Pentraxin 3 as a biomarker for acute coronary syndrome: Comparison with biomarkers for cardiac damage

SummaryBackgroundPentraxin 3 (PTX3) is increased in circulating blood during the acute stage of acute coronary syndrome (ACS). Therefore, we compared diagnostic values of PTX3 for ACS with those of biomarkers for myocardial damage, such as troponin T (TnT) and heart-type fatty acid binding protein (H-FABP).Methods and resultsPatients (n=87) undergoing coronary angiography (CAG), consisting of 16 ACS and 71 non-ACS patients were enrolled. Non-ACS consists of 12 patients with normal CAG, 30 stable angina pectoris (SAP) patients controlled by medical treatment, and 29 SAP patients who required elective coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft). Age, gender, or prevalence of diabetes, hypertension, or smoking was not significantly different between ACS and non-ACS groups. Serum total, high-density lipoprotein, or low-density lipoprotein cholesterol, or triglyceride levels were not significantly different between ACS and non-ACS. PTX3 levels were not significantly correlated with lipid profiles or different between those with and without conventional risk factors. Circulating PTX3, TnT, and H-FABP levels were significantly higher in ACS than non-ACS. In receiver-operating characteristic (ROC) curves, area under the curve (AUC) values for PTX3, TnT and H-FABP were 0.920, 0.674, and 0.690, respectively. ROC curves of PTX3 (AUC: 0.901), TnT (AUC: 0.731), and H-FABP (AUC: 0.633) for ST-elevation ACS were similar to those for whole ACS. In a TnT-negative subgroup, the AUC values of PTX3 and H-FABP for ACS were 0.981 and 0.489, respectively.ConclusionsPTX3 is a sensitive and specific biomarker for the diagnosis of ACS, and shows additional diagnostic values when measured in combination with TnT

Soluble lectin-like oxidized LDL receptor-1 (sLOX-1) as a sensitive and specific biomarker for acute coronary syndrome—Comparison with other biomarkers

SummaryBackgroundLectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) appears to be involved in atherosclerotic plaque vulnerability and rupture. Circulating soluble LOX-1 (sLOX-1) levels are dramatically elevated in patients with acute coronary syndrome (ACS), and its diagnostic sensitivity and specificity is superior to high-sensitivity C-reactive protein (hs-CRP). In this study, we have compared the diagnostic value of sLOX-1 for ACS with those of troponin T (TnT) and heart-type fatty acid binding protein (H-FABP).MethodsOne hundred and seven patients who underwent coronary angiography (CAG), including 18 ACS and 89 non-ACS patients were enrolled. Peripheral blood samples were obtained during the emergent or elective CAG. The non-ACS group consisted of 30 patients with normal CAG, 30 stable angina pectoris patients controlled by medical treatment, and 29 patients with stable angina who required elective coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft).ResultsAge, gender, lipid profiles, or prevalence of diabetes, smoking, or hypertension were not significantly different between ACS and non-ACS. These factors did not significantly affect blood sLOX-1 levels. Circulating sLOX-1, TnT, and H-FABP levels were significantly higher in ACS than non-ACS. Area under the curve (AUC) values of the receiver-operating characteristic curves were 0.948, 0.704, and 0.691 for sLOX-1, TnT, and H-FABP, respectively. In a TnT-negative (<0.03ng/mL) subgroup, the AUC values for sLOX-1 and H-FABP were 0.848 and 0.476, respectively.ConclusionCirculating sLOX-1 is a more sensitive and specific biomarker for ACS than TnT and H-FABP, and provides additional diagnostic values when measured in combination with TnT

Caloric restriction, aerobic exercise training and soluble lectin-like oxidized LDL receptor-1 levels in overweight and obese post-menopausal women

Background—Elevated circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) have been observed in obese persons and are reduced by weight loss. However, it is not known if combining caloric restriction (CR) with exercise training is better in reducing sLOX-1 levels than CR alone. Objective—We examined whether the addition of aerobic exercise to a weight loss intervention differentially affects sLOX-1 levels in 61 abdominally obese postmenopausal women randomly assigned to a CR only (n=22), CR + moderate-intensity exercise (n=22), or CR + vigorous intensity exercise (n=17) intervention for 20 weeks. The caloric deficit was ~2,800 kcal/week for all groups. Results—The intervention groups were similar at baseline with respect to body weight, body composition, lipids, and blood pressure. However, plasma sLOX-1 levels were higher in the CR only group (99.90 ± 8.23 pg/ml) compared to both the CR + moderate-intensity exercise (69.39 ± 8.23 pg/ml, p=0.01) and CR + vigorous-intensity exercise (72.83 ± 9.36 pg/ml, p=0.03) groups. All three interventions significantly reduced body weight (~14%), body fat, and waist and hip circumferences to a similar degree. These changes were accompanied by a 23% reduction in sLOX-1 levels overall (−19.00 ± 30.08 pg/ml, p\u3c0.0001), which did not differ among intervention groups (p=0.13). Changes in body weight, body fat, and VO2 max were not correlated with changes in sLOX-1 levels. In multiple regression analyses in all women combined, baseline sLOX-1 levels (β = − 0.70 ± 0.06, p\u3c0.0001), age (β = 0.92 ± 0.43, p=0.03) and baseline BMI (β = 1.88 ± 0.66, p=0.006) were independent predictors of the change in sLOX-1 with weight loss. Conclusions—Weight loss interventions of equal energy deficit have similar effects on sLOX-1 levels in overweight and obese postmenopausal women, with the addition of aerobic exercise having no added benefit when performed in conjunction with CR

