Association Between ECG Abnormalities and Mortality in a Low-Risk Population.

BACKGROUND: The ECG is a simple, noninvasive screening method for cardiovascular disease and arrhythmia. The impact of ECG abnormality on mortality is not certain in low-risk populations. To address this, we evaluated the association between ECG abnormality and mortality. METHODS AND RESULTS: We retrospectively assessed baseline ECG and all-cause mortality and cardiovascular mortality in 660 383 patients presenting for medical check-ups. Baseline ECG abnormalities were classified according to the Minnesota Code. Among the total 660 383 participants, 23 609 (3.6%) had major and 110 038 (16.7%) had minor ECG abnormalities. All-cause mortality occurred in 7751 patients (1.1%) and cardiovascular mortality in 1180 (0.18%) over a median follow-up period of 8.8 years. Major ECG abnormalities were associated with all-cause mortality (hazard ratio [HR], 1.11 [95%, 1.03-1.2]) and cardiovascular mortality (HR, 1.92 [95% CI, 1.63-2.27]) compared with no ECG abnormalities. All-cause mortality was associated with right atrial enlargement (HR, 2.11 [95% CI, 1.1-4.07]), left atrial enlargement (HR, 1.76 [95% CI, 1.1-2.84]), sinus tachycardia (HR, 1.52 [95% CI, 1.15-2.01]), complete atrioventricular block (HR, 2.1 [95% CI, 1.05-4.2]), atrial fibrillation (HR, 1.52 [95% CI, 1.26-1.84]), and left ventricular hypertrophy (HR, 1.15 [95% CI, 1.02-1.3]). Cardiovascular mortality was associated with left atrial enlargement (HR, 4.52 [95% CI, 2.15-9.5]), atrial fibrillation (HR, 3.22 [95% CI, 2.33-4.46]), left ventricular hypertrophy (HR, 1.72 [95% CI, 1.35-2.19]), major Q-wave abnormality (HR, 1.6 [95% CI, 1.08-2.39]), and major ST-T abnormality (HR, 1.76 [95% CI, 1.01-3.04]). CONCLUSIONS: ECG abnormalities, including left atrial enlargement, left ventricular hypertrophy, atrial fibrillation, and major Q-wave and ST-T abnormalities, were associated with cardiovascular mortality in a low-risk population.

Emotion regulation from a virtue perspective.

BACKGROUND: The ability to regulate one's emotional state is an important predictor of several behaviors such as reframing a challenging situation to reduce anger or anxiety, concealing visible signs of sadness or fear, or focusing on reasons to feel happy or calm. This capacity is referred to as emotion regulation. Deficits in this ability can adversely affect one's adaptive coping, thus are associated with a variety of other psychopathological symptoms, including but not limited to depression, borderline personality disorder, substance use disorders, eating disorders, and somatoform disorders. METHODS: The present study examined emotion regulation in relation to the virtue-based psychosocial adaptation model (V-PAM). 595 participants were clustered based on their Difficulties in Emotion Regulation Scale (DERS) score, producing two clusters (i.e., high functioning vs. low functioning). Then, emotion regulation group membership was discriminated by using five V-PAM virtue constructs, including courage, integrity, practical wisdom, committed action, and emotional transcendence. RESULTS: Results show that five virtues contribute to differentiating group membership. Practical wisdom was the strongest contributor, followed by integrity, emotional transcendence, committed action, and courage. Predictive discriminant analysis was conducted and 71% of cases were correctly classified. A discussion of the relationship between emotion regulation and virtues was elaborated. CONCLUSION: The concept of virtue holds significant importance in the comprehension of an individual's capacity to regulate their emotions, meriting future study.

Comparison of Office Blood Pressure, Automated Unattended Office Blood Pressure, Home Blood Pressure, and 24-Hour Ambulatory Blood Pressure Measurements.

