Influence of Socioeconomic Status on the Presence of Obstructive Coronary Artery Disease and Cardiovascular Outcomes in Patients Undergoing Invasive Coronary Angiography.

This retrospective study investigated the impact of socioeconomic status (SES) on patients at high risk of cardiovascular disease, focusing on obstructive coronary artery disease (CAD) presence and long-term cardiovascular outcomes in individuals undergoing invasive coronary angiography (ICA). Analyzing data from 9530 patients categorized by health insurance type (medical aid beneficiaries (MABs) as the low SES group; national health insurance beneficiaries (NHIBs) as the high SES group), this research explores the relationship between SES and outcomes. Despite a higher prevalence of cardiovascular risk factors, the MAB group exhibited similar rates of obstructive CAD compared to the NHIB group. However, over a median 3.5-year follow-up, the MAB group experienced a higher incidence of composite cardiovascular events, including cardiac death, acute myocardial infarction, coronary revascularization, and ischemic stroke, compared with the NHIB group (20.2% vs. 16.2%, p < 0.001). Multivariable Cox regression analysis, adjusting for potential confounders, revealed independently worse clinical outcomes for the MAB group (adjusted odds ratio 1.28; 95% confidence interval 1.07-1.54; p = 0.006). Despite comparable CAD rates, this study underscores the fact that individuals with low SES encounter an elevated risk of composite cardiovascular events, emphasizing the association between socioeconomic disadvantage and heightened susceptibility to cardiovascular disease, even among those already at high risk.

New onset diabetes mellitus and cardiovascular outcomes according to statin intensity in patients after drug-eluting stent implantation in Asian patients.

We investigated the effect of statin intensity on the development of new onset diabetes mellitus (NODM) in Korean patients after percutaneous coronary intervention (PCI). A total of 1013 consecutive patients without diabetes mellitus were retrospectively analyzed. All study patients received high- or moderate-intensity statin (high-intensity statin; 321 [31.7%], moderate-intensity statin; 692 [68.3%]). The primary endpoint was development of NODM, and the secondary one was the composite of cardiac death, non-fatal myocardial infarction, and any revascularization. In 264 pairs (528 patients) of propensity score-matched patient, NODM developed in 34 patients (6.4%) and composite cardiac events occurred in 73 patients (13.8%) during a median follow-up of 36.7 months. The incidence rate of NODM was significantly higher in patients with high-intensity statin than with moderate-intensity statin (8.3% vs. 4.5%, log-rank P = 0.026). The incidence rate of composite events was not significantly different between the two groups (12.5% vs.15.2%, log-rank P = 0.495). The use of high-intensity statins was associated with NODM after adjustment for multiple risk factors (adjusted hazard ratio, 2.18, 95% confidence interval 1.10‒4.51, P = 0.025). High-intensity statin therapy is associated with a higher incidence of NODM, but not with better cardiovascular outcomes, in Korean patients undergoing PCI. A new cholesterol lowering intensity-based approach rather than stain intensity-based approach to the high-risk patients without diabetes mellitus may be helpful in maximal treatment effect without safety concern of NODM in Asian patients.

Arterial stiffness and its associations with left ventricular diastolic function according to heart failure types.

