Jong Chan Youn

Serum cytokine profiles in healthy young and elderly population assessed using multiplexed bead-based immunoassays

BackgroundLipid metabolites and cytokines, including chemokines and growth factors, are the key regulators of immune cell function and differentiation, and thus, dysregulation of these regulators is associated with various human diseases. However, previous studies demonstrating a positive correlation of cytokine levels with aging may have been influenced by various environmental factors and underlying diseases. Also, data regarding cytokine profiling in the elderly are limited to a small subset of cytokines.MethodsWe compared the profiles of 22 cytokines, including chemokines and growth factors, in a case-controlled study group of a gender-matched, healthy cohort of 55 patients over the age of 65 and 55 patients under the age of 45. Assessment of serum cytokine concentrations was performed using commercially-available multiplex bead-based sandwich immunoassays.ResultsSoluble CD40 ligand (sCD40L) and transforming growth factor alpha (TGF-α) levels were significantly higher in the elderly patients, whereas granulocyte colony-stimulating factor (G-CSF), granulocyte-monocyte colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein-1 (MCP-1) levels were significantly lower in the elderly patients. The partial correlation analysis demonstrating the correlation between cytokine levels when controlled for gender, systolic blood pressure, total cholesterol, HDL cholesterol, triglyceride, and serum creatinine levels further demonstrated that G-CSF, GM-CSF, and MCP-1 had significant negative correlations with age, whereas sCD40L and TGF-α had significant positive correlations.ConclusionsFuture studies will focus on examining the significance of these age-related changes in circulating cytokines and other biological markers and their potential contribution to the development of different age-associated diseases.

Adiponectin and progression of arterial stiffness in hypertensive patients

BACKGROUNDnRecent studies suggest that adiposity is associated with arterial stiffness. However, it is unclear which adipokine or what adiposity related parameters are related with the progression of arterial stiffness. We hypothesized that in hypertensive patients, initial levels of adipokines such as adiponectin and resistin are related to the progression of arterial stiffness, which has been proven to be associated with increased risk of cardiovascular events.nnnMETHODSnOne hundred forty one consecutive patients with treated essential hypertension (81 men, 57.7±8.2 years) were enrolled. Pulse wave velocity (PWV) was measured at baseline, and after 24 months. Clinical variables and laboratory findings at the time of initial enrollment were analyzed to reveal the determinants of arterial stiffening.nnnRESULTSnMean heart to femoral PWV (hfPWV) was 992±202 cm/s at baseline, and 1021±263 cm/s at 24 months follow up. hfPWV progressed in seventy two patients (51.1%) during follow up period. In patients with hfPWV progression, mean plasma adiponectin level was significantly lower than patients with nonprogression (progressor: 5.18±3.21 μg/ml, non-progressor: 7.02±5.19 μg/ml, p=0.013). Multivariate regression analysis revealed plasma adiponectin level to being an independent predictor of hfPWV changes (ß=-0.018, p=0.032) when controlled for age, gender, SBP changes, BP control and HOMA.nnnCONCLUSIONSnPlasma adiponectin levels are associated with progression of arterial stiffness in hypertensive patients. These findings may be one explanation for the high association between adiposity and arterial stiffness in hypertensive patients.

Association of serum proprotein convertase subtilisin/kexin type 9 with carotid intima media thickness in hypertensive subjects

OBJECTIVEnThe clinical significance of the measurement of serum PCSK9 (proprotein subtilisin kexin type 9) is not well defined. This study investigated the association between serum PCSK9 levels and atherosclerosis assessed by carotid intima media thickness (IMT) in hypertensive patients.nnnMETHODSnA total of 126 hypertensive patients over the age of 45 were enrolled. The maximum carotid IMT (max-IMT) and the mean carotid IMT (mean-IMT) were measured at the time of enrollment. Clinical and laboratory parameters including serum PCSK9 were analyzed.nnnRESULTSnPatients were divided into tertiles based on serum PCSK9 levels. After adjusting for age, sex, total cholesterol, HDL-cholesterol and triglyceride, max-IMT was significantly increased in the highest tertile of serum PCSK9 (0.969±0.033 vs 0.959±0.033 vs 1.077±0.033 mm, respectively; P=0.026). Mean-IMT showed a tendency to increase across the tertile groups (0.773±0.025 vs 0.790±0.026 vs 0.856±0.025 mm, respectively; P=0.059). Multivariate regression analysis revealed that serum PCSK9 was independently associated with carotid IMT (max-IMT: β=0.212, P=0.016; mean-IMT: β=0.184, P=0.04).nnnCONCLUSIONnThe present study is the first to report the association between serum PCSK9 levels and carotid IMT in hypertensive patients. These results suggest that serum PCSK9 may have a certain role in early pathogenesis of atherosclerosis.

