Plasma biomarkers and plaque strain predict long-term cardiovascular events in patients with acute coronary syndrome

To test whether circulating and intracoronary biomarkers and coronary plaque strain have additive values to Global Registry of Acute Coronary Events(GRACE) score for predicting long-term cardiovascular events in ACS patients. One hundred ACS patients were enrolled and the GRACE score and plasma levels and intracoronary gradients of a number of biomarkers were measured. Coronary plaque burden and morphology in non-critical stenotic plaques were determined by intravascular ultrasound(IVUS) technique, and the maximal shear strain(SS_(max)) and maximal area strain(AS_(max)) were determined by intravascular ultrasound elastography(IVUSE) technique. Patients were followed for cardiovascular events and the predictive values of clinical characteristics, plasma biomarkers and plaque parameters were compared with GRACE score, and the incremental values of these measurements to the GRACE score were assessed. GRACE score, plasma biomarkers and plaque strain were independent predictors of cardiovascular events. Combination of GRACE score, plasma biomarkers and plaque strains significantly improved the predictive value of the GRACE score alone with the receiver-operating characteristic area increased from0.457 to 0.667(P=0.014). The combination of circulating and intracoronary biomarkers, plaque strain and GRACE score provides a better predictive tool than GRACE score alone in patients with ACS.     

Increased level of advanced oxidation products (AOPP) as a marker of oxidative stress in patients with acute coronary syndrome

Oxidative stress impairs endothelial function and may play an important role in the pathogenesis of acute cardiovascular diseases. Advanced oxidation protein products (AOPP) were proposed as one of the possible markers of oxidative injury, which originates under oxidative and carbonyl stress and increase global inflammatory activity. The present study was undertaken to compare AOPP concentrations in a control group of healthy individuals without ICHS (I), patients with stable angina pectoris (II), patients with acute coronary syndrome over 48 hours without ST elevations (III), and patients with ST elevation myocardial infarction (IV). Coronaronary angiography, risk factors and anamnestic data were analyzed. We examined 73 probands with signs of myocardial ischemia, mean age of 61.5 years (64% males) subjected to coronarography and 21 healthy individuals. No significant difference was found between venous blood and coronary samples, or between infarction and non-infarction arteries in the group IV. AOPP concentrations in healthy individuals in the group I (82.9 +/- 29.3 mmol/l) did not differ significantly from patients in group II (89.6 +/- 26.7 mmol/l) and group III (112.3 +/- 54.6 mmol/l). A significant difference in AOPP values was found between the groups I and IV, and between the groups II and IV (82.9 +/- 29.3 mmol/l vs. 125.8 +/- 101 mmol/l, p = 0.02, and 89.6 +/- 26.7 mmol/l vs. 125.8 +/- 101 mmol/l, p = 0.02). No correlations were found between AOPP and body mass index (BMI), nicotinism, left ventricular ejection fraction, parameters of glucose and lipid metabolism. ROC analysis revealed that AOPP concentrations of 89 mmol/l had 64% sensitivity and 71% specificity for revealing an acute coronary syndrome (AUC 0.65, 95% CI 0.55-0.80). AOPP are significantly increased in patients with acute coronary syndromes with ST segment elevation, but also tend to increase in patients with non-ST elevation myocardial infarction. Our observations suggest that AOPP may be used as a marker of oxidative stress and as a prognostic factor for severe forms of cardiovascular disease. A cut-off value of 89 mmol/l can be used with 64% sensitivity and 71% specificity for revealing acute coronary syndrome.     

Capability of ischemia-modified albumin to predict serious cardiac outcomes in the short term among patients with potential acute coronary syndrome

