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1.  The Effect of Elevated Body Mass Index on Ischemic Heart Disease Risk: Causal Estimates from a Mendelian Randomisation Approach 
PLoS Medicine  2012;9(5):e1001212.
A Mendelian randomization analysis conducted by Børge G. Nordestgaard and colleagues using data from observational studies supports a causal relationship between body mass index and risk for ischemic heart disease.
Adiposity, assessed as elevated body mass index (BMI), is associated with increased risk of ischemic heart disease (IHD); however, whether this is causal is unknown. We tested the hypothesis that positive observational associations between BMI and IHD are causal.
Methods and Findings
In 75,627 individuals taken from two population-based and one case-control study in Copenhagen, we measured BMI, ascertained 11,056 IHD events, and genotyped FTO(rs9939609), MC4R(rs17782313), and TMEM18(rs6548238). Using genotypes as a combined allele score in instrumental variable analyses, the causal odds ratio (OR) between BMI and IHD was estimated and compared with observational estimates. The allele score-BMI and the allele score-IHD associations used to estimate the causal OR were also calculated individually. In observational analyses the OR for IHD was 1.26 (95% CI 1.19–1.34) for every 4 kg/m2 increase in BMI. A one-unit allele score increase associated with a 0.28 kg/m2 (95 CI% 0.20–0.36) increase in BMI and an OR for IHD of 1.03 (95% CI 1.01–1.05) (corresponding to an average 1.68 kg/m2 BMI increase and 18% increase in the odds of IHD for those carrying all six BMI increasing alleles). In instrumental variable analysis using the same allele score the causal IHD OR for a 4 kg/m2 increase in BMI was 1.52 (95% CI 1.12–2.05).
For every 4 kg/m2 increase in BMI, observational estimates suggested a 26% increase in odds for IHD while causal estimates suggested a 52% increase. These data add evidence to support a causal link between increased BMI and IHD risk, though the mechanism may ultimately be through intermediate factors like hypertension, dyslipidemia, and type 2 diabetes. This work has important policy implications for public health, given the continuous nature of the BMI-IHD association and the modifiable nature of BMI. This analysis demonstrates the value of observational studies and their ability to provide unbiased results through inclusion of genetic data avoiding confounding, reverse causation, and bias.
Please see later in the article for the Editors' Summary
Editors' Summary
Ischemic heart disease (IHD; also known as coronary heart disease) is the leading cause of death among adults in developed countries. In the US alone, IHD kills nearly half a million people every year. With age, fatty deposits (atherosclerotic plaques) build up in the walls of the coronary arteries, the blood vessels that supply the heart with oxygen and nutrients. The resultant reduction in the heart's blood supply causes shortness of breath, angina (chest pains that are usually relieved by rest), and potentially fatal heart attacks (myocardial infarctions). Risk factors for IHD include smoking, high blood pressure (hypertension), abnormal amounts of cholesterol and other fat in the blood (dyslipidemia), type 2 diabetes, and being overweight or obese (having excess body fat). Treatments for IHD include lifestyle changes (for example, losing weight) and medications that lower blood pressure and blood cholesterol levels. The narrowed arteries can also be widened using a device called a stent or surgically bypassed.
Why Was This Study Done?
Prospective observational studies have shown an association between a high body mass index (BMI, a measure of body fat that is calculated by dividing a person's weight in kilograms by their height in meters squared; a BMI greater than 30 kg/m2 indicates obesity) and an increased risk of IHD. Observational studies, which ask whether people who are exposed to a suspected risk factor develop a specific disease more often than people who are not exposed to the risk factor, cannot prove, however, that changes in BMI/adiposity cause IHD. Obese individuals may share other characteristics that cause both IHD and obesity (confounding) or, rather than obesity causing IHD, IHD may cause obesity (reverse causation). Here, the researchers use “Mendelian randomization” to examine whether elevations in BMI across the lifecourse have a causal impact on IHD risk. Three common genetic variants—FTO(rs9939609), MC4R(rs17782313), and TMEM18(rs6548238)—which have the largest single genetic variant associations with BMI were used in this study. Given that gene variants are inherited essentially randomly with respect to conventional confounding factors and are not subject reverse causation, use of these as instruments (or proxy measures) for variation in BMI as a risk factor (as opposed to measuring BMI directly) allows researchers to comment on whether obesity is causally involved in IHD.
What Did the Researchers Do and Find?
