Clinical and life style factors related to the nighttime blood pressure, nighttime dipping and their phenotypes in Korean hypertensive patients.

BACKGROUND: Non-dipping or reverse dipping patterns are known to be associated with adverse cardiovascular prognosis among the general population and clinical cohort. Few large sized studies have explored factors including sleep duration and sleep quality related to nighttime blood pressure (BP) and nocturnal dipping patterns. METHODS: Among 5,360 patients enrolled  in Korean multicenter nationwide prospective Registry of ambulatory BP monitoring (KORABP), 981 subjects with complete data on sleep duration, sleep quality assessed using a 4-point Likert scale, and clinical variables were included in the analysis. Phenotypes of nighttime BP pattern were categorized as extreme dipper, dipper, non-dipper, and reverse dipper. Hypertension was defined as a 24-h ambulatory BPs were 130/80 mmHg or higher. RESULTS: Among 981 subjects, 221 were normotensive, 359 were untreated hypertensive, and 401 were treated hypertensive. Age of the participants were 53.87 ± 14.02 years and 47.1% were female. In overall patients, sleep duration was 431.99 ± 107.61 min, and one to four points of sleep quality were observed in 15.5%, 30.0%, 30.4%, and 24.2%, respectively. Of the 760 hypertensive patients, extreme dipper, dipper, non-dipper, and reverse dipper were observed in 58 (7.63%), 277 (36.45%), 325 (42.76%), and 100 (13.16%), respectively. In multiple linear regression analysis, sleep duration (ß = 0.0105, p < 0.001) and sleep quality (ß = -0.8093, p < 0.001) were associated with nighttime systolic BP and sleep quality was associated with extent of nighttime systolic BP dipping (ß = 0.7622, p < 0.001) in hypertensive patients. In addition, sleep quality showed positive association with dipper pattern (odds ratio [OR] = 1.16, 95% confidence interval [CI] = 1.03-1.30) and showed negative association with reverse dipper pattern (OR = 0.73, 95% CI = 0.62-0.86) in multiple logistic regression analyses. CONCLUSION: When adjusted covariates, less sleep duration and poor sleep quality were positively associated with nighttime systolic BP. Additionally, sleep quality was the independent associated factor for dipper and reverse dipper phenotypes. The study also found that male sex, low estimated glomerular filtration rate, high ambulatory BP, low office BP, and poor sleep quality were associated with blunted nighttime SBP dipping.

Remnant cholesterol, low-density lipoprotein cholesterol, and incident cardiovascular disease among Koreans: a national population-based study.

AIMS: The synergistic association of remnant cholesterol (remnant-C) and low-density lipoprotein cholesterol (LDL-C) levels with incident cardiovascular disease (CVD) in various subgroups of Koreans was investigated. METHODS AND RESULTS: Using the national health insurance data, we included subjects aged between 40 and 70 years without a history of CVD and at least two health screenings between 2009 and 2011. The subjects were divided into four groups by LDL-C and remnant-C levels. The primary outcome was CVD, which occurred between 2014 and 2017. Among 3 686 034 (45.6% women) subjects, 144 004 cardiovascular events occurred. Individuals in both high LDL-C and high remnant-C [hazard ratio (HR) 1.266, 95% confidence interval (CI) 1.243-1.289; 7.9%], high LDL-C only (HR 1.098, 95% CI 1.083-1.113; 21.2%), and high remnant-C only groups (HR 1.102, 95% CI 1.087-1.118; 19.1%) had higher risks of CVD than those in the reference group (LDL-C < 3.4 mmol/L and remnant-C < 0.8 mmol/L; 51.8%). A continuous and linear increase in CVD risk was found in those with higher remnant-C levels after adjustment for several confounders, including LDL-C levels. The association of remnant-C ≥ 0.8 mmol/L with an increased CVD risk was consistent across various strata. CONCLUSIONS: Combined high remnant-C and LDL-C levels confer a higher CVD risk than that individually. Elevated remnant-C values independent of LDL-C levels were associated with a risk of incident CVD. Remnant cholesterol levels in addition to LDL-C levels are important considerations in risk stratification for the primary prevention of CVD.

