducted from February to November 2023. Patients who maintained dual antiplatelet therapy (DAPT) event-free for 6 to 18 months following PCI were included., Interventions: Patients were randomized to receive either clopidogrel or aspirin in a 1:1 ratio. Those with sufficient data to assess HBR or complex PCI were analyzed., Main Outcomes and Measures: Coprimary end points were thrombotic composite end point (cardiovascular death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and definite/probable stent thrombosis) and any bleeding (Bleeding Academic Research Consortium type 2 to 5)., Results: Of 3974 patients included (mean [SD] age, 63.4 [10.7] years; 2976 male [74.9%]), 866 had HBR (21.8%), and 849 underwent complex PCI (21.4%). Clopidogrel as compared with aspirin was associated with lower rates of thrombotic and bleeding events regardless of HBR and/or PCI complexity. For the thrombotic composite end point, the hazard ratio (HR) was 0.75 (95% CI, 0.53-1.04) among HBR vs 0.62 (95% CI, 0.48-0.80) among patients without HBR (P for interaction = 0.38) and 0.49 (95% CI, 0.32-0.77) among patients with complex PCI vs 0.74 (95% CI, 0.59-0.92) among patients with noncomplex PCI (P for interaction = 0.12). The reduction in bleeding by clopidogrel compared with aspirin was consistent among both patients with HBR (HR, 0.82; 95% CI, 0.56-1.21) and patients without HBR (HR, 0.58; 95% CI, 0.40-0.85; P for interaction = 0.20) and among patients undergoing complex PCI (HR, 0.79; 95% CI, 0.47-1.33) vs noncomplex PCI (HR, 0.68; 95% CI, 0.50-0.93; P for interaction = 0.62)., Conclusions and Relevance: In this study, in patients who experienced PCI and were event-free during 6 to 18 months of DAPT, the beneficial impact of clopidogrel monotherapy over aspirin monotherapy was consistent, regardless of bleeding risk and/or PCI complexity., Trial Registration: ClinicalTrials.gov Identifier: NCT02044250.

Background and Objectives : We evaluated the prevalence and characteristics of isolated nighttime masked uncontrolled hypertension (IN-MUCH) in treated patients. Materials and Methods : Participants aged 20 years or older who were on antihypertensive medication underwent three-day office blood pressure (BP) and 24 h ambulatory BP measurements. Hypertension phenotypes were classified as controlled hypertension (CH), isolated daytime masked uncontrolled hypertension (ID-MUCH), IN-MUCH, and daytime and nighttime masked uncontrolled hypertension (DN-MUCH). Results : Among 701 participants, 544 had valid BP data and controlled office BP (<140/90 mmHg). The prevalence of IN-MUCH was 34.9%, with a higher prevalence of men and drinkers than in those with CH. Patients with IN-MUCH had higher office systolic BP (SBP) and diastolic BP (DBP) than those with CH. The prevalence of IN-MUCH was 37.6%, 38.5%, and 27.9% in patients with optimal, normal, and high-normal office BP levels, respectively. Among IN-MUCH patients, 51.6% exhibited isolated uncontrolled DBP and 41.1% uncontrolled SBP and DBP. Younger age ( p = 0.043), male sex ( p = 0.033), and alcohol consumption ( p = 0.011) were more prevalent in patients with isolated uncontrolled DBP than in those with uncontrolled SBP and DBP. Age and alcohol consumption were positively associated, whereas high-normal office BP exhibited a negative association with IN-MUCH. Conclusions : The IN-MUCH was significantly more prevalent in patients with normal or optimal office BP, posing treatment challenges. Further investigation is needed to determine whether differentiation between isolated uncontrolled DBP and combined uncontrolled SBP and DBP is necessary for prognostic assessment of IN-MUCH.

Knowledge of the status of real-world home blood pressure (BP) measurements is crucial for establishing policies promoting hypertension treatment through home BP monitoring. However, only a few studies have investigated the status of home BP measurements in real-world settings. This study investigated the practice of Korean patients in measuring BP at home. This study recruited participants aged ≥20 years who were taking antihypertensives and conducted a questionnaire-based survey on home BP measurements. Of 701 participants recruited between August 2018 and April 2020, 673 were included in the analysis. Of these, 359 (53.3%) possessed home BP measurement devices. The devices used by 184 (51.3%) participants were validated, 110 (30.6%) were nonvalidated, and 65 (18.1%) had an unknown validation status. Only 18 patients (5.0%) with home BP devices were aware of the validation tests for home BP measurement devices. Of the 673 participants, 278 (41.3%) measured BP at home (77.4% of the patients owned home BP measurement devices). Among them, at least 74 (26.6%) performed proper measurements (at least once a month, at least twice a day or twice at a time, after at least 1 minute of rest, with at least a 1-min interval between each measurement, and 30 min after drinking coffee, exercising, or smoking). In conclusion, our community-based survey in the nonpresentive Korean population revealed a low rate of home BP measurement, a high rate of using nonvalidated devices, and a high rate of inappropriate measurements, suggesting that more efforts toward patient education regarding home BP measurements are needed., (© 2024 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

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)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

The authors performed this study to investigate the efficacy and safety of a rosuvastatin (RSV)/amlodipine (AML) polypill compared with those of atorvastatin (ATV)/AML polypill. We included 259 patients from 21 institutions in Korea. Patients were randomly assigned to 1 of 3 treatment groups: RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, or ATV 20 mg /AML 5 mg. The primary endpoint was the efficacy of the RSV 10.20 mg/AML 5 mg via percentage changes in LDL-C after 8 weeks of treatment, compared with the ATV 20 mg /AML 5 mg. There was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 10 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (full analysis set [FAS]: -7.08%, 95% CI: -11.79 to -2.38, p = .0034, per-protocol analysis set [PPS]: -6.97%, 95% CI: -11.76 to -2.19, p = .0046). Also, there was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 20 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (FAS: -10.13%, 95% CI: -15.41 to -4.84, p = .0002, PPS: -10.96%, 95% CI: -15.98 to -5.93, p < .0001). There was no significant difference in the adverse events rates between RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, and ATV 20 mg/AML 5 mg. In conclusion, while maintaining safety, RSV 10 mg/AML 5 mg and the RSV 20 mg/AML 5 mg more effectively reduced LDL-C compared with the ATV 20 mg /AML 5 mg (Clinical trial: NCT03951207)., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: Few data are available regarding the efficacy and safety of a single-pill combination (SPC) consisting of four medications in patients with concomitant hypertension and dyslipidemia., Objective: We aimed to determine the efficacy and tolerability of a fixed-dose SPC consisting of 5 mg amlodipine, 100 mg losartan, 20 mg rosuvastatin, and 10 mg ezetimibe (A/L/R/E) in patients with concomitant hypertension and dyslipidemia., Methods: This was a 14-week, randomized, multicenter, double-blind, placebo-controlled, phase III clinical trial. In total, 145 patients were randomized to receive A/L/R/E, A/L, or L/R/E. The primary endpoints were the average change in the low-density lipoprotein cholesterol (LDL-C) level in the A/L/R/E and A/L groups and the sitting systolic blood pressure (sitSBP) in the A/L/R/E and L/R/E groups. The numbers of patients with adverse drug reactions (ADRs) were compared as safety variables., Results: The average percentage change in the LDL-C level as the least squares mean (LSM) from the baseline LDL-C level at the end of the 8-week treatment was - 59.0% in the A/L/R/E group and 0.2% in the A/L group (LSM difference - 59.2, 95% confidence interval [CI] - 68.1 to - 50.4; p < 0.0001). The average change in the sitSBP as the LSM was - 15.8 mmHg in the A/L/R/E group and -4.7 mmHg in the L/R/E group (LSM difference - 11.1, 95% CI - 16.8 to - 5.4; p = 0.0002). No ADRs occurred in the A/L/R/E group., Conclusions: A/L/R/E as an SPC could be an effective treatment for patients with hypertension and dyslipidemia without significant safety issues., Clinical Trials Registration: NCT04074551 (registered 30 August 2019)., (© 2023. The Author(s).)

