Assessing cultural and linquistic appropriateness of the Rose Angina questionnaire in three ethnic groups

Introduction. Meeting the needs of migrant groups in Europe requires cross-culturally valid questionnaires, a substantial challenge to researchers. The Rose Angina Questionnaire (RAQ) is an important measure of coronary heart disease prevalence. It consists of seven items that collectively yield a diagnosis of angina. It has been shown to perform inconsistently across some ethnic groups in Britain. This study aimed to assess the need for modifying the RAQ for cross-culturally valid use in the three main ethnic groups in Scotland.

Methods. Interviews were carried out with Pakistani Punjabi speakers (n=26), Chinese Cantonese speakers (n=29) and European-origin English speakers (n=25). Bilingual project workers interviewed participants and provided translation and commentary to the English-speaking researcher. Participants were asked about general and cardiovascular health beliefs and behaviours, and about attitudes to pain and chest pain. They were also asked to comment on their understanding of an existing version of the RAQ in their language.

Results. No dominant themes in the cultural construction of health, pain or cardiovascular knowledge emerged that may significantly influence RAQ response between language groups. Problems were encountered with the Punjabi and Cantonese translations of the RAQ. For example, the translation for “chest” was interpreted by some Pakistani and fewer Chinese women to mean “breasts”. “Walking uphill” was translated in Chinese as “walking the hill”, without stipulation of the direction, so that some Cantonese speakers interpreted the question as meaning walking downhill. In addition, many Chinese interpreted RAQ items to be referring to breathlessness rather than chest pain due to ambiguous wording.

Conclusion. Existing Punjabi and Cantonese versions of the RAQ should be modified before being used in multi-ethnic surveys. Current versions are unlikely to be yielding data that is comparable across groups. Other language versions also require similar investigation to study the cardiovascular health of Europe’s migrant groups.

Re-considering Type A personality as a risk factor for angina: interactions with perceived effort-reward imbalance at work

This study investigates the role of Type A personality in the effort-reward imbalance (ERI) model (n=899 operational police). Moderated multiple regression analyses, including tests for curvilinear effects, revealed that the model significantly predicted self-reported angina. Two interactions between Type A subscales and the effort-reward imbalance variables were significant. The findings support recent arguments that the pathogenic component of Type A is hostility, and suggest that both overt and covert hostility can have differential effects on employee perceptions of effort-reward imbalance.

Using the Rose Angina Questionnaire cross-culturally : the importance of consulting lay people when translating epidemiological questionnaires

Objectives. The Rose Angina Questionnaire (RAQ) is an important measure of coronary heart disease prevalence. It has been shown to perform inconsistently across some ethnic groups in Britain. This study investigates whether the best available versions of the RAQ in Punjabi and Cantonese were linguistically equivalent to the English version.

Design. Interviews were carried out with lay people from the Pakistani, Chinese and European-origin communities in Scotland to assess the versions of the RAQ used in the Newcastle Heart Project (the best available versions). For each questionnaire item, participants were asked to elaborate on their understanding of the question and the meaning of keywords or phrases.

Results. Problems were discovered with the Punjabi and Cantonese translations of the RAQ. For example, the translation for ‘chest’ was interpreted by some Pakistani and Chinese women to mean ‘breasts’. ‘Walking uphill’ was translated in Chinese as ‘walking the hill’, without stipulation of the direction, so that some Cantonese speakers interpreted the question as pertaining to walking downhill. Many Chinese interpreted RAQ items to be referring to breathlessness rather than chest pain due to ambiguous wording.

Conclusion. Existing versions of the RAQ are unlikely to be yielding data that are cross-culturally valid or comparable. For robust health survey research in languages other than that in which the questionnaire was developed, lay assessment of questionnaires prior to and after translation is a necessity rather than a luxury.

