Age and sex dependent association of uric acid and incident hypertension.

BACKGROUND AND AIMS: A previous meta-analysis suggested that the relationship between hyperuricemia and hypertension may be stronger in younger individuals and women. We aimed to investigate the age and sex dependent association of uric acid (UA) and incident hypertension. METHODS AND RESULTS: We analyzed data from the Health Examinees Study, a community-based prospective cohort study conducted in Korea from 2004 to 2013. It included 29,088 non-hypertensive subjects aged 40-79 (age, 52.5 ± 7.8 years; men, 31.4%) who had serum UA measurement and participated in the follow-up survey. The risk factors of hypertension were assessed using Cox regression. Over a mean 3.8 years of follow-up, 1388 men (15.2%) and 1942 women (9.7%) were newly diagnosed with hypertension. Upon age- and sex-based stratification, the risk of hypertension was highest in hyperuricemic subjects aged 40-49 years (HR: women, 2.16; men, 1.30). Across the entire cohort, the risk of incident hypertension was higher in groups with higher serum UA levels, and highest in women aged 40-49 years (HR, 1.44; P < 0.001). On multivariable linear regression analysis, the higher the baseline serum UA level, the greater the increase in blood pressure during follow-up, and this effect was strongest in women aged 40-49 years (ß = 0.87 and P < 0.01 for systolic blood pressure). CONCLUSIONS: The relationship between uric acid and incident hypertension tended to be dependent on age and sex. Younger women are at highest risk of UA-related incident hypertension.

Fatty liver index and development of cardiovascular disease in Koreans without pre-existing myocardial infarction and ischemic stroke: a large population-based study.

BACKGROUND: Despite the known association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD), whether NAFLD predicts future CVD events, especially CVD mortality, remains uncertain. We evaluated the relationship between fatty liver index (FLI), a validated marker of NAFLD, and risk of major adverse cardiac events (MACEs) in a large population-based study. METHODS: We identified 3011,588 subjects in the Korean National Health Insurance System cohort without a history of CVD who underwent health examinations from 2009 to 2011. The primary endpoint was a composite of cardiovascular deaths, non-fatal myocardial infarction (MI), and ischemic stroke. A Cox proportional hazards regression analysis was performed to assess association between the FLI and the primary endpoint. RESULTS: During the median follow-up period of 6 years, there were 46,010 cases of MACEs (7148 cases of cardiovascular death, 16,574 of non-fatal MI, and 22,288 of ischemic stroke). There was a linear association between higher FLI values and higher incidence of the primary endpoint. In the multivariable models adjusted for factors, such as body weight and cholesterol levels, the hazard ratio for the primary endpoint comparing the highest vs. lowest quartiles of the FLI was 1.99 (95% confidence interval [CIs], 1.91-2.07). The corresponding hazard ratios (95% CIs) for cardiovascular death, non-fetal MI, and ischemic stroke were 1.98 (1.9-2.06), 2.16 (2.01-2.31), and 2.01 (1.90-2.13), respectively (p < 0.001). The results were similar when we performed stratified analyses by age, sex, use of dyslipidemia medication, obesity, diabetes, and hypertension. CONCLUSIONS: Our findings indicate that the FLI, which is a surrogate marker of NAFLD, has prognostic value for detecting individuals at higher risk for cardiovascular events.

Micropuncture Access Set Use During Implantation of Totally Implantable Venous Access Device May Reduce Upper Extremity DVT Incidence Among Patients Undergoing Chemotherapy for Colorectal Cancer.

BACKGROUND: The aim of this study was to compare the perioperative outcomes when using a micropuncture access set (MS) to those when using a conventional puncture set (CS) for implantation of totally implantable venous access device (TAVID). METHODS: A total of 314 patients undergoing chemotherapy for colorectal cancer were included between June 2015 and July 2018. Of these, 123 (39.2%) received TAVID implantation using MS and 191 patients (60.8%) received TAVID using CS. Perioperative outcomes and complications were compared between both groups. RESULTS: Baseline characteristics, including body mass index, American Society of Anesthesiologists score, cardiovascular disease, diabetes mellitus, and hyperlipidemia, were not significantly different between the groups. Postoperative complications occurred in 25 patients (8.0%), and the rate and incidence of venous thrombosis were significantly higher in the CS group. There were no significant differences between the groups in other complications such as the rate of port site infection, deep vein thrombosis, obstruction, catheter dislocation, and skin complications (exposure). No incidence of catheter infection, port rotation, intraoperative bleeding, or pneumothorax was observed in this cohort. CONCLUSIONS: MS is a safe and feasible procedure and results in less thrombosis. MS may play an important role in improving outcomes for the implantation of TAVID.