Red blood cell distribution width predicts early mortality in patients with acute dyspnea.

BACKGROUNDnRed blood cell distribution width (RDW) has been shown to predict clinical outcomes in cardiovascular diseases. We studied whether RDW is useful to predict early mortality in patients with acute dyspnea at an emergency department (ED).nnnMETHODSnWe retrospectively analyzed 907 patients with acute dyspnea who visited the ED from January 2009 to May 2009. Primary outcome was 30-day mortality.nnnRESULTSnAcute decompensated heart failure (29.9%) was the most common adjudicated discharge diagnosis followed by cancer (14.8%) and pneumonia (12.5%). There was a stepwise increase of 30-day mortality risk from lowest (RDW<12.9%) to highest (RDW>14.3%) RDW tertiles (1.4% vs. 8.3% vs. 18.3%; log-rank P<0.001). In multivariate Cox hazard analysis, RDW was an independent predictor of 30-day mortality after adjusting for other risk factors (HR 1.23; 95% CI 1.11-1.36; P<0.001). Adding RDW to conventional clinical predictors significantly improved prediction for 30-day mortality as measured by the area under the ROC curve (AUC, from 0.873 to 0.885; P=0.023) and the net reclassification improvement (NRI=14.1%; P<0.001)/integrated discrimination improvement (IDI=0.038; P=0.006).nnnCONCLUSIONSnOur findings suggest that RDW measured at ED is an independent and additive predictor of early mortality in patients with acute dyspnea.

Fatal scedosporiosis in multiple solid organ allografts transmitted from a nearly-drowned donor.

Scedosporium spp. is the most common mold infection in pneumonia resulting from near‐drowning. Three fatal scedosporiosis cases developed after solid organ transplantation, probably transmitted from the nearly‐drowned donor. One heart transplant recipient and two kidney transplant recipients developed fatal scedosporiosis following deceased donor transplantation from the same donor, a nearly‐drowned victim of a suicide attempt. Genotypically, indistinguishable strains of Scedosporium auratiacum were recovered from the three recipients. Two liver transplant recipients from the same donor received prophylactic voriconazole without any subsequent signs of infection. To determine the safety of donation from nearly‐drowned donors, a national traceback investigation was also performed of the causes of deaths in all transplant recipients who received organs from drowned donors between 2001 and 2013. Over 13 years, 2600 deceased donor transplants were performed in Korea. Among these 2600 deceased donor transplants, 27 (1%) victims of drowning donated their organs. From these 27 donors, 84 patients received organ transplants and 18 died, including the above three. We found no microbiologic evidence of invasive mold transmission from the nearly‐drowned donors to the other 15 recipients. Although disseminated infection in the donor could not be demonstrated by culture, undiagnosed disseminated donor infection and transmission of Scedosporium spp. should be considered in near‐drowning events.

Association of serum RANTES concentrations with established cardiovascular risk markers in middle-aged subjects.

BACKGROUNDnRANTES (regulated upon activation, normal T cells expressed and secreted) is known to be related to an inflammatory part of the atherosclerotic process. We investigated the association of serum concentrations of RANTES with the risk of coronary artery disease (CAD) in a case-control study.nnnMETHODSnOne hundred fifty one CAD male patients aged 40 to 65 years and 151 age-matched healthy male controls were included and the main outcome measure was the odds ratio (OR) for CAD associated with increased levels of RANTES.nnnRESULTSnSerum levels of RANTES were higher in CAD patients when compared with controls (47.1+/-1.57 ng/mL vs 37.3+/-1.48; P<0.001). In addition, values in the second and top tertile of RANTES were associated with an increased OR for CAD when compared with values in the bottom tertile; OR for RANTES top tertile was 2.86 (95% CI, 1.53 to 5.34) in the age- and WHR-adjusted model and 3.23 (95% CI, 1.02 to 10.3) after the fully adjustment. Furthermore, there was a positive correlation of serum RANTES with acute phase proteins such as hs-CRP (r=0.310, P<0.001) and fibrinogen (r=0.333, P<0.001). RANTES concentrations also displayed a moderate correlation of WHR, triglyceride, HDL-cholesterol, interleukin-1 beta, interleukin-6, adiponectin, platelet and white blood cell counts.nnnCONCLUSIONnIn the present study, RANTES is associated with CAD risk in middle-aged subjects.

