Elevated Levels of Oxidized Low-Density Lipoprotein Correlate Positively with C-Reactive Protein in Patients with Acute Coronary Syndrome

The relationship between oxidized low-density lipoprotein (Ox-LDL) and C-reactive protein (CRP) in patients with acute coronary syndrome (ACS) is unknown. We, therefore, measured serum levels of Ox-LDL and high-sensitivity (hs)-CRP in 90 ACS patients, 45 stable angina pectoris (SAP) patients, and 66 healthy controls using sandwich ELISA. ACS patients were subdivided into: (1) acute myocardial infarction (AMI; n = 45); (2) unstable angina pectoris (UAP; n = 45) groups. In AMI patients, Ox-LDL (177.5 mmol/l) and hs-CRP (25.40 mg/l) levels were significantly higher (P < 0.01) than in UAP (Ox-LDL:107.5 mmol/l, hs-CRP:10.7 mg/l) and SAP (Ox-LDL:82.3 mmol/l, hs-CRP:2.10 mg/l) patients as well as controls (Ox-LDL:41.4 mmol/l, hs-CRP:1.76 mg/l). Ox-LDL/hs-CRP levels in UAP patients were significantly higher (P < 0.01) than in SAP patients and controls. Importantly, a positive correlation was found between Ox-LDL and CRP (r = 0.622; P < 0.01) levels. Serum levels of total, HDL, and LDL cholesterol did not differ among these patient groups. In conclusion, our data show that Ox-LDL and hs-CRP levels correlate positively in ACS patients, supporting the hypothesis that Ox-LDL and CRP may play a direct role in promoting the inflammatory component of atherosclerosis in these individuals. We suggest that Ox-LDL/CRP elevated levels may serve as markers of the severity of the disease in evaluation and management of ACS patients.     

Acute Coronary Syndrome Remodels the Protein Cargo and Functions of High-Density Lipoprotein Subfractions

Objectives

This study examined alterations in the functions and proteome of high-density lipoprotein (HDL) subfractions (HDL2 and HDL3) isolated from patients with acute coronary syndrome (ACS) compared with control subjects.

Methods

We measured HDL subfraction cholesterol efflux capacity, inflammatory index (HII), paraoxonase-1 (PON1) activity, and lipid hydroperoxide (LOOH) levels in both male age-matched controls and the ACS group (n = 40/group). Additionally, proteomic analysis was used to monitor changes in the HDL subfraction proteome between controls and ACS subjects.

Results

Both HDL2 and HDL3 from ACS patients had greater HII and LOOH levels compared with controls (P<0.001); PON1 activity and cholesterol efflux capacity in both HDL2 and HDL3 from the ACS group were significantly less than those of controls (P<0.001). Using proteomic analysis, we demonstrated that, compared with the control group, nine proteins were selectively enriched in HDL3 from subjects with ACS, and ras-related protein Rab-7b was decreased in HDL3. Additionally, in the ACS subjects, 12 proteins were decreased in HDL2 and 4 proteins were increased in HDL2.

Conclusions

Functional HDL subfractions shifted to dysfunctional HDL subfractions during ACS, and the functional impairment was linked to remodeled protein cargo in HDL subfractions from ACS patients.     

Localization of Oxidized Low-Density Lipoprotein and Its Relation to Plaque Morphology in Human Coronary Artery

Objectives

Oxidized low-density lipoprotein (oxLDL) plays a key role in the formation of atherosclerotic plaques. However, its localization in human coronary arterial wall is not well understood. The present study was performed to visualize deposition sites and patterns of native oxLDL and their relation to plaque morphology in human coronary artery.

Methods

Evans blue dye (EB) elicits a violet fluorescence by excitation at 345-nm and emission at 420-nm, and a reddish-brown fluorescence by excitation at 470-nm and emission at 515-nm characteristic of oxLDL only. Therefore, native oxLDL in excised human coronary artery were investigated by color fluorescent microscopy (CFM) using EB as a biomarker.

