Serum biomarker discovery related to pathogenesis in acute coronary syndrome by proteomic approach

Acute coronary syndrome (ACS) results from inadequate supply of blood flow from the coronary arteries to the heart or ischemia. ACS has an extremely high morbidity and mortality. The levels of biomarkers currently used for detection of ACS also increase in response to myocardial necrosis and other diseases and are not elevated immediately after symptoms appear, thus limiting their diagnostic capacity. Therefore, we aimed to discover new ACS diagnostic biomarkers with high sensitivity and specificity that are specifically related to ACS pathogenesis. Sera from 50 patients with ACS and healthy controls (discovery cohort) each were analyzed using mass spectrometry (MS) to identify differentially expressed proteins, and protein candidates were evaluated as ACS biomarkers in 120 people in each group (validation cohort). α-1-acid glycoprotein 1 (AGP1), complement C5 (C5), leucine-rich α-2-glycoprotein (LRG), and vitronectin (VN) were identified as biomarkers whose levels increase and gelsolin (GSN) as a biomarker whose levels decrease in patients with ACS. We concluded that these biomarkers are associated with the pathogenesis of ACS and can predict the onset of ACS prior to the appearance of necrotic biomarkers.     

Comparison of temporal changes in established cardiovascular biomarkers after acute coronary syndrome between Caucasian and Chinese patients with diabetes mellitus

Abstract

Background: Population means of conventional cardiovascular biomarkers are known to differ between ethnic groups. In this study we performed detailed comparisons in the temporal pattern of these biomarkers between Caucasian and Chinese diabetic patients with acute coronary syndrome (ACS).

Methods: We studied differences in temporal changes of established cardiovascular biomarkers, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, cardiac Troponin T (TnT), NT-proBNP and C-reactive protein (CRP), in 48 Chinese and 48 clinically matched Caucasian patients with type 2 diabetes mellitus who were admitted for ACS. Blood samples were collected at regular time intervals during 30?days to 1?year after the index ACS.

Results: In the >30?day post ACS period, mean serum levels of LDL (2.16 vs. 1.47?mmol/L; p-value <0.001), total cholesterol (4.08 vs. 3.11?mmol/L; p-value <0.001), TnT (11.0 vs. 7.76?ng/L; p-value 0.010) and CRP (2.0 vs. 0.78?mg/L; p-value <0.001) were systematically higher in Caucasian than in Chinese patients. HDL and NT-proBNP levels were similar.

Conclusions: Our study showed clinically relevant differences in levels of established cardiovascular biomarkers between Caucasian and Chinese post ACS patients. Further cross-ethnic studies are warranted to determine secondary prevention treatment biomarker targets in specific populations.     

Plasma metabolomics reveals a potential panel of biomarkers for early diagnosis in acute coronary syndrome

Discovery of new biomarkers is critical for early diagnosis of acute coronary syndrome (ACS). Recent advances in metabolomic technologies have drastically enhanced the possibility of improving the knowledge of its physiopathology through the identification of the altered metabolic pathways. In this study, analyses of peripheral plasma from non-ST segment elevation ACS patients and healthy controls by gas chromatography–mass spectrometry (GC–MC) permitted the identification of 15 metabolites with statistical differences (p < 0.05) between experimental groups. Additionally, validation by GC–MC and liquid chromatography–MC permitted us to identify a potential panel of biomarkers formed by 5-OH-tryptophan, 2-OH-butyric acid and 3-OH-butyric acid. This panel of biomarkers reflects the oxidative stress and the hypoxic state that suffers the myocardial cells and consequently constitutes a metabolomic signature of the atherogenesis process that could be used for early diagnosis of ACS.     

Blood histamine is associated with coronary artery disease,cardiac events and severity of inflammation and atherosclerosis

