Clinical Implications of DeviceDetected Atrial Fibrillation in Cardiac Resynchronization Therapy

Background and Objectives@#Atrial fibrillation (AF) is associated with decreased cardiac resynchronization therapy (CRT) benefits compared to sinus rhythm (SR). Effective biventricular (BiV) pacing is a determinant of CRT success, but AF can interfere with adequate BiV pacing and affect clinical outcomes. We investigated the effect of device-detected AF on clinical outcomes and optimal BiV pacing in patients with heart failure (HF) treated with CRT. @*Methods@#We retrospectively analyzed 174 patients who underwent CRT implantation between 2012 and 2019 at a tertiary center. The optimal BiV pacing percentage was defined as ≥98%. Device-detected AF was defined as an atrial high-rate episode ≥180 beats per minute lasting more than 6 minutes during the follow-up period. We stratified the patients without preexisting AF at pre-implantation into device-detected AF and no-AF groups. @*Results@#A total of 120 patients did not show preexisting AF at pre-implantation, and 54 had AF. Among these 120 patients, 19 (15.8%) showed device-detected AF during a median follow-up of 25.1 months. The proportion of optimal BiV pacing was significantly lower in the device-detected AF group than in the no-AF group (42.1% vs. 75.2%, p=0.009). The devicedetected AF group had a higher incidence of HF hospitalization, cardiovascular death, and all-cause death than the no-AF group. The device-detected AF and previous AF groups showed no significant differences regarding the percentage of BiV pacing and clinical outcomes. @*Conclusions@#For HF patients implanted with CRT, device-detected AF was associated with lower optimal BiV pacing and worse clinical outcomes than no-AF.

Genetic Variants Associated with Adverse Events after Angiotensin-Converting Enzyme Inhibitor Use: Replication after GWAS-Based Discovery

Purpose@#Angiotensin-converting enzyme inhibitors (ACEIs) are medications generally prescribed for patients with high cardiovascular risk; however, they are suboptimally used due to frequent adverse events (AEs). The present study aimed to identify and replicate the genetic variants associated with ACEI-related AEs in the Korean population. @*Materials and Methods@#A two-stage approach employing genome-wide association study (GWAS)-based discovery and replication through target sequencing was used. In total, 1300 individuals received ACEIs from 2001 to 2007; among these, 228 were selected for GWAS. An additional 336 patients were selected for replication after screening 1186 subjects treated from 2008 to 2018.Candidate genes for target sequencing were selected based on the present GWAS, previous GWASs, and data from the PharmGKB database. Furthermore, association analyses were performed between no AE and AE or cough groups after target sequencing. @*Results@#Five genes, namely CRIM1, NELL1, CACNA1D, VOPP1, and MYBPC1, were identified near variants associated with ACEIrelated AEs. During target sequencing of 34 candidate genes, six single-nucleotide polymorphisms (SNPs; rs5224, rs8176786, rs10766756, rs561868018, rs4974539, and rs10946364) were replicated for association with all ACEI-related AEs. Four of these SNPs and rs147912715 exhibited associations with ACEI-related cough, whereas four SNPs (rs5224, rs81767786, rs10766756, and rs4974539 near BDKRB2, NELL1, NELL1 intron, and CPN2, respectively) were significantly associated with both categories of AEs. @*Conclusion@#Several variants, including novel and known variants, were successfully replicated and found to have associations with ACEI-related AEs. These results provide rare and clinically relevant information for safer use of ACEIs.

Elevated On-Treatment Diastolic Blood Pressure and Cardiovascular Outcomes in the Presence of Achieved Systolic Blood Pressure Targets