The researchers analyzed data from two population-based studies in which adults were physically examined and answered a lifestyle questionnaire before being followed to see how many developed IDH. They also analyzed data from a case-control study on IDH (in a case-control study, people with a disease are matched with similar people without the disease and the occurrence of risk factors in the patients and controls is compared). Overall, the researchers measured the BMI of 75,627 white individuals, among whom 11,056 already had IDH or developed it, and determined which of the BMI-increasing genetic variants each participant carried. On the basis of the observational data, every 4 kg/m2 increase in BMI increased the odds of IDH by 26% (an odds ratio of 1.26). Using a score derived from the combination of the three genetic variants, the researchers confirmed an association between each BMI increasing allele and both BMI (as expected) and IHD (0.28 kg/m2 and an odds ratio for IHD of 1.03, respectively). On average, compared to people carrying no BMI-increasing gene variants, people carrying six BMI-increasing gene variants had a 1.68 kg/m2 increase in BMI and an 18% increase in IHD risk. To extend this and to essentially reassess the original, observational, relationship between BMI and IHD risk, an “instrumental variable analysis” was used to examine the causal effect of a lifetime change in BMI on the risk of IDH. In this, it was found that for every 4 kg/m2 increase in BMI increased the odds of IDH by 52%.
What Do These Findings Mean?
These findings support a causal link between increased BMI and IDH risk, although it may be that BMI affects IDH through intermediate factors such as hypertension, dyslipidemia, and diabetes. The findings also show that observational studies into the impact of elevated BMI on IHD risk were consistent with this, but also that the inclusion of genetic data increases the value of observational studies by making it possible to avoid issues such as confounding and reverse causation. Finally, these findings and those of recent, observational studies have important implications for public-health policy because they show that the association between BMI (which is modifiable by lifestyle changes) and IHD is continuous. That is, any increase in BMI increases the risk of IHD; there is no threshold below which a BMI increase has no effect on IDH risk. Thus, public-health policies that aim to reduce BMI by even moderate levels could substantially reduce the occurrence of IDH in populations.
Additional Information
Please access these Web sites via the online version of this summary at
The American Heart Association provides information about IHD and tips on keeping the heart healthy, including weight management; it also provides personal stories about IHD
The UK National Health Service Choices website provides information about IHD, including information on prevention and personal stories about IHD
Information is available from the British Heart Foundation on heart disease and keeping the heart healthy
The US National Heart Lung and Blood Institute also provides information on IHD (in English and Spanish)
MedlinePlus provides links to many other sources of information on IHD (in English and Spanish)
Wikipedia has a page on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
PMCID: PMC3341326  PMID: 22563304
2.  Performance of the WHO Rose angina questionnaire in post-menopausal women: Are all of the questions necessary? 
Objective: To assess the performance of a shortened version of the Rose angina questionnaire focusing on exertional chest pain.
Methods: Cross sectional analysis of 3987 women aged 60 to 79 years from 23 British towns. The performances of definite Rose angina (using data from the full Rose angina questionnaire) and exertional chest pain (using data from a subset of three questions from the Rose angina questionnaire) were assessed against a medical record of angina.
Results: The sensitivity (the proportion with a medical record of angina who were identified as having angina by the questionnaire) was 29.9% (95% confidence intervals 25.7% to 34.4%) comparing definite Rose angina to any medical record of angina since 1978 and 50.7% (45.9% to 55.5%) comparing exertional chest pain to any medical record diagnosis of angina. The positive predictive values of both questionnaires were similar. When the two questionnaires were compared with a gold standard of a primary care consultation for angina symptoms within the past five years the sensitivity of definite Rose angina was 33.0% (26.9% to 39.6%) and that of exertional chest pain was 51.8% (45.1% to 58.5%). Although the sensitivity of both versions of the questionnaire was greater in those aged 60–69 years compared with those aged 70–79 years, it remained higher in the exertional chest pain version of the questionnaire than for definite Rose angina based on the full version of the questionnaire in both age groups. Performance of either version of the questionnaire was not affected by occupational social class.
Conclusions: With respect to identifying women with a medical diagnosis of angina or those presenting to primary care with anginal symptoms, these results suggest that a shortened version of the Rose angina questionnaire focusing on exertional chest pain performs better than the full version. Other studies suggest that exertional chest pain is the crucial element of the Rose angina questionnaire with respect to predicting future coronary events. It is concluded that using a shortened version of the Rose angina questionnaire is adequate in epidemiological studies.
PMCID: PMC1732510  PMID: 12821705
3.  Social and gender variation in the prevalence, presentation and general practitioner provisional diagnosis of chest pain 
OBJECTIVES—To describe the prevalence of Rose angina and non-exertional chest pain in men and women in socioeconomically contrasting areas; to describe the proportions of men and women who present with the symptom of chest pain and who receive a provisional general practitioner diagnosis of coronary heart disease; to assess the effects of gender and deprivation.
DESIGN—Two random general population samples in socially contrasting areas were surveyed using the Rose angina questionnaire: the case notes of people identified with chest pain were reviewed.
SETTING—Glasgow conurbation.
PARTICIPANTS—1107 men and women, aged 45-64, with chest pain.
OUTCOME MEASURES—Prevalence of Rose angina and non-exertional chest pain; the proportions who had presented with chest pain and received a general practitioner's provisional diagnosis of coronary heart disease.