BACKGROUND: Although previous studies have reported differences of blood pressure (BP) according to BP measurement methods, studies in Korean population were scarce. This study aimed to compare BP differences according to different BP measurement methods and assess hypertension phenotype. METHODS: This prospective study recruited 183 individuals (mean 55.9 years; 51.4% males). The BP measurements included office BP (auscultatory attended office BP [ausAOBP], automated attended office BP [aAOBP], and automated unattended office BP [aUAOBP]) and out-of-office BP (home BP [HBP] and ambulatory BP [ABP]) measurements taken within one week of each other. RESULTS: The mean systolic/diastolic BP differences between ausAOBP and other BPs according to different BP measurement methods were 3.5/2.3 mmHg for aAOBP; 6.1/2.9 mmHg for aUAOBP; 15.0/7.3 mmHg for daytime ABP; and 10.6/3.4 mmHg for average HBP. The increasing disparity between ausAOBP and other BPs in multivariable regression analysis was significantly associated with increasing BP. The prevalence of white-coat hypertension and masked hypertension in 107 individuals not taking antihypertensive medication was 25.4-26.8% and 30.6-33.3% based on ausAOBP, daytime ABP, and average HBP, respectively. The prevalence of white-coat uncontrolled hypertension and masked uncontrolled hypertension in 76 of those taking antihypertensive medication was 31.7-34.1% and 17.1-37.1%, respectively. CONCLUSION: This study showed a large disparity between office BP and out-of-office BP which became more pronounced when office BP by auscultation increased, suggesting that various BP measurement methods should be used to more accurately assess BP status.

Effectiveness of low-intensity atorvastatin 5 mg and ezetimibe 10 mg combination therapy compared with moderate-intensity atorvastatin 10 mg monotherapy: A randomized, double-blinded, multi-center, phase III study.

BACKGROUND: We compared the efficacy and safety of low-intensity atorvastatin and ezetimibe combination therapy with moderate-intensity atorvastatin monotherapy in patients requiring cholesterol-lowering therapy. METHODS: At 19 centers in Korea, 290 patients were randomized to 4 groups: atorvastatin 5 mg and ezetimibe 10 mg (A5E), ezetimibe 10 mg (E), atorvastatin 5 mg (A5), and atorvastatin 10 mg (A10). Clinical and laboratory examinations were performed at baseline, and at 4-week and 8-week follow-ups. The primary endpoint was percentage change from baseline in low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up. Secondary endpoints included percentage changes from baseline in additional lipid parameters. RESULTS: Baseline characteristics were similar among the study groups. At the 8-week follow-up, percentage changes in LDL cholesterol levels were significantly greater in the A5E group (49.2%) than in the E (18.7%), A5 (27.9%), and A10 (36.4%) groups. Similar findings were observed regarding the percentage changes in total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B levels. Triglyceride levels were also significantly decreased in the A5E group than in the E group, whereas high-density lipoprotein levels substantially increased in the A5E group than in the E group. In patients with low- and intermediate-cardiovascular risk, 93.3% achieved the target LDL cholesterol levels in the A5E group, 40.0% in the E group, 66.7% in the A5 group, and 92.9% in the A10 group. In addition, 31.4% of patients in the A5E group, 8.1% in E, 9.7% in A5, and 7.3% in the A10 group reached the target levels of both LDL cholesterol < 70 mg/dL and reduction of LDL ≥ 50% from baseline. CONCLUSIONS: The addition of ezetimibe to low-intensity atorvastatin had a greater effect on lowering LDL cholesterol than moderate-intensity atorvastatin alone, offering an effective treatment option for cholesterol management, especially in patients with low and intermediate risks.

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.

Systematic review of deep learning image analyses for the diagnosis and monitoring of skin disease.