Since remnant-C has recently emerged as a potential risk factor for CVD, the synergistic association of LDL-C and remnant-C with CVD has been investigated among 3 686 034 Koreans (45.6% women) without preceding CVD using nationwide population-based big data. Remnant cholesterol remained proportional to the risk of incident CVD after adjusting for multiple variables, including LDL-C levels.Low-density lipoprotein cholesterol and remnant-C synergistically contributed to incident CVD.

Atherosclerosis Imaging Quantitative Computed Tomography (AI-QCT) to guide referral to invasive coronary angiography in the randomized controlled CONSERVE trial.

AIMS: We compared diagnostic performance, costs, and association with major adverse cardiovascular events (MACE) of clinical coronary computed tomography angiography (CCTA) interpretation versus semiautomated approach that use artificial intelligence and machine learning for atherosclerosis imaging-quantitative computed tomography (AI-QCT) for patients being referred for nonemergent invasive coronary angiography (ICA). METHODS: CCTA data from individuals enrolled into the randomized controlled Computed Tomographic Angiography for Selective Cardiac Catheterization trial for an American College of Cardiology (ACC)/American Heart Association (AHA) guideline indication for ICA were analyzed. Site interpretation of CCTAs were compared to those analyzed by a cloud-based software (Cleerly, Inc.) that performs AI-QCT for stenosis determination, coronary vascular measurements and quantification and characterization of atherosclerotic plaque. CCTA interpretation and AI-QCT guided findings were related to MACE at 1-year follow-up. RESULTS: Seven hundred forty-seven stable patients (60 ± 12.2 years, 49% women) were included. Using AI-QCT, 9% of patients had no CAD compared with 34% for clinical CCTA interpretation. Application of AI-QCT to identify obstructive coronary stenosis at the ≥50% and ≥70% threshold would have reduced ICA by 87% and 95%, respectively. Clinical outcomes for patients without AI-QCT-identified obstructive stenosis was excellent; for 78% of patients with maximum stenosis < 50%, no cardiovascular death or acute myocardial infarction occurred. When applying an AI-QCT referral management approach to avoid ICA in patients with <50% or <70% stenosis, overall costs were reduced by 26% and 34%, respectively. CONCLUSIONS: In stable patients referred for ACC/AHA guideline-indicated nonemergent ICA, application of artificial intelligence and machine learning for AI-QCT can significantly reduce ICA rates and costs with no change in 1-year MACE.

Impact of the ultra-long 48 mm drug-eluting stent on procedural and clinical outcomes in patients with diffuse long coronary artery disease.

BACKGROUND: Diffuse coronary artery disease (CAD) is a prognostic factor after percutaneous coronary intervention (PCI) and requires multiple overlapping stent implantations. HYPOTHESIS: We investigated the impact of ultra-long 48 mm drug-eluting stent (DES) on procedural and clinical outcomes in real-world practice. METHODS: Patients who underwent DES implantation for a lesion length of >40 mm were selected from a prospective registry between 2019 and 2021. Patients treated with one or more ultra-long 48 mm DES were in the ultra-long DES group (n = 221). The others comprised the conventional DES group (n = 428). Procedural and clinical outcomes were compared after propensity score matching (PSM). The primary endpoint was a device-oriented composite outcome (DOCO) consisting of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization at 1-year follow-up. RESULTS: After PSM, 158 matched pairs of patients showed no differences in the baseline clinical and angiographic characteristics. The stent delivery failure rate, the use of guide-extension catheter or anchor balloon technique, and the procedural success rate were similar for both groups. Approximately two-thirds of lesions could be treated with one DES in the ultra-long DES group. At 1-year follow-up, the DOCO was similar for both groups (2.5% vs. 0.6%, p = .168). CONCLUSIONS: In daily clinical practice, ultra-long DES implantation is as safe and effective as multiple overlapping conventional DES implants in treating diffuse long CAD. However, ultra-long DES can reduce the number of stents. (Trial Registration: ClinicalTrials.gov Identifier: NCT02038127).

Identification of Cardiovascular Disease-Related Genes Based on the Co-Expression Network Analysis of Genome-Wide Blood Transcriptome.