Results

(1) By luminal surface scan with CFM, the % incidence of oxLDL in 38 normal segments, 41 white plaques and 32 yellow plaques that were classified by conventional angioscopy, was respectively 26, 44 and 94, indicating significantly (p<0.05) higher incidence in the latter than the former two groups. Distribution pattern was classified as patchy, diffuse and web-like. Web-like pattern was observed only in yellow plaques with necrotic core. (2) By transected surface scan, oxLDL deposited within superficial layer in normal segments and diffusely within both superficial and deep layers in white and yellow plaques. In yellow plaques with necrotic core, oxLDL deposited not only in the marginal zone of the necrotic core but also in the fibrous cap.

Conclusion

Taken into consideration of the well-known process of coronary plaque growth, the results suggest that oxLDL begins to deposit in human coronary artery wall before plaque formation and increasingly deposits with plaque growth, exhibiting different deposition sites and patterns depending on morphological changes.     

血清超敏C-反应蛋白水平与急性缺血性脑卒中预后的关系

目的:探讨急性缺血性脑卒中患者血清超敏C-反应蛋白(hs-CRP)的水平对卒中后功能障碍的预测价值.方法:分别在发病后第1和7天,采用颗粒增强免疫透射比浊法对92例急性缺血性脑卒中患者检测血清hs-CRP水平,并选取40例健康受试者作为对照.随访并记录患者1月、3月和6月mRS评分.结果:①急性缺血性脑卒中患者血清hs-CRP水平较对照组显著升高.②急性缺血性卒中患者入院1d和7d血清hs-CRP水平与1月、3月和6月mRS评分,均有明显的相关性.与入院1d血清hs-CRP水平相比,入院7d血清hs-CRP水平与mRS评分相关性更好.③与无颈动脉粥样硬化危险因素的缺血性卒中患者相比,有颈动脉粥样硬化危险因素的缺血性卒中患者入院7d血清hs-CRP水平明显升高.结论:与入院1d血清hs-CRP水平相比,入院7d血清hs-CRP水平对卒中后功能障碍的预测价值更好.     

The Value and Distribution of High-Density Lipoprotein Subclass in Patients with Acute Coronary Syndrome

Background

High-density lipoprotein (HDL) enhances cholesterol efflux from the arterial wall and exhibits potent anti-inflammatory and anti-atherosclerosis (AS) properties. Whether raised HDL levels will clinically benefit patients with acute coronary syndrome (ACS) and the value at which these effects will be apparent, however, is debatable. This study examined the HDL subclass distribution profile in patients with ACS.

Methods

Plasma HDL subclasses were measured in 158 patients with established ACS and quantified by two-dimensional gel electrophoresis and immunoblotting. ACS diagnosis was based on symptoms of cardiac ischemia, electrocardiogram (ECG) abnormalities, speciality cardiac enzyme change along with presence of coronary heart disease (CHD) on coronary angiography.

Results

The small-sized preβ₁-HDL, HDL_3b, and HDL_3a levels were significantly higher, and the large-sized HDL_2a and HDL_2b levels were significantly lower in patients with ACS than in those with stable angina pectoris (SAP) and in normal control subjects. Meanwhile, with an elevation in the low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), body mass index (BMI), and blood pressure (BP), and the reduction in the high density lipoprotein cholesterol (HDL-C) levels, the HDL_2b contents significantly decreased and the preβ₁-HDL contents significantly increased in patients with ACS. The correlation analysis revealed that the apolipoprotein (apo)A-I levels were positively and significantly with all HDL subclasses contents; plasma total cholesterol (TC) and fasting plasma glucose (FPG) levels were inversely associated with HDL_2a, and HDL_2b. Moreover, the FPG levels were positively related to HDL_3c, HDL_3b, and HDL_3a in ACS patients.

Conclusion

The HDL subclass distribution profile remodeling was noted in the patients with ACS. Plasma lipoprotein and FPG levels, BP, and BMI play an important role in the HDL subclass metabolism disorder for patients with ACS. The HDL subclass distribution phenotype might be useful as a novel biomarker to assist in the risk stratification of patients with ACS.     

The Association between Triglyceride/High-Density Lipoprotein Cholesterol Ratio and All-Cause Mortality in Acute Coronary Syndrome after Coronary Revascularization

Aims

High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) are cardiovascular risk factors. A positive correlation between elevated TG/HDL-C ratio and all-cause mortality and cardiovascular events exists in women. However, utility of TG to HDL-C ratio for prediction is unknown among acute coronary syndrome (ACS).

