Diagnostic Pitfall and Clinical Characteristics of Variant Versus Wild-Type Transthyretin Amyloid Cardiomyopathy in Asian Population: The Korean Nationwide Cohort Study.

BACKGROUND: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure (HF) with clinical phenotypes that vary across regions and genotypes. We sought to characterize the clinical characteristics of ATTR-CM in Asia. METHODS: Data from a nationwide cohort of patients with ATTR-CM from six major tertiary centres in South Korea were analysed between 2010 and 2021. All patients underwent clinical evaluation, biochemical laboratory tests, echocardiography, and transthyretin (TTR) genotyping at the time of diagnosis. The study population comprised 105 Asian ATTR-CM patients (mean age: 69 years; male: 65.7%, wild-type ATTR-CM: 41.9%). RESULTS: Among our cohort, 18% of the patients had a mean left ventricular (LV) wall thickness < 12 mm. The diagnosis of ATTR-CM increased notably during the study period (8 [7.6%] during 2010-2013 vs. 22 [21.0%] during 2014-2017 vs. 75 [71.4%] during 2018-2021). Although the duration between symptom onset and diagnosis did not differ, the proportion of patients with HF presenting mild symptoms increased during the study period (25% NYHA class I/II between 2010-2013 to 77% between 2018-2021). In contrast to other international registry data, male predominance was less prominent in wild-type ATTR-CM (68.2%). The distribution of TTR variants was also different from Western countries and from Japan. Asp38Ala was the most common mutation. CONCLUSION: A nationwide cohort of ATTR-CM exhibited less male predominance, a proportion of patients without increased LV wall thickness, and distinct characteristics of genetic mutations, compared to cohorts in other parts of the world. Our results highlight the ethnic variation in ATTR-CM and may contribute to improving the screening process for ATTR-CM in the Asian population.

Gender Difference of Blood Pressure Control Rate and Clinical Prognosis in Patients With Resistant Hypertension: Real-World Observation Study.

BACKGROUND: There are several differences in the clinical course of hypertension due to the biological and social differences between men and women. Resistant hypertension is an advanced disease state, and significant gender difference could be expected, but much has not been revealed yet. The purpose of this study was to compare gender differences on the current status of blood pressure (BP) control and clinical prognosis in patients with resistant hypertension. METHODS: This is a multicenter, retrospective cohort study using common data model databases of 3 tertiary hospitals in Korea. Total 4,926 patients with resistant hypertension were selected from January 2017 to December 2018. Occurrence of dialysis, heart failure (HF) hospitalization, myocardial infarction, stroke, dementia or all-cause mortality was followed up for 3 years. RESULTS: Male patients with resistant hypertension were younger but had a higher cardiovascular risk than female patients. Prevalence of left ventricular hypertrophy and proteinuria was higher in men than in women. On-treatment diastolic BP was lower in women than in men and target BP achievement rate was higher in women than in men. During 3 years, the incidence of dialysis and myocardial infarction was higher in men, and the incidence of stroke and dementia was higher in women. After adjustment, male sex was an independent risk factor for HF hospitalization, myocardial infarction, and all-cause death. CONCLUSION: In resistant hypertension, men were younger than women, but end-organ damage was more common and the risk of cardiovascular event was higher. More intensive cardiovascular prevention strategies may be required in male patients with resistant hypertension.

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

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

Evaluation of Adherence to Guideline for Heart Failure with Reduced Ejection Fraction in Heart Failure with Preserved Ejection Fraction and with or without Atrial Fibrillation.

BACKGROUND: This study evaluated the relationship between guideline adherence for heart failure (HF) with reduced ejection fraction (HFrEF) at discharge and relevant clinical outcomes in patients with acute HF with preserved ejection fraction (HFpEF) with or without atrial fibrillation (AF). METHODS: We analyzed Korean Acute Heart Failure Registry data for 707 patients with HFpEF with documented AF and 687 without AF. Guideline adherence was defined as good or poor according to the prescription of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, ß-blockers, and mineralocorticoid receptor antagonists. Anticoagulation adherence was also incorporated for the AF group. RESULTS: Among patients with normal sinus rhythm, those with poor guideline adherence had a reduced prevalence of comorbidities and favorable clinical characteristics when compared with those with good guideline adherence. Using inverse probability of treatment weighting (IPTW) to address the bias of nonrandom treatment assignment, good adherence was associated with a poor 60-day composite endpoint in the multivariable Cox model (weighted hazard ratio [wHR], 1.74; 95% confidence interval [CI], 1.01-3.00; P = 0.045). For patients with AF, baseline clinical characteristics were similar according to the degree of adherence. The IPTW-adjusted analysis indicated that good adherence was significantly associated with the 60-day composite endpoint (wHR, 0.47; 95% CI, 0.27-0.79; P = 0.005). In the analysis excluding warfarin, good adherence was associated with 60-day re-hospitalization (wHR, 0.60; 95% CI, 0.37-0.98; P = 0.040), 1-year re-hospitalization (wHR, 0.67; 95% CI, 0.48-0.93; P = 0.018), and the composite endpoint (wHR, 0.77; 95% CI, 0.59-0.99; P = 0.041). CONCLUSION: Our findings indicate that good adherence to guidelines for HFrEF is associated with a better 60-day composite endpoint in patients with HFpEF with AF.