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.

Metabolic Syndrome Severity Score in Korean Adults: Analysis of the 2010-2015 Korea National Health and Nutrition Examination Survey.

BACKGROUND: Continuous metabolic syndrome (MS) severity scores that can track metabolic risk in individuals over time have been developed for Western populations. The present study aimed to develop gender- and age-specific equations for MS severity scores in Korean adults. METHODS: Using data from the Korea National Health and Nutrition Examination Surveys (KNHANES) IV (2010-2012) and VI (2013-2015), we performed a confirmatory factor analysis of single MS factor that allowed for differential loadings across groups to generate gender- and age-specific, continuous MS severity scores. Then, we validated this equation in a different dataset of Korean adults. RESULTS: In confirmatory analysis, waist circumference had the highest factor loading, indicating that waist circumference had the strongest correlation with MS among Korean adults. Lower factor loadings (< 0.4) among Korean adults aged 40-59 years were noted for systolic blood pressure and fasting glucose. MS severity score values were significantly correlated with metabolic parameters, including high-sensitivity C-reactive-protein, glycated hemoglobin, and homeostasis model assessment of insulin resistance. Furthermore, MS severity scores well predicted traditional MS according to receiver operating characteristic analysis in a validation dataset (KNHANES VII). In a longitudinal cohort dataset, participants diagnosed with Adult Treatment Program III (ATP-III) MS after an initial assessment had progressively higher baseline MS severity scores in relationship to their time until ATP-III MS diagnosis. CONCLUSION: The new MS severity score equations for Korean adults proposed in this study provide a clinically-accessible continuous measure of MS for potential use in identifying adults at higher risk for MS-related diseases and following changes within individuals over time.

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.

Association of Age at Menarche With Left Ventricular Diastolic Dysfunction in Middle-Aged Women.

BACKGROUND: There is sparse research on whether if early menarche is related to left ventricular (LV) diastolic dysfunction. The present study examined this relationship in Korean women.Methods and Results:In a cross-sectional study we analyzed the records of 18,910 Korean women (≥30 years) who underwent echocardiography as part of a comprehensive health examination. Age at menarche was assessed using standardized, self-administered questionnaires. Presence of LV diastolic dysfunction was determined from the echocardiographic findings. Of the 18,910 women, 3,449 had LV diastolic dysfunction. Age at menarche was inversely associated with prevalence of LV diastolic dysfunction. In a multivariable-adjusted model, odds ratios (95% confidence interval) for LV diastolic dysfunction comparing menarche age to menarche at 15-18 years were 1.77 (1.38-2.27) for <12 years, 1.31 (1.11-1.54) for 12 years, 1.26 (1.11-1.43) for 13 years, and 1.03 (0.91-1.15) for 14 years (P for trend <0.001). Adjusting for body mass index or percent fat mass partially reduced these associations. CONCLUSIONS: This large study found an inverse relationship between menarche age and LV diastolic dysfunction. Future prospective studies are needed to investigate potential causal relationships.

Subclinical left ventricular diastolic dysfunction and incident type 2 diabetes risk: the Korean Genome and Epidemiology Study.

BACKGROUND: Subclinical left ventricular (LV) diastolic dysfunction in type 2 diabetes (T2D) is a common finding and represents an early sign of diabetic cardiomyopathy. However, the relationship between LV diastolic dysfunction and the incident T2D has not been previously studied. METHODS: A total of 1817 non-diabetic participants (mean age, 54 years; 48% men) from the Korean Genome and Epidemiology Study who were free of cardiovascular disease were studied. LV structure and function were assessed by conventional echocardiography and tissue Doppler imaging. Subclinical LV diastolic dysfunction was defined using age-specific cutoff limits for early diastolic (Em) velocity, mitral E/Em ratio, and left atrial volume index. RESULTS: During the 6-year follow-up period, 273 participants (15%) developed T2D. Participants with incident T2D had greater LV mass index (86.7 ± 16.4 vs. 91.2 ± 17.0 g/m2), worse diastolic function, reflected by lower Em velocity (7.67 ± 1.80 vs. 7.47 ± 1.70) and higher E/Em ratio (9.19 ± 2.55 vs. 10.23 ± 3.00), and higher prevalence of LV diastolic dysfunction (34.6 vs. 54.2%), compared with those who did not develop T2D (all P < 0.001). In a multivariate logistic regression model, lower Em velocity (odd ratio [OR], 0.867; 95% confidence interval [CI] 0.786-0.957) and the presence of LV diastolic dysfunction (OR, 1.617; 95% CI 1.191-2.196) were associated with the development of T2D, after adjusting for potential confounding factors. CONCLUSIONS: In a community-based cohort, the presence of subclinical LV diastolic dysfunction was a predictor of the progression to T2D. These data suggest that the echocardiographic assessment of LV diastolic function may be helpful in identifying non-diabetic subjects at risk of incident T2D.