Background : Mast cells are prevalent in the shoulder of unstable atheromas; cardiac mast cells secrete proteases capable of activating matrix metalloproteinases. Histamine is essential in the inflammatory cascade of the unstable plaque. Ascorbate depletion has been correlated with histaminemia which has been shown to impair endothelial-dependent vasodilation. This study evaluates whether oxidative stress as measured by isoprostanes (PGF_2α) coupled with an inflammatory state characterized by histaminemia predisposes patients to acute coronary syndrome (ACS).
Methods : Whole blood histamine, serum vitamin C, and serum PGF_2α levels were drawn on 50 patients with ACS as determined by standard diagnostic criteria, 50 patients with stable coronary artery disease (SCAD), and 50 age and sex matched normal controls (C).
Results : Data were analyzed by stepwise discriminant and Spearman's rank correlation coefficient. A significant relationship exists between histamine and PGF_2α. As PGF_2α rises above 60 pg/mL, an increase in histamine occurs in both the ACS and SCAD groups. A significant inverse relationship exists between ascorbate and histamine in the ACS versus C groups (P < 0.01) and the SCAD versus C groups (P < 0.01).
Conclusion : Histamine and isoprostane levels increase in SCAD and ACS patients. Mast cell activation and lipid oxidation generated during atherosclerosis manifest this inflammatory response. Accelerated isoprostane formation and depleted ascorbate paired with histaminemia is active in CAD and predispose patients to acute coronary syndrome. Blood histamine alone may be a better risk factor for coronary events, and a better prognostic indicator than CRP even when combined with lipid indexes.     

Gender issues in cardiovascular diseases. Focus on energy metabolism

It is increasingly recognized that sex and gender differences (S&G) influence cardiovascular diseases (CVD), greatly impacting disease management. In terms of definition, sex refers to biological aspects, gender effects being mainly related to socio-cultural factors. Both sex and gender are interpenetrated in humans and difficult to separate. This is more clearly feasible in animal models where sex effects largely predominate. As alterations in energy metabolism are essential features of cardiovascular diseases, sexual dimorphism of energy metabolism and more specifically mitochondria occupies a place of choice. This review presents the basis of sex and gender differences in the cardiovascular pathophysiology, and how it mainly affects woman diseases, effectiveness of therapies and clinical outcome. These differences rely on complex molecular mechanisms that are still poorly understood because of the under-representation of females/women in experimental and clinical studies. Finally, the differing psychological and biological phases of woman's life are largely underestimated. This review presents an overview of the field with focus on differences in cardiac energy metabolism, which are illustrated with specific examples.     

Pregnancy-associated plasma protein A and proform eosinophilic major basic protein in the detection of different types of coronary artery disease

Kryptor system was proven to be a rapid, standard method for pregnancy-associated plasma protein A and proform eosinophilic major basic protein (PAPP-A/proMBP) complex detection in coronary artery disease (CAD). No age and/or gender differences in 51 controls and 110 stable coronary artery disease (SCAD) patients were found. SCAD patients did not differ from controls and no difference in PAPP-A/proMBP levels with regards to the number of affected vessels was found. In 21 unstable angina pectoris (UAP), in 35 without and 66 with ST elevation acute myocardial infarctions (NSTEMI, STEMI respectively) patients PAPP-A/proMBP levels were increased (P=0.004 and P<0.0005, respectively). PAPP-A/proMBP levels did not correlate with cardiac troponin I (cTnI) in STEMI and NSTEMI patients. PAPP-A/ proMBP increase was more frequent than cTnI (P=0.036) within the early phase of STEMI. In NSTEMI patients PAPP-A/proMBP positivity was present in 50 % of cTnI negative cases. Receiver operating characteristic (ROC) analysis revealed the highest diagnostic accuracy of PAPP-A/proMBP (0.919) in STEMI cTnI positive cases. The highest specificity/sensitivity PAPP-A/proMBP levels for particular acute coronary syndrome (ACS) types were 10.65-14.75 mIU/l. Combination of PAPP-A/proMBP with cTnI increases their diagnostic efficacy within the early phase of ACS. Our results suggest that PAPP-A/proMBP complex is involved in processes preceding vulnerable plaque development in ACS.     

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.     

Obesity and Long-Term Clinical and Economic Outcomes in Coronary Artery Disease Patients

Objective: Obesity is an important risk factor for coronary artery disease (CAD); however, its effect on acute coronary syndrome (ACS) patients’ long-term clinical and economic outcomes has not been quantified. We assessed the impact of increasing body mass index (BMI) on 10-year outcomes for ACS patients. Research Methods and Procedures: ACS patients with significant CAD receiving an initial cardiac catheterization at Duke University Medical Center between 1986 and 1997 were included. Patients with a BMI < 18.5 kg/m² were excluded; the remaining patients were classified by BMI as normal, overweight, obese, or very obese. Medical costs were estimated from a prior ACS clinical trial with costs adjusted to 1997 dollars and discounted at 3% per annum. Results: There were 9405 patients with data available for analysis. Follow-up was complete on >95% of patients. Patients who were obese at baseline increased from 20% to 33% between 1986 and 1997. Increased BMI was associated with younger age, multi-morbidity, and less severe CAD at baseline. It was also associated with more clinical events, higher cumulative inpatient medical costs, and significant differences in unadjusted survival at 10 years. However, it was not associated with differences in 10-year survival after adjusting for baseline characteristic differences. Discussion: Obese ACS pateints are younger and are hospitalized more frequently during the first 10 years of their illness than are non-obese patients. They also incur higher cumulative inpatient medical costs, especially the very obese. These findings highlight the opportunities for therapeutic benefit that aggressive weight management and secondary prevention may provide this population.     