Beta-blocker Therapy at Discharge in Patients with Acute Heart Failure and Atrial Fibrillation.

BACKGROUND: ß-blockers (BBs) are considered primary therapy in stable heart failure (HF) with reduced ejection fraction (HFrEF) without atrial fibrillation (AF); evidence-based benefits of BB on outcome have been documented. However, BBs have not been shown to improve mortality or reduce hospital admissions in HF patients with AF. This study assessed the relationship between BBs at discharge and relevant clinical outcomes in acute heart failure (AHF) patients with AF. METHODS: From the Korean Acute Heart Failure Registry, 936 HFrEF and 639 HF patients with preserved ejection fraction (HFpEF) and AF were selected. Propensity score (PS) matching accounted for BB selection bias when assessing associations. RESULTS: BB-untreated patients in the overall cohort of HFrEF and HFpEF had greater deteriorated clinical and laboratory characteristics. In the 670 PS-matched cohort of HFrEF patients, incidences of all clinical events at 60 days and 1 year were not different according to use of BBs. In the 470 PS-matched cohort of HFpEF, rehospitalization and composite outcome at 6 months and 1 year more frequently occurred in non-users of BBs. After adjusting for covariates in the multivariable Cox model of matched cohorts, BB was not associated with clinical outcomes at 60 days and 1 year in HFrEF with AF patients. In HFpEF patients with AF, BB use was associated with reduced 6-month (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20-0.74) and 1-year rehospitalization (HR, 0.53; 95% CI, 0.34-0.82). CONCLUSION: In the HFrEF with AF PS-matched cohort, the use of BBs at discharge was not associated with clinical outcome. However, in HFpEF with AF, the use of BB was associated with reduced rehospitalization during the 6-month and 1-year follow up.

Co-treatment with interferon-γ and 1-methyl tryptophan ameliorates cardiac fibrosis through cardiac myofibroblasts apoptosis.

Cardiac remodeling characterized by cardiac fibrosis is a pathologic process occurring after acute myocardial infarction. Fibrosis can be ameliorated by interferon-gamma (IFN-γ), which is a soluble cytokine showing various effects such as anti-fibrosis, apoptosis, anti-proliferation, immunomodulation, and anti-viral activities. However, the role of IFN-γ in cardiac myofibroblasts is not well established. Therefore, we investigated the anti-fibrotic effects of IFN-γ in human cardiac myofibroblasts (hCMs) in vitro and whether indoleamine 2,3-dioxygenase (IDO), induced by IFN-γ and resulting in cell cycle arrest, plays an important role in regulating the biological activity of hCMs. After IFN-γ treatment, cell signaling pathways and DNA contents were analyzed to assess the biological activity of IFN-γ in hCMs. In addition, an IDO inhibitor (1-methyl tryptophan; 1-MT) was used to assess whether IDO plays a key role in regulating hCMs. IFN-γ significantly inhibited hCM proliferation, and IFN-γ-induced IDO expression caused cell cycle arrest in G0/G1 through tryptophan depletion. Moreover, IFN-γ treatment gradually suppressed the expression of α-smooth muscle actin. When IDO activity was inhibited by 1-MT, marked apoptosis was observed in hCMs through the induction of interferon regulatory factor, Fas, and Fas ligand. Our results suggest that IFN-γ plays key roles in anti-proliferative and anti-fibrotic activities in hCMs and further induces apoptosis via IDO inhibition. In conclusion, co-treatment with IFN-γ and 1-MT can ameliorate fibrosis in cardiac myofibroblasts through apoptosis.

Prognostic Effect of Guideline-Directed Therapy Is More Noticeable Early in the Course of Heart Failure.