Loss of insulin-mediated microvascular perfusion in skeletal muscle is associated with the development of insulin resistance

Aim: The aetiology of the development of type 2 diabetes remains unresolved. In the present study, we assessed whether an impairment of insulin-mediated microvascular perfusion occurs early in the onset of insulin resistance. Materials and methods: Hooded Wistar rats were fed either a normal diet (ND) or a high-fat diet (HFD) for 4 weeks. Anaesthetized animals were subjected to an isoglycaemic hyperinsulinaemic clamp (3 or 10 mU/min/kg × 2 h), and measurements were made of glucose infusion rate (GIR), hindleg glucose uptake, muscle glucose uptake by 2-deoxy-d-glucose (R′g), glucose appearance (Ra), glucose disappearance (Rd), femoral blood flow (FBF) and hindleg 1-methylxanthine disappearance (1-MXD, an index of microvascular perfusion). Results: Compared with ND-fed animal, HFD feeding led to a mild increase in fasting plasma glucose and plasma insulin, without an increase in total body weight. During the clamps, HFD rats showed an impairment of insulin-mediated action on GIR, hindleg glucose uptake, R′g, Ra, Rd and FBF, with a greater loss of insulin responsiveness at 3 mU/min/kg than at 10 mU/min/kg. The HFD also impaired insulin-mediated microvascular perfusion as assessed by 1-MXD. Interestingly, 1-MXD was the only measurement that remained unresponsive to the higher dose of 10 mU/min/kg insulin. Conclusions: We conclude that the early stage of insulin resistance is characterized by an impairment of the insulin-mediated microvascular responses in skeletal muscle. This is likely to cause greater whole body insulin resistance by limiting the delivery of hormones and nutrients to muscle.

Microvascular disease after renal transplantation

Background/Aims: Individuals who reach end-stage kidney disease (CKD5) have a high risk of vascular events that persists even after renal transplantation. This study compared the prevalence and severity of microvascular disease in transplant recipients and patients with CKD5. Methods: Individuals with a renal transplant or CKD5 were recruited consecutively from renal clinics, and underwent bilateral retinal photography (Canon CR5-45, Canon). Their retinal images were deidentified and reviewed for hypertensive/microvascular signs by an ophthalmologist and a trained grader (Wong and Mitchell classification), and for vessel caliber at a grading centre using a computer-assisted method and Knudtson’s modification of the Parr-Hubbard formula. Results: Ninety-two transplant recipients (median duration 6.4 years, range 0.8 to 28.8) and 70 subjects with CKD5 were studied. Transplant recipients were younger (p<0.001), with a higher eGFR (p< 0.001), but were just as likely to have a moderate-severe hypertensive/microvascular retinopathy (46/92, 50%) as subjects with CKD5 (38/70, 54%; OR 0.84, CI 0.45 to 1.57, p=0.64), and had similar mean arteriole and venular calibres (135.1 ± 7.5 μm and 137.9 ± 14.9 μm, p=0.12; and 199.1 ± 17.8 μm and 202.4 ± 27.8 μm, p=0.36, respectively). Arteriole and venular caliber were not different in nine patients examined before and after transplantation (p=0.62 and p=0.11, respectively). Conclusions: Hypertensive/microvascular disease occurred just as often and was generally as severe in transplant recipients and subjects with CKD5. Microvascular disease potentially contributes to increased cardiac events post- transplantation.

Role of P-glycoprotein in the intestinal absorption of tanshinone IIA, a major active ingredient in the root of Salvia miltiorrhiza Bunge

The extracts from the roots of Salvia miltiorrhiza Bunge (Danshen) are widely and traditionally used in the treatment of angina pectoris, acute myocardial infarct, hyperlipidemia and stroke in China and other Asian countries. In this study, we have investigated the role of P-glycoprotein (P-gp) in the intestinal absorption of tanshinone IIA (TSA), a major active constituent of Danshen, using several in vitro and in vivo models. The oral bioavailability of TSA was about 2.9

Role of P-glycoprotein in limiting the brain penetration of glabridin, an active isoflavan from the root of Glycyrrhiza glabra.