Women and the management of acute coronary syndrome

Coronary heart disease (CHD) is the leading cause of morbidity and mortality in both men and women in the developed countries. Despite this fact, females are still under-represented in the majority of clinical trials. At the present time, only limited evidence is available with respect to the female-specific aspects of pathogenesis, management, and outcomes in acute coronary syndrome (ACS). Women less frequently undergo coronary intervention, and a lower proportion of women receive evidence-based pharmacotherapy, compared with men. It has been shown that women benefit from an invasive approach and coronary intervention in ACS as much as men, despite their advanced age and higher rate of bleeding complications. Also, administration of beta-blockers, ACE-inhibitors, and intensive statin therapy is associated with a comparable reduction of cardiovascular event rates in women and men. On the other hand, women may profit less than men from fibrinolytic or glycoprotein IIb/IIIa inhibitor therapy. Both sexes benefit equally from aspirin therapy, whereas contradictory data are available on the efficacy of clopidogrel in women. There is an urgent need for intensive research in the development of female-specific therapeutic strategy in ACS, even though the detailed mechanisms of sex differences are still unknown.     

Sex-Based Differences in Cardiac Arrhythmias, ICD Utilisation and Cardiac Resynchronisation Therapy

Many important differences in the presentation and clinical course of cardiac arrhythmias are present between men and women that should be accounted for in clinical practice. In this paper, we review published data on gender differences in cardiac excitable properties, supraventricular tachycardias, ventricular tachycardias, sudden cardiac death, and the utilisation of implantable defibrillators and cardiac resynchronisation therapy. Women have a higher heart rate at rest, and a longer QT interval than men. They further have a narrower QRS complex and lower QRS voltages on the 12-lead ECG with more often non-specific repolarisation abnormalities at rest. Supraventricular tachycardias, such as AV nodal reentrant tachycardia, are twice as frequent in women compared with men. Atrial fibrillation, however, has a 1.5-fold higher prevalence in men. The triggers for idiopathic right ventricular outflow tract tachycardia (VT) initiation are gender specific, i.e. hormonal changes play an important role in the occurrence of these VTs in women. There are clear-cut gender differences in acquired and congenital LQTS. Brugada syndrome affects men more commonly and severely than women. Sudden cardiac death is less prevalent in women at all ages and occurs 10 years later in women than in men. This may be related to the later onset of clinically manifest coronary heart disease in women. Among patients who receive ICDs and CRT devices, women appear to be under-represented, while they may benefit even more from these novel therapies.     

急性冠脉综合征患者GRACE评分与心功能及冠脉病变的关系研究

目的:探讨全球急性冠状动脉疾病登记(GRACE)风险评分与急性冠脉综合征(ACS)患者心功能及冠脉病变的关系。方法:回顾性分析2015年4月至2017年6月我院收治的276例ACS患者的临床资料,根据GRACE评分结果进行分组,GRACE评分140分者作为高危组(93例),GRACE评分109~140分者作为中危组(96例),GRACE评分109分者作为低危组(87例),比较三组的一般资料、生化指标、心功能指标、冠脉病变严重程度,采用Spearman相关系数分析GRACE评分与心功能指标和冠脉病变严重程度的相关性。结果:高危组和中危组男性所占比例、年龄、高血压比例、载脂蛋白-B(Apo-B)、空腹血糖(FBG)、纤维蛋白原(FIB)、胱抑素-C(Cys-C)、同型半胱胺酸(Hcy)、左心房前后径(LAAP)、左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、多支血管病变所占比例以及重度狭窄和完全闭塞所占比例高于低危组,且高危组高于中危组,差异均有统计学意义(P0.05);高危组和中危组三酰甘油(TG)、载脂蛋白-A(Apo-A)、左心室射血分数(LVEF)低于低危组,且高危组低于中危组,差异均有统计学意义(P0.05)。Spearman相关系数分析显示,GRACE评分与LAAP、LVESD、LVEDD、冠脉病变血管支数、狭窄程度呈正相关关系(P0.05),GRACE评分与LVEF水平呈负相关关系(P0.05)。结论:GRACE评分越高,ACS患者的心功能越差,冠脉病变越严重,GRACE评分可以反映ACS患者的心功能水平和冠脉病变的严重程度。     