BACKGROUND: Little is known about the characteristics of arterial stiffness in heart failure (HF). This study was performed to compare the degree of arterial stiffness and its association with left ventricular (LV) diastolic function among three groups: control subjects, patients with HF with reduced ejection fraction (HFrEF), and patients with HF with preserved ejection fraction (HFpEF). METHODS: A total of 83 patients with HFrEF, 68 patients with HFpEF, and 84 control subjects were analyzed. All HF patients had a history of hospitalization for HF treatment. Brachial-ankle pulse wave velocity (baPWV) measurement and transthoracic echocardiography were performed at the same day in a stable condition. RESULTS: The baPWV was significantly higher in patients with both HFrEF and HFpEF compared to control subjects (1,661 ± 390, 1,909 ± 466, and 1,477 ± 296 cm/sec, respectively; P < 0.05 for each). After adjustment of age, baPWV values were similar between patients with HFrEF and HFpEF (P = 0.948). In the multiple linear regression analysis, baPWV was significantly associated with both septal e' velocity (ß = -0.360, P = 0.001) and E/e' (ß = 0.344, P = 0.001). However, baPWV was not associated with either of the diastolic indices in HFrEF group. The baPWV was associated only with septal e' velocity (ß = -0.429, P = 0.002) but not with E/e' in the HFpEF group in the same multivariable analysis. CONCLUSIONS: Although arterial stiffness was increased, its association with LV diastolic function was attenuated in HF patients compared to control subjects. The degree of arterial stiffening was similar between HFrEF and HFpEF.

Rational design of Lewis base molecules for stable and efficient inverted perovskite solar cells.

Lewis base molecules that bind undercoordinated lead atoms at interfaces and grain boundaries (GBs) are known to enhance the durability of metal halide perovskite solar cells (PSCs). Using density functional theory calculations, we found that phosphine-containing molecules have the strongest binding energy among members of a library of Lewis base molecules studied herein. Experimentally, we found that the best inverted PSC treated with 1,3-bis(diphenylphosphino)propane (DPPP), a diphosphine Lewis base that passivates, binds, and bridges interfaces and GBs, retained a power conversion efficiency (PCE) slightly higher than its initial PCE of ~23% after continuous operation under simulated AM1.5 illumination at the maximum power point and at ~40°C for >3500 hours. DPPP-treated devices showed a similar increase in PCE after being kept under open-circuit conditions at 85°C for >1500 hours.

Clinical Utility of Prostate Health Index for Diagnosis of Prostate Cancer in Patients with PI-RADS 3 Lesions.

The risk of prostate cancer (PCa) in prostate imaging reporting and data system version 2 (PI-RADSv2) score-3 lesions is equivocal; it is regarded as an intermediate status of presented PCa. In this study, we evaluated the clinical utility of the prostate health index (PHI) for the diagnosis of PCa and clinically significant PCa (csPCa) in patients with PI-RADSv2 score-3 lesions. The study cohort included patients who underwent a transrectal ultrasound (TRUS)-guided, cognitive-targeted biopsy for PI-RADSv2 score-3 lesions between November 2018 and April 2021. Before prostate biopsy, the prostate-specific antigen (PSA) derivatives, such as total PSA (tPSA), [-2] proPSA (p2PSA) and free PSA (fPSA) were determined. The calculation equation of PHI is as follows: [(p2PSA/fPSA) × tPSA ½]. Using a receiver operating characteristic (ROC) curve analysis, the values of PSA derivatives measured by the area under the ROC curve (AUC) were compared. For this study, csPCa was defined as Gleason grade 2 or higher. Of the 392 patients with PI-RADSv2 score-3 lesions, PCa was confirmed in 121 (30.9%) patients, including 59 (15.1%) confirmed to have csPCa. Of all the PSA derivatives, PHI and PSA density (PSAD) showed better performance in predicting overall PCa and csPCa, compared with PSA (all p < 0.05). The AUC of the PHI for predicting overall PCa and csPCa were 0.807 (95% confidence interval (CI): 0.710−0.906, p = 0.001) and 0.819 (95% CI: 0.723−0.922, p < 0.001), respectively. By the threshold of 30, PHI was 91.7% sensitive and 46.1% specific for overall PCa, and was 100% sensitive for csPCa. Using 30 as a threshold for PHI, 34.4% of unnecessary biopsies could have been avoided, at the cost of 8.3% of overall PCa, but would include all csPCa.

Utility of Contemporary Health Screening in the Diagnosis of Bladder Cancer.