Efficacy and Safety of 30-Mg Fimasartan for the Treatment of Patients With Mild to Moderate Hypertension: An 8-Week, Multicenter, Randomized, Double-Blind, Phase III Clinical Study

PURPOSEnThe standard 60-mg dose of fimasartan, a newly developed selective angiotensin II receptor blocker, is effective and safe for use in patients with mild to moderate hypertension. This study aimed to compare the efficacy and safety of low-dose (30 mg) fimasartan and placebo or valsartan (80 mg) for 8 weeks in patients with mild to moderate hypertension.nnnMETHODSnIn this randomized trial, 293 patients (219 men; mean age, 54.24 [9.77] years) with mild to moderate hypertension were enrolled. After randomization to receive 30-mg fimasartan (n = 115), placebo (n = 117), or 80-mg valsartan (n = 61), the treatment dose was kept constant without dose escalation for 8 weeks. The primary end point was improvement in sitting diastolic blood pressure (SiDBP) from baseline to 8 weeks that was compared between treatments with low-dose fimasartan and placebo. The secondary end point was the overall efficacy and safety of low-dose fimasartan compared with that of placebo or valsartan.nnnFINDINGSnAt week 8, SiDBP changed by -9.93 (8.86) mm Hg in the fimasartan group and by -2.08 (9.47) mm Hg in the placebo group, which indicated significant antihypertensive efficacy (P < 0.0001). Efficacy was shown at week 4 as measured by SiDBP (-9.96 [7.73] vs -2.27 [7.85] mm Hg; P < 0.0001) or sitting systolic blood pressure (SiSBP) (-16.18 [14.44] vs -1.95 [13.48] mmHg; P < 0.0001) and at week 8 as determined by SiSBP (-15.35 [16.63] vs -2.30 [14.91] mm Hg; P < 0.0001). The fimasartan group exhibited more potent antihypertensive efficacy than the valsartan group both at week 4 (SiDBP, -9.96 [7.73] vs -6.53 [9.58] mm Hg [P = 0.0123]; SiSBP, -16.18 [14.4] vs -7.65 [12.89] mm Hg [P = 0.0002]) and at week 8 (SiDBP, -9.93 [8.86] vs -5.47 [8.96] mm Hg [P = 0.0021]; SiSBP, -15.35 [16.63] vs -7.49 [13.68] mm Hg [P = 0.0021]). Most treatment-emergent adverse events (TEAEs) were mild (89 of 95), and there were no serious TEAEs. The incidence of TEAEs was 19.1% in the fimasartan group, 22.6% in the placebo group, and 13.6% in the valsartan group, with no significant differences.nnnIMPLICATIONSnLow-dose fimasartan (30 mg) was well tolerated during the study period with no significant TEAEs. Low-dose fimasartan had an effective blood pressure-lowering effect that was greater than that of 80-mg valsartan in patients with mild to moderate hypertension. ClinicalTrials.gov identifier: NCT01672476.

Clinical implication of right bundle branch block in hospitalized patients with acute heart failure: data from the Korean Heart Failure (KorHF) Registry.

heart failure: Data from the Korean Heart Failure (KorHF) Registry Sung-Jin Hong , Jaewon Oh , Seok-Min Kang ⁎, Jong Chan Youn , Seongwoo Han , Eun-Seok Jeon , Myeong-Chan Cho , Jae-Joong Kim , Byung-Su Yoo , Shung Chull Chae , Byung-Hee Oh , Dong-Ju Choi , Myung-Mook Lee , Kyu-Hyung Ryu k on behalf of the KorHF Registry a Cardiology Division, Severance Cardiovascular Hospital and Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea b Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea c Division of Cardiology, Korea University Hospital, Seoul, Republic of Korea d Division of Cardiology, Sungkyunkwan University Samsung Medical Center, Seoul, Republic of Korea e Division of Cardiology, Chungbuk National University Hospital, Cheongju, Republic of Korea f Division of Cardiology, Ulsan University Asan Medical Center, Seoul, Republic of Korea g Division of Cardiology, Yonsei university Wonju Christian Hospital, Wonju, Republic of Korea h Division of Cardiology, Kyungpook National University Hospital, Daegu, Republic of Korea i Division of Cardiology, Seoul National University Hospital, Seoul, Republic of Korea j Division of Cardiology, Dongguk University Ilsan Hospital, Goyang, Republic of Korea k Division of Cardiology, Konkuk University Medical Center, Seoul, Republic of Korea