We compared the efficacy and safety of third-standard-dose triple and third-standard-dose dual antihypertensive combination therapies in patients with mild to moderate hypertension. This was a phase II multicenter, randomized, double-blind, parallel-group trial. After a 4-week placebo run-in period, 245 participants were randomized to the third-dose triple combination (ALC group; amlodipine 1.67 mg + losartan potassium 16.67 mg + chlorthalidone 4.17 mg) or third-dose dual combination (AL group; amlodipine 1.67 mg + losartan potassium 16.67 mg, LC group; losartan potassium 16.67 mg + chlorthalidone 4.17 mg, AC group; amlodipine 1.67 mg + chlorthalidone 4.17 mg) therapy groups and followed up for 8 weeks. The mean systolic blood pressure (BP) reduction was -18.3 ± 13.2, -13.0 ± 13.3, -16.3 ± 12.4, and -13.8 ± 13.2 mmHg in the ALC, AL, LC, and AC groups, respectively. The ALC group showed significant systolic BP reduction compared to the AL and AC groups at weeks 4 (P = .010 and P = .018, respectively) and 8 (P = .017 and P = .036, respectively). At week 4, the proportion of systolic BP responders was significantly higher in the ALC group (42.6%) than in the AL (22.0%), LC (23.3%), and AC (27.1%) groups (P = .013, P = .021, and P = .045, respectively). At week 8, the proportion of systolic and diastolic BP responders was significantly higher in the ALC group (59.7%) than in the AL (39.3%) and AC (42.4%) groups (P = .022 and P = .049, respectively) at week 8. Third-standard-dose triple antihypertensive combination therapy demonstrated early effective BP control compared to third-standard-dose dual combination therapies, without increasing adverse drug reactions in patients with mild-to-moderate hypertension., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: The introduction of a fixed-dose combination (FDC) is expected to improve treatment compliance., Methods: There were 181 subjects who were randomized to three groups: ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg, ezetimibe-rosuvastatin 10/20 mg, and telmisartan 80 mg. The primary outcomes were change in mean sitting systolic blood pressure (MSSBP) and percentage change in low-density-lipoprotein cholesterol (LDL-C) compared to baseline at week 8., Results: The least-square mean (SE) in MSSBP changes between the ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg group and the ezetimibe-rosuvastatin 10/20 mg group were -25.81 (2.34) mmHg and -7.66 (2.45) mmHg. There was a significant difference between the two groups (-18.15 (2.83) mmHg, 95% CI -23.75 to -12.56, p < 0.0001). Changes in least-square mean (SE) in LDL-C between the ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg group and the telmisartan 80 mg group were -63.82 (2.87)% and -2.48 (3.12)%. A significant difference was observed between the two groups (-61.34 (3.33)%, 95% CI -67.91 to -54.78, p < 0.0001). No serious adverse events were observed., Conclusions: Ezetimibe-rosuvastatin plus telmisartan treatment is effective and safe when compared to either ezetimibe-rosuvastatin or telmisartan.

Background: This study evaluated the association of body mass index (BMI) with adverse clinical outcomes during chronic maintenance antiplatelet monotherapy after percutaneous coronary intervention (PCI) with drug-eluting stents (DES)., Methods and results: Overall, 5,112 patients were stratified (in kg/m 2 ) into underweight (BMI ≤18.4), normal weight (18.5-22.9), overweight (23.0-24.9), obesity (25.0-29.9) and severe obesity (≥30.0) categories with randomized antiplatelet monotherapy of aspirin 100 mg or clopidogrel 75 mg once daily for 24 months. The primary endpoint was the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome and major bleeding of Bleeding Academic Research Consortium type ≥3. Compared with normal weight, the risk of primary composite outcomes was higher in the underweight (hazard ratio [HR] 2.183 [1.199-3.974]), but lower in the obesity (HR 0.730 [0.558-0.954]) and severe obesity (HR 0.518 [0.278-0.966]) categories, which is partly driven by the difference in all-cause death. The risk of major bleeding was significantly higher in the underweight (HR 4.140 [1.704-10.059]) than in the normal weight category. A decrease in categorical BMI was independently associated with the increased risk of primary composite outcomes., Conclusions: Lower BMI is associated with a higher risk of primary composite outcomes, which is primarily related to the events of all-cause death or major bleeding during chronic maintenance antiplatelet monotherapy after PCI with DES.

Introduction: Studies of the effectiveness of home blood pressure (BP) measurement on the treatment of hypertension in the real world are sparse, and the results are controversial. There is an efficacy-effectiveness gap in the treatment of hypertension using home BP measurements. We aimed to investigate the effect of reporting home BP to physicians on ambulatory BP control as a factor contributing to the efficacy-effectiveness gap in treating patients with hypertension., Methods: We recruited patients ≥20 years of age taking antihypertensive drugs. Office and 24-h ambulatory BP were measured. A questionnaire to the measurement of home BP was conducted. Participants were divided into an HBPM(-) group, home BP was not measured ( n = 467); HBPM(+)-R(-) group, home BP was measured but not reported ( n = 81); and HBPM(+)-R(+) group, home BP was measured and reported ( n = 125)., Results: The HBPM(+)-R(+) group had significantly lower office systolic BP (SBP, p = 0.035), 24-h SBP ( p = 0.009), and daytime SBP ( p = 0.016) than the HBPM(-) group, and lower nighttime SBP ( p = 0.005) and diastolic BP (DBP, p = 0.008) than the HBPM(+)-R(-) group. In the multivariate analysis, the differences in 24-h SBP, daytime SBP, and nighttime DBP remained significant. There was a significant difference between groups in the target achievement rate of 24-h SBP ( p = 0.046), nighttime SBP ( p = 0.021), and nighttime DBP ( p = 0.023). The nighttime SBP and DBP target achievement rates in the HBPM(+)-R(+) group were higher than those in the HBPM(+)-R(-) group ( p = 0.006 and 0.010, respectively). Among patients measuring home BP, the adjusted odds ratio for 24-h and nighttime BP target achievement in the HBPM(+)-R(+) group were 2.233 and 3.658, respectively., Conclusion: Home BP measurements should be reported to the treating physician to effectively manage hypertension., Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT03868384., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rhee, Munakata, Nah, Kim and Kim.)

Objectives: We evaluated the association between cardiovascular risk factors and the magnitude of the difference in systolic blood pressure (SBP) between office and ambulatory measurements (masked effect) in untreated individuals without apparent hypertension-mediated organ damage (HMOD)., Methods: The inclusion criteria were 1) age ≥ 20 years, 2) blood pressure ≥ 140/90 mmHg at the outpatient clinic, and 3) not receiving antihypertensive medications. The difference between office and ambulatory SBP was calculated by subtracting the ambulatory daytime SBP from the office SBP. The association between the masked effect and SBP variability was analyzed in individuals without HMOD (no electrocardiographic left ventricular hypertrophy, spot urine albumin-to-creatinine ratio < 30 mg/g, and estimated glomerular filtration rate ≥ 60 mL/min/1.73 m 2 , n = 296)., Results: Among the cardiovascular risk factors, ambulatory BP variability was significantly correlated with the SBP difference. The standard deviation (SD) and coefficient of variation (cv) of 24-h SBP exhibited a significant negative linear association with the SBP difference in univariate and multivariate analyses adjusted for age, sex, presence of diabetes, and 24-h ambulatory SBP. A significant association was observed in patients with ambulatory daytime hypertension. In the multivariate analysis, individuals with a negative SBP difference > -5 mmHg exhibited a higher SD and cv of 24-h SBP than those with a negative SBP difference ≤ -5 mmHg or a positive SBP difference., Conclusions: The results of our study suggest that the magnitude of the negative difference in office and ambulatory SBP may be a potential risk factor, even in individuals without apparent HMOD., Trial Registration: This trial is registered with ClinicalTrials.gov ( NCT03855605 )., (© 2022. The Author(s).)

Background: To assess the efficacy and safety of a combination therapy involving fimasartan, amlodipine, and rosuvastatin in patients with essential hypertension and dyslipidemia who fail to respond to fimasartan monotherapy., Methods: This phase III, randomized, double-blind, multicenter study was conducted in adults aged 19-70 years. Patients who voluntarily consented were screened for eligibility to enroll in the study. Patients who failed to respond to 4 weeks of fimasartan monotherapy were randomized with a 1:1:1 ratio to the fimasartan 60 mg/amlodipine 10 mg + rosuvastatin 20 mg (FMS/ALD + RSV) as study group, fimasartan 60 mg/amlodipine 10 mg (FMS/ALD) as control 1 group, and fimasartan 60 mg + rosuvastatin 20 mg (FMS + RSV) as control 2 group. The primary efficacy endpoints were the change in the sitting systolic blood pressure and the rate of change in the low-density lipoprotein cholesterol (LDL-C) level from baseline to 8 weeks. The adverse events, adverse drug reactions, physical examination findings, laboratory test results, electrocardiograms, and vital signs were evaluated to assess safety in the study., Results: Of 138 randomized patients, 131 were conducted efficacy analysis, and 125 completed the study. For the change in LDL-C and sitting SBP (SiSBP) as primary efficacy assessments, the change in LDL-C at week 8 was significantly reduce in the FMS/ALD + RSV group than in the control 1 group (P < 0.001). The change in SiSBP at week 8 were greater reduce in the FMS/ALD + RSV group than in the FMS + RSV group (both P < 0.001). For the safety evaluation, there were no differences among the treatment groups in the incidence of adverse drug reactions., Conclusions: The fimasartan/amlodipine + rosuvastatin combination therapy can effectively and safely lower blood pressure and improve lipid levels in patients with essential hypertension and dyslipidemia who fail to respond adequately to fimasartan monotherapy., Trial Registration: NCT03156842, Registered 17 May 2017., (© 2022. The Author(s).)