Methods

Fasting lipid profiles, detailed demographic data, and clinical data were obtained at baseline from 416 patients with ACS after coronary revascularization. Subjects were stratified into three levels of TG/HDL-C. We constructed multivariate Cox-proportional hazard models for all-cause mortality over a median follow-up of 3 years using log TG to HDL-C ratio as a predictor variable and analyzing traditional cardiovascular risk factors. We constructed a logistic regression model for major adverse cardiovascular events (MACEs) to prove that the TG/HDL-C ratio is a risk factor.

Results

The subject’s mean age was 64 ± 11 years; 54.5% were hypertensive, 21.8% diabetic, and 61.0% current or prior smokers. TG/HDL-C ratio ranged from 0.27 to 14.33. During the follow-up period, there were 43 deaths. In multivariate Cox models after adjusting for age, smoking, hypertension, diabetes, and severity of angiographic coronary disease, patients in the highest tertile of ACS had a 5.32-fold increased risk of mortality compared with the lowest tertile. After adjusting for conventional coronary heart disease risk factors by the logistic regression model, the TG/HDL-C ratio was associated with MACEs.

Conclusion

The TG to HDL-C ratio is a powerful independent predictor of all-cause mortality and is a risk factor of cardiovascular events.     

Pre-Treatment Levels of C-Reactive Protein and Squamous Cell Carcinoma Antigen for Predicting the Aggressiveness of Pharyngolaryngeal Carcinoma

The levels of squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) can be used to predict tumor invasion, lymph node metastasis, staging and survival in patients with oral cavity cancer. The present study analyzed the relationship between pre-treatment levels of SCC-Ag and CRP in relation to clinicopathological factors in patients with pharyngolaryngeal cancer (PLC) and determined whether elevated levels of CRP and SCC-Ag were associated with tumor metabolic activity via [18F] fluorodeoxyglucose positron emission tomography (FDG-PET). We retrospectively recruited one hundred and six PLC patients between June 2008 and December 2011. All patients received computed tomography (CT)/magnetic resonance imaging (MRI) and FDG-PET staging analyses, and the serum levels of SCC-Ag and CRP in these patients were measured prior to treatment. A SCC-Ag level ≥2.0 ng/ml and a CRP level ≥5.0 mg/L were significantly associated with clinical stage (P<0.001), clinical tumor status (P<0.001), and clinical nodal status (P<0.001). The elevation of both SCC-Ag and CRP levels was correlated with the standardized uptake value (SUV) max of the tumor (≥8.6 mg/L) and lymph nodes (≥5.7 ng/ml) (P = 0.019). The present study demonstrated that the presence of high levels of both pre-treatment SCC-Ag and CRP acts as a predictor of clinical stage, clinical tumor status, and clinical nodal status in patients with PLC. Moreover, elevated levels of SCC-Ag and CRP were associated with a high metabolic rate as well as the proliferative activity measured according to the SUVmax of the tumor and lymph nodes. Therefore, elevated levels of these two factors have the potential to serve as biomarkers for the prediction of tumor aggressiveness in cases of PLC.     

川芎嗪对急性冠脉综合征患者血清C反应蛋白及血液流变学的影响

目的:观察川芎嗪注射液(LHI)对急性冠脉综合征(ACS)患者血清C-反应蛋白(CRP)及血液流变学的影响,探讨LHI在稳定冠脉粥样斑块中的作用.方法:本研究采用前瞻性开放性病例对照研究,以248例ACS患者(其中急性心肌梗死(AMI)115例,不稳定心绞痛(UA)133例)及100例健康志愿者为研究对象,与发生ACS48h空腹采静脉血,健康对照组空腹采静脉血,测定血清CRP及血液流变学指标.在248例ACS惠者中随机选取100例分为治疗组和对照组:对照组(50例)采用常规治疗;治疗组(50例)在常规治疗的基础上加LHI 80mg+5%葡萄糖250mi静脉滴注,一日一次.于治疗10d后检测患者CRP及血液流变学指标.结果:ACS患者血清CRP及血液流变学各指标均显著高于健康对照组(P＜0.01);AMI患者血清CRP及血液流变学各指标又显著高于UA组(P＜0.01).经治疗10d后,各组CRP及血液流变学各指标较治疗前均改善,差异有显著性(P＜0.01),治疗组血清CRP及血液流变学各指标显著低于对照组(P＜0.01).结论:ACS患者血清CRP增高,血液流变学指标异常.LHI可显著降低ACS患者血清CRP并改善血液流变学指标,提示其有抑制冠脉粥样斑块的炎性反应,稳定斑块,减少心血管不良事件的作用.     