RESULTS—There was no difference between social groups in the prevalence of all chest pain but a greater proportion of those in deprived groups had Rose angina and a greater proportion of these had the more severe grade. The proportion of people who had presented with chest pain was higher among socioeconomically deprived groups but there was no difference in the proportions receiving a general practitioner provisional diagnosis of coronary heart disease. Men were more likely to present with chest pain than women and were more likely to receive a provisional general practitioner diagnosis of coronary heart disease.
CONCLUSIONS—No evidence was found of social differences in patient presentation or general practitioner diagnosis that might explain reported variations in uptake of cardiology services. In contrast, gender variation may originate in part from differences in patient presentation and general practitioner diagnosis. Further investigation of socioeconomic variations in uptake of cardiology services should focus later in the care pathway, on general practitioner referral patterns and clinical decisions taken in secondary care.

Keywords: angina; social class; gender; primary care; chest pain
PMCID: PMC1731754  PMID: 10942455
4.  The autoantibody rheumatoid factor may be an independent risk factor for ischaemic heart disease in men 
Heart  2007;93(10):1263-1267.
Subjects with rheumatoid arthritis have an increased prevalence of ischaemic heart disease (IHD). This is most likely in those people with the autoantibody rheumatoid factor (RF). RF is strongly associated with rheumatoid arthritis (RA) but is also present in up to 15% of all adults.
To determine whether RF might identify people in a general population who also share an increased likelihood of developing IHD.
Subjects from the Hertfordshire Cohort Study were investigated for the presence of RF. Subjects completed a questionnaire and attended a clinic where a history of IHD was recorded (ECG, coronary artery bypass grafting, Rose chest pain). Associations between the presence of RF, antinuclear antibodies (ANA), anticardiolipin antibodies (ACA) and IHD in 567 men and 589 women were investigated and compared with traditional risk factors for IHD.
RF was associated with an increased likelihood of IHD in men (odds ratio (OR) = 3.1, 95% CI 1.7 to 5.4, p<0.001). This increased risk could not be explained by traditional risk factors for IHD (mutually adjusted OR for RF 2.9 (95% CI 1.6 to 5.3), p<0.001). There was no significant association between RF in women or between ANA or ACA with IHD in men or women.
This work suggests that RF is an independent risk factor for IHD in the general population. It lends support to the importance of inflammation in atherosclerosis and suggests that autoimmune processes may be involved. In addition, it raises the intriguing possibility that RF may have a direct role in the pathogenesis of IHD in some subjects.
PMCID: PMC2000921  PMID: 17550930
5.  A population study of the long‐term consequences of Rose angina: 20‐year follow‐up of the Renfrew–Paisley study 
Heart  2006;92(12):1739-1746.
To examine the long‐term cardiovascular consequences of angina in a large epidemiological study.
Prospective cohort study conducted between 1972 and 1976 with 20 years of follow‐up (the Renfrew–Paisley Study).
Renfrew and Paisley, West Scotland, UK.
7048 men and 8354 women aged 45–64 years who underwent comprehensive cardiovascular screening at baseline, including the Rose Angina Questionnaire and electrocardiography (ECG).
Main outcome measures
All deaths and hospitalisations for cardiovascular reasons occurring over the subsequent 20 years, according to the baseline Rose angina score and baseline ECG.
At baseline, 669 (9.5%) men and 799 (9.6%) women had angina on Rose Angina Questionnaire. All‐cause mortality for those with Rose angina was 67.7% in men and 43.3% in women at 20 years compared with 45.4% and 30.4%, respectively, in those without angina (p<0.001). Values are expressed as hazards ratio (HR) (95% confidence interval (CI). In a multivariate analysis, men with Rose angina had an increased risk of cardiovascular death or hospitalisation (1.49 (1.33 to 1.66), myocardial infarction (1.63 (1.41 to 1.85)) or heart failure (1.54 (1.13 to 2.10)) compared with men without angina. The corresponding HR (95% CI) for women were 1.38 (1.23 to 1.55), 1.56 (1.31 to 1.85) and 1.92 (1.44 to 2.56). An abnormality on the electrocardiogram (ECG) increased risk further, and both angina and an abnormality on the ECG increased risk most of all compared with those with neither angina nor ischaemic changes on the ECG. Compared with men, women with Rose angina were less likely to have a cardiovascular event (0.54 (0.46 to 0.64)) or myocardial infarction (0.44 (0.35 to 0.56)), although there was no sex difference in the risk of stroke (1.11 (0.75 to 1.65)), atrial fibrillation (0.84 (0.38 to 1.87)) or heart failure (0.79 (0.51 to 1.21)).
Angina in middle age substantially increases the risk of death, myocardial infarction, heart failure and other cardiovascular events.