Background: The relationship between periodontitis and hypertension remains controversial. This study aimed to investigate the association of periodontitis, missing teeth, and oral hygiene behaviors with the incidence of hypertension., Methods: A total of 104,349 participants were selected from the National Health Insurance System-Health Screening (NHIS-HEALS) cohort. Incident hypertension and periodontitis were diagnosed based on the patients' clinical records and health examinations. A multivariable Cox proportional hazards regression analysis was performed after adjusting for socioeconomic factors, coexisting disease, and health behaviors., Results: The mean age of the participants was 51.1 years (range, 40-79 years) at baseline, and 55.1% were men. A total of 52,855 incident hypertension cases were identified during the median follow-up period of 9.6 years. Among the participants, periodontitis (hazard ratio [HR]: 1.02; 95% confidence interval [95% CI]: 1.00-1.04), number of missing teeth (for ≥15 group, HR: 1.40; 95% CI: 1.29-1.52), dental scaling (HR: 0.93; 95% CI: 0.91-0.95), and toothbrushing frequency (for ≥3 group, HR: 0.85; 95% CI: 0.83-0.88) were significantly associated with incident hypertension after full adjustments for covariates. While periodontitis was significantly associated with incident hypertension (HR: 1.04; 95% CI: 1.02-1.06) in the middle-aged group (40-64 years), the effect was insignificant in the older group (≥65 years)., Conclusions: Oral inflammation could contribute to the incidence of hypertension; thus, efforts to reduce oral inflammation should be encouraged. Future intervention studies are warranted to determine whether oral health care could be beneficial in the management of hypertension., (© 2022 American Academy of Periodontology.)

Candesartan and olmesartan are angiotensin II receptor blockers (ARBs) used for the treatment of hypertension and heart failure. Quantitation methods for candesartan and olmesartan were developed using ultra-high performance liquid chromatography-tandem mass spectrometry following protein precipitation. Candesartan was separated using 5 mM ammonium formate (A) and 100% acetonitrile (B) and olmesartan was separated using 2 mM ammonium formate with 0.1% formic acid (A) and 100% acetonitrile (B). Separation was performed using an isocratic method with a Thermo hypersil GOLD C18 column. Electrospray ionization was used for analyte ionization and detection of candesartan, olmesartan, and the internal standards by multiple reaction monitoring. Developed method showed excellent linearity ( r > 0.99) in the concentration range of 2-500 ng/mL for candesartan and 5-2,500 ng/mL for olmesartan. Accuracies were 86.70-108.8% for candesartan and 87.87-112.6% for olmesartan. These methods were able to successfully measure plasma candesartan or olmesartan concentrations in hypertensive patients. This study can be used for pharmacokinetic studies of candesartan or olmesartan in humans., Competing Interests: Conflict of Interest: - Authors: Nothing to declare - Reviewers: Nothing to declare - Editors: Nothing to declare, (Copyright © 2021 Translational and Clinical Pharmacology.)

The authors developed and validated a diagnostic algorithm using the optimal upper and lower cut-off values of office and home BP at which ambulatory BP measurements need to be applied. Patients presenting with high BP (≥140/90 mm Hg) at the outpatient clinic were referred to measure office, home, and ambulatory BP. Office and home BP were divided into hypertension, intermediate (requiring diagnosis using ambulatory BP), and normotension zones. The upper and lower BP cut-off levels of intermediate zone were determined corresponding to a level of 95% specificity and 95% sensitivity for detecting daytime ambulatory hypertension by using the receiver operator characteristic curve. A diagnostic algorithm using three methods, OBP-ABP: office BP measurement and subsequent ambulatory BP measurements if office BP is intermediate zone; OBP-HBP-ABP: office BP, subsequent home BP measurement if office BP is within intermediate zone and subsequent ambulatory BP measurement if home BP is within intermediate zone; and HBP-ABP: home BP measurement and subsequent ambulatory BP measurements if home BP is within intermediate zone, were developed and validated. In the development population (n = 256), the developed algorithm yielded better diagnostic accuracies than 75.8% (95%CI 70.1-80.9) for office BP alone and 76.2% (95%CI 70.5-81.3) for home BP alone as follows: 96.5% (95%CI: 93.4-98.4) for OBP-ABP, 93.4% (95%CI: 89.6-96.1) for OBP-HBP-ABP, and 94.9% (95%CI: 91.5-97.3%) for HBP-ABP.  In the validation population (n = 399), the developed algorithm showed similarly improved diagnostic accuracy. The developed algorithm applying ambulatory BP measurement to the intermediate zone of office and home BP improves the diagnostic accuracy for hypertension., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Purpose: The efficacy and tolerability of fimasartan in elderly patients have not been fully evaluated. This study was therefore conducted to determine the efficacy and tolerability of fimasartan compared with perindopril in elderly Korean patients aged >70 years with essential hypertension (defined by a mean sitting systolic blood pressure [SBP] ≥140 mm Hg)., Methods: This randomized, double-blind, active-controlled, 2 parallel-group, optional titration, multicenter, Phase IIIb trial (FITNESS [Fimasartan in the Senior Subjects]) enrolled 241 patients from 23 cardiac centers in the Republic of Korea between August 2017 and December 2019. After the placebo run-in period, treatment started with fimasartan 30 mg or perindopril arginine 2.5 mg once daily at a 1:1 ratio; if BP was not controlled at week 4, the dose was doubled. If BP was not controlled at week 8, a diuretic combination (fimasartan 60 mg/hydrochlorothiazide 12.5 mg or perindopril arginine 5 mg/indapamide 1.25 mg) was administered. After 16 weeks of the double-blind treatment, the patients with controlled BP participated in an 8-week open-label extension study, with the 2 groups unified by fimasartan 60 mg with or without hydrochlorothiazide 12.5 mg for 8 weeks. The primary outcome was a change in SBP for 8 weeks. The secondary outcomes included a change in sitting diastolic BP (DBP) for 8 weeks and changes in SBP and DBP for 4, 16, and 24 weeks., Findings: At week 8, mean SBP significantly decreased from baseline in both groups: -14.2 (14.4) mm Hg in the fimasartan group and -9.0 (16.1) mm Hg in the perindopril group. The difference between the 2 groups was 5.4 (2.1) mm Hg, indicating the noninferiority of fimasartan to perindopril. Moreover, fimasartan exhibited a higher BP-lowering effect than perindopril (P = 0.0108). In addition, reductions in SBP and DBP from baseline to weeks 4, 8, and 16 were significantly greater in the fimasartan group than in the perindopril group, although the SBP reduction was comparable at week 16. Both groups reported an excellent mean compliance rate of 97.4% (4.7%) through week 16. During the study period, 82 adverse events were reported in 52 patients, 40 in the fimasartan group and 42 in the perindopril group (P = 0.4647). Dizziness was the most commonly reported adverse event (7 cases). Remarkably, only 1 case of orthostatic hypotension was reported during the study period., Implications: In elderly patients with essential hypertension, fimasartan 30 to 60 mg with a possible hydrochlorothiazide 12.5-mg combination was noninferior to perindopril 2.5 to 5 mg with a possible indapamide 1.25-mg combination. Furthermore, fimasartan exhibited higher BP-lowering efficacy than perindopril. There was no difference in tolerability between the 2 groups. Clinicaltrials.gov Identifier: NCT03246555., Competing Interests: DISCLOSURES The authors have indicated that they have no conflicts of interest regarding the content of this article. The sponsor supported the supply of the IPs, laboratory tests, and clinical research coordinator expenses. The sponsor also participated in the study design, data collection, and analysis. The sponsor was not involved in the interpretation of data, writing of the report, or the decision to submit the article for publication., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: We investigated whether the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy in patients requiring cholesterol-lowering therapy., Methods: This was a multicenter randomized, double-blind study to investigate the safety and efficacy of a fixed-dose combination of rosuvastatin 2.5 mg and ezetimibe 10 mg (R2.5+E10) compared to those of ezetimibe 10 mg monotherapy (E10), rosuvastatin 2.5 mg (R2.5), and rosuvastatin 5 mg monotherapy (R5) in patients with hypercholesterolemia. A total of 348 patients at 15 centers in Korea were screened, and 279 patients were randomized to different groups in the study. Clinical and laboratory examinations were performed at baseline and 4 and 8 weeks after intervention. The primary endpoint was the percentage change of low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up., Findings: Baseline characteristics were similar among the four groups. There were significant changes in lipid profiles at the 8-week follow-up. A greater decrease in the LDL cholesterol levels (primary endpoint) were found in the R2.5+E10 group (-45.7±18.6%) than in the E10 group (-16.7±14.7%, p<0.0001), R2.5 group (-32.6±15.1%, p<0.0001), and R5 group (-38.9±13.9%, p=0.0003). Similar outcomes were observed regarding the decrease in total cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B protein. In addition, changes in the triglyceride and HDL levels in the R2.5+E10 group were significantly different compared with those in the E10 group; however, the changes were similar to those in the other treatment groups. In patients with low and moderate risk, all patients achieved the target LDL cholesterol levels in the R2.5+E10 group (100%) compared to 13.0% in the E10 group, 47.6% in the R2.5 group, and 65.2% in the R5 group. Adverse effects were rare and similar in the four groups., Implications: Fixed-dose combination of low-intensity rosuvastatin and ezetimibe was more effective in lowering LDL cholesterol and achieving LDL cholesterol goals than moderate-intensity rosuvastatin monotherapy. These findings suggest that the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy for cholesterol management, particularly in patients with low and moderate risk. ClinicalTrials.gov identifier: NCT04652349., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/aims: Ascertaining the prevalence of isolated nocturnal hypertension (INHT) in the general population and identifying the characteristics of patients with INHT may be important to determine patients who should receive 24- hour ambulatory blood pressure (BP) measurements. This study aimed to evaluate the prevalence and characteristics of INHT in the general population., Methods: Of 1,128 participants (aged 20 to 70 years), we analyzed 823 who had valid 24-hour ambulatory BP measurements and were not on antihypertensive drug treatment., Results: The prevalence of INHT in the study was 22.8%. Individuals with INHT had a higher office, 24-hour, and daytime and nighttime ambulatory systolic and diastolic BPs compared to individuals with sustained day-night normotension. INHT was more prevalent in individuals with masked hypertension (MH) than in those with sustained hypertension (59.8% vs. 15.6%, p < 0.001). Among individuals with INHT, 92.6% had MH. Among individuals with office BP-based prehypertension, 34.5% had both INHT and MH. The prevalence of INHT was highest in individuals with office BP-based prehypertension. INHT was an independent determinant of MH after adjustment for age, sex, body mass index, diabetes, low-density-lipoprotein cholesterol, 24-hour systolic and diastolic BP, systolic and diastolic BP dipping, and systolic and diastolic BP non-dipping., Conclusion: The present study showed that INHT is not uncommon and is a major determinant of MH. Our findings strongly suggest the use of 24-hour ambulatory BP measurement for individuals within the prehypertension range of office BP owing to the high prevalence of INHT and MH in this population.

