May Measurement Month 2019: an analysis of blood pressure screening results from Korea.

Hypertension is the biggest contributing risk factor to cerebrovascular disease and is associated with increased risk of coronary artery disease. The May Measurement Month (MMM) campaign is a global initiative aimed at raising awareness of hypertension and acting as a temporary solution to the lack of screening programs worldwide. An opportunistic cross-sectional survey of participants aged ≥18 was carried out during May 2019 in Korea. Over 10 000 participants were recruited in the MMM campaign in Korea, with a slogan of 'A simple measure to save lives-#checkyourpressure'. A total of 9975 participants with valid clinical and blood pressure (BP) data were used for analysis. All participants were Korean in ethnicity, mean age was 57.2 (SD ± 21.2) years, 57.7% were females, and the mean body mass index was 23.4 kg/m2 (SD ± 3.3). In total, 37.7% of the participants reported a previous diagnosis of hypertension, and 91.3% of those diagnosed were on antihypertensive medications. For other comorbidities, 11.6% reported having diabetes mellitus, 2.0% had previous stroke, and 1.0% had previous myocardial infarction. Mean BP was 130.0/81.0 mmHg in the overall population. After multiple imputation, 47.6% of participants were classified as hypertensive (systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg or on treatment for raised BP). Among all hypertensive participants, the awareness rate, the treatment rate, and the control rate (systolic BP <140 mmHg and diastolic BP <90 mmHg) were 76.2%, 74.0%, and 50.5%, respectively. Of those on antihypertensive medication, the control rate was 68.2%. While awareness and treatment rates were relatively high in the MMM19 campaign, the BP control rate of the total hypertensive population was still only ∼50%, which demands more emphasis on strict BP control.

Blood pressure levels and cardiovascular risk according to age in patients with diabetes mellitus: a nationwide population-based cohort study.

BACKGROUND: Little is known about age-specific target blood pressure (BP) in hypertensive patients with diabetes mellitus (DM). The aim of this study was to determine the BP level at the lowest cardiovascular risk of hypertensive patients with DM according to age. METHODS: Using the Korean National Health Insurance Service database, we analyzed patients without cardiovascular disease diagnosed with both hypertension and DM from January 2002 to December 2011. Primary end-point was composite cardiovascular events including cardiovascular death, myocardial infarction and stroke. RESULTS: Of 241,148 study patients, 35,396 had cardiovascular events during a median follow-up period of 10 years. At the age of < 70 years, the risk of cardiovascular events was lower in patients with BP < 120/70 mmHg than in those with BP 130-139/80-89 mmHg. At the age of ≥ 70, however, there were no significant differences in the risk of cardiovascular events between patients with BP 130-139/80-89 mmHg and BP < 120/70 mmHg. The risk of cardiovascular events was similar between patients with BP 130-139/80-89 mmHg and BP 120-129/70-79 mmHg, and it was significantly higher in those with BP ≥ 140/90 mmHg than in those with BP 130-139/80-89 mmHg at all ages. CONCLUSIONS: In a cohort of hypertensive patients who had DM but no history of cardiovascular disease, lower BP was associated with lower risk of cardiovascular events especially at the age of < 70. However, low BP < 130-139/80-89 mmHg was not associated with decreased cardiovascular risk, it may be better to keep the BP of 130-139/80-89 mmHg at the age of ≥ 70.

Lipoprotein(a) and Cardiovascular Diseases　- Revisited.

Two decades ago, it was recognized that lipoprotein(a) (Lp(a)) concentrations were elevated in patients with cardiovascular disease (CVD). However, the importance of Lp(a) was not strongly established due to a lack of both Lp(a)-lowering therapy and evidence that reducing Lp(a) levels improves CVD risk. Recent advances in clinical and genetic research have revealed the crucial role of Lp(a) in the pathogenesis of CVD. Mendelian randomization studies have shown that Lp(a) concentrations are causal for different CVDs, including coronary artery disease, calcified aortic valve disease, stroke, and heart failure, despite optimal low-density lipoprotein cholesterol (LDL-C) management. Lp(a) consists of apolipoprotein (apo) B100 covalently bound to apoA. Thus, Lp(a) has atherothrombotic traits of both apoB (from LDL) and apoA (thrombo-inflammatory aspects). Although conventional pharmacological therapies, such as statin, niacin, and cholesteryl ester transfer protein, have failed to significantly reduce Lp(a) levels, emerging new therapeutic strategies using proprotein convertase subtilisin-kexin type 9 inhibitors or antisesnse oligonucleotide technology have shown promising results in effectively lowering Lp(a). In this review we discuss the revisited important role of L(a) and strategies to overcome residual risk in the statin era.