PMCID: PMC1861298  PMID: 16807274
6.  Chest pain and ischaemic heart disease in primary care. 
BACKGROUND: Chest pain is the main symptom of first presentation with ischaemic heart disease (IHD). Little is known about the incidence of IHD among patients consulting the general practitioner (GP) for chest pain. AIMS: To estimate the occurrence of IHD among patients consulting for chest pain, to study the results of the bicycle exercise test, and to estimate the incidence of IHD in the population. DESIGN OF STUDY: Prospective descriptive study. SETTING: Three primary health centres in south-eastern Sweden. METHOD: All patients without a current IHD diagnosis, aged 20 to 79 years, and consulting for a new episode of chest pain, were included consecutively. The outcome was classified as IHD, possible IHD or not IHD, according to the results of a postal questionnaire, an exercise test or hospital care. Data from the hospital registry on patients with a diagnosis of IHD were analysed retrospectively. RESULTS: Out of 38,075 GP consultations, 577 (1.5%) were for chest pain. IHD was diagnosed in 41 (8%) of the chest pain patients, in 441 (83%) the diagnosis was excluded, and in 50 (9%) the diagnosis was judged as being uncertain. Even though the diagnostic criteria were strict, the exercise tests led to a diagnostic conclusion in 77% of the cases, most frequently a normal test result. Combining data from primary and hospital care, the yearly incidence of IHD was 6.5 diagnosed per 1000 inhabitants (aged 20 to 79 years old). CONCLUSION: The incidence of a new episode of chest pain bringing the patients to the GP was low. Eight per cent of the patients received an IHD diagnosis, and in 9% further investigation or clinical assessment is needed.
PMCID: PMC1314597  PMID: 12830565
7.  Assessing the global burden of ischemic heart disease, part 2: analytic methods and estimates of the global epidemiology of ischemic heart disease in 2010 
Global heart  2012;7(4):331-342.
Ischemic Heart Disease (IHD) is the leading cause of death worldwide. The Global Burden of Diseases, Injuries and Risk Factors (GBD) 2010 Study estimated IHD mortality and disability burden for 21 world regions for the years 1990 to 2010.
Data sources for GBD IHD epidemiology estimates were mortality surveillance, verbal autopsy, and vital registration data (for IHD mortality) and systematic review of IHD epidemiology literature published 1980–2008 (for non-fatal IHD outcomes). An estimation and validation process led to an ensemble model of IHD mortality by country for all 21 world regions, adjusted for country-level covariates. Disease models were developed for the nonfatal sequelae of IHD: myocardial infarction, stable angina pectoris, and ischemic heart failure.
Country level covariates including metabolic and nutritional risk factors, education, war, and annual income per capita contributed to the ensemble model for the analysis of IHD death. In the acute myocardial infarction model, inclusion of troponin in the diagnostic criteria of studies published after the year 2000 was associated with a 50% higher incidence. Self-reported diagnosis of angina significantly overestimated stable angina prevalence compared with “definite” angina elicited by the Rose angina questionnaire. For 2010, Eastern Europe and Central Asia had the highest rates of IHD death and the Asia Pacific High-Income, East Asia, Latin American Andean, and sub-Saharan Africa regions had the lowest.
Global and regional IHD epidemiology estimates are needed for estimating the worldwide burden of IHD. Using descriptive meta-analysis tools, the GBD 2010 standardized and pooled international data by adjusting for region-level mortality and risk factor data, and study level diagnostic method. Analyses maximized internal consistency, generalizability, and adjustment for known sources of bias. The GBD IHD analysis nonetheless highlights the need for improved IHD epidemiology surveillance in many regions and the need for uniform diagnostic standards.
PMCID: PMC3595103  PMID: 23505617
8.  The prevalence of angina symptoms and association with cardiovascular risk factors, among rural, urban and rural to urban migrant populations in Peru 
Rural-to-urban migration in low- and middle-income countries causes an increase in individual cardiovascular risk. Cost-effective interventions at early stages of the natural history of coronary disease such as angina may stem an epidemic of premature coronary deaths in these countries. However, there are few data on the prevalence of angina in developing countries, whilst the understanding the aetiology of angina is complicated by the difficulty in measuring it across differing populations.
The PERU MIGRANT study was designed to investigate differences between rural-to-urban migrant and non-migrant groups in specific cardiovascular disease risk factors. Mass-migration seen in Peru from 1980s onwards was largely driven by politically motivated violence resulting in less 'healthy migrant' selection bias. The Rose angina questionnaire was used to record chest pain, which was classified definite, possible and non-exertional. Mental health was measured using the General Health Questionnaire (GHQ-12). Mantel-Haenszel odds ratios (adjusted for age, sex, cardiovascular disease risk factors and mental health) were used to assess the risk of chest pain in the migrant and urban groups compared to the rural group, and further to assess the relationship (age and sex-adjusted) between risk factors, mental health and chest pain.
