Circulating inflammatory and hemostatic biomarkers are associated with risk of myocardial infarction and coronary death, but not angina pectoris, in older men

Aims: The extent to which hemostatic and inflammatory biomarkers are related to angina pectoris as compared with myocardial infarction (MI) remains uncertain. We examined the relationship between a wide range of inflammatory and hemostatic biomarkers, including markers of activated coagulation, fibrinolysis and endothelial dysfunction and viscosity, with incident myocardial infarction (MI) or coronary heart disease (CHD) death and incident angina pectoris uncomplicated by MI or CHD death in older men. Methods: A prospective study of 3217 men aged 60-79 years with no baseline CHD (angina or MI) and who were not on warfarin, followed up for 7 years during which there were 198 MI/CHD death cases and 220 incident uncomplicated angina cases. Results: Inflammatory biomarkers [C-reactive protein (CRP), interleukin-6, fibrinogen], plasma viscosity and hemostatic biomarkers [von Willebrand factor (VWF) and fibrin D-dimer] were associated with a significant increased risk of MI/CHD death but not with uncomplicated angina even after adjustment for age and conventional risk factors. Adjustment for CRP attenuated the relationships between VWF, fibrin D-dimer and plasma viscosity with MI/CHD death. Comparisons of differing associations with risk of MI/CHD deaths and uncomplicated angina were significant for the inflammatory markers (P < 0.05) and marginally significant for fibrin D-dimer (P = 0.05). In contrast, established risk factors including blood pressure and high-density lipoprotein (HDL)-cholesterol were associated with both MI/CHD death and uncomplicated angina. Conclusion: Circulating biomarkers of inflammation and hemostasis are associated with incident MI/CHD death but not incident angina uncomplicated by MI or CHD death in older men

Prevalence, incidence, primary care burden and medical treatment of angina in Scotland: age, sex and socioeconomic disparities: a population-based study

Objective: To examine the epidemiology, primary care burden and treatment of angina in Scotland. Design: Cross-sectional data from primary care practices participating in the Scottish continuous morbidity recording scheme between 1 April 2001 and 31 March 2002. Setting: 55 primary care practices (362 155 patients). Participants: 9508 patients with angina. Results: The prevalence of angina in Scotland was 28/1000 in men and 25/1000 in women (p &#60; 0.05) and increased with age. The prevalence of angina also increased with increasing socioeconomic deprivation from 18/1000 in the least deprived category to 31/1000 in the most deprived group (p &#60; 0.001 for trend). The incidence of angina was higher in men (1.8/1000) than in women (1.4/1000) (p = 0.004) and increased with increasing age and socioeconomic deprivation. Socioeconomically deprived patients (0.48 contacts/patient among the most deprived) were less likely than affluent patients (0.58 contacts/patient among the least deprived) to see their general practitioner on an ongoing basis p = 0.006 for trend). Among men, 52% were prescribed ß blockers, 44% calcium channel blockers, 72% aspirin, 54% statins and 36% angiotensin converting enzyme inhibitors or angiotensin receptor blockers. The corresponding prescription rates for women were 46% (p &#60; 0.001), 41% (p = 0.02), 69% (p &#60; 0.001), 45% (p &#60; 0.001) and 30% (p &#60; 0.001). Among patients &#60; 75 years old 52% were prescribed a &#946; blocker and 58% a statin. The corresponding figures for patients &#8805; 75 years were 42% (p &#60; 0.001) and 31% (p &#60; 0.001). Conclusions: Angina is a common condition, more so in men than in women. Socioeconomically deprived patients are more likely to have angina but are less likely to consult their general practitioner. Guideline-recommended treatments for angina are underused in women and older patients. These suboptimal practice patterns, which are worst in older women, are of particular concern, as in Scotland more women (and particularly older women) than men have angina

Myocardial ischemia after orthotopic liver transplantation

A hypercoagulable state exists after orthotopic liver transplantation. This hematologic abnormality may predispose patients to coronary thrombosis and unstable angina. The incidence of post-operative myocardial ischemia in such patients is unknown. Suitable electrocardiograms and clinical events of consecutive patients undergoing orthotopic liver transplantation (n = 45) and major intraabdominal surgery (n = 28) during a 3-month period at a major university teaching hospital and transplant center were examined retrospectively. Clinical myocardial ischemia or ischemic electrocardiographic changes, or both, occurred in 6 transplant patients compared with no patient in the nontransplant or comparison group. In 4 of the 6 patients with dramatic electrocardiographic changes and ischemic events, coronary arteriography failed to demonstrate significant obstructive disease. It is concluded that severe myocardial ischemia may occur in patients after orthotopic liver transplantation in the absence of significant coronary disease. A hypercoagulable state may predispose to coronary thrombosis in this setting, providing insight (and a future model for study) into the development of unstable angina. © 1994

Health Related Quality of Life in Coronary Patients.