Decline in Left Ventricular Ejection Fraction during Follow-up in Patients with Severe Aortic Stenosis

Objectives: The aim of this study was to investigate the prognostic impact of the decline in left ventricular ejection fraction (LVEF) at 1-year follow-up in patients with severe aortic stenosis (AS) managed conservatively. Background: No previous study has explored the association between LVEF decline during follow-up and clinical outcomes in patients with severe AS. Methods: Among 3, 815 patients with severe AS enrolled in the multicenter CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry in Japan, 839 conservatively managed patients who underwent echocardiography at 1-year follow-up were analyzed. The primary outcome measure was a composite of AS-related deaths and hospitalization for heart failure. Results: There were 91 patients (10.8%) with >10% declines in LVEF and 748 patients (89.2%) without declines. Left ventricular dimensions and the prevalence of valve regurgitation and atrial fibrillation or flutter significantly increased in the group with declines in LVEF. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the group with declines in LVEF than in the group with no decline (39.5% vs. 26.5%; p 10% declines in LVEF at 1 year after diagnosis had worse AS-related clinical outcomes than those without declines in LVEF under conservative management. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140

Initial Surgical Versus Conservative Strategies in Patients With Asymptomatic Severe Aortic Stenosis

AbstractBackgroundCurrent guidelines generally recommend watchful waiting until symptoms emerge for aortic valve replacement (AVR) in asymptomatic patients with severe aortic stenosis (AS).ObjectivesThe study sought to compare the long-term outcomes of initial AVR versus conservative strategies following the diagnosis of asymptomatic severe AS.MethodsWe used data from a large multicenter registry enrolling 3,815 consecutive patients with severe AS (peak aortic jet velocity >4.0 m/s, or mean aortic pressure gradient >40 mm Hg, or aortic valve area <1.0 cm2) between January 2003 and December 2011. Among 1,808 asymptomatic patients, the initial AVR and conservative strategies were chosen in 291 patients, and 1,517 patients, respectively. Median follow-up was 1,361 days with 90% follow-up rate at 2 years. The propensity score–matched cohort of 582 patients (n = 291 in each group) was developed as the main analysis set for the current report.ResultsBaseline characteristics of the propensity score–matched cohort were largely comparable, except for the slightly younger age and the greater AS severity in the initial AVR group. In the conservative group, AVR was performed in 41% of patients during follow-up. The cumulative 5-year incidences of all-cause death and heart failure hospitalization were significantly lower in the initial AVR group than in the conservative group (15.4% vs. 26.4%, p = 0.009; 3.8% vs. 19.9%, p < 0.001, respectively).ConclusionsThe long-term outcome of asymptomatic patients with severe AS was dismal when managed conservatively in this real-world analysis and might be substantially improved by an initial AVR strategy. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140

インターロイキン 18 ワ カヨウガタ LOX-1 ノ ホウシュツ オ シゲキスル

京都大学0048新制・課程博士博士(医学)甲第14101号医博第3276号新制||医||970(附属図書館)UT51-2008-L156京都大学大学院医学研究科内科系専攻(主査)教授 中尾 一和, 教授 光山 正雄, 教授 生田 宏一学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

〈Original〉Atorvastatin promoted in vitro angiogenesis by reduction of geranylgeranyl pyrophosphate in a dose-dependent manner and protected against rho kinase-mediated endothelial cell damage caused by thromboxane A2

[Abstract]Background: Atorvastatin can inactivate Rho/Rho kinase via a reduction in the synthesis of geranylgeranyl pyrophosphate (GGPP).Thromboxane A2 (TxA2) causes endothelial cell (EC) apoptosis via Rho/Rho kinase activation.We tested the hypothesis that atorvastatin protects against the Rho kinase-mediated anti-angiogenic effect of TxA2. Methods: We used human coronary artery ECs to form tubular structures on plates coated with a basement membrane matrix gel. The number of tubular structure was counted under a microscope. The caspase-3 activity was used as a determinant of apoptosis.Results: Atorvastatin significantly increased the number of tubes in a dose-dependent manner, and this effect was blocked by mevalonate or geranylgeranyl pyrophosphate (GGPP). Similar to atorvastatin, a potent selective inhibitor of geranylgeranyl transferase type I enhanced tubular formation. A TxA2 mimetic (IBOP) inhibited formation of EC tubular structures. The inhibitory effect was completely blocked by a TxA2 antagonist (SQ29548), a Rho kinase inhibitor (Y27632), and by atorvastatin. The IBOP-induced increase in caspase-3 activity was attenuated by atorvastatin. Conclusions: Atorvastatin promoted in vitro angiogenesis of ECs in a dose-dependent manner and reversed the TxA2 receptor-mediated antiangiogenic effect. We suggest that reduction of GGPP and inactivation of Rho kinase plays an important role in the proangiogenic effect of atorvastatin