Sex-related differences in the intratubular renin-angiotensin system in two-kidney, one-clip hypertensive rats.

The intratubular renin-angiotensin system (RAS) is thought to play an essential role in hypertensive renal disease, but information regarding sex-related differences in this system is limited. The present study investigated sex differences in the intratubular RAS in two-kidney, one-clip (2K1C) rats. A 2.5-mm clip was placed on the left renal artery of Sprague-Dawley rats, and rats were euthanized 3 or 5 wk after the operation. Systolic blood pressure increased in 2K1C rats in both sexes but was significantly higher in male rats than in female rats, and an antihypertensive effect was not observed in 2K1C ovariectomized (OVX) female rats. Compared with male 2K1C rats, intratubular angiotensin-converting enzyme (ACE) and ANG II were repressed, and intratubular ACE2, angiotensin (1-7), and Mas receptor were increased in both kidneys in female 2K1C rats 5 wk after surgery. Comparison with male and female rats and intratubular mRNA levels of ACE and ANG II type 1 receptor were augmented in OVX female rats, regardless of the clipping surgery 3 wk postoperation. ANG II type 2 receptor was upregulated in female rats with or without OVX; thus, the ANG II type 1-to-type 2 receptor ratio was higher in male rats than in female rats. In conclusion, female rats were protected from hypertensive renal and cardiac injury after renal artery clipping. An increase in the intratubular nonclassic RAS [ACE2/angiotensin (1-7)/Mas receptor] and a decrease in the ANG II type 1-to-type 2 receptor ratio could limit the adverse effects of the classic RAS during renovascular hypertension in female rats, and estrogen is suggested to play a primary role in the regulation of intratubular RAS components.

Controversies in the 2017 ACC/AHA Hypertension Guidelines: Who Can Be Eligible for Treatments Under the New Guidelines?　- An Asian Perspective.

Until the 2017 ACC/AHA Hypertension Guidelines were released, the target blood pressure (BP) for adults with hypertension (HTN) was 140/90 mmHg in most of the guidelines. The new 2018 ESC/ESH, Canadian, Korean, Japan, and Latin American hypertension guidelines have maintained the <140/90 mmHg for the primary target in the general population and encourage reduction to <130/80 if higher risk. This is more in keeping with the 2018 American Diabetes Association guidelines. However, the 2017 ACC/AHA guidelines classify HTN as BP ≥130/80 mmHg and generally recommend target BP levels below 130/80 mmHg for hypertensive patients independently of comorbid disease or age. Although the new guidelines mean that more people (nearly 50% of adults) will be diagnosed with HTN, the cornerstone of therapy is still lifestyle management unless BP cannot be lowered to this level; thus, more people will require BP-lowering medications. To date, there have been many controversies about the definition of HTN and the target BP. Targeting an intensive systolic BP goal can increase the adverse effects of multiple medications and the cardiovascular disease risk by excessively lowering diastolic BP, especially in patients with high risk, including those with diabetes, chronic kidney disease, heart failure, and coronary artery disease, and the elderly. In this review, we discuss these issues, particularly regarding the optimal target BP.

Best Treatment Strategies With Statins to Maximize the Cardiometabolic Benefits.

Statins are important for preventing adverse cardiovascular events in patients with both high and low risk of vascular disease, by reducing the levels of low-density lipoprotein cholesterol (LDL-C). However, statins dose-dependently increase adverse effects and increase the risk of type 2 diabetes. Previously, it was hypothesized this was caused by to off-target effects, but recent studies demonstrate it is caused by on-target effects. Nonetheless, the American guidelines recommend the use of high-intensity statin therapy, and extend its use to most people at risk of vascular diseases, particularly older people. In contrast, European, Korean, and Japanese committees have expressed concerns about the potential adverse effects of using high-intensity statins for lifelong periods in a large fraction of the population. Patients who have achieved LDL-C levels below currently recommended targets may still experience cardiovascular events, resulting from residual risk. Ezetimibe, PCSK9 inhibitors, inclisiran, and ANGPTL3 antisense oligonucleotides are promising alternative non-statin drugs. Of interest, cross-talk between hypercholesterolemia and the renin-angiotensin-system exists at multiple levels of insulin resistance and endothelial dysfunction. There are still unanswered questions on how to maximize the cardiometabolic benefits of statins in patients. We will discuss the results of randomized clinical trials, meta-analysis, and recent clinicopharmacogenetic studies, and propose practical guidelines to maximize the cardiometabolic benefits while reducing adverse effects and overcoming residual risk.