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.

Effect of exercise on the development of new fatty liver and the resolution of existing fatty liver.

BACKGROUND & AIMS: Guidelines about recommendations for amounts of exercise/physical activity are variable in non-alcoholic fatty liver disease. Our aim was to determine the amount of exercise that was associated with two outcomes: a) development of incident liver fat and b) resolution of baseline liver fat, at five-year follow-up. METHODS: In an occupational health screening program, weekly frequency of exercise was assessed using the validated Korean version of the International Physical Activity Questionnaire Short Form (IPAQ-SF). Liver fat was identified by ultrasonography (3.5MHz probe) at baseline and at five-year follow-up. Fully adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs and 95% confidence intervals [CI]) for incident fatty liver and resolution of fatty liver at follow-up. RESULTS: 233,676 men and women were studied between 2002 and 2014. 126,811 individuals were identified without fatty liver, and of these subjects, 29,014 subjects developed incident fatty liver during follow-up. At baseline, there were 42,536 individuals with liver fat and of these individuals, fatty liver resolved in 14,514, during follow-up. After full adjustment, compared to no exercise, exercise was associated with benefit for both outcomes; for exercise ⩾5times per week for incident fatty liver: HR 0.86 (95% CI 0.80,0.92), p<0.001, and for resolution of fatty liver HR 1.40 (95% CI 1.25,1.55), p<0.001. CONCLUSIONS: Moderate to vigorous exercise is beneficial in decreasing risk of development of new fatty liver or improving resolution of existing fatty liver during 5years of follow-up. LAY SUMMARY: The amount of exercise/physical activity to benefit fatty liver disease in non-alcoholic fatty liver disease is not known. In a large study of free-living people, our aim was to determine the amount of exercise that was linked with a decrease in new fatty liver and also improvement of existing fatty liver over 5years of follow-up. Compared to no exercise, exercise ⩾5times per week (lasting at least 10min on each occasion) was linked to a highly significantly benefit for both a decrease in new fatty liver and also improvement of existing fatty liver.

Switching from prasugrel to clopidogrel based on Cytochrome P450 2C19 genotyping in East Asian patients stabilized after acute myocardial infarction.

To evaluate the pharmacodynamic efficacy of de-escalating P2Y12 inhibition from prasugrel to clopidogrel based on cytochrome P450 (CYP) 2C19 genotyping, we genotyped 50 Korean patients with AMI who underwent percutaneous coronary intervention (PCI) for CYP2C19 *2,*3, or *17 using real-time PCR. They were discharged on prasugrel 10 mg daily. A control group of 48 AMI patients who underwent PCI and were discharged on clopidogrel but did not undergo genotyping was identified retrospectively. Based on genotyping results available at 3 weeks, 12 patients found to have 2 copies of either CYP2C19 *2 or *3 loss of function alleles continued prasugrel while the remaining 38 patients switched to clopidogrel 75 mg daily. The rate of patients within the therapeutic window (TW) of on-treatment platelet reactivity (OPR), 85

A prospective study of serum adiponectin and regression of metabolic syndrome: The ARIRANG study.

Increased serum adiponectin levels may play a protective role in metabolic syndrome. However, few prospective studies have examined the effect of serum adiponectin in the improvement of metabolic components in subjects with metabolic syndrome. We investigated the association of serum adiponectin levels with the regression of metabolic syndrome in a population-based longitudinal study. A total of 1308 adults (575 men and 733 women) with metabolic syndrome at baseline were examined and followed. Baseline serum adiponectin concentrations were measured by radioimmunoassay. During an average of 2.6 years of follow-up, metabolic syndrome had disappeared in 184 men (29.8%) and 235 women (32.1%). In multivariable adjusted models, the odds ratio (95% confidence interval) for regression of metabolic syndrome comparing the highest to the lowest quartiles of adiponectin levels was 0.93 (0.56-1.53) in men and 2.48 (1.54-4.01) in women. Increased serum adiponectin is a predictor for the regression of metabolic syndrome in women. Adiponectin may have potential therapeutic applications in metabolic disease.