Skin diseases affect one-third of the global population, posing a major healthcare burden. Deep learning may optimise healthcare workflows through processing skin images via neural networks to make predictions. A focus of deep learning research is skin lesion triage to detect cancer, but this may not translate to the wider scope of >2000 other skin diseases. We searched for studies applying deep learning to skin images, excluding benign/malignant lesions (1/1/2000-23/6/2022, PROSPERO CRD42022309935). The primary outcome was accuracy of deep learning algorithms in disease diagnosis or severity assessment. We modified QUADAS-2 for quality assessment. Of 13,857 references identified, 64 were included. The most studied diseases were acne, psoriasis, eczema, rosacea, vitiligo, urticaria. Deep learning algorithms had high specificity and variable sensitivity in diagnosing these conditions. Accuracy of algorithms in diagnosing acne (median 94%, IQR 86-98; n = 11), rosacea (94%, 90-97; n = 4), eczema (93%, 90-99; n = 9) and psoriasis (89%, 78-92; n = 8) was high. Accuracy for grading severity was highest for psoriasis (range 93-100%, n = 2), eczema (88%, n = 1), and acne (67-86%, n = 4). However, 59 (92%) studies had high risk-of-bias judgements and 62 (97%) had high-level applicability concerns. Only 12 (19%) reported participant ethnicity/skin type. Twenty-four (37.5%) evaluated the algorithm in an independent dataset, clinical setting or prospectively. These data indicate potential of deep learning image analysis in diagnosing and monitoring common skin diseases. Current research has important methodological/reporting limitations. Real-world, prospectively-acquired image datasets with external validation/testing will advance deep learning beyond the current experimental phase towards clinically-useful tools to mitigate rising health and cost impacts of skin disease.

Cardiovascular Outcomes according to Comorbidities and Low-Density Lipoprotein Cholesterol in Korean People with Type 2 Diabetes Mellitus.

BACKGROUND: There are no clear data to support the cardiovascular (CV) risk categories and low-density lipoprotein cholesterol (LDL-C) treatment goals in Korean people with type 2 diabetes mellitus (T2DM). We evaluated the incidence of cardiovascular disease (CVD) according to comorbidities and suggested LDL-C treatment goals in Korean people with T2DM in nationwide cohort data. METHODS: Using the Korean National Health Insurance Service database, 248,002 people aged 30 to 90 years with T2DM who underwent routine health check-ups during 2009 were included. Subjects with previous CVD were excluded from the study. The primary outcome was incident CVD, defined as a composite of myocardial infarction and ischemic stroke during the follow-up period from 2009 to 2018. RESULTS: The mean age of the study participants was 59.6±10.9 years, and median follow-up period was 9.3 years. CVD incidence increased in the order of DM duration of 5 years or more (12.04/1,000 person-years), hypertension (HT) (12.27/1,000 personyears), three or more CV risk factors (14.10/1,000 person-years), and chronic kidney disease (18.28/1,000 person-years). The risk of incident CVD increased linearly from an LDL-C level of ≥70 mg/dL in most patients with T2DM. In T2DM patients without HT or with a DM duration of less than 5 years, the CVD incidence increased from LDL-C level of ≥100 mg/dL. CONCLUSION: For primary prevention of CVD in Korean adults with T2DM, it can be helpful to lower LDL-C targets when there are chronic kidney disease, HT, a long duration of diabetes mellitus, or three or more CV risk factors.

Association between Low-Density Lipoprotein Cholesterol Level and Cardiovascular Outcomes in Korean Adults: A Nationwide Cohort Study.

BACKGROUND: To validate the treatment target of low-density lipoprotein cholesterol (LDL-C) level according to the cardiovascular disease (CVD) risk which was recommended by Korean dyslipidemia guideline. METHODS: We used the Korean National Health Insurance Service database which included 3,958,048 people aged 20 to 89 years who underwent regular health screening. The primary outcome was incident CVD, defined as a composite of myocardial infarction and stroke during the follow-up period from 2009 to 2018. RESULTS: The risk of CVD increased from LDL-C level of 70 mg/dL in very high-risk and high-risk groups and from 130 mg/dL in moderate-risk and low-risk groups. Adjusted hazard ratios (HRs) of LDL-C ranges 70-99, 100-129, 130-159, 160-189, and ≥190 mg/dL were 1.20 (95% confidence interval [CI], 1.08-1.33), 1.27 (1.15-1.42), 1.39 (1.23-1.56), 1.69 (1.45-1.96), and 1.84 (1.49- 2.27) in very high-risk group, and 1.07 (1.02-1.13), 1.16 (1.10-1.21), 1.29 (1.22-1.36), 1.45 (1.36-1.55), and 1.73 (1.58-1.90) in high-risk group. Adjusted HRs (95% CI) of LDL-C ranges 130-159, 160-189, and ≥190 mg/dL were 1.15 (1.11-1.20), 1.28 (1.22- 1.34), and 1.45 (1.36-1.54) in moderate-risk group and 1.07 (1.02-1.13), 1.20 (1.13-1.26), and 1.47 (1.37-1.57) in low-risk group. CONCLUSION: We confirmed the incidence of CVD was increased in higher LDL-C range. The risk of CVD increased from ≥70 mg/dL of LDL-C in very high-risk and high-risk groups, and from ≥130 mg/dL of LDL-C in moderate-risk and low-risk groups in Korean adults.