BACKGROUND: There have been few studies to evaluate the prognostic implications of guideline-directed therapy according to the temporal course of heart failure. This study assessed the relationship between adherence to guideline-directed therapy at discharge and 60-day clinical outcomes in de novo acute heart failure (AHF) and acute decompensated chronic heart failure (ADCHF) separately. METHODS: Among 5,625 AHF patients who were recruited from a multicenter cohort registry of Korean Acute Heart Failure, 2,769 patients with reduced ejection fraction were analyzed. Guideline-directed therapies were defined as the use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor II blocker (ARB), ß-blocker, and mineralocorticoid receptor antagonist. RESULTS: In de novo AHF, ACEI or ARB reduced re-hospitalization (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.34-0.95), mortality (HR, 0.41; 95% CI, 0.24-0.69) and composite endpoint (HR, 0.52; 95% CI, 0.36-0.77) rates. Beta-blockers reduced re-hospitalization (HR, 0.62; 95% CI, 0.41-0.95) and composite endpoint (HR, 0.65; 95% CI, 0.47-0.90) rates. In ADCHF, adherence to ACEI or ARB was associated with only mortality and ß-blockers with composite endpoint. CONCLUSION: The prognostic implications of adherence to guideline-directed therapy at discharge were more pronounced in de novo heart failure. We recommend that guideline-directed therapy be started as early as possible in the course of heart failure with reduced ejection fraction.

Prognostic value of short-term follow-up BNP in hospitalized patients with heart failure.

BACKGROUND: B-type natriuretic peptide (BNP) has prognostic significance in heart failure (HF), and reductions in BNP may predict clinical improvement. However, there are limited data regarding the prognostic value of BNP during short-term follow-up. The aim of this study was to evaluate the relationship between short-term follow-up BNP and mortality after discharge in patients with HF. METHODS: We analyzed 427 patients hospitalized with HF from the Wonju Severance Christian Hospital Heart Failure Registry from April 2011 to December 2013, with a planned follow-up period through February 2016. Of the 427 patients, 240 (mean age, 75 years; 102 males, 42.5%) had BNP measured on admission and within the short-term follow-up period (3 months). We compared all-cause mortality during the clinical follow-up period (median length of follow-up, 709.5 days) according to the median value of BNP on admission (as a baseline value) and over a short-term follow-up period after discharge. RESULTS: Median BNP at admission was 816.5 pg/ml, and median follow-up BNP was 369.7 pg/ml. Multivariate analysis revealed a positive association between risk of death and high BNP. High BNP during follow-up was significantly associated with a greater risk of all-cause mortality compared to low BNP (P < 0.001). Initial BNP was not significantly associated with all-cause mortality. A multivariate model showed that follow-up BNP and percent change in BNP were independently associated with all-cause mortality after adjustment for covariates. Of the 3 BNP measurement strategies, BNP after discharge (IDI of 0.072, P < .0001 and NRI of 0.707, P < .0001) and percent change in BNP (IDI of 0.113, P < .0001 and NRI of 0.782, P < .0001) demonstrated the greatest increase in discrimination and net reclassification for mortality. Unfortunately, we did not find any significant value with initial BNP. Kaplan-Meier survival analysis was performed to assess mortality stratified by BNP according to the median value, high median of follow-up BNP and percent change in BNP were associated with significantly higher mortality compared to the below median (log-rank, p < 0.001). CONCLUSIONS: Short-term follow-up BNP and percent change in BNP level are significant prognostic factors of all-cause mortality. These values will be clinically useful when evaluating prognosis in hospitalized patients with heart failure.

Decreased blood pressure associated with in-vehicle exposure to carbon monoxide in Korean volunteers.

BACKGROUND: Carbon monoxide (CO) is one of the primary components of emissions from light-duty vehicles, and reportedly comprises 77% of all pollutants emitted in terms of concentration. Exposure to CO aggravates cardiovascular disease and causes other health disorders. The study was aimed to assess the negative effects by injecting different amounts of CO concentration directly to human volunteers boarding in the car. METHODS: Human volunteers were exposed to CO concentrations of 0, 33.2, and 72.4 ppm, respectively during the first test and 0, 30.3, and 48.8 ppm respectively during the second test while seated in the car. The volunteers were exposed to each concentration for approximately 45 min. After exposure, blood pressure measurement, blood collection (carboxyhemoglobin [COHb] analysis), medical interview, echocardiography test, and cognitive reaction test were performed. RESULT: In patients who were exposed to a mean concentration of CO for 72.4 ± 1.4 ppm during the first exposure test and 48.8 ± 3.7 ppm during the second exposure test, the COHb level exceeded 2%. Moreover, the diastolic blood pressure was decreased while increasing in CO concentration after exposure. The medical interview findings showed that the degree of fatigue was increased and the degree of concentration was reduced when the exposed concentration of CO was increased. CONCLUSION: Although the study had a limited sample size, we found that even a low concentration of CO flowing into a car could have a negative influence on human health, such as change of blood pressure and degree of fatigue.