BACKGROUND: To evaluate the utility of contemporary health screening (HS) in the diagnosis of bladder cancer (BCa). METHODS: We retrospectively reviewed 279,683 individuals who underwent HS between February 1995 and April 2015. Among these individuals, 74 were diagnosed with BCa within a year after the HS and were included in the analysis. Screen-detected BCa was defined as when a referral was made to a urologist due to microscopic hematuria (MH) on urinalysis, abnormal imaging, or any urological symptoms observed at the HS. Screen-undetected BCa was defined as when no referral was made to a urologist because of no abnormality observed at the HS, but a visit to a urological outpatient clinic later was followed by a BCa diagnosis. The incidences of screen-detected BCa and BCa in the Korean population were compared. Clinicopathological characteristics were compared between the screen-detected BCa and screen-undetected BCa groups. RESULTS: The detection rate of BCa was 17.2 per 100,000, which exceeded the 2020 estimated national crude incidence rate of 9.3 per 100,000 by approximately 1.7 times. Among the 74 patients diagnosed with BCa within a year after HS, 48 (64.9%) had screen-detected BCa. The screen-detected BCa group had a higher T stage (p = 0.009) and grade (p = 0.019) than the screen-undetected BCa group. However, the overall survival was not significantly different between the two groups (p = 0.677). A positive correlation between the MH grade and the T stage was identified (p = 0.001). CONCLUSION: Although HS is not focused on BCa screening, contemporary HS can contribute to the detection of BCa.

Expression and Prognostic Implication of PD-L1 in Patients with Urothelial Carcinoma with Variant Histology (Squamous Differentiation or Micropapillary) Undergoing Radical Cystectomy.

The expression and prognostic role of programmed death ligand-1 (PD-L1) on tumor-infiltrating immune cells (TICs) has not been determined in urothelial carcinoma (UC) with variant histology. We retrospectively reviewed 90 patients (44 with micropapillary variant of UC (MPUC) and 46 with UC with squamous differentiation (UCSD)) who underwent radical cystectomy between January 2013 and December 2019. The expression of PD-L1 in TICs was measured using the VENTANA (SP-142) immunohistochemistry assay and dichotomized using a 5% cutoff value (positive ≥ 5%). Kaplan-Meier survival analysis was used to estimate recurrence-free survival (RFS), and multivariable Cox proportional hazard models were used to identify factors predicting tumor recurrence. Overall, positive PD-L1 expression in TICs was confirmed in 50 of 90 (55.6%) patients (40.1% (18/44) of MPUC and 69.9% (32/46) of UCSD). RFS was significantly shorter in patients with positive PD-L1 expression in TICs than in those with negative PD-L1 expression both in MPUC (p = 0.005) and UCSD (p = 0.046). Positive PD-L1 expression in TICs was significantly associated with an increased risk of tumor recurrence in both MPUC (HR = 1.85; 95% CI: 1.323-2.672; p = 0.017) and UCSD (HR = 1.58; 95% CI: 1.162-2.780; p = 0.032). In conclusion, positive PD-L1 expression in TICs was significantly associated with poorer RFS in both MPUC and UCSD patients. Our results support the use of adjuvant immunotherapy in these patients if they test positive for PD-L1 in their TICs.

Lifestyle Modification in the Management of Metabolic Syndrome: Statement From Korean Society of CardioMetabolic Syndrome (KSCMS).

With the recent rapid increase in obesity worldwide, metabolic syndrome (MetS) has gained significant importance. MetS is a cluster of obesity-related cardiovascular risk factors including abdominal obesity, atherogenic dyslipidemia, high blood pressure and impaired glucose tolerance. MetS is highly prevalent and strongly associated with an increased risk of developing diabetes and cardiovascular disease, putting a great burden on human society. Therefore, it is very important to reduce MetS risk, which can improve patients' cardiovascular prognosis. The primary and most effective strategy to control each component of MetS is lifestyle change such as losing body weight, keeping regular exercise, adopting a healthy diet, quitting smoking and alcohol drinking in moderation. Many studies have shown that lifestyle modification has improved all components of MetS, and reduces the incidence of diabetes and cardiovascular disease. Here, the Korean Society of CardioMetabolic Syndrome has summarized specific and practical methods of lifestyle modification in the management of MetS in the healthcare field.