Plasma miR-122 and miR-3149 Potentially Novel Biomarkers for Acute Coronary Syndrome

ObjectiveWe evaluated the potentiality of plasma microRNAs (miRNAs, or miRs) that were considered as novel biomarkers for acute coronary syndrome (ACS), including acute myocardial infarction (AMI) and unstable angina (UA).ConclusionPlasma miR-122, -140-3p, -720, -2861, and -3149 were associated with and potentially novel biomarkers for ACS.     

Impact of Obstructive Sleep Apnea on the Levels of Placental Growth Factor (PlGF) and Their Value for Predicting Short-Term Adverse Outcomes in Patients with Acute Coronary Syndrome

Background

Placental growth factor (PlGF) induces angiogenesis and promotes tissue repair, and plasma PlGF levels change markedly during acute myocardial infarction (AMI). Currently, the impact of obstructive sleep apnea (OSA) in patients with AMI is a subject of debate. Our objective was to evaluate the relationships between PlGF levels and both the severity of acute coronary syndrome (ACS) and short-term outcomes after ACS in patients with and without OSA.

Methods

A total of 538 consecutive patients (312 OSA patients and 226 controls) admitted for ACS were included in this study. All patients underwent polygraphy in the first 72 hours after hospital admission. The severity of disease and short-term prognoses were evaluated during the hospitalization period. Plasma PlGF levels were measured using an electrochemiluminescence immunoassay.

Results

Patients with OSA were significantly older and more frequently hypertensive and had higher BMIs than those without OSA. After adjusting for age, smoking status, BMI and hypertension, PlGF levels were significantly elevated in patients with OSA compared with patients without OSA (19.9 pg/mL, interquartile range: 16.6–24.5 pg/mL; 18.5 pg/mL, interquartile range: 14.7–22.7 pg/mL; p<0.001), and a higher apnea-hypopnea index (AHI) was associated with higher PlGF concentrations (p<0.003). Patients with higher levels of PlGF had also an increased odds ratio for the presence of 3 or more diseased vessels and for a Killip score>1, even after adjustment.

Conclusions

The results of this study show that in patients with ACS, elevated plasma levels of PlGF are associated with the presence of OSA and with adverse outcomes during short-term follow-up.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01335087","term_id":"NCT01335087"}}NCT01335087     

Multiple Nucleic Acid Binding Sites and Intrinsic Disorder of Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein: Implications for Ribonucleocapsid Protein Packaging