BackgroundIschemia-modified albumin (IMA) has been suggested as a marker of cardiac ischemia. Little, however, is known about its capacity to predict short-term serious cardiac outcomes (death, myocardial infarction, congestive heart failure, serious arrhythmia, or refractory ischemic cardiac pain) in patients arriving at the emergency department with symptoms that may indicate cardiac ischemia.MethodsWe screened 546 patients over a 4-week period, of whom 189 fulfilled our entry criteria by presenting to an emergency department with potential cardiac-ischemia symptoms within 6 hours after chest pain, seeing an emergency physician who chose to order a troponin I test, and having no serious cardiac outcome before the troponin result became available. We followed the study patients for 72 hours to determine if any experienced a serious cardiac outcome. We calculated the likelihood ratios (LRs) of IMA findings predicting serious cardiac outcomes that could not be diagnosed at presentation with current techniques.ResultsOf the 189 patients, 24 had a serious cardiac outcome within 72 hours after their arrival at the emergency department. The likelihood ratios for IMA measurement within 6 hours after chest pain predicting a serious cardiac outcome within the next 72 hours were 1.35 (95% confidence interval [CI] 0.315–5.79) for IMA ≤ 80 U/mL and 0.98 (95% CI 0.86– 1.11) for IMA > 80 U/mL.ConclusionsThese data suggest that in patients presenting with chest pain who have not yet experienced a serious cardiac event, IMA is a poor predictor of serious cardiac outcomes in the short term.Patients who arrive at an emergency department with potential cardiac symptoms present a diagnostic challenge to physicians, who must also decide resource utilization within the medical system. Physicians are under pressure to minimize resource use and to stream patients into a level of care appropriate to their evolving clinical condition. A method to predict the likelihood of a serious cardiac outcome (death, myocardial infarction [MI], congestive heart failure, serious arrhythmia or refractory ischemic cardiac pain) during the next 72 hours would therefore be very advantageous. Appropriate management of patients whose condition cannot be diagnosed at presentation (and who therefore cannot immediately be streamed into an appropriate level of care) is uncertain. The role of cardiac biochemical markers in risk prediction for this group of patients remains unclear.Alteration of human serum albumin by ischemia has recently been evaluated as a serum biomarker of cardiac ischemia.¹ The amino terminal end (N-terminal) of the albumin molecule is a binding site for transitional metals such as cobalt, copper and nickel.¹ Possibly as the result of hypoxia, acidosis, free-radical injury and energy-dependent membrane disruption, the N-terminal undergoes a decrease in binding capacity in the presence of ischemia.^2,3,4 This alteration can be measured: a set amount of cobalt is added to the patient''s serum, after which a colorimetric assay, the albumin– cobalt binding assay, is used to determine the amount of cobalt that remains unbound. An elevated concentration of ischemia-modified albumin (IMA) has, therefore, been proposed as a marker of myocardial ischemic injury.^4,5,6 This assay is reported to be positive within minutes of ischemia and remains so for up to several hours later, allowing detection before the development of myocardial necrosis (as evidenced by normal levels of creatinine kinase isoenzyme [CK-MB], troponin and myoglobin).^5,7The ability to detect ischemia before myocyte destruction would allow for earlier and more accurate management decisions for patients suspected of having acute coronary syndrome (ACS) than is currently possible by measuring serum troponin, CK-MB or myoglobin levels. A test that detects all ongoing ischemia that could ultimately cause adverse events would also allow cardiac ischemia to be ruled out, permitting earlier discharge and fewer unnecessary investigations. Because of its potential capacity to identify acute cardiac ischemia, IMA measurement has been proposed as a means to triage patients arriving with symptoms that might result from cardiac ischemia.⁸ This study sought to determine the capacity of IMA testing to predict serious cardiac outcomes in the short term, in patients presenting to the emergency department with potential cardiac ischemia symptoms.A study of a diagnostic test is valid insofar as the investigators enrol an appropriate sample of patients and conduct an independent, blinded comparison with the method currently accepted as standard.⁹ Those in whom the diagnosis is in doubt represent an appropriate sample of patients. Patients presenting with an obvious disease are likely to have a different distribution of test results than those in whom the diagnosis is uncertain. Including such patients will therefore produce a biased — and likely, excessively sanguine — picture of the usefulness of the test under investigation.In this case, we were interested in detecting ischemia that leads to death, MI, heart failure, serious arrhythmia or refractory pain during the next 72 hours. Our target population was patients at risk of such adverse events. Patients who arrive in the emergency department having had any of the target events, or who have one before the test result is available, do not need further diagnostic evaluation for their likelihood of subsequently having the event of interest. Furthermore, the distribution of test results from such people is likely to differ from that of patients who remain at risk. Our target sample, therefore, was those patients who remained at risk of adverse events when their first IMA test result was available. Our target finding was the incidence of any of the events of interest, determined by blinded adjudication conducted in duplicate.     