Preoperative versus Postoperative Compensation of the Contralateral Normal Kidney in Patients Treated with Radical Nephrectomy for Renal Cell Carcinoma.

BACKGROUND: We sought to identify the factors affecting renal compensatory processes that occur preoperatively as well as postoperatively in patients treated with radical nephrectomy (RNx) for renal cell carcinoma (RCC). METHODS: We retrospectively reviewed the records of 906 patients treated with RNx for RCC. We defined the early compensatory process (process 1) as compensatory adaptation of the contralateral normal kidney (CNK) before RNx. We defined the late compensatory process (process 2) as compensatory adaptation of the CNK after RNx. Total compensation was defined as the combination of these two processes. Multivariable logistic regression analyses were used to identify significant factors associated with processes 1, 2 and total compensation. RESULTS: Mean preoperative, 1-week, and 5-year postoperative estimated glomerular filtration rates (eGFR) were 84.5, 57.6 and 63.7 mL/min/1.73 m2, respectively. Female sex (p < 0.001), lower body mass index (BMI) (p < 0.001), absence of hypertension (p = 0.019), lower preoperative eGFR (p < 0.001), larger tumor volume (p < 0.001), and larger CNK volume (p < 0.001) were significantly associated with process 1. Younger age (p = 0.019), higher BMI (p < 0.001), and absence of diabetes mellitus (DM) (p = 0.033) were significantly associated with process 2. Female sex (p < 0.001), younger age (p < 0.001), absence of DM (p = 0.002), lower preoperative eGFR (p < 0.001), and larger tumor (p = 0.001) and CNK volumes (p < 0.001) were significantly associated with total compensation. CONCLUSIONS: Different factors affected each compensatory process. Process 1 made a greater contribution to the entire renal compensatory process than process 2.

Association between histological severity of Helicobacter pylori infection and cardiovascular risk scores in the Korean population.

BACKGROUND AND AIMS: Although there have been several reports on the association between Helicobacter pylori (HP) infection and cardiovascular disease (CVD), most studies have been done through noninvasive testing such as serologic test or urea breath test. This study investigated the relationship between histological features of HP gastritis and cardiovascular risk scores. METHODS: A total of 21,251 subjects (mean age, 43.8 ± 9.6 years; males, 72.1%) who underwent routine health checkup and gastric biopsy were retrospectively analyzed. The severity of gastritis was assessed using the updated Sydney system (USS). With four different risk predicting algorithms, we calculated Framingham coronary heart disease (CHD) risk score, ATP III revised Framingham CHD risk score, generalized Framingham risk against total CVD, and ACC/AHA 10-year risk of a first hard atherosclerotic-CVD event in each subject. RESULTS: About half of the study subjects (51.2%, n = 10,890) were confirmed to have HP infection. Subjects with HP infection were younger (42.9 ± 9.0 vs. 44.7 ± 10.2 years, p < 0.001) than those without. After adjustment for age, most of the estimated 10-year cardiovascular risk increased as the grade of USS elements increased. As the sum of the USS scores increased, all the 4 estimated 10-year cardiovascular risk scores increased proportionally (p < 0.05 for each). CONCLUSIONS: The histological features of gastritis assessed using USS were associated with various cardiovascular risk scores. This study provides strong evidence on an association between chronic inflammation and increased cardiovascular risk.

Proposal of a New Prognostic Model for Differentiated Thyroid Cancer with TERT Promoter Mutations.