Normal reference values of diastolic strain rate in healthy individuals: Chronological trends and the comparison according to genders.

PURPOSE: Recently, the diastolic strain rate (DSR) utilizing speckle-tracking echocardiography has been proposed as a novel parameter for left ventricular diastolic function. We aimed to present normal reference data for those in a large-sized, selected group of healthy individuals. METHODS: The current study was a part of the Normal echOcardiogRaphic Measurements in KoreAn popuLation (NORMAL), a prospective nationwide survey from 23 centers in Korea. We analyzed 447 subjects (age 48 ± 15 years, 234 females) without any history of cardiovascular disease and presented the early and late DSRs (SRe and SRa , respectively) in a total and gender-/age-specified groups. RESULTS: Among the total subjects, the mean SRe and SRa were 1.6 ± 0.4 S-1 and 0.8 ± 0.3 S-1 , respectively. With increasing age, there were significant trends of decreasing SRe and increasing SRa . Although both gender groups showed comparable age, the female group presented significantly higher SRe compared to male subjects with age of 20-59 years, which diminished after the age of 60 years. However, the SRa was comparable between genders in all age groups. On multiple linear regression, age showed independent associations with both SRe (ß = -0.132, P = .010) and SRa (ß = 0.440, P < .001), whereas gender did not show any association with SRe or SRa . CONCLUSION: We present normal reference data of a novel parameter, DSR, in a large-sized selected group with healthy Korean subjects. Additionally, we present significant age-related changes both in SRe and SRa without the impact of their gender.

Sequential activation of the intrarenal renin-angiotensin system in the progression of hypertensive nephropathy in Goldblatt rats.

The intrarenal renin-angiotensin system (RAS) has an important role in generating and maintaining hypertension in two-kidney, one-clip (2K1C) rats. This study evaluated how various intrarenal RAS components contributed to hypertension not only in the maintenance period (5w; 5 wk after operation) but also earlier (2w; 2 wk after operation). We inserted a 2.5-mm clip into the left renal artery of Sprague-Dawley rats and euthanized them at 2w and 5w following the operation. Systolic blood pressure increased within 1 wk after the operation, and left ventricular hypertrophy occurred in 2K1C rats. At 2w, juxtaglomerular apparatus (JGA) and collecting duct (CD) renin increased in clipped kidney (CK) of 2K1C rats. The tubular angiotensin I-converting enzyme (ACE) was not changed, but peritubular ACE2 decreased in nonclipped kidney (NCK) and CK of 2K1C rats. At 5w, ACE and CD renin were enhanced, and ACE2 was still lessened in both kidneys of 2K1C rats. However, plasma renin activity (PRA) was not different from that in sham rats. In proximal tubules of CK, the ANG II type 1 receptor (AT1R) was not suppressed, but the Mas receptor (MasR) was reduced; thus the AT1R/MasR ratio was elevated. Although hypoxic change in CK could not be excluded, the JGA renin of CK and CD renin in both kidneys was highly expressed independent of time. Peritubular ACE2 changed in the earlier period, and uninhibited AT1R in proximal tubules of CK was presented in the maintenance period. In 2K1C rats, attenuated ACE2 seems to contribute to initiating hypertension while upregulated ACE in combination with unsuppressed AT1R may have a key role in maintaining hypertension.

Full-blown cardiac manifestations in ankylosing spondylitis.

Ankylosing spondylitis often involves a heart, such as aortic or mitral regurgitation, conduction disorder, or cardiomyopathy. We present a 34-year-old male patient with ankylosing spondylitis who has severe aortic regurgitation, mild mitral stenosis, and a conduction disturbance of the left bundle branch block, identified using multimodal images.

Evolutionary change mimicking apical hypertrophic cardiomyopathy in a patient with takotsubo cardiomyopathy.