Inference of co-expression network and identification of disease-related modules and gene sets can help us understand disease-related molecular pathophysiology. We aimed to identify a cardiovascular disease (CVD)-related transcriptomic signature, specifically, in peripheral blood tissue, based on differential expression (DE) and differential co-expression (DcoE) analyses. Publicly available blood sample datasets for coronary artery disease (CAD) and acute coronary syndrome (ACS) statuses were integrated to establish a co-expression network. A weighted gene co-expression network analysis was used to construct modules that include genes with highly correlated expression values. The DE criterion is a linear regression with module eigengenes for module-specific genes calculated from principal component analysis and disease status as the dependent and independent variables, respectively. The DcoE criterion is a paired t-test for intramodular connectivity between disease and matched control statuses. A total of 21 and 23 modules were established from CAD status- and ACS-related datasets, respectively, of which six modules per disease status (i.e., obstructive CAD and ACS) were selected based on the DE and DcoE criteria. For each module, gene-gene interactions with extremely high correlation coefficients were individually selected under the two conditions. Genes displaying a significant change in the number of edges (gene-gene interaction) were selected. A total of 6, 10, and 7 genes in each of the three modules were identified as potential CAD status-related genes, and 14 and 8 genes in each of the two modules were selected as ACS-related genes. Our study identified gene sets and genes that were dysregulated in CVD blood samples. These findings may contribute to the understanding of CVD pathophysiology.

Home blood pressure monitoring: a position statement from the Korean Society of Hypertension Home Blood Pressure Forum.

Home blood pressure measurement (HBPM) has the advantage of measuring blood pressure (BP) multiple times over a long period. HBPM effectively diagnoses stress-induced transient BP elevations (i.e., white coat hypertension), insufficient BP control throughout the day (i.e., masked hypertension), and even BP variability. In most cases, HBPM may increase self-awareness of BP, increasing the compliance of treatment. Cumulative evidence has reported better improved predictive values of HBPM in cardiovascular morbidity and mortality than office BP monitoring. In this position paper, the Korean Society of Hypertension Home Blood Pressure Forum provides comprehensive information and clinical importance on HBPM.

Prediction Model for Hypertension and Diabetes Mellitus Using Korean Public Health Examination Data (2002-2017).

Hypertension and diabetes mellitus are major chronic diseases that are important factors in the management of cardiovascular disease. In order to prevent the occurrence of chronic diseases, proper health management through periodic health check-ups is necessary. The purpose of this study is to determine the incidence of hypertension and diabetes mellitus according to the health check-up, and to develop a predictive model for hypertension and diabetes according to the health check-up. We used the National Health Insurance Corporation database of Korea and checked whether hypertension or diabetes occurred from that date according to the number of health check-ups over the past 10 years. Compared to those who underwent five health check-ups, those who participated in the first screening had hypertension (OR = 2.18, 95% CI = 2.14-2.22), diabetes mellitus (OR = 1.33, 95% CI = 1.30-1.35) and both diseases (OR = 2.46, 95% CI = 2.39-2.53); individuals who underwent 10 screenings had hypertension (OR = 0.86, 95% CI = 0.83-0.88), diabetes mellitus (OR = 0.83, 95% CI = 0.81-0.85) and both diseases (OR = 0.83, 95% CI = 0.79-0.87). Individuals who attended fewer than five screenings compared with individuals who attended five or more screenings had hypertension (OR = 1.61, 95% CI = 1.59-1.62; AUC = 0.66), diabetes mellitus (OR = 1.21, 95% CI = 1.20-1.22; AUC = 0.59) and both diseases (OR = 1.75, 95% CI = 1.72-1.78, AUC = 0.63). The machine learning-based prediction model using XGBoost showed higher performance in all datasets than the conventional logistic regression model in predicting hypertension (accuracy, 0.828 vs. 0.628; F1-score, 0.800 vs. 0.633; AUC, 828 vs. 0.630), diabetes mellitus (accuracy, 0.707 vs. 0.575; F1-score, 0.663 vs. 0.576; AUC, 0.710 vs. 0.575) and both diseases (accuracy, 0.950 vs. 0.612; F1-score, 0.950 vs. 0.614; AUC, 0.952 vs. 0.612). It was found that health check-up had a great influence on the occurrence of hypertension and diabetes, and screening frequency was more important than other factors in the variable importances.