Background and Objectives@#This study aimed to investigate the association between cardiovascular events and 2 different levels of elevated on-treatment diastolic blood pressures (DBP) in the presence of achieved systolic blood pressure targets (SBP). @*Methods@#A nation-wide population-based cohort study comprised 237,592 patients with hypertension treated. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Elevated DBP was defined according to the Seventh Report of Joint National Committee (JNC7; SBP <140 mmHg, DBP ≥90 mmHg) or to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) definitions (SBP <130 mmHg, DBP ≥80 mmHg). @*Results@#During a median follow-up of 9 years, elevated on-treatment DBP by the JNC7 definition was associated with an increased risk of the occurrence of primary endpoint compared with achieved both SBP and DBP (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 1.05–1.24) but not in those by the 2017 ACC/AHA definition. Elevated ontreatment DBP by the JNC7 definition was associated with a higher risk of cardiovascular mortality (aHR, 1.42; 95% CI, 1.18–1.70) and stroke (aHR, 1.19; 95% CI, 1.08–1.30). Elevated on-treatment DBP by the 2017 ACC/AHA definition was only associated with stroke (aHR, 1.10;95% CI, 1.04–1.16). Similar results were seen in the propensity-score-matched cohort. @*Conclusion@#Elevated on-treatment DBP by the JNC7 definition was associated a high risk of major cardiovascular events, while elevated DBP by the 2017 ACC/AHA definition was only associated with a higher risk of stroke. The result of study can provide evidence of DBP targets in subjects who achieved SBP targets.

In silico screening method for non‑responders to cardiac resynchronization therapy in patients with heart failure: a pilot study

Background@#Cardiac resynchronization therapy (CRT) is an effective treatment option for patients with heart failure (HF) and left ventricular (LV) dyssynchrony. However, the problem of some patients not responding to CRT remains unresolved. This study aimed to propose a novel in silico method for CRT simulation. @*Methods@#Three-dimensional heart geometry was constructed from computed tomography images. The finite ele‑ ment method was used to elucidate the electric wave propagation in the heart. The electric excitation and mechani‑ cal contraction were coupled with vascular hemodynamics by the lumped parameter model. The model parameters for three-dimensional (3D) heart and vascular mechanics were estimated by matching computed variables with measured physiological parameters. CRT effects were simulated in a patient with HF and left bundle branch block (LBBB). LV end-diastolic (LVEDV) and end-systolic volumes (LVESV), LV ejection fraction (LVEF), and CRT responsiveness measured from the in silico simulation model were compared with those from clinical observation. A CRT responder was defined as absolute increase in LVEF ≥ 5% or relative increase in LVEF ≥ 15%. @*Results@#A 68-year-old female with nonischemic HF and LBBB was retrospectively included. The in silico CRT simu‑ lation modeling revealed that changes in LVEDV, LVESV, and LVEF by CRT were from 174 to 173 mL, 116 to 104 mL, and 33 to 40%, respectively. Absolute and relative ΔLVEF were 7% and 18%, respectively, signifying a CRT responder.In clinical observation, echocardiography showed that changes in LVEDV, LVESV, and LVEF by CRT were from 162 to 119 mL, 114 to 69 mL, and 29 to 42%, respectively. Absolute and relative ΔLVESV were 13% and 31%, respectively, also signifying a CRT responder. CRT responsiveness from the in silico CRT simulation model was concordant with that in the clinical observation. @*Conclusion@#This in silico CRT simulation method is a feasible technique to screen for CRT non-responders in patients with HF and LBBB.

Sodium-glucose Co-transporter 2 Inhibitors: a New Path for Heart Failure Treatment

Results from cardiovascular outcome trials (CVOT) with 5 different sodium-glucose cotransporter 2 inhibitors (SGLT2i; empagliflozin, canagliflozin, dapagliflozin, ertugliflozin, sotagliflozin), initially developed for their glucose-lowering effect by blocking tubular glucose reabsorption in kidney, have been shown to decrease the risk of heart failure hospitalization (HFH) across a range of patients with and without atherosclerotic cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Following these CVOT results, SGLT2i (dapagliflozin, empagliflozin, sotagliflozin) also were reported to reduce HFH and cardiovascular death in patients with heart failure with reduced ejection fraction (HFrEF), regardless of existence or absence of T2DM. Ongoing studies have been conducted to evaluate the clinical benefit of SGLT2i (empagliflozin, dapagliflozin) in patients with heart failure with preserved ejection fraction (HFpEF). Although SGLT2i brought us to the entrance of a new era for prevention of HF incidence and worsening of HF, the search for pivotal mechanism of SGLT2i to improve our pharmacological armamentarium should continue in order to protect every HF patient from fatal progression of HF disease. In this review, we summarized the updated clinical evidences on SGLT2i (rather than basic and translational evidence) for reduction of HF risk in T2DM patients and favorable clinical outcomes in both HFrEF and HFpEF patients.