In this report, we introduce a case of thickening of the involved left ventricular apical segment on echocardiography and deep T-wave inversions in precordial leads on electrocardiography transiently seen in the course of recovery from biventricular takotsubo cardiomyopathy, mimicking apical hypertrophic cardiomyopathy. This result suggests that the echocardiographic finding of transient myocardial edema can be identified by cardiac magnetic resonance imaging in takotsubo cardiomyopathy. Additionally, it persisted a few weeks after full functional recovery. We believe that this case will contribute in part toward clarifying the pathophysiology of takotsubo cardiomyopathy.

Breast Cancer and Therapy-Related Cardiovascular Toxicity.

The global incidence of breast cancer is on the rise, a trend also observed in South Korea. However, thanks to the rapid advancements in anticancer therapies, survival rates are improving. Consequently, post-treatment health and quality of life for breast cancer survivors are emerging as significant concerns, particularly regarding treatment-related cardiotoxicity. In this review, we delve into the cardiovascular complications associated with breast cancer treatment, explore surveillance protocols for early detection and diagnosis of late complications, and discuss protective strategies against cardiotoxicity in breast cancer patients undergoing anticancer therapy, drawing from multiple guidelines.

Double-chambered left ventricle with a thrombus in an asymptomatic patient: A case report.

BACKGROUND: Double-chambered left ventricle (DCLV) is an extremely rare congenital disease in which the left ventricle (LV) is divided by abnormal muscle tissue. Due to its rarity, there is a lack of data on the disease, including its diagnosis, treatment, and prognosis. Accordingly, we report a case in which DCLV was diagnosed and followed up. CASE SUMMARY: A 45-year-old man presented to our hospital due to abnormal findings on an electrocardiogram recorded during a health check. He had no specific cardiac symptoms, comorbidities or relevant past medical history. Echocardiography revealed that the LV was divided into two by muscle fibers. There were no findings of ischemia on coronary angiography and coronary computed tomography angiography performed to exclude differential diagnoses. After comprehensive analysis of the images, DCLV was diagnosed. As it seemed to be asymptomatic DCLV, we decided the patient was to be observed without administering any medication. However, follow-up echocardiography revealed a thrombus in the accessory chamber (AC). Anticoagulant medication was initiated, the thrombus resolved, and the patient is currently undergoing follow-up without any specific symptoms. CONCLUSION: Asymptomatic, uncomplicated DCLV was diagnosed through multimodal imaging; however, a thrombus in the AC occurred during the follow-up. The findings highlight that multimodal imaging is essential in diagnosing DCLV, and that anticoagulation is important in its management.

Efficacy and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe in patients with dyslipidemia and hypertension: A randomized, double-blind, multicenter, therapeutic confirmatory, phase III clinical trial.

This study aimed to compare and evaluate the efficacy of the blood pressure (BP) control and cholesterol-lowering effects and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe versus rosuvastatin and ezetimibe double therapy or telmisartan single therapy in dyslipidemia patients with hypertension. After a wash-out/therapeutic lifestyle change period of ≥4 weeks, a total of 100 eligible patients were randomized and received one of three treatments for 8 weeks: (1) telmisartan 80 mg/rosuvastatin 20 mg/ezetimibe 10 mg (TRE), (2) rosuvastatin 20 mg/ezetimibe 10 mg (RE), or (3) telmisartan 80 mg (T). The primary endpoint was the efficacy evaluation of TRE by comparing changes in mean sitting systolic blood pressure (msSBP) and mean percentage change in low-density lipoprotein-C (LDL-C) from baseline after 8 weeks of treatment. The least square (LS) mean (SE) changes in msSBP at 8 weeks compared with baseline were -23.02 (3.04) versus -7.18 (3.09) mmHg in the TRE and RE groups, respectively (p < .0001), and -25.80 (2.74) versus -14.92 (2.65) mmHg in the TRE and T groups, respectively (p = .0005). The percentage changes in the mean (SD) LDL-C at 8 weeks compared with baseline were -54.97% (3.49%) versus -0.17% (3.23%) in the TRE and T groups, respectively (p < .0001). No serious adverse events occurred, and no statistically significant differences in the incidence of overall AEs and adverse drug reactions occurred among the three groups. TRE therapy significantly decreased msSBP and LDL-C compared to RE or T therapy with comparable safety and tolerability profiles.

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

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

Adherence and clinical outcomes for twice-daily versus once-daily dosing of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: Is dosing frequency important?