Lymphocyte DNA damage in patients with acute coronary syndrome and its relationship with severity of acute coronary syndrome

OBJECTIVE: The aim of this study was to investigate the association between lymphocyte DNA damage and acute coronary syndromes (ACS). METHODS: The study population contained 53 patients with ACS, 48 patients with stable angina and 35 voluntary healty subjects. DNA damage was assessed by alkaline comed assay in peripheral lymphocyte and plasma levels of total antioxidant capacity (TAC) were determined using a novel automated measurement method. RESULTS: In ACS patients, DNA damage was significantly higher than in patients with stable angina and control subjects (144+/-52 AU, 116+/-37, 68+/-34 AU; for three p<0.001, respectively). The TAC levels in patients with ACS were lower than the other groups (1.24+/-0.31 mmol Trolox equiv./l, 1.46+/-0.29 mmol Trolox equiv./l, p<0.05, respectively). DNA damage values in patients with acute miyocardial infarction were significantly higher than in patients with unstable angina (159.8+/-53.0 AU versus 131.8+/-48.4 AU; p<0.05, respectively). Lymphocyte DNA damage values in patients with ACS showed positive correlation with d-dimer (r=0.880, p<0.001) troponin I (r=538, p<0.001) and C-reactive protein (r=0.544, p<0.001) and negative correlation with TAC (r=-0.346, p=0.011). In multiple linear regression analysis, TAC (beta=-0.213, p=0.001) and d-dimer (beta=0.697, p<0.001) were independent predictors of DNA damage in patients with ACS. CONCLUSIONS:These findings indicate that lymphocyte DNA damage level increases in patients with ACS. Elevated DNA damage may be related with plaque instability and be useful for the identification of patients with acute coronary syndromes.     

Sex-related differences in access to care among patients with premature acute coronary syndrome

Background:

Access to care may be implicated in disparities between men and women in death after acute coronary syndrome, especially among younger adults. We aimed to assess sex-related differences in access to care among patients with premature acute coronary syndrome and to identify clinical and gender-related determinants of access to care.

Methods:

We studied 1123 patients (18–55 yr) admitted to hospital for acute coronary syndrome and enrolled in the GENESIS-PRAXY cohort study. Outcome measures were door-to-electrocardiography, door-to-needle and door-to-balloon times, as well as proportions of patients undergoing cardiac catheterization, reperfusion or nonprimary percutaneous coronary intervention. We performed univariable and multivariable logistic regression analyses to identify clinical and gender-related determinants of timely procedures and use of invasive procedures.

Results:

Women were less likely than men to receive care within benchmark times for electrocardiography (≤ 10 min: 29% v. 38%, p = 0.02) or fibrinolysis (≤ 30 min: 32% v. 57%, p = 0.01). Women with ST-segment elevation myocardial infarction (MI) were less likely than men to undergo reperfusion therapy (primary percutaneous coronary intervention or fibrinolysis) (83% v. 91%, p = 0.01), and women with non–ST-segment elevation MI or unstable angina were less likely to undergo nonprimary percutaneous coronary intervention (48% v. 66%, p < 0.001). Clinical determinants of poorer access to care included anxiety, increased number of risk factors and absence of chest pain. Gender-related determinants included feminine traits of personality and responsibility for housework.

Interpretation:

Among younger adults with acute coronary syndrome, women and men had different access to care. Moreover, fewer than half of men and women with ST-segment elevation MI received timely primary coronary intervention. Our results also highlight that men and women with no chest pain and those with anxiety, several traditional risk factors and feminine personality traits were at particularly increased risk of poorer access to care.Despite improvements in the management of acute coronary syndrome over the past few decades, differences in mortality between men and women persist, especially among younger adults.¹ The reasons for poorer outcomes among women are thought to be multifactorial and may include higher baseline prevalence of risk factors for cardiovascular disease^2–4 and poorer access to care.^2–6 However, in the cited studies, patients were relatively old, and only one study⁴ considered clinical factors as potential confounders in the relationship. Moreover, determinants of access to care in men and women with premature acute coronary syndrome remain unknown.The effect of gender-related factors on access to care has not been investigated. Unlike sex, which is a biological characteristic, gender has a wider scope, incorporating the effects of social norms and expectations for men and women. Gender-related variables include gender identity, social roles, socioeconomic status and interpersonal relationships. There has been a considerable reduction in the gender gap in North America in the past decades.⁷ As a result, more women are gaining access to education and employment, and sharing of household and workplace responsibilities is becoming more common. Therefore, assessing sex alone cannot adequately account for differences in access to care among young adults with premature acute coronary syndrome. To better understand differences in access to care between men and women, a detailed examination of both sex- and gender-related factors is required.Our primary objective in this study was to assess sex-related differences in access to care among adults with premature acute coronary syndrome. Our secondary objective was to identify clinical and gender-related determinants of access to care among men and women.     

Primary percutaneous coronary angioplasty in patients with acute coronary syndrome and concomitant cancer

The paper gives the results of X-ray surgical treatment in patients with acute coronary syndrome who have been ascertained to have concomitant cancer during their examination. Cancer was found in 11 patients in their medical history and diagnosed in 2 patients during examination after surgical treatment and 1 patient one year after his hospital discharge. The results of combination treatment showed the high efficiency of X-ray surgical treatment for acute coronary syndrome. Recovery of TIMI-III blood flow through the infarct-related coronary artery was achieved in 100% of cases; immediate clinical efficiency was 97.4%. In the concomitant cancer group, the therapeutic efficacy was 100%; there were no complications during X-ray surgery. All the patients from this group were discharged from hospital in a satisfactory state to be followed up by a cardiologist and oncologist for further treatment. The study performed suggests that concomitant cancer is not a contraindication to primary coronary angioplasty in patients with acute coronary syndrome. Primary coronary angioplasty with stenting is a safe effective treatment for acute coronary syndrome in this category of patients.     

Dysregulated mitochondrial genes and networks with drug targets in postmortem brain of patients with posttraumatic stress disorder (PTSD) revealed by human mitochondria-focused cDNA microarrays

Posttraumatic stress disorder (PTSD) is associated with decreased activity in the dorsolateral prefrontal cortex (DLPFC), the brain region that regulates working memory and preparation and selection of fear responses. We investigated gene expression profiles in DLPFC Brodmann area (BA) 46 of postmortem patients with (n=6) and without PTSD (n=6) using human mitochondria-focused cDNA microarrays. Our study revealed PTSD-specific expression fingerprints of 800 informative mitochondria-focused genes across all of these 12 BA46 samples, and 119 (+/->1.25, p<0.05) and 42 (+/->1.60, p<0.05) dysregulated genes between the PTSD and control samples. Quantitative RT-PCR validated the microarray results. These fingerprints can essentially distinguish the PTSD DLPFC BA46 brains from controls. Of the 119 dysregulated genes (+/-> or =125%, p<0.05), the highest percentages were associated with mitochondrial dysfunction (4.8%, p=6.61 x 10(-6)), oxidative phosphorylation (3.8%, p=9.04 x 10(-4)), cell survival-apoptosis (25.2%, p<0.05) and neurological diseases (23.5%, p<0.05). Fifty (50) dysregulated genes were present in the molecular networks that are known to be involved in neuronal function-survival and contain 7 targets for neuropsychiatric drugs. Thirty (30) of the dysregulated genes are associated with a number of neuropsychiatric disorders. Our results indicate mitochondrial dysfunction in the PTSD DLPFC BA46 and provide the expression fingerprints that may ultimately serve as biomarkers for PTSD diagnosis and the drugs and molecular targets that may prove useful for development of remedies for prevention and treatment of PTSD.     