Levels of BNP and Stress Blood Glucose in Acute Coronary Syndrome Patients and Their Relationships with the Severity of Coronary Artery Lesion

This study aims to analyze the clinical significance of the measuring B-type natriuretic peptide (BNP) and stress glycemia in patients with acute coronary syndrome (ACS), and to investigate the relationships between the two biomarkers and the severity of coronary artery lesions. One hundred and five consecutive patients with ACS admitted for coronary artery angiography were divided into three clinical subgroups. These patients were then further assigned into either of three subgroups according to their Gensini score. Moreover, a group of patients with stable angina (SA) and those with no history of coronary disease served as controls. The patients’ BNP levels were analyzed on admission and their fasting blood glucose was measured the next morning. BNP and fasting blood glucose concentrations were highly elevated in patients with ACS irrespective of their subgroups compared to SA and control patients. This observation was statistically significant (P < 0.001). Further, the concentrations of BNP and fasting blood glucose between the three ACS subgroups were significantly different (P < 0.001) depending on the severity of the coronary artery disease. There is a positive correlation between levels of BNP and blood glucose concentration and Gensini score in ACS patients (r = 0.782, P < 0.05, r = 0.732, P < 0.05). BNP level and stress glycemia were significantly higher in ACS patients than those in SA and control groups. There is a correlation between BNP level and stress blood glucose concentration and the severity of coronary artery lesions. Combined analysis of BNP and stress blood glucose can be helpful and effective for risk stratification of patients with ACS after admission.     

Soluble CD40 Ligand in Aspirin-Treated Patients Undergoing Cardiac Catheterization

Plasma soluble CD40 ligand (sCD40L) is mainly generated by cleavage of CD40L from the surface of activated platelets, and therefore considered a platelet activation marker. Although the predictive value of sCD40L for ischemic events has been demonstrated in patients with acute coronary syndromes (ACS), studies on the association of sCD40L with cardiovascular outcomes in lower risk populations yielded heterogeneous results. We therefore sought to investigate factors influencing sCD40L levels, and the predictive value of sCD40L for long-term ischemic events in unselected, aspirin-treated patients undergoing cardiac catheterization. sCD40L was determined by a commercially available enzyme-linked immunosorbent assay in 682 consecutive patients undergoing cardiac catheterization. Two-year follow-up data were obtained from 562 patients. Dual antiplatelet therapy with aspirin and clopidogrel was associated with significantly lower levels of sCD40L and lower platelet surface expressions of P-selectin and activated GPIIb/IIIa compared to aspirin monotherapy (all p≤0.01). Hypertension was linked to lower plasma concentrations of sCD40L, whereas female sex, increasing high-sensitivity C-reactive protein, and hematocrit were associated with higher sCD40L concentrations (all p<0.05). sCD40L levels were similar in patients without and with the primary endpoint in the overall study population (p = 0.4). Likewise, sCD40L levels did not differ significantly between patients without and with the secondary endpoints (both p≥0.4). Similar results were obtained when only patients with angiographically-proven coronary artery disease (n = 459), stent implantation (n = 205) or ACS (n = 125) were analyzed. The adjustment for differences in patient characteristics by multivariate regression analyses did not change the results. ROC curve analyses did not reveal cut-off values for sCD40L for the prediction of the primary or secondary endpoints. In conclusion, plasma sCD40L levels are reduced by antiplatelet therapy with clopidogrel, but not associated with long-term ischemic outcomes in unselected consecutive aspirin-treated patients undergoing cardiac catheterization.     