Validation of age- and sex-dependent association of uric acid and incident hypertension in rural areas.

BACKGROUND: A previous study based on urban areas suggested the age- and sex-dependent association of uric acid (UA) and incident hypertension. We aimed to investigate whether this association is valid even in rural areas with different lifestyle. METHODS: Data from the cardiovascular disease association study, a prospective cohort study based on rural residents, was analyzed. A total of 4,592 subjects (mean age, 60.1 ± 9.5 years; men, 37.7%) without hypertension were included. We first investigated whether UA was a risk factor for incident hypertension using Cox regression, and then compared the relative risk by stratification according to age and sex. RESULTS: During the follow-up period (mean, 2.0 years), 579 subjects (12.6%) were newly diagnosed with hypertension. The risk factors for incident hypertension were age (Hazard ratios [HR] for ≥ 65, 1.26), systolic blood pressure (HR per 1 mmHg increase, 1.07), and serum UA concentration (HR per 1 mmHg increase, 1.10). The risk of UA-related incident hypertension was higher in the non-elderly than in the elderly for both men and women (HR, 1.74 for non-elderly men; 1.88 for non-elderly women; 1.66 for elderly men; 1.10 for elderly women). Even after adjusting for multiple confounders, the risk of UA-related incident hypertension was significantly higher in non-elderly women (HR, 1.59; P < 0.05). CONCLUSIONS: Age- and sex-dependent association of UA with incident hypertension suggested in cohort study based on urban areas was consistently found in rural areas as well. In particular, non-elderly women were at a higher risk for UA-related incident hypertension.

Metabolic Stress Index Including Mitochondrial Biomarker for Noninvasive Diagnosis of Hepatic Steatosis.

Background: Mitochondrial dysfunction with oxidative stress contributes to nonalcoholic fatty liver disease (NAFLD) progression. We investigated the steatosis predictive efficacy of a novel non-invasive diagnostic panel using metabolic stress biomarkers. Methods: Altogether, 343 subjects who underwent magnetic resonance imaging-based liver examinations from a population-based general cohort, and 41 patients enrolled in a biopsy-evaluated NAFLD cohort, participated in the development and validation groups, respectively. Serologic stress biomarkers were quantitated by enzyme-linked immunosorbent assay. Results: Multivariate regression showed that waist-to-hip ratio, fibroblast growth factor (FGF) 21, FGF19, adiponectin-to-leptin ratio, insulin, albumin, triglyceride, total-cholesterol, and alanine-aminotransferase were independent predictors of steatosis (rank-ordered by Wald). The area under receiver-operator characteristics curve [AUROC (95%CI)] of the metabolic stress index for steatosis (MSI-S) was 0.886 (0.85-0.92) and 0.825 (0.69-0.96) in development and validation groups, respectively. MSI-S had higher diagnostic accuracy (78.1%-81.1%) than other steatosis indices. MSI-S notably differentiated steatosis severities, while other indices showed less discrimination. Conclusion: MSI-S, as a novel non-invasive index, based on mitochondrial stress biomarker FGF21 effectively predicted steatosis. Furthermore, MSI-S may increase the population that could be excluded from further evaluation, reducing unnecessary invasive investigations more effectively than other indices.

Effectiveness and safety of non-vitamin K direct oral anticoagulants in atrial fibrillation patients with bioprosthetic valve.