No association of the norepinephrine transporter gene (SLC6A2) and cognitive and behavioural phenotypes of patients with autism spectrum disorder.

We examined the association between the norepinephrine transporter (SLC6A2) gene and autism spectrum disorder (ASD) in a Korean population. In addition, we investigated which phenotypes of ASD are best attributed to the genotype of SLC6A2. A total of 184 subjects with ASD, their 156 unaffected siblings and both biological parents were recruited through university hospitals. We used the Autism Diagnostic Interview-Revised, the Aberrant Behaviour Checklist (ABC), the Child Behaviour Checklist (CBCL), the Stroop Colour-Word Interference Test and the Wisconsin Card Sorting Test (WCST) as quantitative measures of the ASD phenotypes. The associations between the quantitative measures and specific single-nucleotide polymorphisms (SNPs) were tested with linear regression analyses. We did not find any evidence of the over-transmission of either allele of the 10SLC6A2 SNPs in the DFAM test. At an empirical p value <0.05, findings that were consistent between the linear regression analyses and the QFAM tests were the positive associations between the A allele of rs36020 and attention problems on the CBCL and stereotypical behaviours on the ABC and between the C allele of rs1814270 and the number of trials required to complete the first WCST category. However, these associations did not remain after correction for multiple testing. The study results of this study do not support the association between the SLC6A2 and the diagnosis or phenotype of ASD. However, the study must be replicated in larger populations and with using more genetic markers.

Neural responses to various rewards and feedback in the brains of adolescent Internet addicts detected by functional magnetic resonance imaging.

AIM: This study aimed to examine differences in brain activation for various types of reward and feedback in adolescent Internet addicts (AIA) and normal adolescents (NA) using functional magnetic resonance imaging (fMRI). METHODS: AIA (n = 15) and NA (n = 15) underwent fMRI while performing easy tasks for which performance feedback (PF), social reward (SR) (such as compliments), or monetary reward (MR) was given. Using the no reward (NR) condition, three types of contrasts (PF-NR, SR-NR, and MR-NR) were analyzed. RESULTS: In NA, we observed activation in the reward-related subcortical system, self-related brain region, and other brain areas for the three contrasts, but these brain areas showed almost no activation in AIA. Instead, AIA showed significant activation in the dorsolateral prefrontal cortex for the PF-NR contrast and the negative correlation was found between the level of activation in the left superior temporal gyrus (BA 22) and the duration of Internet game use per day in AIA. CONCLUSION: These findings suggest that AIA show reduced levels of self-related brain activation and decreased reward sensitivity irrespective of the type of reward and feedback. AIA may be only sensitive to error monitoring regardless of positive feelings, such as sense of satisfaction or achievement.

The Last Rise and Fall Shown to us by the Man Who Chose "Swollen Foot": The Film The Whale.

The film The Whale goes beyond just depicting one aspect of the life of a morbidly obese man. As the audience watches Charlie, the main character who helplessly chose to live a morbidly obese life, we are compelled to reflect on what it means for ourselves to rise from the ground as we live in a gravitational field. Ultimately, this film is in line with director Darren Arnofsky's previous masterpiece, Black Swan. While the Oedipus complex runs through both films, this film goes one step further than Black Swan to face head-on the theme of "swollen foot," which is the original meaning of Oedipus. Through this move, we realize the essence of the Oedipus complex-something more fundamental than castration anxiety-something that we have been missing.

Basic Management Strategies by Life Cycle for Treatment of the Persons With Autism Spectrum Disorder.

Interventions for targeted symptoms are important when setting treatment strategies for individuals with autism spectrum disorder (ASD) and developmental disabilities. Especially, the goal should be to achieve individual "niche construction" by allowing them to select and adjust an environment where they can demonstrate their special characteristics and strengths. In addition, these choices should vary depending on the stage of development of each person with ASD and developmental disabilities. It is necessary to establish a detailed and systematic plan for diagnosis and treatment necessary for infants and toddlers, school placement in school age, and employment or self-reliance in adult transition period to establish customized treatment strategies that fit the individual level of people with ASD and developmental disabilities.