The role of telomerase reverse transcriptase (TERT) promoter mutations as an independent poor prognostic factor in differentiated thyroid cancer (DTC) patients is well known, but there is no prognostic system that combines the TERT promoter mutation status with tumor-node-metastasis (TNM) stage to predict cancer-specific survival (CSS). A total of 393 patients with pathologically confirmed DTC after thyroidectomy were enrolled. After incorporating wild-type TERT and mutant TERT with stages I, II, and III/IV of the AJCC TNM system 8th edition (TNM-8), we generated six combinations and calculated 10-year and 15-year CSS and adjusted hazard ratios (HRs) for cancer-related death using Cox regression. Then, a new mortality prediction model termed TNM-8T was derived based on the CSS and HR of each combination in the four groups. Of the 393 patients, there were 27 (6.9%) thyroid cancer-related deaths during a median follow-up of 14 years. Patients with a more advanced stage had a lower survival rate (10-year CSS for TNM-8T stage 1, 2, 3, and 4: 98.7%, 93.5%, 77.3%, and 63.0%, respectively; p < 0.001). TNM-8T showed a better spread of CSS (p < 0.001) than TNM-8 (p = 0.002) in the adjusted survival curves. The C-index for mortality risk predictability was 0.880 (95% CI, 0.665-0.957) in TNM-8T and 0.827 (95% CI, 0.622-0.930) in TNM-8 (p < 0.001). TNM-8T, a new prognostic system that incorporates the TERT mutational status into TNM-8, showed superior predictability to TNM-8 in the long-term survival of DTC patients.

Tips and Tricks for Safe Retrieval of Tine-based Leadless Pacemakers.

As leadless pacing (LP) use is expected to increase, it becomes increasingly essential that operators become familiar with the tools and techniques needed to retrieve an LP successfully. The purpose of this review is to describe a stepwise approach for the successful retrieval of tine-based LP devices, including ways to minimize complications.

Association between household income and pulse pressure: data from the Korean National Health and Nutrition Examination Survey.

PURPOSE: There has been limited evidence for the association between socioeconomic status (SES) and arterial stiffness. This study was performed to investigate the association between household income and brachial pulse pressure (PP) in the general Korean population. MATERIALS AND METHODS: This study was based on data acquired in the 2018 Korea National Health and Nutrition Examination Survey (2018 KNHANES). A total of 13004 subjects at the age of 20 years or older analysed. The information on monthly household income was obtained through the questionnaire, and was stratified into 5 groups for each quintile. Brachial blood pressure (BP) was measured 3 times, and the average of the second and third measured BPs were used. PP was calculated as the difference between systolic and diastolic BPs. RESULTS: A lower household income was associated with a higher prevalence of cardiovascular risk factors. As household income increased, PP decreased proportionally (p < .001). In multiple linear regression analysis, household income (per quintile) was independently associated with PP even after controlling for potential confounders (ß = -.125, p < .001). Multiple binary logistic regression analysis showed that the increased household income level was significantly associated lower probability having higher PP (≥ 43.5 mmHg) even after controlling for multiple covariates (the lowest vs. the highest household income; odds ratio, 0.48; 95% confidence interval, .41-.55; p < .001). CONCLUSION: Low household income was associated with higher PP. This provides additional evidence for the association between low SES and high arterial stiffness.

Comparison of Four Ultrasonography-Based Risk Stratification Systems in Thyroid Nodules with Nondiagnostic/Unsatisfactory Cytology: A Real-World Study.