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., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

The objective of this study was to compare the diagnostic accuracy of office blood pressure (BP) threshold of 140/90 and 130/80 mmHg for correctly identifying uncontrolled out-of-office BP in apparent treatment-resistant hypertension (aTRH). We analyzed 468 subjects from a prospectively enrolled cohort of patients with resistant hypertension in South Korea (clinicaltrials.gov: NCT03540992). Resistant hypertension was defined as office BP ≥ 130/80 mmHg with three different classes of antihypertensive medications including thiazide-type/like diuretics, or treated hypertension with four or more different classes of antihypertensive medications. We conducted different types of BP measurements including office BP, automated office BP (AOBP), home BP, and ambulatory BP. We defined uncontrolled out-of-office BP as daytime BP ≥ 135/85 mmHg and/or home BP ≥ 135/85 mmHg. Among subjects with office BP < 140/90 mmHg and subjects with office BP < 130/80 mmHg, 66% and 55% had uncontrolled out-of-office BP, respectively. The prevalence of controlled and masked uncontrolled hypertension was lower, and the prevalence of white-coat and sustained uncontrolled hypertension was higher, with a threshold of 130/80 mmHg than of 140/90 mmHg, for both office BP and AOBP. The office BP threshold of 130/80 mmHg was better able to diagnose uncontrolled out-of-office BP than 140/90 mmHg, and the net reclassification improvement (NRI) was 0.255. The AOBP threshold of 130/80 mmHg also revealed better diagnostic accuracy than 140/90 mmHg, with NRI of 0.543. The office BP threshold of 130/80 mmHg showed better than 140/90 mmHg in terms of the correspondence to out-of-office BP in subjects with aTRH., (© 2020 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Among the 146 patients enrolled in the Korean FH registry, 83 patients who had undergone appropriate LLT escalation and were followed-up for ≥ 6 months were analyzed for pathogenic variants (PVs). The achieved percentage of expected low-density lipoprotein-cholesterol (LDL-C) reduction (primary variable) and achievement rates of LDL-C < 70 mg/dL were assessed. The correlations between the treatment response and the characteristics of PVs, and the weighted 4 SNP-based score were evaluated. The primary variables were significantly lower in the PV-positive patients than in the PV-negative patients (p = 0.007). However, the type of PV did not significantly correlate with the primary variable. The achievement rates of LDL-C < 70 mg/dL was very low, regardless of the PV characteristics. Patients with a higher 4-SNP score showed a lower primary variable (R 2  = 0.045, p = 0.048). Among evolocumab users, PV-negative patients or those with only defective PVs revealed higher primary variable, whereas patients with at least one null PV showed lower primary variables. The adjusted response of patients with FH to LLT showed significant associations with PV positivity and 4-SNP score. These results may be helpful in managing FH patients with diverse genetic backgrounds.

Home and ambulatory blood pressure (BP) measurements are recommended for the diagnosis of hypertension. However, the clinical characteristics of individuals showing a diagnostic disagreement between their home and ambulatory BP measurements are unclear. Of the 470 individuals who were not on antihypertensive drug treatment with a BP ≥140/90 mmHg at an outpatient clinic, 399 who had valid office, home, and ambulatory BP results were included. Hypertension was diagnosed based on an average home BP ≥135/85 mmHg and/or an average daytime ambulatory BP ≥135/85 mmHg. The participants were divided into three groups: Agree-NT (home and ambulatory BP normotension), Disagree (home BP normotension and ambulatory BP hypertension, or home BP normotension and ambulatory BP hypertension), and Agree-HT (home and ambulatory BP hypertension). Eighty-four individuals (21.1%) were classified as the Disagree group. The mean serum creatinine, triglycerides, and electrocardiogram voltage in the Disagree group were intermediate between those observed in the Agree-NT and the Agree-HT group. In the Disagree group, the mean levels of office and home diastolic BP, all of the components of ambulatory BP, the aortic systolic BP, and the BP variabilities were found to be intermediate between those of the Agree-NT and the Agree-HT groups. These results indicate that individuals showing a diagnostic disagreement between their home and ambulatory BP may have cardiovascular risks that are intermediate between those with sustained home and ambulatory normotension and hypertension.

Background and Objectives: The relationship between the hospital percutaneous coronary intervention (PCI) volumes and the in-hospital clinical outcomes of patients with acute myocardial infarction (AMI) remains the subject of debate. This study aimed to determine whether the in-hospital clinical outcomes of patients with AMI in Korea are significantly associated with hospital PCI volumes., Methods: We selected and analyzed 17,121 cases of AMI, that is, 8,839 cases of non-ST-segment elevation myocardial infarction and 8,282 cases of ST-segment elevation myocardial infarction, enrolled in the 2014 Korean percutaneous coronary intervention (K-PCI) registry. Patients were divided into 2 groups according to hospital annual PCI volume, that is, to a high-volume group (≥400/year) or a low-volume group (<400/year). Major adverse cardiovascular and cerebrovascular events (MACCEs) were defined as composites of death, cardiac death, non-fatal myocardial infarction (MI), stent thrombosis, stroke, and need for urgent PCI during index admission after PCI., Results: Rates of MACCE and non-fatal MI were higher in the low-volume group than in the high-volume group (MACCE: 10.9% vs. 8.6%, p=0.001; non-fatal MI: 4.8% vs. 2.6%, p=0.001, respectively). Multivariate regression analysis showed PCI volume did not independently predict MACCE., Conclusions: Hospital PCI volume was not found to be an independent predictor of in-hospital clinical outcomes in patients with AMI included in the 2014 K-PCI registry., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2020. The Korean Society of Cardiology.)