Compared to the urban group, rural dwellers had a greatly increased likelihood of possible/definite angina (multi-adjusted OR 2.82 (1.68- 4.73)). Urban and migrant groups had higher levels of risk factors (e.g. smoking - 20.1% urban, 5.5% rural). No diabetes was seen in the rural dwellers who complained of possible/definite angina. Rural dwellers had a higher prevalence of mood disorder and the presence of a mood disorder was associated with possible/definite angina in all three groups, but not consistently with non-exertional chest pain.
Rural groups had a higher prevalence of angina as measured by Rose questionnaire than migrants and urban dwellers, and a higher prevalence of mood disorder. The presence of a mood disorder was associated with angina. The Rose angina questionnaire may not be of relevance to rural populations in developing countries with a low pre-test probability of coronary disease and poor mental health.
PMCID: PMC2964551  PMID: 20932298
9.  Enhanced External Counterpulsation (EECP) 
Executive Summary
To assess the effectiveness, and cost effectiveness of EECP in patients with severe anginal symptoms, secondary to chronic coronary disease, who are unresponsive to exhaustive pharmacotherapy and not candidates for surgical/percutaneous revascularization procedures (e.g., angioplasty, coronary bypass surgery).
To assess the effectiveness, and cost effectiveness of EECP in patients with heart failure.
Clinical Need
Angina is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back or arm. Angina usually occurs in patients with coronary artery disease (CAD) involving ≥1 large epicardial artery. However it can also occur in people with valvular heart disease, hypertrophic cardiomyopathy, and uncontrolled hypertension.
Conventional approaches to restoring the balance between oxygen supply and demand focus on the disruption of the underlying disease through: drug therapy (β blockers, calcium channel blockers, nitrates, antiplatelet agents, ACE inhibitors, statins); life-style modifications (smoking cessation, weight loss); or revascularization techniques such as coronary artery bypass graft surgery (CABG) or percutaneous coronary interventions (PCI). (1) Limitations of each of these approaches include: adverse drug effects, procedure-related mortality and morbidity, restenosis after PCI, and time dependent graft attrition after CABG. Furthermore, an increasing number of patients are not appropriate candidates for standard revascularization options, due to co-morbid conditions (HF, peripheral vascular disease), poor distal coronary artery targets, and patient preference. The morbidity and mortality associated with repeat surgical revascularization procedures are significantly higher, and often excludes these patients from consideration for further revascularizations. (2)
Patients with CAD who have chronic ischemic symptoms that are unresponsive to both conventional medical therapy and revascularization techniques have refractory angina pectoris. It has been estimated that greater than 100,000 patients each year in the US may be diagnosed as having this condition. (3) Patients with refractory angina have marked limitation of ordinary physical activity or are unable to perform any ordinary physical activity without discomfort (CCS functional class III/IV). Also, there must be some objective evidence of ischemia as demonstrated by exercise treadmill testing, stress imaging studies or coronary physiologic studies. (1)
Dejongste et al. (4)estimated that the prevalence of chronic refractory angina is about 100,000 patients in the United States. This would correspond to approximately 3,800 (100,000 x 3.8% [Ontario is approximately 3.8% of the population of the United States]) patients in Ontario having chronic refractory angina.
Heart Failure
Heart failure results from any structural or functional cardiac disorder that impairs the ability of the heart to act as a pump.
A recent study (5) revealed 28,702 patients were hospitalized for first-time HF in Ontario between April 1994 and March 1997. Women comprised 51% of the cohort. Eighty-five percent were aged 65 years or older, and 58% were aged 75 years or older.
Patients with chronic HF experience shortness of breath, a limited capacity for exercise, high rates of hospitalization and rehospitalization, and die prematurely. (6) The New York Heart Association (NYHA) has provided a commonly used functional classification for the severity of HF (7):
Class I: No limitation of physical activity. No symptoms with ordinary exertion.
Class II: Slight limitations of physical activity. Ordinary activity causes symptoms.
Class III: Marked limitation of physical activity. Less than ordinary activity causes symptoms. Asymptomatic at rest.
Class IV: Inability to carry out any physical activity without discomfort. Symptoms at rest.
The National Heart, Lung, and Blood Institute (7) estimates that 35% of patients with HF are in functional NYHA class I; 35% are in class II; 25%, class III; and 5%, class IV. Surveys (8) suggest that from 5% to 15% of patients with HF have persistent severe symptoms, and that the remainder of patients with HF is evenly divided between those with mild and moderately severe symptoms.