We compared American Thyroid Association (ATA) guidelines, Korean (K)-Thyroid Imaging, Reporting and Data Systems (TIRADS), EU-TIRADS, and American College of Radiology (ACR) TIRADS in diagnosing malignancy for thyroid nodules with nondiagnostic/unsatisfactory cytology. Among 1143 nondiagnostic/unsatisfactory aspirations from April 2011 to March 2016, malignancy was detected in 39 of 89 excised nodules. The minimum malignancy rate was 7.82% in EU-TIRADS 5 and 1.87-3.00% in EU-TIRADS 3-4. In the other systems, the minimum malignancy rate was 14.29-16.19% in category 5 and ≤3% in the remaining categories. Although the EU-TIRADS category ≥ 5 exhibited the highest positive likelihood ratio (LR) of only 2.214, category ≥ 5 in the other systems yielded the highest positive LR of >5. Receiver operating characteristic (ROC) curves of all systems to predict malignancy were located statistically above the diagonal nondiscrimination line (P for ROC curve: EU-TIRADS, 0.0022; all others, 0.0001). The areas under the ROC curve (AUCs) were not significantly different among the four systems. The ATA guidelines, K-TIRADS, and ACR TIRADS may be useful to guide management for nondiagnostic/unsatisfactory nodules. The EU-TIRADS, although also useful, exhibited inferior performance in predicting malignancy for nondiagnostic/unsatisfactory nodules in Korea, an iodine-sufficient area.

Prognostic Value of the Neutrophil-to-Lymphocyte Ratio before and after Radiotherapy for Anaplastic Thyroid Carcinoma.

The neutrophil-lymphocyte ratio (NLR) is a marker of systemic inflammation, and its elevation has recently been associated with poor survival in many solid cancers. Leukocyte elevation and lymphocyte reduction are associated with a poor response to radiotherapy (RT). This study aimed to assess the prognostic value of NLR before and after RT for anaplastic thyroid carcinoma (ATC). This retrospective study analyzed 40 patients with ATC who received RT with available complete blood cell count data from November 1995 through May 2020 at Samsung Medical Center (Seoul, Korea). Patients were classified into two groups according to the NLR before and after RT. The median overall survival (OS) was 8.9 months (range, 3.5-18.2) in the low NLR group (<3.47) and 5.2 months (range, 2.7-7.5) months in the high NLR group (≥3.47). The association between NLR and OS was also observed in multivariable Cox regression analysis (hazard ratio, 3.18; 95% confidence interval, 1.15-8.85; p = 0.026). The OS curves differed significantly according to post-RT NLR (p = 0.036). A high NLR before and after RT may be significantly associated with poor OS in patients with ATC who receive RT.

Impact of etiology on force and kinetics of left ventricular end-stage failing human myocardium.

BACKGROUND: Heart failure (HF) is associated with highly significant morbidity, mortality, and health care costs. Despite the significant advances in therapies and prevention, HF remains associated with poor clinical outcomes. Understanding the contractile force and kinetic changes at the level of cardiac muscle during end-stage HF in consideration of underlying etiology would be beneficial in developing targeted therapies that can help improve cardiac performance. OBJECTIVE: Investigate the impact of the primary etiology of HF (ischemic or non-ischemic) on left ventricular (LV) human myocardium force and kinetics of contraction and relaxation under near-physiological conditions. METHODS AND RESULTS: Contractile and kinetic parameters were assessed in LV intact trabeculae isolated from control non-failing (NF; n = 58) and end-stage failing ischemic (FI; n = 16) and non-ischemic (FNI; n = 38) human myocardium under baseline conditions, length-dependent activation, frequency-dependent activation, and response to the ß-adrenergic stimulation. At baseline, there were no significant differences in contractile force between the three groups; however, kinetics were impaired in failing myocardium with significant slowing down of relaxation kinetics in FNI compared to NF myocardium. Length-dependent activation was preserved and virtually identical in all groups. Frequency-dependent activation was clearly seen in NF myocardium (positive force frequency relationship [FFR]), while significantly impaired in both FI and FNI myocardium (negative FFR). Likewise, ß-adrenergic regulation of contraction was significantly impaired in both HF groups. CONCLUSIONS: End-stage failing myocardium exhibited impaired kinetics under baseline conditions as well as with the three contractile regulatory mechanisms. The pattern of these kinetic impairments in relation to NF myocardium was mainly impacted by etiology with a marked slowing down of kinetics in FNI myocardium. These findings suggest that not only force development, but also kinetics should be considered as a therapeutic target for improving cardiac performance and thus treatment of HF.