Single risk factors, such as hypertension and dyslipidemia, can combine to exacerbate the development and severity of cardiovascular disease. Treatment goals may be more effectively achieved if multiple disease factors are targeted with combination treatment. We enrolled 202 patients who were randomly divided into the following three groups: telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg, telmisartan 80 mg + rosuvastatin 20 mg, and telmisartan/amlodipine 80/5 mg. The primary efficacy variables were changes from baseline in mean sitting systolic blood pressure (MSSBP) between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg at 8 weeks, and the percent changes from baseline in low-density lipoprotein (LDL) cholesterol between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg at 8 weeks. The secondary efficacy variables were changes in MSSBP, mean sitting diastolic blood pressure (MSDBP), LDL cholesterol and other lipid levels at 4 weeks and 8 weeks, as well as observed adverse events during follow-up. There were no significant differences between the three groups in demographic characteristics and no significant difference among the three groups in terms of baseline characteristics for the validity evaluation variables. The mean overall treatment compliance in the three groups was, respectively, 98.42%, 96.68%, and 98.12%, indicating strong compliance for all patients. The Least-Square (LS) mean (SE) for changes in MSSBP in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg) groups were -19.3 (2.68) mm Hg and -6.69 (2.76) mm Hg. The difference between the two groups was significant (-12.60 (2.77) mm Hg, 95% CI -18.06 to -7.14, P < .0001). The LS Mean for the percent changes from baseline in LDL cholesterol in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg) groups were -52.45 (3.23) % and 2.68 (3.15) %. The difference between the two groups was significant (-55.13 (3.20) %, 95% CI -61.45 to -48.81, P < .0001). There were no adverse events leading to discontinuation or death. Combined administration of telmisartan/amlodipine 80/5 mg and rosuvastatin 20 mg for the treatment of hypertensive patients with dyslipidemia significantly reduces blood pressure and improves lipid control. ClinicalTrials.gov identifier: NCT03067688., (© 2020 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background/objectives: Hypertension is the major risk factor for cardiovascular disease, a leading cause of deaths in Korea. The objective of this study was to evaluate the effect of a nutrition education in reducing sodium intake and increasing potassium intake in hypertensive adults., Subjects/methods: Subjects who participated in this study were 88 adults (28 males and 60 females) who were pre-hypertension or untreated hypertensive patients aged ≥ 30 yrs in Gyeonggi Province, Korea. These subjects were divided into 2 groups: a low-sodium education (LS) group and a low-sodium high-potassium education (LSHP) group. Nutrition education of 3 sessions for 12 weeks was conducted. Blood pressure, blood and urine components, nutrient intake, and dietary behavior were compared between the two education groups., Result: Blood pressure was decreased in both groups after the nutrition education ( P < 0.05). In the LSHP group, levels of blood glucose ( P < 0.05), total cholesterol ( P < 0.01), and low-density lipoprotein-cholesterol ( P < 0.05) were decreased after the program completion. Sodium intake was decreased in both groups after the nutrition education ( P < 0.05). However, Na/K ratio was only decreased in the LS group ( P < 0.05). Intake frequency of fish & shellfish was only significantly reduced in the LS group ( P < 0.05), while intake frequencies of cooked rice, noodles & dumplings, breads & snacks, stew, kimchi, and fish & shellfish were reduced in the LSHP group ( P < 0.05). Total score of dietary behavior appeared to be effectively decreased in both groups after the education program ( P < 0.001)., Conclusions: This education for reducing sodium intake was effective in reducing blood pressure and sodium intake. The education for enhancing potassium intake resulted in positive changes in blood glucose and serum cholesterol levels., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2020 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Background/objectives: Arterial stiffness and endothelial dysfunction are 2 of the independent predictors for cardiovascular disease, while Acanthopanax senticosus Harms (ASH) is a traditional medicinal plant that can improve cardiovascular health. This study aimed to investigate the efficacy of the fruit of ASH on vascular function in apparently healthy subjects., Subjects/methods: A 12-week, randomized, double-blind, placebo-controlled design, consisting of healthy adults with at least 2 of the following 3 conditions: borderline high blood pressure (BP; 120 mmHg ≤ systolic BP ≤ 160 mmHg or 80 mmHg ≤ diastolic BP ≤ 100 mmHg), smoking (≥10 cigarettes/day), and borderline blood lipid levels (220 ≤ total cholesterol ≤ 240, 130 ≤ low density lipoprotein cholesterol ≤ 165, or 150 ≤ triglyceride ≤ 220 mg/dL). Randomly assigned 76 subjects who received a placebo or 2 doses of ASH fruit (low, 500 mg/day; high, 1,000 mg/day) completed the intervention. Brachial-ankle pulse wave velocity (baPWV), flow-mediated dilation, carotid intima-media thickness, and BP were measured both at baseline and following the 12-week intervention. Endothelial nitric oxide synthase (eNOS) phosphorylation was assessed by western blotting., Results: Compared with the placebo group, the low-dose group showed more significant changes after the 12-week intervention period in terms of systolic BP (0.1 vs. -7.7 mmHg; P = 0.044), baPWV (31.3 vs. -98.7 cm/s; P = 0.007), and the ratio of phospho-eNOS/eNOS (0.8 vs. 1.22; P = 0.037)., Conclusions: These results suggest that ASH fruit extract at 500 mg/day has the potential to improve BP and arterial stiffness via endothelial eNOS activation in healthy adults with smoking and the tendency of having elevated BP or blood lipid parameters., Trial Registration: Clinical Research Information Service Identifier: KCT0001072., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2020 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Sodium intake reduction has been emphasized because sodium adversely impacts health, especially blood pressure (BP), and the cardiovascular (CV) disease risk. However, data obtained from several cohort studies have raised questions regarding the effects of high sodium intake on BP and the CV disease risk. In the present study, we systematically reviewed the literature to evaluate these associations. Studies showing negative associations between urine sodium and BP and CV outcomes relied on estimated 24-hour urine sodium from spot urine that is inappropriate for determining sodium intake at an individual level. Furthermore, controversy about the association between 24-hour urine sodium and BP may have been caused by different characteristics of study populations, such as age distribution, ethnicity, potassium intake and the inclusion of patients with hypertension, the different statistical methods and BP measurement methods. Regarding the association between sodium intake and the CV disease risk, studies showing negative or J- or U-shaped associations used a single baseline measurement of 24-hour urine sodium in their analyses. However, recent studies that employed average of subsequently measured 24-hour urine sodium showed positive, linear associations between sodium intake and CV outcomes, indicating that controversies are caused by the different sodium intake measurement methods and analytic designs. In conclusion, the study shows that positive associations exist between sodium intake and BP, CV outcomes, and mortality, and that the argument that reducing sodium intake is dangerous is invalid. Sodium intake reduction should be recommended to all, and not limited to patients with hypertension or CV disease., Competing Interests: Rhee MY has received lecture honoraria from Pfizer Inc., LG Life Sciences Ltd, Boehringer Ingelheim Pharma GmbH & Co. KG., Hanmi Pharm. Co. Ltd., Yuhan Co. Ltd., Boryung Pharmaceutical Co. Ltd., Fees for consulting from Hanmi Pharm. Co. Ltd., and research grant from Boryung Pharmaceutical Co. Ltd. and Dong-A Pharmaceutical Co., Ltd., (Copyright © 2020. The Korean Society of Cardiology.)

Our study evaluated whether there were differences in the prevalence of white-coat hypertension (WH) and masked hypertension (MH) based on the 2018 ESC/ESH and 2017 ACC/AHA hypertension guidelines in Korea. The motivation was the lowering of the diagnostic threshold for hypertension in the 2017 ACC/AHA guidelines. Of 319 participants without antihypertensive drug history and with suspected hypertension based on outpatient clinic blood pressure (BP) measured by physicians, 263 participants (51.6 ± 9.6 years; 125 men) who had valid research-grade office BP and 24-h ambulatory BP measurements were enrolled. WH prevalence based on daytime ambulatory BP among normotensive individuals was lower with the ESC/ESH guidelines than the ACC/AHA guidelines (29.0% vs. 71.4%, p < 0.001). However, MH prevalence based on daytime ambulatory BP among hypertensive individuals was higher based on the ESC/ESH guidelines (21.6% vs. 1.8%, p < 0.001). Seventy percent of WH cases (2017 ACC/AHA guidelines) and 95.2% of MH cases (2018 ESC/ESH guidelines) occurred in individuals with systolic BP of 130-139 mmHg and/or diastolic BP of 80-89 mmHg. The diagnostic threshold of the 2017 ACC/AHA guidelines yielded a higher prevalence of WH compared to that of the 2018 ESC/ESH guidelines. However, the prevalence of MH was higher with the 2018 ESC/ESH guidelines than with the 2017 ACC/AHA guidelines. The high prevalence of WH and MH in people with a systolic BP of 130-139 mmHg or diastolic BP of 80-89 mmHg suggests the need for a more active out-of-office BP measurement in this patient group.