Lipoprotein(a)-related cardiovascular and all-cause mortalities in Korean adults.

AIMS: There are inconsistent results on the association between lipoprotein(a) and mortality-related outcomes due to a lack of evidence from large-scale observational studies of Asians. This study aims to evaluate the effects of lipoprotein(a) on mortality-related outcomes in the Korean population. METHODS AND RESULTS: This cohort study included 275 430 individuals (mean age: 38 years; 50.1% men) enrolled in the Kangbuk Samsung Health Study between 2003 and 2016. The median follow-up period was 6.6 years. Cox proportional hazards analysis was used to estimate the adjusted hazard ratios (HRs) for evaluating mortality risk based on lipoprotein(a) levels and specific lipoprotein(a) categories. The median lipoprotein(a) value was 18.5 mg/dL, and the proportion of lipoprotein(a) ≥50 mg/dL was 12.8%. Multivariable Cox regression analysis showed that the group with lipoprotein(a) ≥50 mg/dL had a significantly increased risk of cardiovascular mortality (HR[95% CI]: 1.83[1.26, 2.64]) and all-cause mortality (1.20[1.03, 1.41]) than the group with lipoprotein(a) < 50 mg/dL without increased risk of cancer mortality (1.05[0.81, 1.34]). The relationship between lipoprotein(a) and cardiovascular mortality was significant regardless of low-density lipoprotein cholesterol. Specifically, lipoprotein(a) ≥100 mg/dL was associated with more than twice as increased a risk of cardiovascular mortality (2.45[1.12, 5.34]) than lipoprotein(a) < 10 mg/dL. In subgroup analyses, there was an interaction in the relationships between the two lipoprotein(a) categories and cardiovascular mortality for only high-density lipoprotein cholesterol. CONCLUSIONS: High lipoprotein(a) concentration is an independent predictor of cardiovascular mortality in the Korean population, regardless of low-density lipoprotein cholesterol levels.

2022 Consensus Statement on the Management of Familial Hypercholesterolemia in Korea.

Familial hypercholesterolemia (FH) is the most common monogenic disorder. Due to the marked elevation of cardiovascular risk, the early detection, diagnosis, and proper management of this disorder are critical. Herein, the 2022 Korean guidance on this disease is presented. Clinical features include severely elevated low-density lipoprotein-cholesterol (LDL-C) levels, tendon xanthomas, and premature coronary artery disease. Clinical diagnostic criteria include clinical findings, family history, or pathogenic mutations in the LDLR, APOB, or PCSK9. Proper suspicion of individuals with typical characteristics is essential for screening. Cascade screening is known to be the most efficient diagnostic approach. Early initiation of lipid-lowering therapy and the control of other risk factors are important. The first-line pharmacological treatment is statins, followed by ezetimibe, and PCSK9 inhibitors as required. The ideal treatment targets are 50% reduction and <70 mg/dL or <55 mg/dL (in the presence of vascular disease) of LDL-C, although less strict targets are frequently used. Homozygous FH is characterized by untreated LDL-C >500 mg/dL, xanthoma since childhood, and family history. In children, the diagnosis is made with criteria, including items largely similar to those of adults. In women, lipid-lowering agents need to be discontinued before conception.

Association of environmental tobacco smoke exposure with metabolic syndrome: A longitudinal Cohort Study of 71,055 never smokers.