Nlrp3, Csf3, and Edn1 in Macrophage Response to Saturated Fatty Acids and Modified Low-Density Lipoprotein

Background and Objectives@#The relationship between metabolic stress, inflammation, and cardiovascular disease is being studied steadily. The aim of this study was to evaluate the effect of palmitate (PA) and minimally modified low-density lipoprotein (mmLDL) on macrophages and to identify the associated pathways. @*Methods@#J774 macrophages were incubated with PA or mmLDL and lipopolysaccharide (LPS). Secretion of inflammatory chemokines and the expression of corresponding genes were determined. The phosphorylation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase was also assessed. RNA sequencing of macrophages was performed to identify the genes regulated by PA or mmLDL. Some of the genes regulated by the 2 agents were validated by knocking down the cells using small interfering RNA. @*Results@#PA or mmLDL promoted the secretion of interleukin (IL)-6 and IL-1β in LPSstimulated macrophages, and this was accompanied by higher phosphorylation of ERK. RNA sequencing revealed dozens of genes that were regulated in this process, such as Csf3 and Edn1, which were affected by PA and mmLDL, respectively. These agents also increased Nlrp3 expression. The effect of Csf3 or Edn1 silencing on inflammation was modest, whereas toll-like receptor (TLR) 4 inhibition reduced a large proportion of macrophage activation. @*Conclusions@#We demonstrated that the proinflammatory milieu with high levels of PA or mmLDL promoted macrophage activation and the expression of associated genes such as Nlrp3, Csf3, and Edn1. Although the TLR4 pathway appeared to be most relevant, additional role of other genes in this process provided insights regarding the potential targets for intervention.

Sodium-glucose Co-transporter 2 Inhibitors: a New Path for Heart Failure Treatment

Results from cardiovascular outcome trials (CVOT) with 5 different sodium-glucose cotransporter 2 inhibitors (SGLT2i; empagliflozin, canagliflozin, dapagliflozin, ertugliflozin, sotagliflozin), initially developed for their glucose-lowering effect by blocking tubular glucose reabsorption in kidney, have been shown to decrease the risk of heart failure hospitalization (HFH) across a range of patients with and without atherosclerotic cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Following these CVOT results, SGLT2i (dapagliflozin, empagliflozin, sotagliflozin) also were reported to reduce HFH and cardiovascular death in patients with heart failure with reduced ejection fraction (HFrEF), regardless of existence or absence of T2DM. Ongoing studies have been conducted to evaluate the clinical benefit of SGLT2i (empagliflozin, dapagliflozin) in patients with heart failure with preserved ejection fraction (HFpEF). Although SGLT2i brought us to the entrance of a new era for prevention of HF incidence and worsening of HF, the search for pivotal mechanism of SGLT2i to improve our pharmacological armamentarium should continue in order to protect every HF patient from fatal progression of HF disease. In this review, we summarized the updated clinical evidences on SGLT2i (rather than basic and translational evidence) for reduction of HF risk in T2DM patients and favorable clinical outcomes in both HFrEF and HFpEF patients.

Nlrp3, Csf3, and Edn1 in Macrophage Response to Saturated Fatty Acids and Modified Low-Density Lipoprotein