Purpose: The goal of this study was to compare the lipid-lowering efficacy of the combination of ezetimibe and low- or intermediate-intensity statin therapy versus that of high-intensity statin monotherapy., Methods: This study is a post hoc analysis of an 8-week, randomized, double-blind, Phase III trial. Patients who had hypercholesterolemia and required lipid-lowering treatment were randomly assigned to 1 of 6 treatment groups: rosuvastatin 5 mg (R5, n = 68), rosuvastatin 10 mg (R10, n = 67), rosuvastatin 20 mg (R20, n = 69), and ezetimibe 10 mg combined with rosuvastatin 5 mg (R5 + E10, n = 67), rosuvastatin 10 mg (R10 + E10, n = 68), and rosuvastatin 20 mg (R20 + E10, n = 68) daily. The effects of coadministration of ezetimibe and a low dose of rosuvastatin on lipid parameters and the target achievement rate were compared between the R5 + E10 and R10 treatment groups, the R5 + E10 and R20 treatment groups, and the R10 + E10 and R20 treatment groups., Findings: Reductions in total cholesterol, LDL-C, apolipoprotein B, the apolipoprotein B/A1 ratio, and non-HDL-C were not different between the R5 + E10 and R10 treatment groups (all, P > 0.017), the R5 + E10 and R20 treatment groups (all, P > 0.017), and the R10 + E10 and R20 treatment groups (all, P > 0.017). R5 + E10 treatment showed efficacy comparable to that of R10 or R20 in affording LDL levels <50% of the baseline level (R5 + E10 vs R10, 73.13% vs 62.69% [P = 0.1952]; R5 + E10 vs R20, 73.13% vs 73.91% [P = 0.9180]), LDL-C levels <70 mg/dL (R5 + E10 vs R10, 64.18% vs 55.22% [P = 0.2906]; R5 + E10 vs R20, 64.18% vs 62.32% [P = 0.8220]), and LDL-C levels <50% of the baseline level or <70 mg/dL (R5 + E10 vs R10, 77.61% vs 70.15% [P = 0.3255]; R5 + E10 vs R20, 77.61% vs 78.26% [P = 0.9273]). The R10 + E10 treatment group was better than the R20 treatment group in achieving the target LDL-C level <70 mg/dL (83.82% vs 62.32%; P = 0.0046), even among participants with a baseline LDL-C level >135 mg/dL (77.5% vs 48.8%, respectively; P = 0.0074)., Implications: Ezetimibe combined with low- or intermediate-intensity statin therapy has lipid-lowering efficacy comparable to or better than that of high-intensity rosuvastatin monotherapy. The results of the present study indicate that the combination treatment with ezetimibe is advantageous in that it permits dose reduction of rosuvastatin without compromising the lipid-lowering efficacy of rosuvastatin. ClinicalTrials.gov identifier: NCT02205606., (Copyright © 2019. Published by Elsevier Inc.)

Brachial-ankle pulse wave velocity (baPWV) provides a useful means of assessing cardiovascular events and diabetic complications. However, the nature of associations between baPWV and microalbuminuria (MAU) and its presence in Type 2 diabetes mellitus (Type 2 DM) have rarely been investigated. This study aimed to examine the association between baPWV and MAU coupled with prediction of MAU using baPWV measurement among Type 2 DM patients. In this cross-sectional study, we enrolled 424 Type 2 DM patients who visited the cardiology and endocrinology department at a tertiary level health care facility, Republic of Korea between 1 January 2006 to 31 December 2008. Clinical and laboratory data were collected, and risk factors associated with MAU and prediction of risk for the development of MAU using baPWV measurement. The association between MAU and baPWV was examined using multivariable logistic regression analysis and predicted MAU by using receiver operating characteristic (ROC) curve analysis. Of the 424 Type 2 DM patients, 93 (21.9%) had MAU (20-200 μg/min). baPWV (cm/sec) was found to be significantly correlated with MAU levels (ug/min) ( r = 0.791, p < 0.001). Further, baPWV was significantly associated MAU with higher odds ratio (adjusted odds ratio (AOR) 10.899; 95% confidence interval (CI) (4.518-26.292)). Similarly, smoking (AOR 10.899; 95% CI (4.518-26.292)), and low-density lipoprotein (LDL)-cholesterol (mg/dL) (AOR 1.017; 95% CI (1.001-1.033)) were also significantly associated with MAU. The appropriate cut-off value for baPWV to predict MAU 20 μg/min in our study was 1700 cm/sec (area under ROC curve = 0.976). This study shows that baPWV, cigarette smoking, and LDL-cholesterol are associated with MAU in Type 2 DM patients and suggests that a baPWV cut-off of 1700 cm/sec could be used to predict the presence of MAU (20 μg/min) in Type 2 DM patients in the Korean community.

The objective of this study was to evaluate the association between sodium intake and blood pressure (BP) control in hypertensive patients taking antihypertensive medications by using 24-hour urine collection and 24-hour ambulatory BP. This is a cross-sectional community-based study and conducted in 2011 and 2012. A total of 1128 participants were recruited from five cities in Korea. Among them, 740 participants who had complete 24-hour urine collection and valid 24-hour ambulatory BP data were included in this study. Participants were divided into four groups: normotensives (NT, n = 441), untreated hypertensive patients (UTHT, n = 174), controlled hypertensive patients (CHT, n = 62), and uncontrolled hypertensive patients (UCHT, n = 63). UCHT and CHT groups showed higher mean age than NT and UTHT groups. UCHT and UTHT groups showed higher 24-hour systolic BP (SBP) and diastolic BP (DBP) than NT and CHT groups. UCHT group had the highest level of 24-hour urine sodium. Multivariate analysis adjusted with age, gender, body mass index, estimated glomerular filtration rate, and use of diuretics showed higher level of 24-hour urine sodium in UCHT group than that in CHT group. Multivariate logistic regression analysis revealed independent association of the amount of 24-hour urine sodium with uncontrolled BP in hypertensive patients on antihypertensive drug treatment. Higher level of 24-hour urine sodium excretion in uncontrolled hypertensive patients suggests that excessive sodium intake could be associated with blunted BP lowering efficacy of antihypertensive medications., (©2019 Wiley Periodicals, Inc.)

Background: Hypertension is an important risk factor for cardiovascular disease, even in the elderly. Fimasartan is a new non-peptide angiotensin II receptor blocker with a selective type I receptor blocking effect. The objective of this study is to confirm the safety and the non-inferiority of the blood pressure-lowering effect of fimasartan compared with those of perindopril, which has been proven safe and effective in elderly patients with hypertension., Methods: This is a randomized, double-blind, active-controlled, two-parallel group, optional-titration, multicenter, phase 3 study comparing the efficacy and safety of fimasartan and perindopril arginine. The study population consists of individuals 70 years old or older with essential hypertension. The primary outcome will be a change in sitting systolic blood pressure from baseline after the administration of the investigational product for 8 weeks. The secondary outcomes will be a change in sitting diastolic blood pressure from baseline and changes in sitting systolic blood pressure and diastolic blood pressure from baseline after the administration of the investigational product for 4, 16, and 24 weeks. The sample size will be 119 subjects for each group to confer enough power to test for the primary outcome., Discussion: Research to confirm the efficacy and safety of a new medicine compared with those of previously proven anti-hypertensive drugs is beneficial to guide physicians in the selection of therapeutic agents. If it is confirmed that the new drug is not inferior to the existing drug, the drug will be considered as an option in the treatment of hypertension in elderly patients., Trial Registration: ClinicalTrials.gov Identifier: NCT03246555 , registered on July 25, 2017.