BACKGROUND AND AIMS: Effects of environmental tobacco smoke (ETS) exposure and a change in ETS exposure status on metabolic syndrome (MetS) remain unknown. Thus, the aim of this study was to evaluate the effect of ETS exposure on MetS in self-reported and cotinine-validated never smokers. METHODS AND RESULTS: From a large longitudinal cohort study, 71,055 cotinine-validated never smokers without MetS at baseline were included. These participants were divided into four groups (no, new, former, and continuous ETS exposure groups) based on their ETS exposure status at baseline and follow-up. The association between ETS exposure and MetS was assessed using multivariable Cox hazard regression analyses. During a median follow-up of 33 months, 15.0 cases/10,000 person-years (PY) developed MetS. Incidence rates per 10,000 PY of MetS in no, new, former, and continuous ETS exposure groups were 14.0, 18.5, 16.5, and 19.0, respectively. In multivariable Cox hazard regression analyses, the new and continuous ETS exposure groups showed increased risk of MetS compared to the no ETS exposure group (hazard ratio [95% confidence interval]: 1.35 [1.16, 1.56], p-value < 0.001 for the new ETS exposure group and 1.19 [1.06, 1.34], p-value = 0.004 for the continuous ETS exposure group). However, the former ETS exposure group did not show an increased risk of MetS (0.96 [0.88, 1.05], p-value = 0.36). CONCLUSION: This study showed that ETS exposure and changes in ETS exposure status over approximately three years could modify the risk of MetS, suggesting that avoidance of ETS may not increase the risk of incidence of MetS.

2022 Consensus statement on the management of familial hypercholesterolemia in Korea.

Familial hypercholesterolemia (FH) is the most common monogenic disorder. Due to the marked elevation of cardiovascular risk, the early detection, diagnosis, and proper management of this disorder are critical. Herein, the 2022 Korean guidance on this disease is presented. Clinical features include severely elevated low-density lipoprotein cholesterol (LDL-C) levels, tendon xanthomas, and premature coronary artery disease. Clinical diagnostic criteria include clinical findings, family history, or pathogenic mutations in the LDLR, APOB, or PCSK9. Proper suspicion of individuals with typical characteristics is essential for screening. Cascade screening is known to be the most efficient diagnostic approach. Early initiation of lipid-lowering therapy and the control of other risk factors are important. The first-line pharmacological treatment is statins, followed by ezetimibe, and PCSK9 inhibitors as required. The ideal treatment targets are 50% reduction and < 70 or < 55 mg/dL (in the presence of vascular disease) of LDL-C, although less strict targets are frequently used. Homozygous FH is characterized by untreated LDL-C > 500 mg/dL, xanthoma since childhood, and family history. In children, the diagnosis is made with criteria, including items largely similar to those of adults. In women, lipid-lowering agents need to be discontinued before conception.

Assessment for Macular Thickness after Uncomplicated Phacoemulsification Using Optical Coherence Tomography.

PURPOSE: Macular edema including cystoid macular edema is one of the main causes of unfavorable visual outcomes after cataract surgery. The macular thickness and the occurrence of macular edema after uncomplicated cataract surgery was evaluated using optical coherence tomography (OCT) in this study. METHODS: Macular map images were taken by OCT before surgery and at 1 week, 1 month, and 2 months postsurgery. The subjects were classified into two groups (group 1, patients with no macular edema; group 2, patients with macular edema). Group 2 was defined as increase in central macular thickness (CMT) by 30% compared with that before surgery. The risk factors for macular edema were evaluated. Group 2 was divided into two subgroups: subclinical macular edema (group 2A) and cystoid macular edema (group 2B) and they were assessed in terms of the clinical course of best-corrected visual acuity and CMT. RESULTS: A total of 376 patients were enrolled in this study, of which 36 (9.57%, group 2) showed macular edema measured by OCT after the surgery. Univariate analysis for group 1 and 2 revealed that intracameral injection of epinephrine during phacoemulsification was associated with the development of macular edema. In group 2, five patients (1.33%) developed cystoid macular edema. Statistically significant differences in the clinical course of CMT were observed at 2 months (201.2 ± 23.1, 250.0 ± 29.8, and 371.0 ± 160.3 in group 1, group 2A, and group 2B, respectively; p < 0.001) and 1 month postoperatively (198.5 ± 23.6, 237.8 ± 40.9, and 314.0 ± 104.5 in group 1, group 2A, and group 2B, respectively; p < 0.001). Group 2B required additional treatment and eventually achieved best-corrected visual acuity of >0.2 with CMT in the normal range. CONCLUSIONS: The intracameral injection of epinephrine may cause macular edema after uncomplicated cataract surgery. Examination of CMT using OCT is recommended for the early detection of macular edema.