Background and Objectives@#The relationship between metabolic stress, inflammation, and cardiovascular disease is being studied steadily. The aim of this study was to evaluate the effect of palmitate (PA) and minimally modified low-density lipoprotein (mmLDL) on macrophages and to identify the associated pathways. @*Methods@#J774 macrophages were incubated with PA or mmLDL and lipopolysaccharide (LPS). Secretion of inflammatory chemokines and the expression of corresponding genes were determined. The phosphorylation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase was also assessed. RNA sequencing of macrophages was performed to identify the genes regulated by PA or mmLDL. Some of the genes regulated by the 2 agents were validated by knocking down the cells using small interfering RNA. @*Results@#PA or mmLDL promoted the secretion of interleukin (IL)-6 and IL-1β in LPSstimulated macrophages, and this was accompanied by higher phosphorylation of ERK. RNA sequencing revealed dozens of genes that were regulated in this process, such as Csf3 and Edn1, which were affected by PA and mmLDL, respectively. These agents also increased Nlrp3 expression. The effect of Csf3 or Edn1 silencing on inflammation was modest, whereas toll-like receptor (TLR) 4 inhibition reduced a large proportion of macrophage activation. @*Conclusions@#We demonstrated that the proinflammatory milieu with high levels of PA or mmLDL promoted macrophage activation and the expression of associated genes such as Nlrp3, Csf3, and Edn1. Although the TLR4 pathway appeared to be most relevant, additional role of other genes in this process provided insights regarding the potential targets for intervention.

Novel Associations between Related Proteins and Cellular Effects of High-Density Lipoprotein

BACKGROUND AND OBJECTIVES: Recent studies have examined the structure-function relationship of high-density lipoprotein (HDL). This study aimed to identify and rank HDL-associated proteins involved in several biological function of HDL.METHODS: HDLs isolated from 48 participants were analyzed. Cholesterol efflux capacity, effect of HDL on nitric oxide production, and vascular cell adhesion molecule-1 expression were assessed. The relative abundance of identified proteins in the highest vs. lowest quartile was expressed using the normalized spectral abundance factor ratio.RESULTS: After adjustment by multiple testing, six proteins, thyroxine-binding globulin, alpha-1B-glycoprotein, plasma serine protease inhibitor, vitronectin, angiotensinogen, and serum amyloid A-4, were more abundant (relative abundance ratio ≥2) in HDLs with the highest cholesterol efflux capacity. In contrast, three proteins, complement C4-A, alpha-2-macroglobulin, and immunoglobulin mu chain C region, were less abundant (relative abundance ratio <0.5). In terms of nitric oxide production and vascular cell adhesion molecule-1 expression, no proteins showed abundance ratios ≥2 or <0.5 after adjustment. Proteins correlated with the functional parameters of HDL belonged to diverse biological categories.CONCLUSIONS: In summary, this study ranked proteins showing higher or lower abundance in HDLs with high functional capacities and newly identified multiple proteins linked to cholesterol efflux capacity.

Novel Associations between Related Proteins and Cellular Effects of High-Density Lipoprotein

BACKGROUND AND OBJECTIVES@#Recent studies have examined the structure-function relationship of high-density lipoprotein (HDL). This study aimed to identify and rank HDL-associated proteins involved in several biological function of HDL.@*METHODS@#HDLs isolated from 48 participants were analyzed. Cholesterol efflux capacity, effect of HDL on nitric oxide production, and vascular cell adhesion molecule-1 expression were assessed. The relative abundance of identified proteins in the highest vs. lowest quartile was expressed using the normalized spectral abundance factor ratio.@*RESULTS@#After adjustment by multiple testing, six proteins, thyroxine-binding globulin, alpha-1B-glycoprotein, plasma serine protease inhibitor, vitronectin, angiotensinogen, and serum amyloid A-4, were more abundant (relative abundance ratio ≥2) in HDLs with the highest cholesterol efflux capacity. In contrast, three proteins, complement C4-A, alpha-2-macroglobulin, and immunoglobulin mu chain C region, were less abundant (relative abundance ratio <0.5). In terms of nitric oxide production and vascular cell adhesion molecule-1 expression, no proteins showed abundance ratios ≥2 or <0.5 after adjustment. Proteins correlated with the functional parameters of HDL belonged to diverse biological categories.@*CONCLUSIONS@#In summary, this study ranked proteins showing higher or lower abundance in HDLs with high functional capacities and newly identified multiple proteins linked to cholesterol efflux capacity.