BACKGROUND: Twice-daily dosing of non-vitamin K antagonist oral anticoagulants (NOACs) may reduce drug adherence compared with once-daily dosing of NOACs in patients with atrial fibrillation (AF), thus worsening clinical outcomes. We evaluated adherence to apixaban and dabigatran requiring twice-daily dosing compared with edoxaban or rivaroxaban with a once-daily dosing regimen and the subsequent clinical outcomes in patients with AF. METHODS: Adherence to each NOAC and outcomes were compared between patients who were diagnosed with AF and initiated NOACs between 2016 and 2017 using Korean claims data. High adherence was defined as the proportion of days covered (PDC) of the index NOAC ≥80%. The clinical outcomes included stroke, acute myocardial infarction, death, and composite outcome. RESULTS: A total of 33,515 patients were analyzed (mean follow-up, 1.7 ± 1.3 years). The proportion of patients with high adherence to NOACs was 95%, which did not significantly differ according to the dosing regimen. The mean PDC for NOACs was as high as ~96%, which was the highest for apixaban users, intermediate for edoxaban or rivaroxaban users, and lowest for dabigatran users, regardless of the dosing regimen. Adverse outcomes in low adherence patients for each NOAC were higher than that of high adherence patients, regardless of the dosing frequency. CONCLUSIONS: Adherence between once- and twice-daily dosing NOACs in patients with AF was high and similar among both dosing regimens. Patients with low NOAC adherence had poorer clinical outcomes, regardless of the dosing frequency.

Efficacy and Safety of a Single-Pill Triple Combination of Olmesartan, Amlodipine, and Rosuvastatin in Hypertensive Patients with Low-to-Moderate Cardiovascular Risk: A Multicenter, Randomized, Open-Label, Active-Control, Phase IV Clinical Trial.

INTRODUCTION: This study evaluated the efficacy and safety of a single-pill triple-combination of olmesartan/amlodipine/rosuvastatin (Olme/Amlo/Rosu) in comparison with a single-pill dual-combination of olmesartan/amlodipine (Olme/Amlo) in hypertensive patients with low-to-moderate cardiovascular risk. METHODS: This multicenter, active-control, randomized study included 106 hypertensive patients at low-to-moderate cardiovascular risk who were randomly assigned to receive either Olme/Amlo/Rosu 20/5/5 mg (Treatment 1), Olme/Amlo/Rosu 20/5/10 mg (Treatment 2), or Amlo/Olme 20/5 mg (Control) once daily for 8 weeks. The primary endpoint was the difference of the percent change in low-density lipoprotein cholesterol (LDL-C) level at 8 weeks from baseline in the 3 groups. RESULTS: The difference in the least square mean percent change (standard deviation) of LDL-C in the Treatment 1 and 2 groups compared with the Control group at 8 weeks was -32.6 (3.7) % and -45.9 (3.3) %, respectively (P < .001). The achievement rates of LDL-C level <100 mg/dL at 8 weeks were significantly different between the 3 groups (65.8%, 86.7%, and 6.3% for Treatment 1, 2, and Control groups, respectively, P < .001). The results of total cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoprotein B, and apolipoprotein B/apolipoprotein A1 were superior in the Treatment 1 and 2 groups compared with the Control group. Serious adverse drug reaction did not occur in the 3 groups. Medication adherence rates were excellent in the 3 groups (98.0% for Treatment 1 group, 99.7% for Treatment 2 group, and 96.3% for the Control group, P > .05). CONCLUSION: Single-pill triple-combination of olmesartan/amlodipine/rosuvastatin was superior to the single-pill dual-combination of amlodipine/olmesartan in LDLC-lowering effects, with excellent safety profiles and adherence rates, in hypertensive patients at low-to-moderate cardiovascular risk.Trial Registration: CLinicalTrials.gov identifier NCT04120753.

Advancing Cardio-Oncology in Asia.

Cardio-oncology is an emerging multi-disciplinary field, which aims to reduce morbidity and mortality of cancer patients by preventing and managing cancer treatment-related cardiovascular toxicities. With the exponential growth in cancer and cardiovascular diseases in Asia, there is an emerging need for cardio-oncology awareness among physicians and country-specific cardio-oncology initiatives. In this state-of-the-art review, we sought to describe the burden of cancer and cardiovascular disease in Asia, a region with rich cultural and socio-economic diversity. From describing the uniqueness and challenges (such as socio-economic disparity, ethnical and racial diversity, and limited training opportunities) in establishing cardio-oncology in Asia, and outlining ways to overcome any barriers, this article aims to help advance the field of cardio-oncology in Asia.