Effect of physical activity on the development and the resolution of nonalcoholic fatty liver in relation to body mass index.

BACKGROUND: Data on whether physical activity (PA) levels are related to nonalcoholic fatty liver disease (NAFLD) when considering body mass index (BMI) are scarce. We assessed whether PA affects the development or resolution of NAFLD in conjunction with BMI changes. METHODS: Overall, 130,144 participants who underwent health screening during 2011-2016 were enrolled. According to the PA level in the Korean version of the validated International PA Questionnaire Short Form, participants were classified into the inactive, active, and health-enhancing PA (HEPA) groups. RESULTS: In participants with increased BMI, the hazard ratio (HR) and 95% confidence interval after multivariable Cox hazard model for incident NAFLD was 0.97 (0.94-1.01) in the active group and 0.94 (0.89-0.99) in the HEPA group, whereas that for NAFLD resolution was 1.03 (0.92-1.16) and 1.04 (0.88-1.23) (reference: inactive group). With increased BMI, high PA affected only new incident NAFLD. PA enhancement or maintenance of sufficient PA prevented new incident NAFLD. In participants with decreased BMI, the HRs were 0.98 (0.90-1.07) and 0.88 (0.78-0.99) for incident NAFLD and 1.07 (0.98-1.17) and 1.33 (1.18-1.49) for NAFLD resolution in the active and HEPA groups, respectively. With decreased BMI, high PA reduced incident NAFLD and increased NAFLD resolution. Maintenance of sufficient PA led to a considerable resolution of NAFLD. CONCLUSION: In this large longitudinal study, PA prevented incident NAFLD regardless of BMI changes. For NAFLD resolution, sufficient PA was essential along with BMI decrease. Maintaining sufficient PA or increasing the PA level is crucial for NAFLD prevention or resolution.

Association of inter-arm systolic blood pressure differences with arteriosclerosis and atherosclerosis: A cohort study of 117,407 people.

BACKGROUND AND AIMS: Inter-arm blood pressure differences (IADs) are known to be associated with adverse cardiovascular outcomes. We evaluated the distribution of IADs in a large cohort of apparently healthy people and the association of IADs with brachial-ankle pulse wave velocity (baPWV) and coronary artery calcium (CAC). METHODS: Blood pressure was measured in both arms of 117,407 people who participated in the Kangbuk Samsung Health Study. IAD was defined as the absolute difference in systolic blood pressure in both arms and was confirmed by measuring the baPWV using an automatic oscillometric device. Arterial stiffness was measured by the baPWV, and CAC was assessed using multi-detector computed tomography. RESULTS: The mean IAD in the overall subjects was 3.09 ± 2.83 mmHg, 6 mmHg in the 90th percentile, 8 mmHg in the 95th percentile, and 10 mmHg in the 97th percentile. In the multivariable-adjusted analysis of 92,949 subjects excluding those with a history of HTN, DM, and cardiovascular disease (CVD), increasing IAD did not statistically increase the risk of developing a CAC >0. However, IAD was associated with a baPWV >1400 cm/s (odds ratio [95% confidence interval], 1.23 [1.13-1.35] in the total cohort, 1.19 [1.08-1.31] in males, and 1.39 [1.11-1.73] in females). CONCLUSIONS: More than 97% of all participants had an IAD of 10 mmHg or less. IAD was significantly associated with arterial stiffness, reflecting arteriosclerosis, but not with the presence of CAC, reflecting atherosclerosis. IAD may be a valuable tool for the early detection of asymptomatic, low-risk individuals with subclinical arterial disease.

Phenotypic and Genetic Analyses of Korean Patients with Familial Hypercholesterolemia: Results from the KFH Registry 2020.