Fluvastatin in the therapy of acute coronary syndrome: Rationale and design of a multicenter, randomized, double-blind, placebo-controlled trial (The FACS Trial)[ISRCTN81331696

BACKGROUND: Activation of inflammatory pathways plays an important contributory role in coronary plaque instability and subsequent rupture, which can lead to the development of acute coronary syndrome (ACS). Elevated levels of serum inflammatory markers such as C-reactive protein (CRP) represent independent risk factors for further cardiovascular events. Recent evidence indicates that in addition to lowering cholesterol levels, statins also decrease levels of inflammatory markers. Previous controlled clinical trials reporting the positive effects of statins in participants with ACS were designed for very early secondary prevention. To our knowledge, no controlled trials have evaluated the potential benefits of statin therapy, beginning immediately at the time of hospital admission. A previous pilot study performed by our group focused on early initiation of cerivastatin therapy. We demonstrated a highly significant reduction in levels of inflammatory markers (CRP and interleukin-6). Based on these preliminary findings, we are conducting a clinical trial to evaluate the efficacy of another statin, fluvastatin, as an early intervention in patients with ACS. METHODS: The FACS-trial (Fluvastatin in the therapy of Acute Coronary Syndrome) is a multicenter, randomized, double-blind, placebo-controlled study evaluating the effects of fluvastatin therapy initiated at the time of hospital admission. The study will enroll 1,000 participants admitted to hospital for ACS (both with and without ST elevation). The primary endpoint for the study is the influence of fluvastatin therapy on levels of inflammatory markers (CRP and interleukin-6) and on pregnancy associated plasma protein A (PAPP-A). A combined secondary endpoint is 30-day and one-year occurrence of death, nonfatal myocardial infarction, recurrent symptomatic ischemia, urgent revascularization, and cardiac arrest. CONCLUSION: The primary objective of the FACS trial is to demonstrate that statin therapy, when started immediately after hospital admission for ACS, results in reduction of inflammation and improvement of prognosis. This study may contribute to new knowledge regarding therapeutic strategies for patients suffering from ACS and may offer additional clinical indications for the use of statins.     

Sex,gender, and pharmaceutical politics: From drug development to marketing

Background: Biological sex differences and sociocultural gender norms affect the provision of health care products and services, but there has been little explicit analysis of the impact of sex differences and gender norms on the regulation of pharmaceutical development and marketing.Objectives: This article provides an overview of the regulation of pharmaceuticals and examines the ways that regulatory agencies account for sex and gender in their review of scientific data and marketing materials.Methods: The primary focus is on the US context, but information is also included about regulatory models in Europe, Canada, and Japan for comparative purposes. Specific examples show how sex differences and gender norms influence scientific and policy decisions about pharmaceuticals.Results: The United States and Canada were found to be the only countries that have explicit requirements to include women in clinical trials and to perform sex-based subgroup analysis on study results. The potential influence of politics on regulatory decisions may have led to an uneven application of standards, as seen through the examples of mifepristone (for abortion) and sildenafil citrate (for erectile dysfunction). Three detailed case studies illustrate the importance of considering sex and gender in pharmaceutical development and marketing: Phase I clinical trials; human papillomavirus quadrivalent vaccine; and tegaserod, a drug for irritable bowel syndrome.Conclusions: Sex and gender play important roles in pharmaceutical regulation, from the design of clinical trials and the approval of new drugs to advertising and postmarketing surveillance. However, regulatory agencies pay insufficient attention to both biological sex differences and sociocultural gender norms. This disregard perpetuates inequalities by ignoring drug safety problems that predominate in women and by allowing misleading drug marketing that reinforces gender stereotypes. Recommendations have been made to improve the regulation of pharmaceuticals in regard to sex and gender.     

Effects of Clopidogrel and Proton Pump Inhibitors on Cardiovascular Events in Patients with Type 2 Diabetes Mellitus after Drug-Eluting Stent Implantation: A Nationwide Cohort Study

Objective

To investigate whether there is an increased risk of cardiac events in diabetic patients with a combined therapy of clopidogrel (CLO) and proton pump inhibitors (PPIs) after drug-eluting stent (DES) deployment.

Methods

By using National Health Insurance Research Database, all patients who received CLO with or without PPI therapy within 90 days after undergoing DES (limus-eluting or paclitaxel-eluting stents) deployment were enrolled. Endpoints were acute coronary syndrome (ACS) and readmission for revascularization (percutaneous coronary intervention or coronary artery bypass graft surgery) after 3, 6, and 12 months.

Results

A total of 6,603 diabetic patients received LESs (5,933 in the CLO subgroup and 670 in the CLO plus PPIs subgroup), and 3,202 patients received PESs (2,923 in the CLO subgroup and 279 in the CLO plus PPIs subgroup). The patients who received CLO plus PPIs were at higher risk of ACS than those receiving CLO within 1 year after DES deployment (LESs: 6-month hazard ratio [HR] = 1.63, and 1-year HR = 1.37; PESs: 3-month HR = 1.72). Patients with a history of ACS who received CLO plus PPIs were at higher risk of ACS after LES implantation (HR = 1.55) than those in the CLO group.