Clinical Midterm Results of Surgical Aortic Valve Replacement with Sutureless Valves.

Background: Sutureless aortic valves may enable shorter procedure times, which benefits patients with elevated surgical risk. We describe the outcomes of patients with aortic stenosis who underwent aortic valve replacement (AVR) using the sutureless Perceval aortic bioprosthesis. Methods: Data from a retrospective cohort were obtained from a clinical database. The study enrolled patients with symptomatic severe aortic stenosis who underwent surgical AVR with a sutureless bioprosthesis between August 2015 and December 2020. In total, 113 patients were included (mean age, 75.3±8.4 years; 57.5% women; median Society of Thoracic Surgeons score, 9.7%; mean follow-up period, 51.19±20.6 months). Of these patients, 41 were octogenarians (36.2%) and 3 were nonagenarians (2.6%). Transthoracic echocardiography was employed to assess changes in ejection fraction (EF), left ventricular mass index (LVMI), and mean pressure gradient (MPG). Results: The in-hospital mortality rate was 2.6%, and 13 patients developed new-onset atrial fibrillation. A permanent pacemaker was implanted in 3 patients (2.6%). The median intensive care unit stay was 1 day (interquartile range [IQR], 1-2 days), and the median hospital stay was 12 days (IQR, 9.5-15 days). The overall survival rate at 5 years was 95.9%. LVMI and MPG were reduced postoperatively, while EF increased over the follow-up period. No structural valve deterioration was observed, and no meaningful paravalvular leakage developed during follow-up. Conclusion: The use of a sutureless valve in the aortic position is safe and feasible, even for high-risk elderly patients requiring surgical AVR. LVMI and MPG decreased postoperatively, while EF increased over the follow-up period.

Practical Recommendations for the Evaluation and Management of Cardiac Injury Due to Carbon Monoxide Poisoning.

Carbon monoxide (CO) is a relatively frequent cause of poisoning evaluated in emergency departments. The risk of neurologic injuries, such as cognitive, psychological, vestibular, and motor deficits, is 25% to 50%. However, the risk of cardiac injuries should also be considered. Among patients with CO poisoning, the mortality in patients with myocardial injury is approximately 3 times greater than that in patients without myocardial injury. In large-scale studies, up to 69.2% of patients with acute CO poisoning exhibiting elevated troponin I levels and no underlying cardiovascular illnesses had late gadolinium enhancement on cardiac magnetic resonance, suggesting covert CO-induced myocardial fibrosis. Myocardial damage can be evaluated using electrocardiography, echocardiography, computed tomography, and cardiac magnetic resonance. This paper offers recommendations for cardiac evaluations based on our collective experience of managing >2,000 cases of acute CO poisoning with supporting information taken from peer-reviewed published reports on CO poisoning.

The Relationship Between Brain Activation for Taking Others' Perspective and Interoceptive Abilities in Autism Spectrum Disorder: An fMRI Study.

Objectives: In this functional magnetic resonance imaging study, we aimed to investigate the differences in brain activation between individuals with autism spectrum disorder (ASD) and typically developing (TD) individuals during perspective taking. We also examined the association between brain activation and empathic and interoceptive abilities. Methods: During scanning, participants from the ASD (n=17) and TD (n=22) groups were shown pain stimuli and asked to rate the level of the observed pain from both self- and other-perspectives. Empathic abilities, including perspective taking, were measured using an empathic questionnaire, and three dimensions of interoception were assessed: interoceptive accuracy, interoceptive sensibility, and interoceptive trait prediction errors. Results: During self-perspective taking, the ASD group exhibited greater activation in the left precuneus than the TD group. During other-perspective taking, relative hyperactivation extended to areas including the right precuneus, right superior frontal gyrus, left caudate nucleus, and left amygdala. Brain activation levels in the right superior frontal gyrus while taking other-perspective were negatively correlated with interoceptive accuracy, and those in the left caudate were negatively correlated with perspective taking ability in the ASD group. Conclusion: Individuals with ASD show atypical brain activation during perspective taking. Notably, their brain regions associated with stress reactions and escape responses are overactivated when taking other-perspective. This overactivity is related to poor interoceptive accuracy, suggesting that individuals with ASD may experience difficulties with the self-other distinction or atypical embodiment when considering another person's perspective.