Association of non-alcoholic steatohepatitis with subclinical myocardial dysfunction in non-cirrhotic patients

BACKGROUND & AIMSnNon-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular risk. Among categories of NAFLD, hepatic fibrosis is most likely to affect mortality. Myocardial function and its energy metabolism are tightly linked, which might be altered by an insulin resistant condition such as NAFLD. We investigated whether hepatic steatosis and fibrosis were associated with myocardial dysfunction relative to myocardial glucose uptake.nnnMETHODSnA total of 308 patients (190 without NAFLD, 118 with NAFLD) were studied in a tertiary care hospital. Myocardial glucose uptake was evaluated at fasted state using [18F]-fluorodeoxyglucose-positron emission tomography (18FDG-PET). Hepatic steatosis and fibrosis were assessed by transient liver elastography (Fibroscan®) with controlled attenuation parameter, which quantifies hepatic fat and by surrogate indices (fatty liver index and NAFLD fibrosis score). Cardiac structure and function were examined by echocardiogram.nnnRESULTSnCompared to those without NAFLD, patients with NAFLD had alterations in cardiac remodeling, manifested by increased left ventricular mass index, left ventricular end-diastolic diameter, and left atrial volume index (all pu202f<0.05). Hepatic steatosis was significantly associated with left ventricular filling pressure (E/e ratio), which reflects diastolic dysfunction (p for trend <0.05). Those without NAFLD were more likely to have higher myocardial glucose uptake compared to those with NAFLD. Significant hepatic fibrosis was also correlated with diastolic dysfunction and impaired myocardial glucose uptake. Using multivariable linear regression, E/e ratio was independently associated with hepatic fibrosis (standardized βu202f=u202f0.12 to 0.27; all pu202f<0.05). Association between hepatic steatosis and E/e ratio was also significant (standardized βu202f=u202f0.10 to 0.15; all pu202f<0.05 excluding the model adjusted for adiposity).nnnCONCLUSIONSnHepatic steatosis and fibrosis are significantly associated with diastolic heart dysfunction. This association is linked with myocardial glucose uptake evaluated by 18FDG-PET.nnnLAY SUMMARYnNon-alcoholic fatty liver disease is associated with an increased risk of cardiovascular disease. More severe forms of non-alcoholic fatty liver disease, where hepatic fibrosis occurs, are linked to increased mortality. In this study, we have shown that hepatic steatosis and fibrosis are associated with subclinical myocardial dysfunction. This association is linked to altered myocardial glucose uptake.

Post-Exercise Heart Rate Recovery Independently Predicts Clinical Outcome in Patients with Acute Decompensated Heart Failure

Background Post-exercise heart rate recovery (HRR) is an index of parasympathetic function associated with clinical outcome in patients with chronic heart failure. However, its relationship with the pro-inflammatory response and prognostic value in consecutive patients with acute decompensated heart failure (ADHF) has not been investigated. Methods We measured HRR and pro-inflammatory markers in 107 prospectively and consecutively enrolled, recovered ADHF patients (71 male, 59 ± 15 years, mean ejection fraction 28.9 ± 14.2%) during the pre-discharge period. The primary endpoint included cardiovascular (CV) events defined as CV mortality, cardiac transplantation, or rehospitalization due to HF aggravation. Results The CV events occurred in 30 (28.0%) patients (5 cardiovascular deaths and 7 cardiac transplantations) during the follow-up period (median 214 days, 11–812 days). When the patients with ADHF were grouped by HRR according to the Contal and O’Quigley’s method, low HRR was shown to be associated with significantly higher levels of serum monokine-induced by gamma interferon (MIG) and poor clinical outcome. Multivariate Cox regression analysis revealed that low HRR was an independent predictor of CV events in both enter method and stepwise method. The addition of HRR to a model significantly increased predictability for CV events across the entire follow-up period. Conclusion Impaired post-exercise HRR is associated with a pro-inflammatory response and independently predicts clinical outcome in patients with ADHF. These findings may explain the relationship between autonomic dysfunction and clinical outcome in terms of the inflammatory response in these patients.