Purpose. Glabridin is a major active constituent of Glycyrrhiza glabra which is commonly used in the treatment of cardiovascular and central nervous system (CNS) diseases. Recently, we have found that glabridin is a substrate of P-glycoprotein (PgP/MDR1). This study aimed to investigate the role of PgP in glabridin penetration across the blood–brain barrier (BBB) using several in vitro and in vivo models.
Materials and Methods. Cultured primary rat brain microvascular endothelial cells (RBMVECs) were used in the uptake, efflux and transcellular transport studies. A rat bilateral in situ brain perfusion model was used to investigate the brain distribution of glabridin. The brain and tissue distribution of glabridin in rats with or without coadministered verapamil or quinidine were examined with correction for the tissue residual blood. In addition, the brain distribution of glabridin in mdr1a(-/-) mice was compared with the wild-type mice. Glabridin in various biological matrices was determined by a validated liquid chromatography mass spectrometric method.
Results. The uptake and efflux of glabridin in cultured RBMVECs were ATP-dependent and significantly altered in the presence of a PgP or multi-drug resistance protein (Mrp1/2) inhibitor (e.g. verapamil or MK-571). A polarized transport of glabridin was found in RBMVEC monolayers with
facilitated efflux from the abluminal (BL) to luminal (AP) side. Addition of a PgP or Mrp1/2 inhibitor in both luminal and abluminal sides attenuated the polarized transport across RBMVECs. In a bilateral in situ brain perfusion model, the uptake of glabridin into the cerebrum increased from 0.42 T 0.09% at 1 min to 9.27 T 1.69% (ml/100 g tissue) at 30 min and was significantly greater than that for sucrose. Coperfusion of a PgP or Mrp1/2 inhibitor significantly increased the brain distribution of glabridin by 33.6j142.9%. The rat brain levels of glabridin were only about 27% of plasma levels when corrected by tissue residual blood and it was increased to up to 44% when verapamil or quinidine was coadministered. The area under the brain concentration-time curve (AUC) of glabridin in mdr1a(-/-) mice was 6.0-fold higher than the wild-type mice.
Conclusions. These findings indicate that PgP limits the brain penetration of glabridin through the BBB and PgP may cause drug resistance to glabridin (licorice) therapy for CNS diseases and potential drugglabridin interactions. However, further studies are needed to explore the role of other drug transporters (e.g. Mrp1-4) in restricting the brain penetration of glabridin.

Role of the ATP-binding cassette drug transporters in the intestinal absorption of tanshinone IIB, one of the major active diterpenoids from the root of Salvia miltiorrhiza

There is an increasing use of herbal medicines worldwide, and the extracts from the root of Salvia miltiorrhiza are widely used in the treatment of angina and stroke. In this study, we investigated the mechanism for the intestinal absorption of tanshinone IIB (TSB), a major constituent of S. miltiorrhiza. The oral bioavailability of TSB was about 3% in rats with less proportional increase in its maximum plasma concentration (C_max) and area under the plasma concentration-time curve (AUC) with increasing dosage. The time to C_max (T_max) was prolonged at higher oral dosage. In a single pass rat intestinal perfusion model, the permeability coefficients (P_app) based on TSB disappearance from the lumen (P_lumen) were 6.2- to 7.2-fold higher (p < 0.01) than those based on drug appearance in mesenteric venous blood (P_blood). The uptake and efflux of TSB in Caco-2 cells were also significantly altered in the presence of an inhibitor for P-glycoprotein (PgP) or for multi-drug resistance associated protein (MRP1/2). TSB transport from the apical (AP) to basolateral (BL) side in Caco-2 monolayers was 3.3- to 5.7-fold lower than that from BL to AP side, but this polarized transport was attenuated by co-incubation of PgP or MRP1/2 inhibitors. The P_app values of TSB in the BL-AP direction were significantly higher in MDCKII cells over-expressing MDR1 or MRP1, but not in cells over-expressing MRP2-5, as compared with the wild-type cells. The plasma AUC_0-24hr in mdr1a and mrp1 gene-deficient mice was 10.2- to 1.7-fold higher than that in the wild-type mice. Furthermore, TSB significantly inhibited the uptake of digoxin and vinblastine in membrane vesicles containing PgP or MRP1. TSB also moderately stimulated PgP ATPase activity. Taken collectively, our findings indicate that TSB is a substrate for PgP and MRP1 and that drug resistance to TSB therapy and drug interactions may occur through PgP and MRP1 modulation.