Long-term efficacy of vasodilating ß-blocker in patients with acute myocardial infarction: nationwide multicenter prospective registry.

BACKGROUND/AIMS: Long-term benefit of vasodilating ß-blockers is unknown. This study aimed to investigate the long-term benefit of vasodilating ß-blockers over conventional ß-blockers in patients with acute myocardial infarction (AMI). METHODS: Using nationwide prospective multicenter Korean Acute Myocardial Infarction Registry data, we analyzed 3-year clinical outcomes of 7,269 patients with AMI who received percutaneous coronary intervention (PCI) and ß-blocker therapy. Patients were classified according to treatment strategy (vasodilating ß-blockers vs. conventional ß-blockers). The primary endpoint was a composite of cardiac death, myocardial infarction (MI), and hospitalization for heart failure (HF) at 3 years. Secondary outcomes were each component of the primary outcome. Propensity score matching was performed to adjust for differences of baseline characteristics. RESULTS: In 3,079 pairs (6,158 patients) of propensity score-matched patients, the primary outcome occurred significantly less in the vasodilating ß-blockers group compared with the conventional ß-blockers group (7.6% vs. 9.8%, p = 0.003). Among the secondary outcomes, cardiac death occurred significantly less in the vasodilating ß-blockers group than in the conventional group (3.5% vs. 4.8%, p = 0.015). The incidence rates of MI (2.4% vs. 3.0%, p = 0.160) or hospitalization for HF (2.6% vs. 3.2%, p = 0.192) were not significantly different between the two groups. CONCLUSION: Vasodilating ß-blocker therapy was associated with better clinical outcomes compared with conventional ß-blocker therapy in AMI patients undergoing PCI during 3 years follow-up. Vasodilating ß-blockers could be recommended preferentially for these patients.

Association of the Serum Osteoprotegerin Level With Target Organ Damage in Patients at High Risk of Coronary Artery Disease.

BACKGROUND: There is little data as to whether osteoprotegerin (OPG) is associated with target organ damage (TOD), so we evaluated the association in patients at high risk of coronary artery disease (CAD).Methods and Results:A total of 349 patients who underwent invasive coronary angiography (ICA) for suspected CAD were prospectively recruited. During the index admission, 6 TOD parameters were collected: extent of CAD, glomerular filtration rate (GFR), left ventricular mass index (LVMI), E/e', brachial-ankle pulse wave velocity (baPWV), and ankle-brachial index (ABI). Serum OPG levels were measured using enzyme-linked immunosorbent assay. The OPG level was significantly higher in patients with ≥1 TOD parameter than in those without (314±186 vs. 202±74 pg/mL, P<0.001). For each TOD parameter, the serum OPG level was significantly higher in patients with TOD than in those without (P<0.05 for each) except for ABI. In correlation analysis, OPG was significantly associated with GFR, LVMI, E/e', baPWV and ABI (P<0.05 for each). The OPG concentration increased proportionally with increasing TOD (P<0.001). Higher OPG concentrations (≥198 pg/mL) was significantly associated with the presence of TOD (odds ratio 3.22; 95% confidence interval 1.51-6.85; P=0.002) even after controlling for potential confounders. CONCLUSIONS: Serum OPG level was significantly associated with a variety of TOD in patients undergoing ICA. OPG may be a useful marker for TOD and in the risk stratification of patients at high risk of CAD.

Pathological manifestation of the induced pluripotent stem cell-derived cortical neurons from an early-onset Alzheimer's disease patient carrying a presenilin-1 mutation (S170F).