Association between brachial-ankle pulse wave velocity and progression of coronary artery calcium: a prospective cohort study.

BACKGROUND: Few studies have investigated the association between coronary artery calcium (CAC) progression and arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV). We examined the influence of the severity of baseline baPWV on CAC progression in a large prospective cohort. METHODS: A total of 1600 subjects who voluntarily participated in a comprehensive health-screening program between March 2010 and December 2013 and had baseline baPWV as well as CAC on baseline and serial follow-up computed tomography performed approximately 2.7 ± 0.5 years apart were enrolled in the study. RESULTS: A total of 1124 subjects were included in the analysis (1067 men; mean age, 43.6 ± 5.1 years). An increased CAC score was found in 318 subjects (28.3%) during the follow-up period. Baseline higher baPWV was significantly correlated with CAC progression, especially in subjects with third- and fourth-quartile values (adjusted odds ratio [OR] 2.04; 95% confidence interval [CI] 1.33-3.15 and OR 2.14; 95% CI 1.34-3.41, respectively) compared with the lowest-quartile values (P for trend <0.001). A similar effect was observed in diabetic subjects. Among the 835 subjects with a baseline CAC score = 0, progression to CAC score >0 was associated with male sex, diabetes, and higher baPWV. However, among the 289 individuals with a baseline CAC score >0, only the presence of CAC itself was predictive of CAC progression. CONCLUSIONS: Higher arterial stiffness measured by baPWV could be significantly associated with CAC progression.

Addition of N-terminal pro-B-type natriuretic peptide levels to electrocardiography criteria for detection of left ventricular hypertrophy: the ARIRANG study.

The utility of electrocardiography (ECG) in screening for left ventricular hypertrophy (LVH) in general populations is limited mainly because its low sensitivity. B-type natriuretic peptide (BNP) is released due to the remodeling processes of LVH and could improve the diagnostic accuracy for the ECG criteria for LVH. We hypothesized that addition of BNP levels to ECG criteria could aid LVH detection compared with ECG alone in a general population. We enrolled consecutive 343 subjects from a community-based cohort. LVH was defined as LV mass index > 95 g/m(2) for females and > 115 g/m(2) for males according to echocardiography. The area under the receiver operator characteristic (ROC) curve to detect LVH was 0.55 (95% confidence interval [CI], 0.50-0.61) in Sokolow-Lyon criteria and 0.53 (0.47-0.59) in the Cornell voltage criteria. After addition of N-terminal-proBNP levels to the model, the corresponding areas under the ROC were 0.63 (0.58-0.69) and 0.64 (0.59-0.69), respectively. P values for the comparison in areas under the ROC for models with and without N-terminal-proBNP levels were < 0.001. These data suggest that addition of N-terminal-proBNP levels to ECG criteria could significantly improve the diagnostic accuracy of LVH in general populations.

Comparison of the safety and efficacy of biodegradable polymer biolimus-eluting stents and durable polymer everolimus-eluting stents: propensity score-matched analysis.

OBJECTIVES: We investigated and compared the clinical outcomes between biodegradable polymer biolimus-eluting stents (BES) and durable polymer everolimus-eluting stents (EES) in a single-center prospective registry. BACKGROUND: There is limited data regarding the safety and efficacy of the biodegradable BES compared to second-generation drug-eluting stents. METHODS: From January 2010 to April 2012, a total of 1,279 patients were treated with BES (n = 647) or EES (n = 632) in a single center. We included 1,231 patients (BES = 625, EES = 606) after excluding 48 patients (BES = 22, EES = 26) with acute myocardial infarction accompanied by cardiogenic shock. The 1-year incidences of target lesion failure (TLF), patient-oriented composite outcomes (POCO), and stent thrombosis (ST) after the index procedure were compared in propensity score-matched analyses. RESULTS: Propensity score matching yielded 406 well-balanced pairs (EES = 406, BES-B = 406). In the propensity-matched population, the 1-year incidence of TLF (BES = 3.0% vs. EES = 2.5%, P = 0.666) and POCO (BES = 5.4% vs. EES = 6.4%, P = 0.552) were similar between the 2 groups. In addition, the incidence of definite or probable ST was also similar (BES = 0.74% vs. EES = 0.74%, P = 1.000). In subgroup analysis, the number of patients who reached the primary end-point did not differ significantly between the 2 groups. CONCLUSION: In a single-center registry with unrestricted use of EES and BES-B, these stents showed comparable efficacy and safety in terms of TLF, POCO, and ST at 1-year follow-up.