BACKGROUND: Non-vitamin K direct oral anticoagulant (DOAC) is effective for prevention of embolic events in nonvalvular atrial fibrillation (AF) patients. However, the effectiveness and safety of DOAC in AF patients who have bioprosthetic heart valve (BPHV) is largely unknown. METHODS: We retrospectively identified patients with AF and BPHV, using the diagnostic code and medical device and surgery information from the Korean National Health Insurance Service database, between 2013 and 2018. A 1:2 propensity score-matched cohort (n = 724 taking warfarin; n = 362 taking DOAC) was constructed and analyzed for the primary clinical outcome, a composite of ischemic stroke and systemic embolism. Important secondary outcomes included major bleeding, all-cause death, and the net clinical outcome, defined as a composite of all embolic events, major bleeding, and death. RESULTS: The mean age was 78.9±6.8 years old, and 45% (n = 489) were male. The mean CHA2DS2-VASc score was 4.7±1.4. DOAC was non-inferior to warfarin for preventing ischemic stroke and systemic embolism (hazard ratio [HR] 1.14, 95% confidence interval [CI] 0.56-2.34), major bleeding (HR 0.80, 95% CI 0.32-2.03) and all-cause death (HR 1.09, 95% CI 0.73-1.63). As for the net clinical outcome, DOAC was also similar to warfarin (HR 1.06, 95% CI 0.76-1.47). These outcomes were not different in various subgroups analyzed. CONCLUSION: In this nationwide Korean AF population with a BPHV, DOAC was at least as effective and safe as warfarin for the prevention of systemic embolic events. These results suggest that DOAC may be an excellent alternative to warfarin in AF patients with BPHV.

Impact of NT-proBNP on prognosis of acute decompensated chronic heart failure versus de novo heart failure.

BACKGROUND: NT-pro B-type natriuretic peptide (NT-proBNP) is a powerful prognostic factor for acute heart failure. We investigated whether NT-proBNP levels differ based on the type of heart failure present. METHODS: Using the Korean Acute Heart Failure Registry, a prospective, multicenter cohort, we categorized patients into two groups: de novo heart failure (DNHF, n = 1617) and acute decompensated chronic heart failure (ADHF, n = 1212). NT-proBNP levels were measured on admission. The primary outcome was all-cause mortality, and the secondary outcomes were re-hospitalization for heart failure and a composite of all-cause mortality or re-hospitalization for heart failure at 90 days and 1 year. RESULTS: NT-proBNP levels were significantly lower in patients with DNHF than in those with ADHF (median 4213 vs. 5523 ng/L, p < 0.001). Compared to patients with DNHF, patients with ADHF had a significantly worse prognosis for 1-year all-cause mortality (adjusted hazard ratio (HR) = 1.46 [95% confidence interval (CI) = 1.07-1.98], p = 0.017). A higher NT-proBNP level was associated with higher 1-year all-cause mortality for both heart failure types (adjusted HR = 2.00, p = 0.002 in ADHF; adjusted HR = 2.41, p = 0.003 in DNHF). However, all-cause mortality risk was always higher in patients with ADHF than in those with DNHF for any given NT-proBNP level. CONCLUSION: NT-proBNP levels are an important prognostic factor for both DNHF and ADHF. Notably, patients with ADHF had consistently higher risks than those with DNHF with the same NT-proBNP level for 1-year all-cause mortality.

Reference diameter and characteristics of the distal radial artery based on ultrasonographic assessment.

BACKGROUND/AIMS: While distal radial artery (DRA) access is increasingly being used for diagnostic coronary angiography, limited information is available regarding DRA size. We aimed to determine the DRA reference diameters of Korean patients and identify the predictors of DRA diameter < 2.3 mm. METHODS: The outer bilateral DRA diameters were assessed using a linear ultrasound probe in 1,162 consecutive patients who underwent transthoracic echocardiography. The DRA diameter was measured by the perpendicular angle in the dorsum of the hand, and the average values were compared by sex. DRA diameter < 2.3 mm was defined as unsuitable for routine diagnostic coronary angiography using a 5 Fr introducer sheath. RESULTS: The mean DRA diameters were 2.31 ± 0.43 mm (right) and 2.35 ± 0.45 mm (left). The DRA was smaller in women than men (right: 2.15 ± 0.38 mm vs. 2.43 ± 0.44 mm, p < 0.001; left: 2.18 ± 0.39 mm vs. 2.47 ± 0.45 mm, p < 0.001). The DRA diameter was approximately 20% smaller than the radial artery diameter. A total of 630 (54.2%) and 574 (49.4%) patients had DRA diameter < 2.3 mm in the right and left hands, respectively. Female sex, low body mass index (BMI), and low body surface area (BSA) were significant predictors of DRA diameter < 2.3 mm. CONCLUSION: We provided reference DRA diameters for Korean patients. Approximately 50% of the studied patients had DRA diameter < 2.3 mm. Female sex, low BMI, and low BSA remained significant predictors of DRA diameter < 2.3 mm.