The increase observed in the survival of patients with ischemic cardiopathy, together with the effect of the disease on the social, professional, and family life of those suffering from it, have led researchers to consider that the traditional ways of measuring morbidity and mortality are not adequate for assessing the potential benefits of health care interventions. For this reason, there is common agreement on the need to use an indicator of subjective assessment of health, and of health related quality of life (HRQL), as a complementary criterion for monitoring the results of medical interventions in these patients. The term "quality of life" (QoL) or health related quality of life (HRQL) came into use during the 1970s as a multidimensional concept reflecting the overall subjective condition of the physical and mental welfare of the individual, which is a consequence not only of the disease but also of the family and social conditions forming the patient’s environment. The assessment of these patients’ HRQL has been tackled by several authors using both disease-specific and generic instruments such as the Nottingham Health Profile, the Sickness Impact Profile, the SF-36 or the SF-12 health questionnaire. Both types of instrument have advantages and disadvantages, and they may provide additional information since they quantify the patient’s overall health. Using different multidimensional measures, poorer HRQL has been observed in patients with Acute Myocardial Infarction (AMI) and angina pectoris than in other populations, and these differences have been related to low social class, female sex, the presence of mental disorders and the severity of the clinical condition. Measuring changes in the HRQL of coronary patients is also important as a way of assessing interventions and predicting needs for social care, because it has been shown that the focus of attention in the immediate period following a cardiac attack is generally the physical functioning, but following discharge from hospital and in the longer term, general health, vitality, social and emotional functions could be at least as important. In this chapter, we aim to provide an overview of the concept of HRQL and the usefulness of this measure from the perspective of a coronary patient. Likewise, we intend to review the main instruments used to assess HRQL and we analyse the factors that have been seen to affect the quality of life of these patients

Phenotypic characteristics of the p.Asn215Ser (p.N215S) GLA mutation in male and female patients with Fabry disease: A multicenter Fabry Registry study.

BackgroundThe p.Asn215Ser or p.N215S GLA variant has been associated with late-onset cardiac variant of Fabry disease.MethodsTo expand on the scarce phenotype data, we analyzed natural history data from 125 p.N215S patients (66 females, 59 males) enrolled in the Fabry Registry (NCT00196742) and compared it with data from 401 patients (237 females, 164 males) harboring mutations associated with classic Fabry disease. We evaluated interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), estimated glomerular filtration rate and severe clinical events.ResultsIn p.N215S males, mildly abnormal mean IVST and LVPWT values were observed in patients aged 25-34 years, and values gradually increased with advancing age. Mean values were similar to those of classic males. In p.N215S females, these abnormalities occurred primarily in patients aged 55-64 years. Severe clinical events in p.N215S patients were mainly cardiac (males 31%, females 8%) while renal and cerebrovascular events were rare. Renal impairment occurred in 17% of p.N215S males (mostly in patients aged 65-74 years), and rarely in females (3%).Conclusionp.N215S is a disease-causing mutation with severe clinical manifestations found primarily in the heart. Cardiac involvement may become as severe as in classic Fabry patients, especially in males

Five year prognosis in patients with angina identified in primary care : incident cohort study

Peer reviewedPublisher PD

Prognostic Value of Ciculating Pregnancy-Associated Plasma Protein-A (PAPP-A) and Proform of Eosinophil Major Basic Protein (pro-MBP) Levels in Patients with Chronic Stable Angina Pectoris