To date, the diagnosis and management of chronic HF has concentrated on patients with the clinical syndrome of HF accompanied by severe left ventricular systolic dysfunction. Major changes in treatment have resulted from a better understanding of the pathophysiology of HF and the results of large clinical trials. Treatment for chronic HF includes lifestyle management, drugs, cardiac surgery, or implantable pacemakers and defibrillators. Despite pharmacologic advances, which include diuretics, angiotensin-converting enzyme inhibitors, beta-blockers, spironolactone, and digoxin, many patients remain symptomatic on maximally tolerated doses. (6)
The Technology
Patients are typically treated by a trained technician in a medically supervised environment for 1 hour daily for a total of 35 hours over 7 weeks. The procedure involves sequential inflation and deflation of compressible cuffs wrapped around the patient’s calves, lower thighs and upper thighs. In addition to 3 sets of cuffs, the patient has finger plethysmogram and electrocardiogram (ECG) attachments that are connected to a control and display console.
External counterpulsation was used in the United States to treat cardiogenic shock after acute myocardial infarction. (9;10) More recently, an enhanced version namely “enhanced external counterpulsation” (EECP) was introduced as a noninvasive procedure for outpatient treatment of patients with severe, uncontrollable cardiac ischemia. EECP is said to increase coronary perfusion pressure and reduce the myocardial oxygen demand. Currently, EECP is not applicable for all patients with refractory angina pectoris. For example, many patients are considered ineligible for therapy due to co-morbidities, including those with severe pulmonary vascular disease, deep vein thrombosis, phlebitis and irregular heart rhythms, and heart failure. (1)
Very recently, investigation began into EECP as an adjunctive treatment for patients with HF. Anecdotal reports suggested that EECP may benefit patients with coronary disease and left ventricular dysfunction. The safety and effectiveness of EECP in patients with symptomatic heart failure and coronary disease and its role in patients with nonischemic heart failure secondary to LV dysfunction is unclear. Furthermore, the safety and effectiveness of EECP in the different stages of HF and whether it is only for patients who are refractive to pharmacotherapy is unknown.
2003 Health Technology Assessment by the Medical Advisory Secretariat
The Medical Advisory Secretariat health technology assessment (originally published in February 2003) reported on the effectiveness of EECP for patients with angina and HF. The report concluded that there was insufficient evidence to support the use of EECP in patients with refractory stable CCS III/IV angina as well as insufficient evidence to support the use of EECP in patients with HF.
Review Strategy
The aim of this literature review was to assess the effectiveness, safety, and cost effectiveness of EECP for the treatment of refractory stable CCS III/IV angina or HF.
The standard search strategy used by the Medical Advisory Secretariat was used. This included a search of all international health technology assessments as well as a search of the medical literature from December 2002 to March 2006.
A modification of the GRADE approach (11) was used to make judgments about the quality of evidence and strength of recommendations systematically and explicitly. GRADE provides a framework for structured reflection and can help to ensure that appropriate judgments are made. GRADE takes into account a study’s design, quality, consistency, and directness in judging the quality of evidence for each outcome. The balance between benefits and harms, quality of evidence, applicability, and the certainty of the baseline risks are considered in judgments about the strength of recommendations.
Summary of Findings
The Cochrane and INAHTA databases yielded 3 HTAs or systematic reviews on EECP treatment (Blue Cross Blue Shield Technology Evaluation Center [BCBS TEC], ECRI, and the Centers for Medicare and Medicaid Services [CMS]). A search of Medline and Embase December 2005 – March 2006 (after the literature search cutoff from the most recent HTA) was conducted using key words enhanced external counterpulsation, EECP, angina, myocardial ischemia, congestive heart failure. This search produced 1 study which met the inclusion criteria. This level 4a study was inferior in quality to the RCT which formed the basis of the 2003 Medical Advisory Secretariat recommendation.
BCBS reviewed the evidence through November 2005 to determine if EECP improves health outcomes for refractory chronic stable angina pectoris or chronic stable HF. (12) BCBS concluded that the available evidence is not sufficient to permit conclusions of the effect of EECP on health outcomes. Both controlled trials had methodologic flaws (MUST EECP and MUST EECP quality of life studies). The case series and observational studies for both indications while suggestive of a treatment benefit from EECP have shortcomings as well.
On March 20 2006, CMS posted their proposed coverage decision memorandum for external counterpulsation therapy. (13) Overall, CMS stated that the evidence is not adequate to conclude that external counterpulsation therapy is reasonable and necessary for:
Canadian Cardiovascular Society Classification (CCSC) II angina
Heart failure
NYHA class II/III stable HF symptoms with an EF≤35%
NYHA class II/III stable HF symptoms with an EF≤40%
NYHA class IV HF
Acute HF
Cardiogenic shock
Acute MI
In January 2005, ECRI (14) stated that there was insufficient evidence available to draw conclusions about the long-term effectiveness of EECP, with respect to morbidity, survival, or quality of life, for any coronary indication (refractory angina, congestive heart failure, cardiogenic shock and acute MI).
GRADE Quality of the Studies
According to the GRADE Working Group criteria, the quality of the trials was examined (Table 1). (11)
Quality refers to the criteria such as the adequacy of allocation concealment, blinding and followup.