AIMS: Familial hypercholesterolemia (FH) is currently a worldwide health issue. Understanding the characteristics of patients is important for proper diagnosis and treatment. This study aimed to analyze the phenotypic and genetic features, including threshold cholesterol levels, of Korean patients with FH. METHODS: A total of 296 patients enrolled in the Korean FH registry were included, according to the following criteria: low-density lipoprotein-cholesterol (LDL-C) ＞190 mg/dL with tendon xanthoma or family history compatible with FH, or LDL-C ＞225 mg/dL. DNA sequences of three FH-associated genes were obtained using whole-exome or target exome sequencing. Threshold cholesterol levels for differentiating patients with FH/pathogenic variant (PV) carriers and predictors of PVs were identified. RESULTS: Of the 296 patients, 104 had PVs and showed more obvious clinical findings, including higher cholesterol levels. PV rates ranged from 30% to 64% when patients were categorized by possible or definite type according to the Simon Broome criteria. Frequent PV types included missense variants and copy number variations (CNVs), while the most frequent location of PVs was p.P685L in LDLR. The threshold LDL-C levels for patient differentiation and PV prediction were 177 and 225 mg/dL, respectively. Younger age, tendon xanthoma, and higher LDL-C levels were identified as independent predictors of PVs, while traditional cardiovascular risk factors were predictors of coronary artery disease. CONCLUSIONS: Korean patients with FH had variable PV rates depending on diagnostic criteria and distinctive PV locations. The reported threshold LDL-C levels pave the way for efficient patient care in this population.

Clinical impact of guideline-based practice and patients' adherence in uncontrolled hypertension.

BACKGROUND: Chronic diseases like hypertension need comprehensive lifetime management. This study assessed clinical and patient-reported outcomes and compared them by treatment patterns and adherence at 6 months among uncontrolled hypertensive patients in Korea. METHODS: This prospective, observational study was conducted at 16 major hospitals where uncontrolled hypertensive patients receiving anti-hypertension medications (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg) were enrolled during 2015 to 2016 and studied for the following 6 months. A review of medical records was performed to collect data on treatment patterns to determine the presence of guideline-based practice (GBP). GBP was defined as: (1) maximize first medication before adding second or (2) add second medication before reaching maximum dose of first medication. Patient self-administered questionnaires were utilized to examine medication adherence, treatment satisfaction and quality of life (QoL). RESULTS: A total of 600 patients were included in the study. Overall, 23% of patients were treated based on GBP at 3 months, and the GBP rate increased to 61.4% at 6 months. At baseline and 6 months, 36.7 and 49.2% of patients, respectively, were medication adherent. The proportion of blood pressure-controlled patients reached 65.5% at 6 months. A higher blood pressure control rate was present in patients who were on GBP and also showed adherence than those on GBP, but not adherent, or non-GBP patients (76.8% vs. 70.9% vs. 54.2%, P < 0.001). The same outcomes were found for treatment satisfaction and QoL (P < 0.05). CONCLUSIONS: This study demonstrated the importance of physicians' compliance with GBP and patients' adherence to hypertensive medications. GBP compliance and medication adherence should be taken into account when setting therapeutic strategies for better outcomes in uncontrolled hypertensive patients.

Association between secondhand smoke exposure and new-onset hypertension in self-reported never smokers verified by cotinine.

BACKGROUND/AIMS: There is no study assessing the effect of changes of secondhand smoke (SHS) exposure and new-onset hypertension. We investigated the effect of a change of SHS exposure status on new-onset hypertension in self-reported and cotinine-verified never smokers. METHODS: Out of individuals enrolled in the Kangbuk Samsung Health Study between 2011 and 2016, 87,486 self-reported and cotinine-verified never smokers without hypertension at baseline visit were included with a median follow-up of 36 months. Individuals were divided into four groups on the basis of their SHS exposure status at baseline and at follow-up: no, new, former, and sustained SHS exposure groups. RESULTS: The incidence rates per 10,000 person-year of new-onset hypertension in no, new, former, and sustained SHS exposure groups were 84.7, 113.3, 102.0, and 123.7, respectively (p < 0.001). A multivariable Cox-hazard analyses showed that new and sustained SHS exposure groups increased their hazard ratio (HR) for new-onset hypertension compared to no SHS exposure group (HR, 1.31; 95% confidence interval [CI], 1.08 to 1.60 for new SHS exposure group; and HR, 1.24; 95% CI, 1.06 to 1.45 for sustained SHS exposure group). However, being part of the former SHS exposure group did not increase the risk of new-onset hypertension (HR, 0.91; 95% CI, 0.81 to 1.03). CONCLUSION: This study showed that either new, or sustained SHS exposure, but not former SHS exposure, increased the risk for new-onset hypertension in self-reported never smokers verified as nonsmokers by urinary cotinine. These findings show the possibility that changing exposure to SHS even for a relatively short period can modify the risk of new-onset hypertension in self-reported and cotinine-verified never smokers.