Conclusion

In “real-world” diabetic patients with LES deployment, the combination of PPIs and CLO is associated with higher rates of ACS after 6 months and 1 year. Even after correction for confounding factors, concomitant PPI use remained an independent predictor of cardiac events, emphasizing the clinical importance of this drug—drug interaction.     

The utility of inflammation and platelet biomarkers in patients with acute coronary syndromes

Introduction

Thrombotic and inflammatory mechanisms are involved in the pathophysiology of acute coronary syndrome (ACS). The aim of the study was the evaluation of inflammation (white blood cells count/WBC, C-reactive protein/CRP, interleukin-6/IL-6) and platelet (platelet count/PLT, mean platelet volume/MPV, large platelet/LPLT, beta-thromboglobulin/β-TG) biomarkers in the groups of ACS patients depending on the severity of signs and symptoms and compared to controls without coronary artery disease.

Integrating PoCT into Clinical Care

In South Australia, the Integrated Cardiovascular Clinical Network SA (iCCnet SA) is the provider which enacts the recommendations and policies of the state-wide cardiac clinical network working parties in rural and remote areas by developing appropriate clinical tools.Pathology tests play a significant role in contributing to best practice for patient diagnosis and management. As most South Australian country hospitals do not have timely access to pathology results, point-of-care testing (PoCT) for troponin and N-terminal pro-brain natriuretic peptide (NT-proBNP) has been integrated into clinical pathways for the management of possible acute coronary syndrome (ACS) and suspected heart failure patients respectively. Compared with control hospitals of similar size and resources, preliminary results from an iCCnet SA regional hospital showed improved patient outcomes for ACS: 30-day readmission rates were reduced from 10.4% to 4.2% (p = 0.03) and there was a corresponding trend in the reduction of in-hospital death rates from 15.8% to 9.8% (p = 0.1).The establishment of iCCnet SA has improved outcomes for rural patients presenting to hospital with symptoms suggestive of ACS by facilitating the uptake of evidence-based acute cardiac care. Implementation of PoCT equipment into clinical care requires a systematic approach that engages all stakeholders involved in patient care. Provider clinical networks, such as iCCnet SA, provide a structure for effective working relationships between health professionals. PoCT has been critical to the success of the network, but it needs to be implemented within an integrated system of care to produce optimal outcomes.     

Gender roles in persistent sex differences in health-related quality-of-life outcomes of patients with coronary artery disease

Background: The increased recognition of significant sex/gender differences in health status outcomes, and the implications for clinical practice and service delivery, has led to calls for more gender sensitivity and specificity in research endeavors as well as within clinical practice. Previous investigations by our research group have consistently identified important sex differences in both changes in health status from baseline to 1 year and in health status outcomes of patients treated for coronary artery disease (CAD), with women reporting poorer health-related quality of life (HRQoL) compared with men.Objective: The objective of this study was to examine whether persistent sex differences in the health status of patients with CAD may be attributed to social factors such as gender roles.Methods: Sex differences in baseline clinical and demographic characteristics of patients who completed the 1-year follow-up survey were examined using t tests and χ² analyses. Structural equation modeling, an inclusive statistical modeling approach for testing hypotheses about relationships among measured and latent variables (concepts not observed or measured directly), was used to test our theoretical model.Results: HRQoL data were collected on 2403 patients 1 year after index catheterization. The results indicated that the model fit was substantially improved by the addition of the conceptualized gender-role variable. Furthermore, there was a significant effect of gender role on QoL (?0.106; P < 0.05). Age, coronary anatomy, ejection fraction, physical limitation, anginal frequency, and gender role variables in this model were able to explain 51% of the variance in HRQoL. In particular, reported physical limitations, anginal frequency, and gender role had large statistically significant direct effects on HRQoL.Conclusions: Advances in the treatment of CAD have led to significant decreases in mortality rates. Our current challenge is to minimize the long-term impact of CAD on HRQoL outcomes. While a substantial body of literature has examined the correlations between gender-role attributes and a wide variety of both positive and negative outcomes, this area has not been explored in patients with cardiovascular disease. These findings suggest that further study of the influence of gender role (using a gender-role measurement) on HRQoL is needed.