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.

Adiponectin and cardiometabolic trait and mortality: where do we go?

Adiponectin is an adipocyte-derived cytokine known for its cardioprotective effects in preclinical studies. Early epidemiologic studies replicated these findings and drew great interest. Subsequent large-scale prospective cohorts, however, showed that adiponectin levels seemed not to relate to incident coronary artery disease (CAD). Even more surprisingly, a paradoxical increase of all-cause and cardiovascular (CV) mortality with increased adiponectin levels was reported. The adiponectin-mortality paradox has been explained by some groups asserting that adiponectin secretion is promoted by elevated natriuretic peptides (NP). Other groups have proposed that adiponectin is elevated due to adiponectin resistance in subjects with metabolic syndrome or heart failure (HF). However, there is no unifying theory that can clearly explain this paradox. In patients with HF with reduced ejection fraction (HFrEF), stretched cardiomyocytes secrete NPs, which further promote release of adiponectin from adipose tissue, leading to adiponectin resistance. On the other hand, adiponectin biology may differ in patients with heart failure with preserved ejection fraction (HFpEF), which constitutes 50% of all of HF. Most HFpEF patients are obese, which exerts inflammation and myocardial stiffness, i.e. likely to prevent myocardial stretch and subsequent NP release. This segment of the patient population may display different adiponectin biology from its HFrEF counterpart. Dissecting the adiponectin-mortality relationship in terms of different HF subtypes may help to comprehensively understand this paradox. Mendelian randomization (MR) analyses claimed that adiponectin levels are not causally related to CAD or metabolic syndrome. Results from MR studies, however, should be interpreted with great caution because the underlying history of CAD or CHF was not taken into account in these analyses, an issue that may substantially confound the results. Here, we discuss many aspects of adiponectin; cardiometabolic traits, therapeutic interventions, and the ongoing debate about the adiponectin paradox, which were recently described in basic, epidemiologic, and clinical studies.

Differential association of metabolic syndrome and low-density lipoprotein cholesterol with incident cardiovascular disease according to sex among Koreans: a national population-based study.

AIMS: To investigate sex differences in the association of metabolic syndrome (MetS) and/or low-density lipoprotein cholesterol (LDL-C) with the incidence of cardiovascular and cerebrovascular disease (CCVD). METHODS AND RESULTS: A total of 4 702 458 individuals, aged between 40 and 70, without a previous diagnosis of CCVD, underwent at least two health screenings between 2009 and 2011. Of them, 4 193 878 individuals (48.6% women) fulfilled the study requirements. The main outcome measured was the incidence of CCVD. By the end of 2017, 68 921 CCVD events occurred. Men in high LDL-C only, MetS only, and both MetS and high LDL-C groups had higher risks of CCVD. Women in MetS only and both MetS and high LDL-C groups, but not those in high LDL-C only group, had higher risks of CCVD than those in the reference group. The effect of the interaction between the presence of MetS and high LDL-C levels on the primary outcome was found among women (P for interaction 0.016) but not among men (P for interaction 0.897). A combination of MetS and LDL-C > 3.4 mmol/L increased the risk of CCVD as compared to MetS or LDL-C > 3.4 mmol/L alone in both men and women. CONCLUSIONS: Metabolic syndrome confers an increased risk of CCVD irrespective of sexes; LDL-C > 3.4 mmol/L alone has a greater influence on CCVD occurrence in men than in women. Metabolic syndrome and high LDL-C beget a synergistically detrimental impact on the incidence of CCVD in both men and women. Treatment of dyslipidaemia and metabolic syndrome should be tailored according to patient characteristics.

A Deep Neural Network for Estimating Low-Density Lipoprotein Cholesterol From Electronic Health Records: Real-Time Routine Clinical Application.