Consistency refers to the similarity of estimates of effect across studies. If there is important unexplained inconsistency in the results, our confidence in the estimate of effect for that outcome decreases. Differences in the direction of effect, the size of the differences in effect and the significance of the differences guide the decision about whether important inconsistency exists.
Directness refers to the extent to which the people interventions and outcome measures are similar to those of interest. For example, there may be uncertainty about the directness of the evidence if the people of interest are older, sicker or have more comorbidity than those in the studies.
As stated by the GRADE Working Group, the following definitions were used in grading the quality of the evidence. (11)
GRADE Quality of Studies
Economic Analysis - Literature Review
No economic analysis of EECP was identified in the published literature.
Estimated Prevalence of Angina in Ontario
3,800 patients with chronic refractory angina:
The number of patients with chronic refractory angina in the US is estimated to be approximately 100,000 (4), this corresponds to about 3,800 patients in Ontario (3.8% × 100,000) with refractory angina.
3,800 patients × $7,000 Cdn (approximate cost for a full course of therapy) ~ $26.6M Cdn.
Estimated Prevalence of Heart Failure in Ontario
23,700 patients EF ≤ 0.35:
This estimate is from an expert (personal communication) at the Institute for Clinical Evaluative Sciences (ICES), where they examined a sample of echocardiography studies drawn from a diagnostic lab in 2001. They found that the prevalence of EF ≤ 0.35 was 8.3%, and if generalized to all patients undergoing echocardiography, there would be 23,700 patients.
23,700 patients with EF ≤35% × $7,000 Cdn ~ $166 M Cdn.
There is insufficient evidence to support the effectiveness and safety of EECP treatment for patients with refractory stable CCS III-IV angina or HF.
As per the GRADE Working Group, overall recommendations consider 4 main factors. (11)
The tradeoffs, taking into account the estimated size of the effect for the main outcome, the confidence limits around those estimates and the relative value placed on the outcome.
The quality of the evidence.
Translation of the evidence into practice in a specific setting, taking into consideration important factors that could be expected to modify the size of the expected effects such as proximity to a hospital or availability of necessary expertise.
Uncertainty about the baseline risk for the population of interest.
The GRADE Working Group also recommends that incremental costs of healthcare alternatives should be considered explicitly alongside the expected health benefits and harms. (11) Recommendations rely on judgments about the value of the incremental health benefits in relation to the incremental costs. The last column in Table 2 is the overall trade-off between benefits and harms and incorporates any risk/uncertainty.
For angina and heart failure, the overall GRADE and strength of the recommendations is “weak” – the quality of the evidence is “low” (uncertainties due to methodological limitations in the study design in terms of study quality and directness), and the corresponding risk/uncertainty is increased due to a budget impact of approximately $26.6 M Cdn or $166 M Cdn respectively while the cost-effectiveness of EECP is unknown and difficult to estimate considering that there are no high quality studies of effectiveness.
Overall GRADE and Strength of Recommendation (Including Uncertainty)
PMCID: PMC3379533  PMID: 23074496
10.  Gender differences in pain characteristics of chronic stable angina and perceived physical limitation in patients with coronary artery disease 
Pain  2003;101(0):45-53.
Chronic stable angina pectoris, the chest pain associated with reversible myocardial ischemia has detrimental effects on health-related quality of life, particularly in women. The limited research on gender differences in chronic stable angina suggests that angina may be experienced differently in women and that women report greater functional disability related to angina symptoms. No studies have examined gender differences in chronic stable angina from a multidimensional pain perspective or have included reliable and valid measures of pain that would facilitate comparing chronic angina patients with other chronic pain populations. The purpose of this descriptive study was to examine gender differences in characteristics of chronic stable angina using the short-form McGill pain questionnaire (SF-MPQ) and to explore relationships among these pain characteristics and perceived limitation in performing physical activities in patients with coronary artery disease (CAD) (physical limitation subscale of the Seattle angina questionnaire). One hundred and twenty-eight subjects (30.5% women) with stable CAD and angina pectoris documented by a cardiologist completed study questionnaires in an outpatient cardiology clinic. Results of the study suggest that men and women with chronic stable angina had more similarities than differences in chest pain characteristics. No significant gender differences were demonstrated in total sensory or affective intensity scores, the present pain intensity index, or the number of pain words chosen. However, women did report significantly greater pain intensity on the SF-MPQ visual analogue scale. Women were also significantly more likely to describe their chronic angina as ‘hot-burning’ and ‘tender’ and to have greater intensity of pain for these two descriptors. Despite the similarities in pain characteristics, women reported greater physical limitation related to anginal pain. The variables of social status and years diagnosed with CAD significantly interacted with gender in predicting physical limitation suggesting that gender-specific models of physical limitation in angina patients need to be explored. To our knowledge, this is one of the first studies that has assessed chronic anginal pain using a reliable and valid generic pain instrument. More research is needed to better understand the nature of gender differences in functional limitation secondary to anginal pain and the physiologic, cognitive-perceptual and psychosocial mechanisms that lead to angina-related functional disability.