Transport of cryptotanshinone, a major active triterpenoid in Salvia miltiorrhiza Bunge widely used in the treatment of stroke and Alzheimers disease, across the blood-brain

Cryptotanshinone (CTS), a major constituent from the roots of Salvia miltiorrhiza (Danshen), is widely used in the treatment of coronary heart disease, stroke and less commonly Alzheimer's disease. Our recent study indicates that CTS is a substrate for Pglycoprotein (PgP/MDR1/ABCB1). This study has investigated the nature of the brain distribution of CTS across the brain-blood barrier (BBB) using several in vitro and in vivo rodent models. A polarized transport of CTS was found in rat primary microvascular endothelial cell (RBMVEC) monolayers, with facilitated efflux from the abluminal side to luminal side. Addition of a PgP (e.g. verapamil and quinidine) or multi-drug resistance protein 1/2 (MRP1/2) inhibitor (e.g. probenecid and MK-571) in both luminal and abluminal sides attenuated the polarized transport. In a bilateral in situ brain perfusion model, the uptake of CTS into the cerebrum increased from 0.52 ± 0.1% at 1 min to 11.13 ± 2.36 ml/100 g tissue at 30 min and was significantly greater than that of sucrose. Co-perfusion of a PgP/MDR1 (e.g. verapamil) or MRP1/2 inhibitor (e.g. probenecid) significantly increased the brain distribution of CTS by 35.1-163.6%. The brain levels of CTS were only about 21% of those in plasma, and were significantly increased when coadministered with verapamil or probenecid in rats. The brain levels of CTS in rats subjected to middle cerebral artery occlusion and rats treated with quinolinic acid (a neurotoxin) were about 2- to 2.5-fold higher than the control rats. Moreover, the brain levels in mdr1a(-/-) and mrp1(-/-) mice were 10.9- and 1.5-fold higher than those in the wild-type mice, respectively. Taken collectively, these findings indicate that PgP and Mrp1 limit the brain penetration of CTS in rodents, suggesting a possible role of PgP and MRP1 in limiting the brain penetration of CTS in patients and causing drug resistance to Danshen therapy and interactions with conventional drugs that are substrates of PgP and MRP1. Further studies are needed to explore the role of other drug transporters in restricting the brain penetration of CTS and the clinical relevance.

Integrating cost-effectiveness evidence into clincal practice guidelines in Australia for acute myocardial infarction

 A teaching hospital is working with the Victorian State Government and universities, integrating cost-effectiveness evidence into clinical practice guidelines (CPGs), protocols and pathways for respiratory and cardiology interventions. Acute myocardial infarction (AMI) findings are reported. Results will stimulate cost-effective practice and inform medical associations, federal and state governments and international organisations developing CPGs. Published CPGs by the American College of Cardiology/American Heart Foundation for AMI in 1999 are reviewed by a large interdis- ciplinary hospital-based committee given cost-effectiveness evidence. Levels of evi- dence criteria rating on methodological rigor for effectiveness and costs are applied. National Health and Medical Research Council (NHMRC) grades of recommendation criteria for combinations of relative effectiveness versus relative costs and cut-off points are used. Extrapolating results between countries was addressed by applying the OECD's health purchasing power parity series. Recommendations for revisions to United States guidelines and for local application are formulated. United States Guide- lines require updating: Regarding angioplasty, percutaneous transluminal coronary angioplasty (PTCA) is cost-effective for men aged 60 years relative to recombinant tissue plasminogen activator (tPA),with additional cost per life year saved of 274 ecu. PTCA with discharge after 3 days is cost-effective in low-risk AMI. Regarding GP llb/Illa drugs, Abciximab during intervention incurred equal mean hospital costs for placebabciximab bolus, and abciximab bolus+ infusion with incremental 6-month cost for the latter treatment costing US$ 293 per patient. Agent recouped almost all initial therapy costs with significant benefits. Incre- mental cost of abciximab per event prevent- ed is US$ 3,258.Tirofiban was compared to placebo after high-risk angioplasty for AMI or unstable angina.Tirofiban decreased the rate of hospital deaths, myocardial infarc- tion, revascularisation at 2 days by 36% relative to placebo (8% vs. 12%) without increased cost. Clinical benefits were similar at 30 days.Tirofiban+heparin+aspirin was compared to heparin+aspirin.Tirofiban arm resulted in net savings of 33,418 ecu per 100 patients for the first 7 days of treatment. Regarding thrombolytics,tPA is more cost- effective than streptokinase. Incremental costs for each life saved when streptokinase is substituted by recombinant tissue plasmi- nogen are 31%,45%, 97% higher in Germa- ny, Italy and the United States than in the United Kingdom. Regarding anticoagulants, enoxaparin is a promising alternative to unfractionated heparin for hospitalised patients with non-Q-wave myocardiai infarc- tion or unstable angina, saving C$ 1,485 per patient over 12 months with 10% reduction in 1 year risk of death, myocardial infarction or recurrent angina. Regarding anti- arrhymics, the cost-effectiveness of no amiodarone, amiodarone for patients with depressed heart rate variability (DHRV),and amiodarone for patients with DHRV plus positive programmed ventricular stimula- tion (PPVS) for high-risk post-AMI was investigated. Amiodarone for DHRV+PPVS patients was dominated by a blend of the two alternatives. Compared to no amioda- rone, the incremental cost-effectiveness of amiodarone for DHRV patients was US$ 39,422 per quality adjusted life year gained. Amiodarone for DHRV is the most appropriate. Other CPG updates concern serum markers, for example, cardiac troponin I assay (c-Tnl), cost advantages of ad hoc angioplasty and secondary prevention through antioxidants and pravastatin. Australian costs are reported later in the paper.