OBJECTIVES: Alzheimer's disease (AD) is the most common neurodegenerative disease which is characterized by the formation of amyloid beta (Aß) plaques and neurofibrillary tangles. These abnormal proteins induce disturbance in mitochondrial dynamics and defect in autophagy system. Since presenilin-1 (PS1) is a core component in γ-secretase complex, the mutations of PS1 gene cause the interference of γ-secretase activity and lead to the increased Aß42 secretion. We aimed to characterize the patient-specific induced pluripotent stem cell (iPSC) line carrying PS1-S170F mutation. Furthermore, we tested whether disease-modifying drug can reduce AD pathology in the AD iPSC-derived neurons. MATERIALS AND METHODS: Mononuclear cells (MNCs) were isolated freshly from the peripheral blood of an autosomal dominant AD (ADAD) patient carrying presenilin-1 (PS1) mutation (Ser170Phe; PS1-S170F) and a cognitively normal control. We generated induced pluripotent stem cell (iPSC) lines, which were differentiated into functional cortical neurons. Then, we measured the markers indicative of AD pathogenesis using immunocytochemistry and Western blot. We also investigated the mitochondrial dynamics in the AD iPSC-derived neurons using Mito-tracker. RESULTS: We observed that both extracellular and intracellular Aß levels were dramatically increased in the PS1-S170F iPSC-derived neurons, compared with the control iPSC-derived neurons. Furthermore, PS1-S170F iPSC-derived neurons showed high expression levels of p-Tau, which were detected both in the soma and neurites. The mitochondrial velocity in the PS1-S170F iPSC-derived neurons was much reduced, compared with that of the control. We also found a significant decrease of fusion-related protein Mfn1 (membrane proteins mitofusin 1) and an increase of fission-related protein DRP1 (dynamin-related protein 1) in the PS1-S170F iPSC-derived neurons. We further observed the defects of autophagy-related clearance in the PS1-S170F iPSC-derived neurons. Finally, we demonstrated the levels of Aß and p-Tau can be dramatically reduced by the treatment of LY-2886721, a BACE1 inhibitor. CONCLUSIONS: Taken together, we have established and characterized the pathological features of an AD patient carrying PS1-S170F mutation using iPSC technology, which will be the first case on this mutation and this iPSC line will serve as a useful resource for studying AD pathogenesis and drug screening in the future.

Association between invasively measured aortic pulse pressure and orthostatic hypotension in patients undergoing invasive coronary angiography.

OBJECTIVE: Underlying pathophysiology of orthostatic hypotension has been poorly understood. We hypothesized that aortic pulse pressure (APP) reflecting aortic stiffness may be involved in the development of orthostatic hypotension. METHODS: A total of 200 patients (age 64.3 ±â€Š10.9 years, 62.5% men) who underwent invasive coronary angiography (ICA) were prospectively recruited. Orthostatic hypotension was defined as SBP drop at least 20 mmHg or DBP drop at least 10 mmHg within 3 min of the standing position compared with the supine position. Hemodynamic parameters were measured at the ascending aorta using a pig-tail catheter immediately before ICA. APP was calculated as a difference between the aortic peak systolic pressure and the end-diastolic pressure. RESULTS: A total of 156 patients (78.0%) had obstructive coronary artery disease on ICA. Orthostatic hypotension was present in 58 patients (29.0%). Diabetes mellitus was more prevalent in patients with orthostatic hypotension than those without (48.3% vs. 23.2%; P < 0.001). Other clinical parameters including age, cardiovascular risk factors, laboratory findings and concomitant medications were not different between patients with and without orthostatic hypotension (P > 0.05 for each). In hemodynamic parameters, APP was higher in patients with orthostatic hypotension than those without (78.4 ±â€Š25.8 vs. 68.3 ±â€Š21.3 mmHg; P = 0.005). Higher APP was significantly associated with the presence of orthostatic hypotension even after controlling for potential confounders (odds ratio, 2.99; 95% confidence interval 1.15-7.78; P = 0.025). CONCLUSION: In patients undergoing ICA, APP was associated with increased risk of orthostatic hypotension. Central aortic stiffness may play a role in the development of orthostatic hypotension.