Efficacy and Safety of Fenofibrate-Statin Combination Therapy in Patients With Inadequately Controlled Triglyceride Levels Despite Previous Statin Monotherapy: A Multicenter, Randomized, Double-blind, Phase IV Study.

PURPOSE: Residual cardiovascular risk reduction by fenofibrate in patients with high serum triglyceride (TG) levels despite previous statin monotherapy is not well characterized. The purpose of this study was to evaluate the efficacy and safety of a combination of choline fenofibrate and statin in patients with inadequately controlled TG levels despite previous statin monotherapy. METHODS: This prospective, multicenter, randomized, double-blind study was conducted in Korea. A total of 133 patients with controlled LDL-C but elevated TG levels, already receiving statin monotherapy, were enrolled in the study, which was conducted from July 2018 to December 2019. Patients were randomly assigned to receive combination therapy with choline fenofibrate and statin or statin monotherapy in a 1:1 ratio. After 8 weeks of treatment, the lipid profiles and safety parameters of the patients in the 2 groups were compared. FINDINGS: The study included 127 patients (64 in the combination group and 63 in the control group) older than 19 years. After 8 weeks of therapy, mean serum TG levels significantly decreased from 269.8 to 145.5 mg/dL (P < 0.0001) in the combination therapy group, whereas no significant changes occurred in the statin monotherapy group (from 271.1 to 280.5 mg/dL). Contrarily, the mean serum HDLC levels significantly increased from 45.0 to 50.4 mg/dL (P = 0.0004) in the combination therapy group, whereas there were no significant changes in the monotherapy group (from 44.3 to 44.7 mg/dL). There were no additional serious adverse events in the combination therapy group compared with the statin monotherapy group. IMPLICATIONS: The combination therapy using choline fenofibrate and statin was found to be effective in serum TG control and likely tolerable in patients with high TG levels despite statin monotherapy. A larger study, conducted for a longer duration, is needed to evaluate the effectiveness of this combination in reducing cardiovascular risk. ClinicalTrials.gov identifier: NCT03874260.

Relationship between alcohol consumption and insulin resistance measured using the homeostatic model assessment for insulin resistance: A retrospective cohort study of 280,194 people.

BACKGROUND AND AIM: Alcohol consumption causes metabolic disorders and is a known risk factor for cardiovascular disease. However, some studies suggested that low level alcohol consumption improves insulin resistance. We evaluated the effects of alcohol consumption on insulin resistance using the homeostatic model assessment for insulin resistance (HOMA-IR). METHODS AND RESULTS: This study included 280,194 people without diabetes who underwent comprehensive health examinations more than twice between 2011 and 2018. The levels of alcohol intake were obtained through a self-questionnaire. All subjects were divided into two groups based on the Korean standard cut-off value of HOMA-IR, 2.2. Cox proportional hazard analysis was used to assess the risk of insulin resistance according to alcohol consumption. The mean age of the study subjects was 38.2 years and 55.7% were men. During the follow-up period (median 4.13 years), HOMA-IR progressed from <2.2 to ≥2.2 in 64,443 subjects (23.0%) and improved from ≥2.2 to <2.2 in 21,673 subjects (7.7%). In the parametric survival analysis, alcohol consumption was associated with improvement of HOMA-IR (HR [95% CI], 1.09[1.03-1.14], 1.11[1.06-1.17] and 1.20[1.13-1.26], respectively). In the analysis classified according to changes in alcohol consumption amounts, increased alcohol consumption tended to prevent the progression of HOMA-IR (0.97[0.96-0.99]; p = 0.004). However, the association between the changes in alcohol consumption amounts and improvement of HOMA-IR was not statistically significant. CONCLUSION: This retrospective observational study has shown that alcohol consumption can improve insulin resistance and increased alcohol consumption amounts may have preventive effects on the progression of HOMA-IR compared to the baseline level.