Patients' experiences of cardiology procedures using minimal conscous sedation

Aim: The study's purpose was to describe patients' experiences of minimal conscious sedation during diagnostic and interventional cardiology procedures.

Methods: Over a 6-week period, 119 consecutive patients (10% of annual throughput) from a major metropolitan hospital in Melbourne, Australia, were interviewed using a modified version of the American Pain Society Patient Outcome Questionnaire. Patients identified pain severity using a 10-point visual analogue scale and rated their overall comfort on a 6-point Likert scale ranging from very comfortable to very uncomfortable.

Results: Patients were aged 67.6 years (standard deviation 11.1), 70.8% were male, and the mean body mass index was 27.7 (standard deviation 4.8). Patients underwent diagnostic coronary angiography (67.5%), percutaneous coronary interventions (13.3%), or combined procedures (19.2%). Most patients (65%) were comfortable in the context of low-dose conscious sedation. Slight discomfort was reported by 26% of patients; 9% reported feeling uncomfortable primarily as a result of a combination of musculoskeletal pain, angina, and vasovagal symptoms experienced during the procedure. There was significant correlation (rho = .25, P = .01) between procedure length and patients' report of overall comfort, suggesting longer procedures were less comfortable for patients.

Conclusions: The minimal sedation protocol was effective for the majority of patients; however, 9% of patients experienced significant discomfort related to preexisting conditions, highlighting the need for individual patient assessment before, during, and after the procedure.

Identifying the health and mental health information needs of people with coronary heart disease, with and without depression

Objective:
To identify the health and mental health information needs of people with coronary heart disease (CHD), with and without comorbid depression.

Design and setting:
A qualitative study conducted in Melbourne in 2006, using thematic analysis of semi-structured interviews on the types of health information that patients with CHD considered useful to assist with the management of their illness. Structured clinical interviews were used to assess current and prior depressive episodes in these patients.

Participants:
14 general practice patients (eight with current or prior history of major depression) who had experienced myocardial infarction, coronary artery bypass graft surgery, angioplasty or angina (confirmed via testing).

Results:
Four themes relating to information on how patients could manage their cardiovascular health and improve their psychosocial wellbeing emerged: psychosocial; physical activity; medical; and information for family. The most prominent information needs included identification and management of risk-related physical symptoms, and psychosocial information, most notably to enhance patients’ social support. Patients considered this information important for alleviating health anxiety and negative affect.

Conclusion:
This small patient sample endorsed the need for health and mental health information on a range of psychosocial and physical health topics. Participants desired specific types of information to assist with the self-management of their health and to assuage their health concerns.

Cardiovascular surveys : manual of operations

Cardiovascular disease (CVD) is the leading cause of death and hospitalization in both men and women in nearly all countries of Europe. The most frequent forms of CVD are those of an atherosclerotic origin, mainly ischaemic heart disease, stroke and heart failure. The magnitude of the problem contrasts with the usual paucity and poor quality of data available on incidence and prevalence of CVD, except for few rigorous but limited studies.

The objectives of the health interview and health examination surveys (HIS/HES) are to evaluate the frequency and the distribution of the disease, to evaluate trends and treatment effectiveness, to estimate risk factors distribution and prevalence of high risk conditions and to monitor prevention programmes.