Background: The search for markers to improve risk prediction for individuals at risk of developing serious cardiovascular events is ongoing. New markers of coronary artery disease progression have been identified in recent years, among which, circulating levels of pregnancy-associated plasma protein-A (PAPP-A) offer an interesting profile. PAPP-A may play a role in the development of atherosclerotic lesions and represent also a marker of atheromatous plaque instability and extent of cardiovascular disease. PAPP-A has been shown to be a marker of adverse outcome in the acute coronary syndrome. The proform of eosinophil major basic protein (pro-MBP) is the endogenous inhibitor of the proteolytic activity of PAPP-A. PAPP-A levels and PAPP-A/pro-MBP ratio are increased in chronic stable angina (CSA) patients with complex coronary artery stenoses. Little is known however, about the long-term prognostic value of PAPP-A and pro-MBP in “real-life” CSA patients. We sought to assess whether PAPP-A, pro-MBP and PAPP-A/pro-MBP levels predict long-term all-cause mortality in patients with CSA. Methods: We recruited 663 consecutive patients (169 women [25.5 %]; mean age 62.9 ± 9.7 years) undergoing routine diagnostic coronary angiography. Samples for PAPP-A and pro-MBP were taken at study entry. Patients were followed for a median of 8.8 years (interquartile range 3 - 10.6 years). Results: One hundred and six patients (16 %) died during follow-up. On a Cox proportional hazards model, increased PAPP-A concentration (> 4.8 mIU/L) was an independent predictor of the occurrence of all-cause mortality (HR 1.953, 95% CI 1.135-3.360, p = 0.016). Neither pro-MBP nor PAPP-A/pro-MBP ratio were markers of all-cause mortality (p = 0.45 and 0.54, respectively). Conclusions: High PAPP-A levels (> 4.8 mIU/L) showed an association with all-cause mortality during long-term follow-up in patients with CSA. Keywords: PAPP-A, pro-MBP, chronic stable angina, prognosis.Antecedentes: La búsqueda de marcadores para mejorar la predicción de individuos en riesgo de desarrollar eventos cardiovasculares está en marcha. Recientemente se han identificado nuevos marcadores de progresión de la enfermedad coronaria, entre los cuales, la proteína plasmática asociada a embarazo tipo A (PAPP-A) presenta un perfil interesante. PAPP-A podría desempeñar un papel en el desarrollo de las lesiones ateroscleróticas, así como representar un marcador de inestabilidad de placa ateromatosa y extensión de la enfermedad aterosclerótica. Además PAPP-A es un marcador de eventos adversos en el contexto del síndrome coronario agudo. La proforma de la proteína mayor básica eosinofílica (pro-MBP) es un inhibidor endógeno de la actividad proteolítica de PAPP-A. Los niveles de PAPP-A y del cociente PAPP-A/pro-MBP están aumentados en pacientes angina crónica estable que presentan lesiones coronarias complejas en la angiografía. Se desconoce el valor pronóstico a largo plazo de los niveles de PAPP-A y pro-MBP en pacientes con angina crónica estable de la “práctica real”. Se pretendió en este estudio evaluar si los niveles de PAPP-A, pro-MBP y del cociente PAPP-A/pro-MBP predicen la mortalidad por cualquier causa a largo plazo en pacientes con angina crónica estable. Métodos: Reclutamos 663 pacientes consecutivos (169 mujeres [25.5 %]; edad media 62.9 años ± 9.7 años) con angina crónica estable remitidos para angiografía coronaria diagnóstica. Se tomaron muestras para medir PAPP-A y pro-MBP al inicio del estudio. Los pacientes fueron seguidos por una mediana de tiempo de 8.8 años (rango intercuartílico 3 – 10.6 años). Resultados: Ciento seis (16 %) pacientes murieron durante el seguimiento. La concentración de PAPP-A (> 4.8 mIU/L) fué un predictor independiente de la mortalidad por cualquier causa (HR 1.953, 95% CI 1.135-3.360, p = 0.016) en un modelo de riesgos proporcionales de Cox. Ni pro-MBP ni el cociente PAPP-A/pro-MBP fueron marcadores de mortalidad por cualquier causa (p = 0.45 and 0.54, respectivamente). Conclusiones: En el presente estudio, los niveles altos de PAPP-A superiores a 4.8 mIU/L se asociaron con la muerte por cualquier causa a largo plazo en pacientes con angina crónica estable. Palabras clave: Proteína plasmática asociada a embarazo tipo A, proforma de la proteína mayor básica eosinofílica, angina crónica estable, pronóstico

Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data

OBJECTIVE: To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. DESIGN: Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. DATA SOURCES: Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. RESULTS: Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). CONCLUSIONS: In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012002780