The nucleocapsid protein (N) of the severe acute respiratory syndrome coronavirus (SARS-CoV) packages the viral genomic RNA and is crucial for viability. However, the RNA-binding mechanism is poorly understood. We have shown previously that the N protein contains two structural domains—the N-terminal domain (NTD; residues 45 to 181) and the C-terminal dimerization domain (CTD; residues 248 to 365)—flanked by long stretches of disordered regions accounting for almost half of the entire sequence. Small-angle X-ray scattering data show that the protein is in an extended conformation and that the two structural domains of the SARS-CoV N protein are far apart. Both the NTD and the CTD have been shown to bind RNA. Here we show that all disordered regions are also capable of binding to RNA. Constructs containing multiple RNA-binding regions showed Hill coefficients greater than 1, suggesting that the N protein binds to RNA cooperatively. The effect can be explained by the “coupled-allostery” model, devised to explain the allosteric effect in a multidomain regulatory system. Although the N proteins of different coronaviruses share very low sequence homology, the physicochemical features described above may be conserved across different groups of Coronaviridae. The current results underscore the important roles of multisite nucleic acid binding and intrinsic disorder in N protein function and RNP packaging.Severe acute respiratory syndrome (SARS) is the first pandemic of the 21st century that spread to multiple nations, with a fatality rate of ca. 8%. The disease is caused by a novel SARS-associated coronavirus (SARS-CoV) closely related to the group II coronaviruses, which include the human coronavirus OC43 and murine hepatitis virus (6, 18). Traditional antiviral treatments have had little success against SARS during the outbreak, and vaccines have yet to be developed (35).Coronaviruses are positive-sense single-stranded RNA (ssRNA) viruses. The coronavirus genomic RNA is encapsidated into a helical capsid by the nucleocapsid (N) protein, which is one of the most abundant coronavirus proteins (19). The N protein has nonspecific binding activity toward nucleic acids, including ssRNA, single-stranded DNA, and double-stranded DNA (33). It can also act as an RNA chaperone (39). However, the mechanism of binding of the N protein to nucleic acids is poorly understood.The SARS-CoV N protein is a homodimer composed of 422 amino acids (aa) in each chain. The N protein can be divided into two structural domains interspersed with disordered (unstructured) regions (Fig. ​(Fig.1A)1A) (2). The N-terminal domain (NTD; also called RBD) serves as a putative RNA-binding domain, while the C-terminal domain (CTD; also called DD) is a dimerization domain (13, 36). Both the NTD and the CTD bind to nucleic acids through electropositive regions on their surfaces (3, 13, 32). All coronaviruses share similar domain architectures at both the sequence and structure levels. No structure of N protein or any of its domains in complex with nucleic acids is available.Open in a separate windowFIG. 1.(A) Schematic of the domain architecture of the SARS-CoV N protein. Structured domains are shown as balls, and unstructured regions are shown as lines. (B) Protein constructs used in the current study. Numbers represent the amino acid residue range relative to the full-length N protein (NP). Sumo-1-FL contains a Sumo-1 tag (shown as an oval), followed by the flexible linker of the N protein between residues 181 and 246.The functions of the disordered regions in the SARS-CoV N protein have not been clearly defined, although some evidence suggests that they are involved in protein-protein interactions between the N protein and other viral and host proteins (11, 20, 22, 38). A previous report has shown that part of the C-terminal disordered region with a polylysine sequence also binds to RNA (21). Unlike the structural domains, the disordered regions of the different coronaviruses share little sequence homology. However, they share a common physicochemical property: they are highly enriched in basic residues. Intrinsic disorder coupled with an abundance of positive charges leads to the possibility of nonspecific binding to nucleic acids (34). These findings prompted us to investigate the role of intrinsically disordered (ID) regions in the RNA-binding mechanism of the SARS-CoV N protein.Here we tested all three disordered regions of the SARS-CoV N protein and found that they are all involved in RNA binding. The central region, in particular, had a large impact on binding behavior as monitored by electrophoretic mobility shift assays (EMSA). Small-angle X-ray scattering (SAXS) and nuclear magnetic resonance (NMR) results show that this central region is a flexible linker (FL) that connects the two structural domains in an extended conformation. Our results provide new insights into the functional coupling of intrinsic disorder, RNA binding, and oligomerization.     

Efficacy and Safety of Intracoronary versus Intravenous Administration of Tirofiban during Percutaneous Coronary Intervention for Acute Coronary Syndrome: A Meta-Analysis of Randomized Controlled Trials

Background

Percutaneous coronary intervention (PCI) is known as the most effective treatment for acute coronary syndrome (ACS). However, without proper therapy and patient management, stent thrombosis after PCI may lead to another myocardial infarction. In addition to aspirin and clopidogrel, tirofiban is often used as an antiplatelet therapy in patients with ACS. To date, there has been no comprehensive evaluation of the efficacy and safety of intracoronary (IC) tirofiban administration for ACS patients undergoing PCI compared with intravenous (IV) administration. Therefore, this meta-analysis was conducted to investigate the clinical efficiency and safety of IC versus intravenous (IV) tirofiban in ACS patients undergoing PCI.

Methods

We searched PubMed and Medline for randomized controlled trials (RCTs) comparing IC versus IV administration of tirofiban in ACS patients undergoing PCI. We evaluated the effects of tirofiban on thrombolysis in myocardial infarction (TIMI) grade 3 flow after PCI, TIMI myocardial perfusion grade 3 (TMP grade 3), left ventricular ejection fraction (LVEF), major adverse cardiovascular events (MACE), target vessel revascularization (TVR), death, reinfarction and adverse drug effects (specifically bleeding events).