A randomized, open-label, multicenter trial for the safety and efficacy of adult mesenchymal stem cells after acute myocardial infarction.

Recent studies suggest that the intracoronary administration of bone marrow (BM)-derived mesenchymal stem cells (MSCs) may improve left ventricular function in patients with acute myocardial infarction (AMI). However, there is still argumentative for the safety and efficacy of MSCs in the AMI setting. We thus performed a randomized pilot study to investigate the safety and efficacy of MSCs in patients with AMI. Eighty patients with AMI after successful reperfusion therapy were randomly assigned and received an intracoronary administration of autologous BM-derived MSCs into the infarct related artery at 1 month. During follow-up period, 58 patients completed the trial. The primary endpoint was changes in left ventricular ejection fraction (LVEF) by single-photon emission computed tomography (SPECT) at 6 month. We also evaluated treatment-related adverse events. The absolute improvement in the LVEF by SPECT at 6 month was greater in the BM-derived MSCs group than in the control group (5.9% ± 8.5% vs 1.6% ± 7.0%; P=0.037). There was no treatment-related toxicity during intracoronary administration of MSCs. No significant adverse cardiovascular events occurred during follow-up. In conclusion, the intracoronary infusion of human BM-derived MSCs at 1 month is tolerable and safe with modest improvement in LVEF at 6-month follow-up by SPECT. (ClinicalTrials.gov registration number: NCT01392105).

Comparison of Statin With Ezetimibe Combination Therapy Versus Statin Monotherapy for Primary Prevention in Middle-Aged Adults.

BACKGROUND AND OBJECTIVES: Lipid lowering therapy is essential to reduce the risk of major cardiovascular events; however, limited evidence exists regarding the use of statin with ezetimibe as primary prevention strategy for middle-aged adults. We aimed to investigate the impact of single pill combination therapy on clinical outcomes in relatively healthy middle-aged patients when compared with statin monotherapy. METHODS: Using the Korean National Health Insurance Service database, a propensity score match analysis was performed for baseline characteristics of 92,156 patients categorized into combination therapy (n=46,078) and statin monotherapy (n=46,078) groups. Primary outcome was composite outcomes, including death, coronary artery disease, and ischemic stroke. And secondary outcome was all-cause death. The mean follow-up duration was 2.9±0.3 years. RESULTS: The 3-year composite outcomes of all-cause death, coronary artery disease, and ischemic stroke demonstrated no significant difference between the 2 groups (10.3% vs. 10.1%; hazard ratio (HR), 1.022; 95% confidence interval [CI], 0.980-1.064; p=0.309). Meanwhile, the 3-year all-cause death rate was lower in the combination therapy group than in the statin monotherapy group (0.2% vs. 0.4%; p<0.001), with a significant HR of 0.595 (95% CI, 0.460-0.769; p<0.001). Single pill combination therapy exhibited consistently lower mortality rates across various subgroups. CONCLUSIONS: Compared to the statin monotherapy, the combination therapy for primary prevention showed no difference in composite outcomes but may reduce mortality risk in relatively healthy middle-aged patients. However, since the study was observational, further randomized clinical trials are needed to confirm these findings.

A prospective study of epicardial adipose tissue and incident metabolic syndrome: the ARIRANG study.

Increased epicardial adipose tissue (EAT) may be closely associated with the development of metabolic abnormalities. We investigated whether EAT predicts the incident metabolic syndrome in a community-based, middle-aged population. The study subjects were comprised of 354 adults (134 men and 220 women) aged 40 to 70 yr without metabolic syndrome. Baseline EAT thickness, measured by echocardiography, was compared between subjects who developed new-onset metabolic syndrome at follow-up survey and those who did not. After an average of 2.2 yr of follow-up, 32 men (23.9%) and 37 women (16.8%) developed metabolic syndrome. Median EAT thickness at baseline was significantly higher in male subjects who developed metabolic syndrome than those who did not (1.52 mm vs 2.37 mm, P<0.001). The highest quartile of EAT thickness (≥2.55 mm) was associated with increased risk of progression to metabolic syndrome (Odds ratio [OR], 3.09; 95% confidence interval [CI], 1.11-8.66) after adjustment for age, smoking, alcohol intake, regular exercise, total energy intake, high sensitive C-reactive protein and homeostasis model assessment of insulin resistance in men. A significant association of EAT with incident metabolic syndrome was not seen in women (OR, 1.25; 95% CI, 0.54-2.90). In conclusion, increased EAT thickness is an independent predictor for incident metabolic syndrome in men.

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.