BACKGROUND: Previously, we constructed a deep neural network (DNN) model to estimate low-density lipoprotein cholesterol (LDL-C). OBJECTIVE: To routinely provide estimated LDL-C levels, we applied the aforementioned DNN model to an electronic health record (EHR) system in real time (deep LDL-EHR). METHODS: The Korea National Health and Nutrition Examination Survey and the Wonju Severance Christian Hospital (WSCH) datasets were used as training and testing datasets, respectively. We measured our proposed model's performance by using 5 indices, including bias, root mean-square error, P10-P30, concordance, and correlation coefficient. For transfer learning (TL), we pretrained the DNN model using a training dataset and fine-tuned it using 30% of the testing dataset. RESULTS: Based on 5 accuracy criteria, deep LDL-EHR generated inaccurate results compared with other methods for LDL-C estimation. By comparing the training and testing datasets, we found an overfitting problem. We then revised the DNN model using the TL algorithms and randomly selected subdata from the WSCH dataset. Therefore, the revised model (DNN+TL) exhibited the best performance among all methods. CONCLUSIONS: Our DNN+TL is expected to be suitable for routine real-time clinical application for LDL-C estimation in a clinical laboratory.

Central blood pressure lowering effect of telmisartan-rosuvastatin single-pill combination in hypertensive patients combined with dyslipidemia: A pilot study.

This multicenter, phase 4, Prospective Randomized Open, Blinded End-point (PROBE) study aimed to evaluate safety and efficacy of telmisartan/rosuvastatin single-pill combination (SPC) therapy on lowering central blood pressure (BP) compared with telmisartan monotherapy in hypertensive patients with dyslipidemia in Korea. Study was terminated earlier than planned due to COVID-19 pandemic, thus should be considered as a pilot study. Among 125 patients who met the inclusion criteria of hypertension and dyslipidemia (defined as 10-year Atherosclerotic Cardiovascular Disease risk score over 5%), 80 patients went through 4-week single-group run-in period with telmisartan 40-80 mg, then randomized to telmisartan 80 mg + rosuvastatin (10 or 20 mg) SPC group or telmisartan 80 mg monotherapy group. The central/brachial BP, brachial-ankle pulse wave velocity (baPWV), and augmentation index (AIx) were assessed at baseline and 16 weeks later. Mean brachial SBP changed from 135.80 ± 14.22 mmHg to 130.69 ± 13.23 mmHg in telmisartan/rosuvastatin group and from 134.37 ± 12.50 mmHg to 133.75 ± 12.30 mmHg in telmisartan monotherapy group without significant difference (between-group difference p = .149). Mean central SBP were reduced significantly in the telmisartan/rosuvastatin group with change from 126.72 ± 14.44 mmHg to 121.56 ± 14.56 mmHg while telmisartan monotherapy group showed no significant change (between-group difference p = .028). BaPWV changed from 1672.57 ± 371.72 m/s to 1591.75 ± 272.16 m/s in telmisartan/rosuvastatin group and from 1542.85 ± 263.70 m/s to 1586.12 ± 297.45 m/s in telmisartan group with no significance (between-group difference p = .078). Change of AIx had no significant difference (between-group difference p = .314). Both groups showed excellent compliance rate of 96.9 ± 4.5% with no significant difference in adverse rate. Telmisartan/rosuvastatin SPC therapy was more effective in lowering central BP compared with the telmisartan monotherapy. The results of this study showed benefit of additive statin therapy in hypertensive patients combined with dyslipidemia.

Effect of hepatic steatosis on native T1 mapping of 3T magnetic resonance imaging in the assessment of T1 values for patients with non-alcoholic fatty liver disease.