Access to catheterisation facilities in patients admitted with acute coronary syndrome: multinational registry study

Objective To investigate the relation between access to a cardiac catheterisation laboratory and clinical outcomes in patients admitted to hospital with suspected acute coronary syndrome.Design Prospective, multinational, observational registry.Setting Patients enrolled in 106 hospitals in 14 countries between April 1999 and March 2003.Participants 28 825 patients aged ≥ 18 years.Main outcome measures Use of percutaneous coronary intervention or coronary artery bypass graft surgery, death, infarction after discharge, stroke, or major bleeding.Results Most patients (77%) across all regions (United States, Europe, Argentina and Brazil, Australia, New Zealand, and Canada) were admitted to hospitals with catheterisation facilities. As expected, the availability of a catheterisation laboratory was associated with more frequent use of percutaneous coronary intervention (41% v 3.9%, P < 0.001) and coronary artery bypass graft (7.1% v 0.7%, P < 0.001). After adjustment for baseline characteristics, medical history, and geographical region there were no significant differences in the risk of early death between patients in hospitals with or without catheterisation facilities (odds ratio 1.13, 95% confidence interval 0.98 to 1.30, for death in hospital; hazard ratio 1.05, 0.93 to 1.18, for death at 30 days). The risk of death at six months was significantly higher in patients first admitted to hospitals with catheterisation facilities (hazard ratio 1.14, 1.03 to 1.26), as was the risk of bleeding complications in hospital (odds ratio 1.94, 1.57 to 2.39) and stroke (odds ratio 1.53, 1.10 to 2.14).Conclusions These findings support the current strategy of directing patients with suspected acute coronary syndrome to the nearest hospital with acute care facilities, irrespective of the availability of a catheterisation laboratory, and argue against early routine transfer of these patients to tertiary care hospitals with interventional facilities.     

Oxidative stress markers in patients with post-traumatic stress disorder

Recent study data support the role of oxidative stress in diverse psychiatric disorders. Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants and/or a depletion of antioxidants. There are numerous studies that indicate that free radicals (FRs) damage neurons, and then play an important role in the pathophysiology of schizophrenia and depression. Active oxygen can cause considerable damage and disrupt the important physiological functions of proteins, lipids, enzymes and DNA. The aim of our study was to investigate the possible differences in the concentration of tromboxane B2, 8-OHdG and protein carbonyls, as significant markers of oxidative damage, and urate, albumin and total protein concentrations as antioxidative molecules in PTSD patients in comparison to the healthy control group. The study included 74 male participants who were active soldiers in the Croatian armed forces from 1991 to 1995. 46 subjects with chronic and current PTSD were recruited from the Department of Psychiatry of Dubrava University Hospital during 2010, 28 healthy subjects were recruited in the same period during the regular medical examination at the Dubrava University Hospital. Study results have shown that there is no statistically significant difference in urinary concentrations of 8-OHdG, serum thromboxane B2, and serum urates between two studied groups. Statistically significant difference of the protein carbonyl concentrations was examined. Concentrations were significantly lower in the PTSD group than in the control group. The clinical significance of these results was examined using ROC analysis. The obtained ROC curves did not separate the groups in a satisfactory manner.     

Plasma apolipoprotein O level increased in the patients with acute coronary syndrome

Apolipoprotein (apo) O is a novel apolipoprotein that is present predominantly in high density lipoprotein (HDL). However, overexpression of apoO does not impact on plasma HDL levels or functionality in human apoA-I transgenic mice. Thus, the physiological function of apoO is not yet known. In the present study, we investigated relationships between plasma apoO levels and high-sensitive C-reactive protein (hs-CRP) levels, as well as other lipid parameters in healthy subjects (n = 111) and patients with established acute coronary syndrome (ACS) (n = 50). ApoO was measured by the sandwich dot-blot technique with recombinant apoO as a protein standard. Mean apoO level in healthy subjects was 2.21 ± 0.83 μg/ml whereas it was 4.94 ± 1.59 μg/ml in ACS patients. There were significant differences in plasma level of apoO between two groups (P < 0.001). In univariate analysis, apoO correlated significantly with lg(hsCRP) (r = 0.48, P < 0.001) in ACS patients. Notably, no significant correlation between apoO and other lipid parameters was observed. Logistic regression analysis showed that plasma apoO level was an independent predictor of ACS (OR = 5.61, 95% CI 2.16-14.60, P < 0.001). In conclusion, apoO increased in ACS patients, and may be regarded as an independent inflammatory predictor of ACS patients.     