2023 Korean Society of Echocardiography position paper for the diagnosis and management of valvular heart disease, part II: mitral and tricuspid valve disease.

This manuscript represents the official position of the Korean Society of Echocardiography on valvular heart diseases. This position paper focuses on the diagnosis and management of valvular heart diseases with referring to the guidelines recently published by the American College of Cardiology/American Heart Association and the European Society of Cardiology. The committee sought to reflect national data on the topic of valvular heart diseases published to date through a systematic literature search based on validity and relevance. In the part II of this article, we intend to present recommendations for diagnosis and treatment of mitral valve disease and tricuspid valve disease.

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.

Norepinephrine genes predict response time variability and methylphenidate-induced changes in neuropsychological function in attention deficit hyperactivity disorder.

Noradrenergic dysfunction may be associated with cognitive impairments in attention-deficit/hyperactivity disorder (ADHD), including increased response time variability, which has been proposed as a leading endophenotype for ADHD. The aim of this study was to examine the relationship between polymorphisms in the α-2A-adrenergic receptor (ADRA2A) and norepinephrine transporter (SLC6A2) genes and attentional performance in ADHD children before and after pharmacological treatment.One hundred one medication-naive ADHD children were included. All subjects were administered methylphenidate (MPH)-OROS for 12 weeks. The subjects underwent a computerized comprehensive attention test to measure the response time variability at baseline before MPH treatment and after 12 weeks. Additive regression analyses controlling for ADHD symptom severity, age, sex, IQ, and final dose of MPH examined the association between response time variability on the comprehensive attention test measures and allelic variations in single-nucleotide polymorphisms of the ADRA2A and SLC6A2 before and after MPH treatment.Increasing possession of an A allele at the G1287A polymorphism of SLC6A2 was significantly related to heightened response time variability at baseline in the sustained (P = 2.0 × 10) and auditory selective attention (P = 1.0 × 10) tasks. Response time variability at baseline increased additively with possession of the T allele at the DraI polymorphism of the ADRA2A gene in the auditory selective attention task (P = 2.0 × 10). After medication, increasing possession of a G allele at the MspI polymorphism of the ADRA2A gene was associated with increased MPH-related change in response time variability in the flanker task (P = 1.0 × 10).Our study suggested an association between norepinephrine gene variants and response time variability measured at baseline and after MPH treatment in children with ADHD. Our results add to a growing body of evidence, suggesting that response time variability is a viable endophenotype for ADHD and suggesting its utility as a surrogate end point for measuring stimulant response in pharmacogenetic studies.

Association between the GRM7 rs3792452 polymorphism and attention deficit hyperacitiveity disorder in a Korean sample.

BACKGROUND: The purpose of this study was to investigate the association between the ionotropic and glutamate receptors, N-methyl D-asparate 2A (GRIN2A) and 2B (GRIN2B), and the metabotropic glutamate receptor mGluR7 (GRM7) gene polymorphisms and attention-deficit hyperactivity disorder (ADHD) in Korean population. METHODS: We conducted a case-control analysis of 202 ADHD subjects and 159 controls, performed a transmission disequilibrium test (TDT) on 149 trios, and compared scores from the continuous performance test (CPT), the Children's Depression Inventory (CDI), and the State-Trait Anxiety Inventory for Children (STAIC) according to the genotype of the glutamate receptor genes. RESULTS: There were no significant differences in the genotype or allele frequencies of the GRIN2A rs8049651, GRIN2B rs2284411, or GRM7 rs37952452 polymorphisms between the ADHD and control groups. For 148 ADHD trios, the TDT analysis also showed no preferential transmission of the GRIN2A rs8049651 or GRIN2B rs2284411 polymorphisms. However, the TDT analysis of the GRM7 rs3792452 polymorphism showed biased transmission of the G allele (χ2 = 4.67, p = 0.031). In the ADHD probands, the subjects with GG genotype in the GRM7 rs37952452 polymorphism had higher mean T-scores for omission errors on the CPT than did those with the GA or AA genotype (t = 3.38, p = 0.001). In addition, the ADHD subjects who were homozygous for the G allele in the GRM7 rs37952452 polymorphism had higher STAIC-T (t = 5.52, p < 0.001) and STAIC-S (t = 2.74, p = 0.007) scores than did those with the GA or AA genotype. CONCLUSIONS: These results provide preliminary evidence of an association between the GRM7 rs37952452 polymorphism and selective attention deficit and anxiety found within the Korean ADHD population.