Cohort Profile: Firefighter Research on the Enhancement of Safety and Health (FRESH), a Prospective Cohort Study on Korean Firefighters

40 years or new hires with less than 1 year of service.

Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin

Objective@#The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. @*Methods@#One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. @*Results@#After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (−45.5%±19.9% and −45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p=0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p=0.79). The percentage change in the other lipid profiles was not significantly different. Although generic- and proprietary rosuvastatins modestly affected creatine kinase and blood pressure, respectively, the changes were all within normal ranges. Incidence of adverse events did not differ between the receivers of the 2 formulations. @*Conclusion@#The new generic rosuvastatin was non-inferior to the proprietary rosuvastatin in terms of lipid-lowering efficacy. The rosuvastatin formulations did not exhibit clinically significant non-lipid effects with good safety profiles. Our study provides comprehensive data regarding 2 rosuvastatin formulations in East Asian subjects.

Effect of Niacin on Carotid Atherosclerosis in Patients at Low-Density Lipoprotein-Cholesterol Goal but High Lipoprotein (a) Level: a 2-Year Follow-Up Study

OBJECTIVE: To examine the effect of niacin on the progression of carotid intima-media thickness (IMT) in patients with high level of lipoprotein (Lp) (a). METHODS: Patients at low-density lipoprotein-cholesterol goal but with Lp (a) >25 mg/dL and mean carotid IMT >0.75 mm were included. Eligible patients were randomized at a 1:2 ratio into one of two groups for 24 months: control or 1,500 mg extended release niacin. The primary study outcomes were the percentage changes in mean and maximal carotid IMT. The percentage change in lipid profiles including Lp (a) was analyzed as a secondary study outcome. RESULTS: Among 96 randomized patients, 31 completed the study (mean age: 65 years; male: 44%). At follow-up, the percentage change in mean carotid IMT was not significantly different between the two groups (−1.4%±15.5% and −1.1%±7.3% in the control and niacin groups, respectively, p=0.95). The percentage change in maximal carotid IMT was also similar in the two groups (0.7%±16.5% and −4.4%±11.6%, respectively, p=0.35). Elevation of high-density lipoprotein-cholesterol tended to be higher in the niacin group (p=0.07), and there was a significant difference in the percentage change in hemoglobin A1c between the two groups (−1.9%±2.2% and 3.3%±6.7%, respectively, p=0.02). Reduction of Lp (a) was greater in the niacin-treated group compared to placebo, but the difference was not statistically significant. CONCLUSION: Treatment with niacin for two years did not inhibit the progression of carotid intima-media thickening in patients with high Lp (a) level. However, this study may have been underpowered to evaluate the primary study outcome.

Screening, Diagnosis, and Treatment of Familial Hypercholesterolemia: Symposium of the Education Committee, Korean Society of Lipid and Atherosclerosis

Familial hypercholesterolemia (FH) is typically associated with single gene mutation that is inherited by autosomal dominant manner. Due to high cardiovascular risk, aggressive discovery, diagnosis, and treatment of FH are critical. Although FH is being increasingly spotlighted, we do not have sufficient data on Korean patients with FH. Here, we present the content of symposium of the Education Committee, Korean Society of Lipid and Atherosclerosis held in May 2018: 1) epidemiology, clinical diagnosis, Korean FH data, and regulation in Korea; 2) genes associated with FH, sequencing process in suspicious proband, cascade screening, and difficulty in genetic diagnosis in FH; 3) the importance of lipid-lowering therapy in FH, conventional and novel therapeutics for FH; 4) diagnosis of FH in children and adolescence, screening, and treatment of FH in children and adolescence; 5) history of FH studies in Korea, the structure and current status of FH registry of Korean Society of Lipid and Atherosclerosis; and 6) difficulty in diagnosis of heterozygous and homozygous FH, drug intolerance and achievement of treatment target. Discussion between speakers and panels were also added. We hope that this article is helpful for understanding FH and future studies performed in Korea.