Results

Seven trials involving 1,027 patients were included in this meta-analysis. IC administration of tirofiban significantly increased TIMI grade 3 flow (OR 2.11; 95% CI 1.02 to 4.37; P = 0.04) and TMP grade 3 (OR 2.67; 95% CI 1.09 to 6.49; P = 0.03, I² = 64%) while reducing MACE (OR 0.46, 95% CI: 0.28 to 0.75; P = 0.002) compared with IV administration of tirofiban. No significant differences were observed in the occurrence of TVR, death, reinfarction and the incidence of bleeding events between the two groups.

Conclusions

This meta-analysis supports the use of IC over IV administration of tirofiban in patients with ACS to improve TIMI flow, TMP flow and MACE. However, there was no statistically significant difference in the risk of bleeding complications between the two groups.     

Risk Models and Scoring Systems for Predicting the Prognosis in Critically Ill Cirrhotic Patients with Acute Kidney Injury: A Prospective Validation Study

Background

Cirrhotic patients with acute kidney injury (AKI) admitted to intensive care units (ICUs) show extremely high mortality rates. We have proposed the MBRS scoring system, which can be used for assessing patients on the day of admission to the ICU; this new system involves determination of mean arterial pressure (MAP) and bilirubin level and assessment of respiratory failure and sepsis. We had used this scoring system to analyze the prognosis of ICU cirrhotic patients with AKI in 2008, and the current study was an external validation of this scoring system.

Methods

A total of 190 cirrhotic patients with AKI were admitted to the ICU between March 2008 and February 2011. We prospectively analyzed and recorded the data for 31 demographic parameters and some clinical characteristic variables on day 1 of admission to the ICU; these variables were considered as predictors of mortality.

Results

The overall in-hospital mortality rate was 73.2% (139/190), and the 6-month mortality rate was 83.2% (158/190). Hepatitis B viral infection (43%) was observed to be the cause of liver disease in most of the patients. Multiple logistic regression analysis indicated that the MBRS and Acute Physiology and Chronic Health Evaluation III (ACPACHE III) scores determined on the first day of admission to the ICU were independent predictors of in-hospital mortality in patients. In the analysis of the area under the receiver operating characteristic (AUROC) curves, the MBRS scores showed good discrimination (AUROC: 0.863±0.032, p<0.001) in predicting in-hospital mortality.

Conclusion

On the basis of the results of this external validation, we conclude that the MBRS scoring system is a reproducible, simple, easy-to-apply evaluation tool that can increase the prediction accuracy of short-term prognosis in critically ill cirrhotic patients with AKI.     

Impaired Thymic Export and Increased Apoptosis Account for Regulatory T Cell Defects in Patients with Non-ST Segment Elevation Acute Coronary Syndrome

Regulatory T (Treg) cells play a protective role against the development of atherosclerosis. Previous studies have revealed Treg cell defects in patients with non-ST elevation acute coronary syndrome (NSTACS), but the mechanisms underlying these defects remain unclear. In this study, we found that the numbers of peripheral blood CD4⁺CD25⁺CD127^low Treg cells and CD4⁺CD25⁺CD127^lowCD45RA⁺CD45RO⁻ naive Treg cells were lower in the NSTACS patients than in the chronic stable angina (CSA) and the chest pain syndrome (CPS) patients. However, the number of CD4⁺CD25⁺CD127^lowCD45RA⁻CD45RO⁺ memory Treg cells was comparable in all of the groups. The frequency of CD4⁺CD25⁺CD127^lowCD45RO⁻CD45RA⁺CD31⁺ recent thymic emigrant Treg cells and the T cell receptor excision circle content of purified Treg cells were lower in the NSTACS patients than in the CSA patients and the CPS controls. The spontaneous apoptosis of Treg cells (defined as CD4⁺CD25⁺CD127^lowannexin V⁺7-AAD⁻) was increased in the NSTACS patients compared with the CSA and CPS groups. Furthermore, oxidized LDL could induce Treg cell apoptosis, and the oxidized LDL levels were significantly higher in the NSTACS patients than in the CSA and CPS groups. In accordance with the altered Treg cell levels, the concentration of TNF-α was increased in the NSTACS patients, resulting in a decreased IL-10/TNF-α ratio. These findings indicate that the impaired thymic output of Treg cells and their enhanced susceptibility to apoptosis in the periphery were responsible for Treg cell defects observed in the NSTACS patients.     