Aims: We investigated the dose-response association of 24-hour urine sodium and potassium with 24-hour ambulatory blood pressure., Design: Cross-sectional community-based study., Methods: Among the 1128 participants in the community-based cross-sectional survey, 740 participants (aged 20-70 years) with complete 24-hour urine collection and valid 24-hour ambulatory blood pressure monitoring were included in the study. Participants were grouped into younger (<55 years, n = 523) and older (≥55 years, n = 217)., Results: In the older population, nighttime blood pressure linearly increased with 24-hour urine sodium and the sodium to potassium ratio. For 24-hour urine sodium, adjusted β was 0.171 (95% confidence interval (CI) 0.036-0.305) for nighttime systolic blood pressure and 0.144 (95% CI 0.012-0.276) for nighttime diastolic blood pressure. For the 24-hour urine sodium to potassium ratio, adjusted β was 0.142 (95% CI 0.013-0.270) for nighttime systolic blood pressure and 0.144 (95% CI 0.018-0.270) for nighttime diastolic blood pressure. The 24-hour blood pressure linearly increased with the 24-hour urine sodium to potassium ratio and adjusted β was 0.133 (95% CI 0.003-0.262) for 24-hour systolic blood pressure and 0.123 (95% CI 0.003-0.244) for 24-hour diastolic blood pressure. Daytime blood pressure and 24-hour systolic blood pressure showed a significant but non-linear association with 24-hour urine sodium among the older population. In the younger population, 24-hour urine sodium, potassium and the sodium to potassium ratio were not associated with ambulatory blood pressure., Conclusion: In the older population, 24-hour urine sodium and the sodium to potassium ratio showed a linear and positive association with nighttime blood pressure, and 24-hour urine sodium was associated with 24-hour systolic blood pressure and daytime blood pressure in a non-linear fashion.

Purpose: Dyslipidemia and hypertension increase the risk for cardiovascular disease. Combination therapy improves patient compliance. This study was conducted to compare the efficacy and tolerability of the combination therapies telmisartan/amlodipine + rosuvastatin, telmisartan/amlodipine, and telmisartan + rosuvastatin in patients with hypercholesterolemia and hypertension., Methods: In this Phase III, multicenter, 8-week randomized, double-blind study, participants with hypertension and dyslipidemia (defined as a sitting systolic blood pressure [sitSBP] of ≥140 mm Hg, a low-density lipoprotein-cholesterol [LDL-C] level of ≤250 mg/dL, and a triglyceride level of ≤400 mg/dL) were screened. After a 4-week washout/run-in period involving therapeutic lifestyle changes and telmisartan 80 mg once a day, eligible patients had a sitSBP of ≥140 mm Hg and met the LDL-C level criteria according to the National Cholesterol Education Program Adult Treatment Panel III cardiovascular disease risk category. Patients were randomly assigned to 1 of 3 groups: (1) telmisartan/amlodipine 80/10 mg + rosuvastatin 20 mg (TAR group); (2) telmisartan/amlodipine 80/10 mg (TA group); or (3) telmisartan 80 mg + rosuvastatin 20 mg (TR group). The primary efficacy end points were the percentage changes from baseline in LDL-C in the TAR and TA groups and the mean changes in sitSBP in the TAR and TR groups at week 8 compared to baseline. Continuous variables were compared using the unpaired t test or the Wilcoxon rank sum model, and categorical variables were compared using the χ 2 or Fisher exact test. Tolerability was assessed based on adverse events found on physical examination including vital sign measurements, laboratory evaluations, and 12-lead ECG., Findings: A total of 134 patients were enrolled. The least squares mean percentage changes in LDL-C at 8 weeks after administration of the drug compared to baseline were -51.9% (3.0%) in the TAR group and -3.2% (2.9%) in the TA group (P < 0.001). At 8 weeks after baseline, the least squares mean (SE) changes sitSBP were -28.3 (2.4) mm Hg in the TAR group and -10.7 (2.1) mm Hg in the TR group (P < 0.001). The prevalence rates of treatment-emergent adverse events were 15.0%, 25.0%, and 12.2% in the TAR, TA, and TR groups, respectively; those of adverse drug reactions were 15.0%, 22.7%, and 10.2%. None of the differences in rates were significant among 3 groups., Implications: Triple therapy with TAR can be an effective treatment in patients with dyslipidemia and hypertension. The TAR combination has value for hypertensive patients with hyperlipidemia in terms of convenience, tolerability, and efficacy. ClinicalTrials.gov identifier: NCT03566316., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Masked uncontrolled hypertension (MUCH) carries an increased risk of cardiovascular (CV) complications and can be identified through combined use of office (O) and ambulatory (A) blood pressure (BP) monitoring (M) in treated patients. However, it is still debated whether the information carried by ABPM should be considered for MUCH management. Aim of the MASked-unconTrolled hypERtension management based on OBP or on ambulatory blood pressure measurement (MASTER) Study is to assess the impact on outcome of MUCH management based on OBPM or ABPM., Methods and Analysis: MASTER is a 4-year prospective, randomised, open-label, blinded-endpoint investigation. A total of 1240 treated hypertensive patients from about 40 secondary care clinical centres worldwide will be included -upon confirming presence of MUCH (repeated on treatment OBP <140/90 mm Hg, and at least one of the following: daytime ABP ≥135/85 mm Hg; night-time ABP ≥120/70 mm Hg; 24 hour ABP ≥130/80 mm Hg), and will be randomised to a management strategy based on OBPM (group 1) or on ABPM (group 2). Patients in group 1 will have OBP measured at 0, 3, 6, 12, 18, 24, 30, 36, 42 and 48 months and taken as a guide for treatment; ABPM will be performed at randomisation and at 12, 24, 36 and 48 months but will not be used to take treatment decisions. Patients randomised to group 2 will have ABPM performed at randomisation and all scheduled visits as a guide to antihypertensive treatment. The effects of MUCH management strategy based on ABPM or on OBPM on CV and renal intermediate outcomes (changing left ventricular mass and microalbuminuria, coprimary outcomes) at 1 year and on CV events at 4 years and on changes in BP-related variables will be assessed., Ethics and Dissemination: MASTER study protocol has received approval by the ethical review board of Istituto Auxologico Italiano. The procedures set out in this protocol are in accordance with principles of Declaration of Helsinki and Good Clinical Practice guidelines. Results will be published in accordance with the CONSORT statement in a peer-reviewed scientific journal., Trial Registration Number: NCT02804074; Pre-results., Competing Interests: Competing interests: GP: honoraria as lecturer for Pfizer, Daiichi Sankyo, Menarini, Omron Healthcare. EA-R: honoraria and/or support from Menarini, Servier, Recordati,Guidotti,Malesci, Ferrer, DOC gen, Bruno farm. GLB: principal investigator (FIDElio)-Bayer, Steering committee (CREDENCE(Janssen), SONAR (AbbVie)-Consultant for Merck, Relypsa, Vascular Dynamics, Elceyx, Bayer, Janssen, AbbVie. FC: collaboration with Smart Solutions Technologies S.A.; AMICUS; Boston Scientific International S.A . ADS: honoraria as lecturer for Abbott, Daiichi-Sankyo, Lacer, Menarini, and Pfizer. MD: Honoria from Recordati and Servier. TK: Research grants Karolinska Institutet from Amgen, Medtronic, Pfizer, and Record, all outside the presented work. SL: Honoraria for lecturing from Axelife, Daichi-Sankyo, Fukuda-Denshi, Menarini, Novartis, Omron, Servier and Recordati. GM: honoraria aslecturer Actavis, Amgen, Boehringer Ingelheim, CVRx, Daiichi Sankyo, Ferrer, Medtronic, Menarini, Merck, Novartis, Recordati, Sanofi,Servier. RJM: has received BP Monitors forresearch use from Omron. JR: hasbeen paid as lecturer by Daiichi Sankyo, Menarini, BoehringerIngelheim, MSD. MYR: Lecture honoraria from Pfizer,LG Life Sciences, Bayer Korea, Hanmi Pharm. Co., Yuhan Co., Boryung Pharmaceutical Co., Research grant fromBoryung Pharmaceutical Co. and Dong-A Pharmaceutical Co., CJ HealthCare Co. GS: Conductedvalidation studies for various manufacturers; advised manufacturerson device development. JGW: lecture and consulting fees from Bayer, Daiichi-Sankyo, Novartis,Omron, Pfizer, Sanofi, and Servier. AZ: Honoraria from Menarini International., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To determine whether the effectiveness and safety of fixed-dose combinations (FDCs) of amlodipine orotate/valsartan (AML/VAL) 5/160 mg are noninferior to those of valsartan/hydrochlorothiazide (VAL/HCTZ) 160/12.5 mg in hypertensive patients with inadequate response to valsartan 160 mg monotherapy., Methods: This 8-week, active-controlled, parallel-group, fixed-dose, multicenter, double-blind randomized controlled, and noninferiority trial was conducted at 17 cardiovascular centers in the Republic of Korea. Eligible patients had mean sitting diastolic blood pressure (msDBP) ≥90 mm Hg despite monotherapy with valsartan 160 mg for 4 weeks. Patients were randomly assigned to treatment with AML/VAL 5/160 mg FDC (AML/VAL) group or VAL/HCTZ 160/12.5 mg FDC (VAL/HCTZ) group once daily for 8 weeks. A total of 238 patients were enrolled (AML/VAL group, n = 121; VAL/HCTZ group, n = 117), of whom 228 completed the study., Results: At 8 weeks after randomization, msDBP was significantly decreased in both groups (-9.44 ± 0.69 mm Hg in the AML/VAL group and -7.47 ± 0.71 mm Hg in the VAL/HCTZ group, both P < .001 vs baseline). Between group difference was -1.96 ± 1.00 mm Hg, indicating that AML/VAL 5/160 mg FDC was not inferior to VAL/HCTZ 160/12.5 mg FDC at primary efficacy endpoint. Control rate of BP defined as the percentage of patients achieving mean sitting SBP (msSBP) <140 mm Hg or msDBP <90 mm Hg (target BP) from baseline to week 8 was significantly higher in the AML/VAL group than that in the VAL/HCTZ group (84.3% [n = 102] in the AML/VAL group vs 71.3% [n = 82] in the VAL/HCTZ group, P = .016). At 8 weeks after randomization, mean uric acid level was significantly increased in the VAL/HCTZ group compared to that at baseline (0.64 ± 0.08 mg/dL; P < .001). However, it was slightly decreased from baseline in the AML/VAL group (-0.12 ± 0.08 mg/dL; P = .085). The intergroup difference was significant (P < .001)., Conclusion: The effectiveness and safety AML/VAL 5/160 mg FDC are noninferior to those of VAL/HCTZ 160/12.5 mg FDC in patients with hypertension inadequately controlled by valsartan 160 mg monotherapy.