Concentration of vascular endothelial growth factor in patients with acute coronary syndrome

Vascular endothelial growth factor (VEGF) is a regulator of vascular formation in physiological and pathological conditions. The aim of our study was to evaluate the value of VEGF as a surrogate marker of myocardial injury in acute ischemic conditions.Materials and methodsIn 104 consecutive patients with acute coronary syndrome (ACS) with and without ST segment elevation (STEMI and NSTEMI) the plasma and serum human VEGF (hVEGF) concentration was measured two times i.e. immediately after admission due to ACS and 24 h later. According to ECG findings and coronary angiography results, patients were divided into three groups. Group A represented major myocardial injury due to ST-segment elevation in precordial leads and/or in I and aVL leads and with left anterior descending (LAD) artery responsible for STEMI symptoms or additionally with significant atherosclerotic lesions (lumen vessel narrowed >50%) in other than LAD coronary arteries. Group B (medium myocardial injury) consisted of patients with ST-segment elevation in II, III and aVF leads and/or ST-segment depression in V2-V3 leads with one-vessel disease and the culprit artery was not LAD. Group C included patients with changes in ECG other than ST-segment elevation independently of the site of atherosclerotic lesions in coronary arteries.ResultsIn all 104 patients with ACS the highest values of serum hVEGF were observed in second measurement (357.9 ± 346 pg/ml, p < 0.01). Although in the first measurement, plasma and serum hVEGF concentration did not differentiate groups, the difference between deltas for serum hVEGF was observed (p < 0.05). Increased number of neutrophils in the first measurement increased the OR of the high serum hVEGF concentration in the first measurement (OR = 1.155; 95%CI: 1.011; 1.32) (p < 0.05). The number of neutrophils in the second measurement also revealed significant relationship with high serum hVEGF in the first assessment (OR = 1.318, 95%CI: 1.097; 1.583) (p < 0.01). Increased values of triglycerides (exceeding the upper limit) were connected with decreased OR of high serum hVEGF concentrations in the first measurement (OR = 0.152, 95%CI: 0.033; 0.695, p < 0.05).ConclusionsIn acute coronary syndrome, serum VEGF concentrations are elevated and can serve as a surrogate marker of myocardial injury. The elevated number of neutrophils increases odds ratio of high VEGF concentrations in ACS. In patients with high concentrations of triglycerides, odds ratio of low level of hVEGF is expected.     

双联抗血小板治疗急性冠脉综合征临床疗效观察

目的:探讨双联抗血小板治疗急性冠脉综合征(ACS)的临床疗效和安全性。方法:60例ACS患者随机分为治疗组和对照组。对照组给予阿司匹林单抗血小板治疗,治疗组采用阿司匹林+氯吡格雷双联抗血小板治疗,治疗3个月后评价临床疗效。结果:治疗组临床疗效总有效率为93.3%,显著高于对照组(76.7%),相比较有显著性差异(P<0.05);治疗后,两组LVEF、CO、E/A显著上升,与治疗前比较均有显著性差异(P<0.05);且治疗组与对照组比较有显著性差异(P<0.05)。结论:阿司匹林和氯吡格雷双联抗血小板药物治疗ACS,可以强化对血小板聚集的抑制,并增强抗栓效果,值得临床应用。     

双联抗血小板治疗急性冠脉综合征临床疗效观察

目的：探讨双联抗血小板治疗急性冠脉综合征（ACS）的临床疗效和安全性。方法：60例ACS患者随机分为治疗组和对照组。对照组给予阿司匹林单抗血小板治疗,治疗组采用阿司匹林＋氯吡格雷双联抗血小板治疗,治疗3个月后评价临床疗效。结果：治疗组临床疗效总有效率为93.3%,显著高于对照组（76.7%）,相比较有显著性差异（P〈0.05）;治疗后,两组LVEF、CO、E/A显著上升,与治疗前比较均有显著性差异（P〈0.05）;且治疗组与对照组比较有显著性差异（P〈0.05）。结论：阿司匹林和氯吡格雷双联抗血小板药物治疗ACS,可以强化对血小板聚集的抑制,并增强抗栓效果,值得临床应用。     