Statement on chronotherapy for the treatment of hypertension: consensus document from the Korean society of hypertension.

Nocturnal blood pressure (BP) has been shown to have a significant predictive value for cardiovascular disease. In some cases, it has a superior predictive value for future cardiovascular outcomes than daytime BP. As efficacy of BP medications wanes during nighttime and early morning, control of nocturnal hypertension and morning hypertension can be difficult. As such, chronotherapy, the dosing of BP medication in the evening, has been an ongoing topic of interest in the field of hypertension. Some studies have shown that chronotherapy is effective in reducing nocturnal BP, improving non dipping and rising patterns to dipping patterns, and improving cardiovascular prognosis. However, criticism and concerns have been raised regarding the design of these studies, such as the Hygia study, and the implausible clinical benefits in cardiovascular outcomes considering the degree of BP lowering from bedtime dosing. Studies have shown that there is no consistent evidence to suggest that routine administration of antihypertensive medications at bedtime can improve nocturnal BP and early morning BP control. However, in some cases of uncontrolled nocturnal hypertension and morning hypertension, such as in those with diabetes mellitus, chronic kidney disease, and obstructive sleep apnea, bedtime dosing has shown efficacy in reducing evening and early morning BP. The recently published the Treatment in Morning versus Evening (TIME) study failed to demonstrate benefit of bedtime dosing in reducing cardiovascular outcomes in patients with hypertension. With issues of the Hygia study and negative results from the TIME study, it is unclear at this time whether routine bedtime dosing is beneficial for reducing cardiovascular outcomes.

APACHE II score, rather than cardiac function, may predict poor prognosis in patients with stress-induced cardiomyopathy.

While the disease course of stress-induced cardiomyopathy (SIC) is usually benign, it can be fatal. The prognostic factors to predict poorer outcome are not well established, however. We analyzed the Acute Physiology And Chronic Health Evaluation (APACHE) II score to assess its value for predicting poor prognosis in patients with SIC. Thirty-seven consecutive patients with SIC were followed prospectively during their hospitalization. Clinical factors, including APACHE II score, coronary angiogram, echocardiography and cardiac enzymes at presentation were analyzed. Of the 37 patients, 27 patients (73%) were women. The mean age was 66.1 ± 15.6 yr, and the most common presentation was chest pain (38%). Initial echocardiographic left ventricular ejection fraction (EF) was 42.5% ± 9.3%, and the wall motion score index (WMSI) was 1.9 ± 0.3. Six patients (16%) expired during the follow-up period of hospitalization. Based on the analysis of characteristics and clinical factors, the only predictable variable in prognosis was APACHE II score. The patients with APACHE II score greater than 20 had tendency to expire than the others (P = 0.001). Based on present study, APACHE II score more than 20, rather than cardiac function, is associated with mortality in patients with SIC.

Efficacy and safety of low-dose antihypertensive combination of amlodipine, telmisartan, and chlorthalidone: A randomized, double-blind, parallel, phase II trial.

The aim of this clinical trial was to assess the efficacy and safety of low-dose triple combinations of amlodipine, telmisartan, and chlorthalidone in patients with essential hypertension. After a 2-week placebo run-in period, 176 patients were randomized to seven treatment groups (placebo, quarter-dose combination, third-dose combination, half-dose combination, amlodipine 5 mg, amlodipine 10 mg, and telmisartan 80 mg) and administered the assigned study drug orally for 8 weeks. The primary efficacy endpoint was the change in the mean sitting systolic blood pressure (BP) (MSSBP) at Week 8. The MSSBP and mean sitting diastolic BP in the quarter-dose and half-dose groups were significantly lower compared to the placebo and amlodipine 5 mg groups, with similar BP-lowering effects observed compared to the amlodipine 10 mg and telmisartan 80 mg groups. However, the third-dose group showed significant BP improvement only compared to the placebo group. A similar pattern was observed for the control rate of hypertension and response rates. Additional analysis was conducted after correcting for gender and age effects, and, as a result, the third-dose group showed similar results with regard to the BP-lowering effect as the quarter-dose and half-dose groups. In terms of safety, no special adverse events and clinically significant results were noted, and all dose groups of the triple combination are considered safe for use in essential hypertension patients. The current findings indicated that low-dose triple combination of amlodipine, telmisartan, and chlorthalidone over 8 weeks effectively improved the BP-lowering effect in patients with essential hypertension without any safety concerns.