Various home blood-pressure (HBP) measurement schedules were compared to determine the optimal schedule of HBP measurement for the diagnosis of hypertension. Out of 319 individuals who were suspected of having hypertension based on office BP measurements and who did not take antihypertensive drugs, 157 individuals who completed 42 HBP measurements over 7 days and who had a valid 24-h ambulatory blood pressure (ABP) measurement were included in this analysis. We evaluated five HBP measurement schedules to determine the optimal HBP measurement schedule for the diagnosis of hypertension. The cumulatively averaged HBP from 5 to 6 measurement days showed a Pearson correlation coefficient of >0.990 compared to HBP averaged for 6 or 7 days depending on the method. The intraclass correlation coefficient of the cumulatively averaged HBP measurements compared with the 24-h ABP measurement was excellent (≥0.75) from the average of three measurement days and increased steadily with increasing averaged days of HBP measurements. Compared with a diagnosis using a 24-h ABP measurement, the diagnostic sensitivity, specificity, and positive and negative predictive values of HBP measurements were not different among the five methods. The diagnostic agreement of cumulatively averaged HBP measurements was nearly perfect (kappa ≥ 0.9) from the average of five measurement days compared with a diagnosis based on HBP measurements averaged for 6 or 7 days and diagnosis based on averaged HBP measurements of previous days. We suggest obtaining HBP measurements over 5 days or more, in the morning and evening, taking two or more measurements per occasion, and averaging all of the readings as the optimal schedule of HBP measurement for the diagnosis of hypertension.

Appropriate prescription writing is one of the critical medical processes affecting the quality of public health care. However, this is a complex task for newly qualified intern doctors because of its complex characteristics requiring sufficient knowledge of medications and principles of clinical pharmacology, skills of diagnosis and communication, and critical judgment. This study aims to gather data on the current status of undergraduate prescribing education in South Korea. Two surveys were administered in this study: survey A to 26 medical schools in South Korea to gather information on the status of undergraduate education in clinical pharmacology; and survey B to 244 intern doctors in large hospitals to gather their opinions regarding prescribing education and ability. In survey A, half of the responding institutions provided prescribing education via various formats of classes over two curriculums including lecture, applied practice, group discussions, computer-utilized training, and workshops. In survey B, we found that intern doctors have the least confidence when prescribing drugs for special patient populations, especially pregnant women. These intern doctors believed that a case-based practical training or group discussion class would be an effective approach to supplement their prescribing education concurrently or after the clerkship in medical schools or right before starting intern training with a core drug list. The results of the present study may help instructors in charge of prescribing education when communicating and cooperating with each other to improve undergraduate prescribing education and the quality of national medical care., Competing Interests: Reviewer: This article reviewed by peer experts who are not TCP editors. Conflict of interest: - Authors: Nothing to declare - Reviewers: Nothing to declare - Editors: Nothing to declare, (Copyright © 2018 Translational and Clinical Pharmacology.)

Purpose: The aim of this study was to evaluate the safety and efficacy of combination treatment of rosuvastatin with ezetimibe in patients with primary hypercholesterolemia., Methods: This multicenter, randomized, double-blind study comprised a main study and an extension study. In the main study, the efficacy and safety of a combination of rosuvastatin (5, 10, and 20 mg) with ezetimibe (10 mg) were compared with those of rosuvastatin (5, 10, and 20 mg) alone. The subjects who achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C goal in the main study and agreed to a further study were enrolled for the extension study. In the extension study, ezetimibe 10 mg was also administered to subjects who had received rosuvastatin (5, 10, and 20 mg) alone in the main study, and the same treatment was continued for subjects who had received a combination of rosuvastatin with ezetimibe in the main study., Findings: At the end of the main study (week 8), LDL-C levels were significantly lower in subjects receiving combination therapy than in those receiving rosuvastatin monotherapy. Other lipid profiles also significantly improved in the combination therapy group. These improvements continued in the extension study. The combination therapy of rosuvastatin and ezetimibe was generally well tolerated. At the end of the main study, more subjects achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C goal in the combination therapy group than in the monotherapy group. The increased dosage of rosuvastatin was also well tolerated in the combination treatment., Implications: Combination therapy of ezetimibe 10 mg with varying doses of rosuvastatin that are commonly used in the clinical field improved the lipid profile and allowed more subjects to reach the LDL-C goal in primary hypercholesterolemia compared with rosuvastatin monotherapy. In addition, the efficacy of the combination therapy was maintained for the extended period. Additional beneficial changes were also achieved with combination therapy even in patients who responded well to rosuvastatin monotherapy. ClinicalTrials.gov identifier: NCT03288038., (Copyright © 2018. Published by Elsevier Inc.)

Purpose: Hypertension and dyslipidemia are 2 risk factors of cardiovascular disease that often present simultaneously. Traditionally, treatment of these multiple conditions required separate medications for each disease, which may result in poor compliance and thus lead to possible treatment failure. Fixed-dose combination (FDC) therapy with a single pill may be a solution in these situations., Methods: This multicenter, 8-week, randomized, double-blind, Phase III study evaluated the efficacy and safety of FDC treatment with telmisartan (80 mg) and rosuvastatin calcium (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. Patients were randomly assigned to 4 groups: (1) FDC drug (80 mg of telmisartan and 20 mg of rosuvastatin); (2) 80 mg of telmisartan; (3) 20 mg of rosuvastatin; or (4) placebo. After 8 weeks of treatment, the change in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) between the FDC group and the rosuvastatin group, and the percent change in LDL-C between the FDC group and the telmisartan group, were compared., Findings: A total of 210 patients were enrolled in the study (84 in the FDC group, 42 in the rosuvastatin group, 43 in the telmisartan group, and 41 in the placebo group). The reduction in blood pressure was significantly greater in the FDC group than in the rosuvastatin group after 8 weeks of treatment (least squares mean change from baseline, -16.1 [1.6] mm Hg vs -1.7 [2.2] mm Hg [P < 0.001] for MSSBP; -8.8 [1.0] mm Hg vs -1.6 [1.4] mm Hg [P < 0.001] for MSDBP). Least squares mean percent change in LDL-C from baseline was also significantly greater in the FDC group compared with the telmisartan group (-49.3% [2.2%] vs 1.5% [3.0%]; P < 0.001). FDC therapy also had a higher rate of achieving the treatment goal in both blood pressure (60% vs 45%; P = 0.024) and LDL-C (88.8% vs 16.3%; P < 0.001) compared with rosuvastatin or telmisartan alone, respectively. In regression analysis, higher baseline MSSBP, female sex, and lower body mass index were associated with increased reductions in MSSBP, whereas higher baseline LDL-C level and lower body mass index were associated with greater reductions in LDL-C. There were 48 adverse events in 36 patients (17.3% [36 of 208]), and 17 adverse drug reactions in 12 patients (5.8% [12 of 208]), indicating no significant differences in short-term safety among study groups., Implications: Treatment with an FDC drug containing telmisartan and rosuvastatin showed similar efficacy in lowering blood pressure and LDL-C levels compared with that of each single drug. ClinicalTrials.gov identifier: NCT01914432., (Copyright © 2018. Published by Elsevier Inc.)