Modeling cortisol dynamics in the neuro-endocrine axis distinguishes normal, depression, and post-traumatic stress disorder (PTSD) in humans

Cortisol, secreted in the adrenal cortex in response to stress, is an informative biomarker that distinguishes anxiety disorders such as major depression and post-traumatic stress disorder (PTSD) from normal subjects. Yehuda et al. proposed a hypothesis that, in humans, the hypersensitive hypothalamus-pituitary-adrenal (HPA) axis is responsible for the occurrence of differing levels of cortisol in anxiety disorders. Specifically, PTSD subjects have lower cortisol levels during the late subjective night in comparison to normal subjects, and this was assumed to occur due to strong negative feedback loops in the HPA axis. In the present work, to address this hypothesis, we modeled the cortisol dynamics using nonlinear ordinary differential equations and estimated the kinetic parameters of the model to fit the experimental data of three categories, namely, normal, depressed, and PTSD human subjects. We concatenated the subjects (n = 3) in each category and created a model subject (n = 1) without considering the patient-to-patient variability in each case. The parameters of the model for the three categories were simultaneously obtained through global optimization. Bifurcation analysis carried out with the optimized parameters exhibited two supercritical Hopf points and, for the choice of parameters, the oscillations were found to be circadian in nature. The fitted kinetic parameters indicate that PTSD subjects have a strong negative feedback loop and, as a result, the predicted oscillating cortisol levels are extremely low at the nadir in contrast to normal subjects, albeit within the endocrinologic range. We also simulated the phenotypes for each of the categories and, as observed in the clinical data of PTSD patients, the simulated cortisol levels are consistently low at the nadir, and correspondingly the negative feedback was found to be extremely strong. These results from the model support the hypothesis that high stress intensity and strong negative feedback loop may cause hypersensitive neuro-endocrine axis that results in hypocortisolemia in PTSD.     

Elevated homocysteine level and prognosis in patients with acute coronary syndrome: a meta-analysis

Objective: Controversial results exist with respect to the association between elevated homocysteine level and adverse prognosis in acute coronary syndrome (ACS) patients. We performed a meta-analysis to evaluate the prognostic value of homocysteine level on ACS patients.

Materials and methods: A comprehensive literature search of PubMed and Embase databases was conducted prior to August 2018. Prospective observational studies reporting the association of baseline homocysteine level with major adverse cardiovascular events (MACE), cardiovascular or all-cause mortality in ACS patients were selected. Pooled risk ratio (RR) and corresponding 95% confidence intervals (CI) were calculated for the highest versus the lowest homocysteine level.

Results: Ten studies including 4120 ACS patients were identified. ACS patients with the highest homocysteine level had an increased risk of MACE (RR 2.01; 95% CI 1.53–2.64) and all-cause mortality (RR 2.05; 95% CI 1.50–2.79) after controlling confounding factors. However, the association between elevated homocysteine level and cardiovascular mortality (RR 1.08; 95% CI 0.83–1.39) was not statistically significant.

Conclusions: Elevated homocysteine level was associated with an increased risk of MACE and all-cause mortality among ACS patients. However, the association of elevated homocysteine level with cardiovascular mortality in ACS patients should be further confirmed in future studies.     

高龄急性冠脉综合征患者经皮冠状动脉支架治疗的临床观察

目的:评价高龄急性冠脉综合征(acute coronary syndrome,ACS)患者行经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗的安全性和有效性.方法:对比分析108例高龄ACS患者(≥75岁组)和176例非高龄ACS患者(<75岁组)冠状动脉造 影特征、PCI治疗的情况,即刻手术成功率、住院及随访期间主要心血管事件的发生情况.结果:高龄组与非高龄组比较,冠状动脉病变多为多支病变(72.2%比31.8%,P<001);2组手术即刻成功率无明显差异;2组术后达到心肌梗塞溶检(thrombolysis in myocardial infarction,TIMI)3级血流患者比率无明显差异;高龄组手术操作时间非高龄组长[(68.4±25.4)min比(53.7±21.8)min,P<0.05];高龄组住院期间、随访期间累计总的主要心血管事件发生率明显高于非高龄组.结论:对高龄ACS患者行PCI治疗是比较安全而有效的再灌注手段.