According to the EUROCISS project (EUROpean Cardiovascular Surveillance Set) recommendations, surveys are aimed at describing the prevalence of the following CVD conditions: myocardial infarction, heart failure, angina pectoris, peripheral arterial disease, stroke, and ischaemic heart disease.

HIS and HES were developed to supplement information collected from routine databases and population-based registers to implement consistent public health policies. HIS can be repeated periodically in a new sample of the population, or can follow up over time the population recruited at baseline. Procedures and methods to collect information from participants include self-administered questionnaires, direct interviewer-administered questions and telephone interviews. A minimum set of questions to be administered every year, along with a longer, more detailed module to be administered periodically are recommended to evaluate CVD prevalence. The addition of HES provides more detailed and objective information that can be used to improve estimates regarding prevalence of both risk factors and disease status.

The selection of more specialized CVD-specific tests will depend on the objective the survey is designed to achieve, the assumed response rate and the cost and time considerations. For HES on CVD the minimum required is to perform the following measurements: height, weight, blood pressure, waist circumference, total and high density lipoprotein-cholesterol and glucose assay in a nonfasting blood sample. The next appropriate step would be to perform an electrocardiogram. High costs usually make HES difficult to carry out.

Standardization of measurements, training of personnel and quality control are essential to assure reliable data. A high response rate is extremely important, as nonrespondents tend to have different health characteristics from the rest of the sample and their omission therefore results in bias.

This manual of operations is intended for health professionals and policy makers and provides a standardized and simple model for the implementation of a CVD survey.

Laboratory and non-laboratory-based risk prevention models for secondary prevention of cardiovascular disease : the LIPID study

Aims : The aims of this study were to examine whether risk prediction models for recurrent cardiovascular disease (CVD) events have prognostic value, and to particularly examine the performance of those models based on non-laboratory data. We also aimed to construct a risk chart based on the risk factors that showed the strongest relationship with CVD.

Methods and results : Cox proportional hazards models were used to calculate a risk score for each recurrent event in a CVD patient who was enrolled in a very large randomized controlled clinical trial. Patients were then classified into groups according to quintiles of their risk score. These risk models were validated by calibration and discrimination analyses based on data from patients recruited in New Zealand for the same study. Non-laboratory-based risk factors, such as age, sex, body mass index, smoking status, angina grade, history of myocardial infarction, revascularization, stroke, diabetes or hypertension and treatment with pravastatin, were found to be significantly associated with the risk of developing a recurrent CVD event. Patients who were classified into the medium and high-risk groups had two-fold and four-fold the risk of developing a CVD event compared with those in the low-risk group, respectively. The risk prediction models also fitted New Zealand data well after recalibration.

Conclusion : A simpler non-laboratory-based risk prediction model performed equally as well as the more comprehensive laboratory-based risk prediction models. The risk chart based on the further simplified Score Model may provide a useful tool for clinical cardiologists to assess an individual patient's risk for recurrent CVD events.

Reducing risk in coronary artery disease. Are Australian patients in general practice achieving targets? The coronary artery disease in general practice study (CADENCE)

Background The benefits of secondary preventive measures for stable coronary artery disease are well established and risk factor treatment targets are defined.

Aim The aim of this study was to examine Australian general practitioners' (GP) perception and management of risk factors in chronic stable angina patients in primary care.

Methods Using a cluster-stratified design, 2031 consecutive stable angina patients were recruited between October 2006 and March 2007 by 207 GP who documented their risk factors and reported if they were optimally controlled.

Results Among the patients, 93% had objective evidence of coronary artery disease and 63% were male, and mean age was 71 ± 11 years. Based upon national guidelines, recommended targets were achieved in: 60% for blood pressure, 24% for body mass index, 23% for waist circumference, 17% for lipid profiles (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) and 54% of diabetics for haemoglobin A1c. However, GP perceived risk factors to be ‘optimally controlled’ in: 86% for blood pressure (kappa statistic (κ) = 0.37), 44% for weight (κ = 0.3), 70% for lipids (κ = 0.20) and 60% for haemoglobin A1c (κ = 0.74).

Conclusions In this representative cohort of chronic stable angina patients attending GP, cardiovascular risk factor control was frequently suboptimal despite being perceived as satisfactory by the clinicians. New strategies that raise awareness and address this treatment gap need to be implemented.