The Effects of Diet Alone or in Combination with Exercise in Patients with Prehypertension and Hypertension: a Randomized Controlled Trial

BACKGROUND AND OBJECTIVES: Supervised lifestyle interventions, including dietary and exercise programs, may be infeasible to implement in real-world settings. Therefore, this study aimed to evaluate the effectiveness of a home-based lifestyle modification intervention on blood pressure (BP) management. METHODS: Eighty-five patients aged over 20 years and diagnosed with prehypertension or mild hypertension were randomly assigned to an advice-only comparison group (C group, n=28), a Dietary Approaches to Stop Hypertension (DASH) diet education group (D group, n=30), or a DASH and home-based exercise group (D+Ex group, n=27). The intervention lasted for 8 weeks. The primary outcome was the difference in office systolic blood pressure (SBP) before and after the study period (Trial registry at ClinicalTrials.gov, NCT01637909). RESULTS: Seventy-two participants (87.8%) completed the trial. The degree of change in office SBP did not significantly differ among the intervention groups; however, the D+Ex group demonstrated a tendency toward decreased SBP. Upon analysis of 24-hour ambulatory BP measurements, daytime ambulatory SBP was significantly lower in the D+Ex group (134 mmHg; 95% confidence interval [CI], 131 to 137; p=0.011) than in the C group (139.5 mmHg; 95% CI, 130.9 to 137), and daytime ambulatory SBP was significantly decreased in the D+Ex group (−5.2 mmHg; 95% CI, −8.3 to −2.1; p=0.011) compared to the C group (0.4 mmHg, 95% CI, −2.5 to 3.3). CONCLUSIONS: In conclusion, lifestyle modification emphasizing both diet and exercise was effective for lowering BP and should be favored over diet-only modifications.

Variants of Lipolysis-Related Genes in Korean Patients with Very High Triglycerides

We investigated the prevalence and characteristics of variants of five lipolysis-related genes in Korean patients with very high triglycerides (TGs). Twenty-six patients with TG levels >885 mg/dL were selected from 13545 Korean subjects. Five candidate genes, LPL, APOC2, GPIHBP1, APOA5, and LMF1, were sequenced by targeted next-generation sequencing. Predictions of functional effects were performed and matched against public databases of variants. Ten rare variants of three genes were found in nine (34.6%) patients (three in LPL, four in APOA5, and three in LMF1). Five were novel and all variants were suspected of being disease-causing. Nine were heterozygous, and one (3.8%) had a homozygous rare variant of LPL. Six common variants of four genes were observed in 25 (96.2%) patients (one in LPL, one in GPIHBP1, two in APOA5, and two in LMF1). The c.G41T variant of GPIHBP1 and c.G533T variant of APOA5 were most frequent and found in 15 (57.7%) and 14 (53.8%) patients, respectively. Rare homozygous variants of the genes were very uncommon, while diverse rare heterozygous variants were commonly identified. Taken together, most study subjects may be manifesting the combined effects of rare heterozygous variants and common variants.

Comparison of the Effects of Ezetimibe-Statin Combination Therapy on Major Adverse Cardiovascular Events in Patients with and without Diabetes: A Meta-Analysis

BACKGROUND: Ezetimibe-statin combination therapy has been found to reduce low density lipoprotein cholesterol levels and the risk of major adverse cardiovascular events (MACEs) in large trials. We sought to examine the differential effect of ezetimibe on MACEs when added to statins according to the presence of diabetes. METHODS: Randomized clinical trials with a sample size of at least 50 participants and at least 24 weeks of follow-up that compared ezetimibe-statin combination therapy with a statin- or placebo-controlled arm and reported at least one MACE, stratified by diabetes status, were included in the meta-analysis and meta-regression. RESULTS: A total of seven trials with 28,191 enrolled patients (mean age, 63.6 years; 75.1% men; 7,298 with diabetes [25.9%]; mean follow-up, 5 years) were analysed. MACEs stratified by diabetes were obtained from the published data (two trials) or through direct contact (five trials). No significant heterogeneity was observed among studies (I 2=14.7%, P=0.293). Ezetimibe was associated with a greater reduction of MACE risk in subjects with diabetes than in those without diabetes (pooled relative risk, 0.84 vs. 0.93; P heterogeneity=0.012). In the meta-regression analysis, the presence of diabetes was associated with a greater reduction of MACE risk when ezetimibe was added to statins (β=0.87, P=0.038). CONCLUSION: Ezetimibe-statin combination therapy was associated with greater cardiovascular benefits in patients with diabetes than in those without diabetes. Our findings suggest that ezetimibe-statin combination therapy might be a useful strategy in patients with diabetes at a residual risk of MACEs.