Blood Levels of S-100 Calcium-Binding Protein B,High-Sensitivity C-Reactive Protein,and Interleukin-6 for Changes in Depressive Symptom Severity after Coronary Artery Bypass Grafting: Prospective Cohort Nested within a Randomized,Controlled Trial

Background

Cross-sectional and retrospective studies have associated major depressive disorder with glial activation and injury as well as blood–brain barrier disruption, but these associations have not been assessed prospectively. Here, we aimed to determine the relationship between changes in depressive symptom severity and in blood levels of S-100 calcium-binding protein B (S-100B), high-sensitivity C-reactive protein, and interleukin-6 following an inflammatory challenge.

Methods

Fifty unselected participants were recruited from a randomized, controlled trial comparing coronary artery bypass grafting procedures performed with versus without cardiopulmonary bypass for the risk of neurocognitive decline. Depressive symptom severity was measured at baseline, discharge, and six-month follow-up using the Beck Depression Inventory II (BDI-II). The primary outcome of the present biomarker study was acute change in depressive symptom severity, defined as the intra-subject difference between baseline and discharge BDI-II scores. Blood biomarker levels were determined at baseline and 2 days postoperative.

Results

Changes in S-100B levels correlated positively with acute changes in depressive symptom severity (Spearman ρ, 0.62; P = 0.0004) and accounted for about one-fourth of their observed variance (R², 0.23; P = 0.0105). This association remained statistically significant after adjusting for baseline S-100B levels, age, weight, body-mass index, or β-blocker use, but not baseline BDI-II scores (P = 0.064). There was no statistically significant association between the primary outcome and baseline S-100B levels, baseline high-sensitivity C-reactive protein or interleukin-6 levels, or changes in high-sensitivity C-reactive protein or interleukin-6 levels. Among most participants, levels of all three biomarkers were normal at baseline and markedly elevated at 2 days postoperative.

Conclusions

Acute changes in depressive symptom severity were specifically associated with incremental changes in S-100B blood levels, largely independent of covariates associated with either. These findings support the hypothesis that glial activation and injury and blood–brain barrier disruption can be mechanistically linked to acute exacerbation of depressive symptoms in some individuals.     

Strategies for Primary Prevention of Coronary Heart Disease Based on Risk Stratification by the ACC/AHA Lipid Guidelines,ATP III Guidelines,Coronary Calcium Scoring,and C-Reactive Protein,and a Global Treat-All Strategy: A Comparative--Effectiveness Modeling Study

Background

Several approaches have been proposed for risk-stratification and primary prevention of coronary heart disease (CHD), but their comparative and cost-effectiveness is unknown.

Methods

We constructed a state-transition microsimulation model to compare multiple approaches to the primary prevention of CHD in a simulated cohort of men aged 45–75 and women 55–75. Risk-stratification strategies included the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on the treatment of blood cholesterol, the Adult Treatment Panel (ATP) III guidelines, and approaches based on coronary artery calcium (CAC) scoring and C-reactive protein (CRP). Additionally we assessed a treat-all strategy in which all individuals were prescribed either moderate-dose or high-dose statins and all males received low-dose aspirin. Outcome measures included CHD events, costs, medication-related side effects, radiation-attributable cancers, and quality-adjusted-life-years (QALYs) over a 30-year timeframe.

Results

Treat-all with high-dose statins dominated all other strategies for both men and women, gaining 15.7 million QALYs, preventing 7.3 million myocardial infarctions, and saving over $238 billion, compared to the status quo, far outweighing its associated adverse events including bleeding, hepatitis, myopathy, and new-onset diabetes. ACC/AHA guidelines were more cost-effective than ATP III guidelines for both men and women despite placing 8.7 million more people on statins. For women at low CHD risk, treat-all with high-dose statins was more likely to cause a statin-related adverse event than to prevent a CHD event.

Conclusions

Despite leading to a greater proportion of the population placed on statin therapy, the ACC/AHA guidelines are more cost-effective than ATP III. Even so, at generic prices, treating all men and women with statins and all men with low-dose aspirin appears to be more cost-effective than all risk-stratification approaches for the primary prevention of CHD. Especially for low-CHD risk women, decisions on the appropriate primary prevention strategy should be based on shared decision making between patients and healthcare providers.