PURPOSE: This study investigated whether T1 values in native T1 mapping of 3T magnetic resonance imaging (MRI) of the liver were affected by the fatty component. METHODS: This prospective study involved 340 participants from a population-based cohort study between May 8, 2018 and August 8, 2019. Data obtained included: (1) hepatic stiffness according to magnetic resonance elastography (MRE); (2) T1 value according to T1 mapping; (3) fat fraction and iron concentration from multi-echo Dixon; and (4) clinical indices of hepatic steatosis including body mass index, waist circumference, history of diabetes, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, and triglycerides. The correlations between T1 value and fat fraction, and between T1 value and liver stiffness were assessed using Pearson's correlation coefficient. The independent two-sample t-test was used to evaluate the differences in T1 values according to the presence or absence of hepatic steatosis, and the one-way analysis of variance was used to evaluate the difference in T1 value by grading of hepatic steatosis according to MRI-based proton density fat fraction (PDFF). In addition, univariate and multivariate linear regression analyses were performed to determine whether other variables influenced the T1 value. RESULTS: T1 value showed a positive correlation with the fat fraction obtained from PDFF (r = 0.615, P < 0.001) and with the liver stiffness obtained from MRE (r = 0.370, P < 0.001). Regardless of the evaluation method, the T1 value was significantly increased in subjects with hepatic steatosis (P < 0.001). When comparing hepatic steatosis grades based on MRI-PDFF, the mean T1 values were significantly different in all grades, and the T1 value tended to increase as the grade increased (P < 0.001, P for trend <0.001). On multiple linear regression analysis, the T1 value was influenced by MRI-PDFF, calculated liver iron concentration, liver stiffness, and serum aspartate aminotransferase level. CONCLUSION: The T1 value obtained by current T1 mapping of 3T MRI was affected by the liver fat component and several other factors such as liver stiffness, iron concentration, and inflammation.

Physical Activity and the Risk of COVID-19 Infection and Mortality: A Nationwide Population-Based Case-Control Study.

Regular physical activity (PA) is known to reduce the risk of serious community-acquired infections. We examined the association of PA with the morbidity and mortality resulting from coronavirus disease (COVID-19) infection in the South Korean population. Patients who tested positive for severe acute respiratory coronavirus 2 and who underwent public health screening between 2014 and 2017 (n = 6288) were included. Age- and sex-matched controls (n = 125,772) were randomly selected from the Korean National Health Insurance Service database. Leisure-time PA was assessed using a self-reported questionnaire. The mean PA levels were lower in the patient than in the control group (558.2 ± 516.3 vs. 580.2 ± 525.7 metabolic equivalent of task (MET)-min/week, p = 0.001). Patients with moderate to vigorous PA (MVPA) were associated with a lower risk of COVID-19 morbidity (odds ratio (OR), 0.90; 95% confidence interval (CI), 0.86-0.95). In addition, a standard deviation (SD) increment in MET/week (525.3 MET-min/week) was associated with a 4% decrease in the risk of COVID-19 morbidity (OR, 0.96; 95% CI, 0.93-0.99). MVPA and an SD increment in MET/week were associated with lower mortality (MVPA: OR, 0.47; 95% CI, 0.26-0.87; per SD increment: OR, 0.65; 95% CI, 0.48-0.88). Higher levels of regular PA were associated with a lower risk of COVID-19 infection and mortality, highlighting the importance of maintaining appropriate levels of PA along with social distancing amid the COVID-19 pandemic.

Antihypertensive Drugs and the Risk of Cancer: A Nationwide Cohort Study.

We sought to assess the association between common antihypertensive drugs and the risk of incident cancer in treated hypertensive patients. Using the Korean National Health Insurance Service database, the risk of cancer incidence was analyzed in patients with hypertension who were initially free of cancer and used the following antihypertensive drug classes: Angiotensin-converting enzyme inhibitors (ACEIs); angiotensin receptor blockers (ARBs); beta blockers (BBs); calcium channel blockers (CCBs); and diuretics. During a median follow-up of 8.6 years, there were 4513 (6.4%) overall cancer incidences from an initial 70,549 individuals taking antihypertensive drugs. ARB use was associated with a decreased risk for overall cancer in a crude model (hazard ratio (HR): 0.744, 95% confidence interval (CI): 0.696-0.794) and a fully adjusted model (HR: 0.833, 95% CI: 0.775-0.896) compared with individuals not taking ARBs. Other antihypertensive drugs, including ACEIs, CCBs, BBs, and diuretics, did not show significant associations with incident cancer overall. The long-term use of ARBs was significantly associated with a reduced risk of incident cancer over time. The users of common antihypertensive medications were not associated with an increased risk of cancer overall compared to users of other classes of antihypertensive drugs. ARB use was independently associated with a decreased risk of cancer overall compared to other antihypertensive drugs.