The Effects of Diet Alone or in Combination with Exercise in Patients with Prehypertension and Hypertension: a Randomized Controlled Trial

BACKGROUND AND OBJECTIVES@#Supervised lifestyle interventions, including dietary and exercise programs, may be infeasible to implement in real-world settings. Therefore, this study aimed to evaluate the effectiveness of a home-based lifestyle modification intervention on blood pressure (BP) management.@*METHODS@#Eighty-five patients aged over 20 years and diagnosed with prehypertension or mild hypertension were randomly assigned to an advice-only comparison group (C group, n=28), a Dietary Approaches to Stop Hypertension (DASH) diet education group (D group, n=30), or a DASH and home-based exercise group (D+Ex group, n=27). The intervention lasted for 8 weeks. The primary outcome was the difference in office systolic blood pressure (SBP) before and after the study period (Trial registry at ClinicalTrials.gov, NCT01637909).@*RESULTS@#Seventy-two participants (87.8%) completed the trial. The degree of change in office SBP did not significantly differ among the intervention groups; however, the D+Ex group demonstrated a tendency toward decreased SBP. Upon analysis of 24-hour ambulatory BP measurements, daytime ambulatory SBP was significantly lower in the D+Ex group (134 mmHg; 95% confidence interval [CI], 131 to 137; p=0.011) than in the C group (139.5 mmHg; 95% CI, 130.9 to 137), and daytime ambulatory SBP was significantly decreased in the D+Ex group (−5.2 mmHg; 95% CI, −8.3 to −2.1; p=0.011) compared to the C group (0.4 mmHg, 95% CI, −2.5 to 3.3).@*CONCLUSIONS@#In conclusion, lifestyle modification emphasizing both diet and exercise was effective for lowering BP and should be favored over diet-only modifications.

Bioptome Perforation at Superior Vena Cava Anastomosis Site in Transplanted Heart

No abstract available.

The Impact of Diabetes Mellitus on Vascular Biomarkers in Patients with End-Stage Renal Disease

PURPOSE: Diabetes mellitus (DM) is the most common cause of end-stage renal disease (ESRD) and an important risk factor for cardiovascular (CV) disease. We investigated the impact of DM on subclinical CV damage by comprehensive screening protocol in ESRD patients. MATERIALS AND METHODS: Echocardiography, coronary computed tomography angiogram, 24-h ambulatory blood pressure monitoring, and central blood pressure with pulse wave velocity (PWV) were performed in 91 ESRD patients from the Cardiovascular and Metabolic disease Etiology Research Center-HIgh risk cohort. RESULTS: The DM group (n=38) had higher systolic blood pressure than the non-DM group (n=53), however, other clinical CV risk factors were not different between two groups. Central aortic systolic pressure (148.7±29.8 mm Hg vs. 133.7±27.0 mm Hg, p= 0.014), PWV (12.1±2.7 m/s vs. 9.4±2.1 m/s, p<0.001), and early mitral inflow to early mitral annulus velocity (16.7±6.4 vs. 13.7±5.9, p=0.026) were higher in the DM group. Although the prevalence of coronary artery disease (CAD) was not different between the DM and the non-DM group (95% vs. 84.4%, p=0.471), the severity of CAD was higher in the DM group (p=0.01). In multivariate regression analysis, DM was an independent determinant for central systolic pressure (p=0.011), PWV (p<0.001) and the prevalence of CAD (p=0.046). CONCLUSION: Diabetic ESRD patients have higher central systolic pressure and more advanced arteriosclerosis than the non-DM control group. These findings suggest that screening for subclinical CV damage may be helpful for diabetic ESRD patients.