PMCID: PMC4310562  PMID: 12507699
McGill pain questionnaire – short form; Gender differences; Physical functional limitation; Quality of life
11.  Epidemiology of angina pectoris: role of natural language processing of the medical record 
American heart journal  2007;153(4):666-673.
The diagnosis of angina is challenging as it relies on symptom descriptions. Natural language processing (NLP) of the electronic medical record (EMR) can provide access to such information contained in free text that may not be fully captured by conventional diagnostic coding.
To test the hypothesis that NLP of the EMR improves angina pectoris (AP) ascertainment over diagnostic codes.
Billing records of in- and out-patients were searched for ICD-9 codes for AP, chronic ischemic heart disease and chest pain. EMR clinical reports were searched electronically for 50 specific non-negated natural language synonyms to these ICD-9 codes. The two methods were compared to a standardized assessment of angina by Rose questionnaire for three diagnostic levels: unspecified chest pain, exertional chest pain, and Rose angina.
Compared to the Rose questionnaire, the true positive rate of EMR-NLP for unspecified chest pain was 62% (95%CI:55–67) vs. 51% (95%CI:44–58) for diagnostic codes (p<0.001). For exertional chest pain, the EMR-NLP true positive rate was 71% (95%CI:61–80) vs. 62% (95%CI:52–73) for diagnostic codes (p=0.10). Both approaches had 88% (95%CI:65–100) true positive rate for Rose angina. The EMR-NLP method consistently identified more patients with exertional chest pain over 28-month follow-up.
EMR-NLP method improves the detection of unspecified and exertional chest pain cases compared to diagnostic codes. These findings have implications for epidemiological and clinical studies of angina pectoris.
PMCID: PMC1929015  PMID: 17383310
12.  Clinical presentation and functional prognosis in syndrome X. 
British Heart Journal  1993;70(4):346-351.
OBJECTIVES--To assess the effect of clinical presentation on functional prognosis in patients with syndrome X. DESIGN--A prospective study. Patients with syndrome X presenting with unstable angina and stable angina were followed up with a questionnaire to examine their functional state. PATIENTS--41 patients with syndrome X and unstable angina and 41 patients with syndrome X and stable angina. Syndrome X was defined as typical anginal chest pain, a positive exercise test, and normal coronary angiogram. SETTING--Regional cardiothoracic centre. RESULTS--The mean follow up time was 36 (range 20-51) months for the unstable angina group and 35 (range 19-51) months for the stable angina group. No patient was lost to follow up in either group. At follow up 28 patients in the unstable angina group were pain free compared with 15 patients in the stable angina group (p = 0.008). Seven patients in the unstable angina group had further hospital admission with chest pain after the cardiac catheterisation compared wtih 12 patients in the stable angina group (NS). Seven patients in the unstable angina group believed that they had heart disease compared with 27 in the stable angina group (p < 0.001). 26 patients in the unstable angina group but only eight patients in the stable angina group were unlimited in their physical activity (p < 0.001). 12 patients in the unstable angina group compared with 27 patients in the stable angina group were unable to work normally because of chest pain (p < 0.001). The mean (SD) duration of symptoms before cardiac catheterisation was 7.9 (4.7) months in the unstable angina group and 13.4 (5.6) months in the stable angina group (p < 0.001). 10 patients in the unstable angina group and 24 patients in the stable angina group still attended hospital outpatient clinics because of chest pain (p = 0.004). 16 patients in the unstable angina group and 29 patients in the stable angina group were still taking regular antianginal medication (p < 0.001). CONCLUSIONS--Patients with syndrome X who present with unstable angina have a significantly better functional prognosis than those presenting with symptoms of stable angina. This may reflect differences in underlying pathophysiological mechanisms.
PMCID: PMC1025330  PMID: 8217443
13.  Chest pain without established ischaemic heart disease in primary care patients: associated comorbidities and mortality 
Ischaemic heart disease (IHD) can be excluded in the majority of patients with unspecific chest pain. The remainder have what is generally referred to as non-cardiac chest pain, which has been associated with gastrointestinal, neuromusculoskeletal, pulmonary, and psychiatric causes.
To assess morbidity and mortality following a new diagnosis of non-specific chest pain in patients without established IHD.
Design of study
Population-based cohort study with nested case-control analysis.
UK primary care practices contributing to the General Practice Research Database.
Patients aged 20–79 years with chest pain who had had no chest pain consultation before 2000 and no IHD diagnosis before 2000 or within 2 weeks after the index date were selected from the General Practice Research Database. The selected 3028 patients and matched controls were followed-up for 1 year.
The incidence of chest pain in patients without established IHD was 12.7 per 1000 person-years. In the year following the index date, patients who had chest pain but did not have established IHD were more likely than controls to receive a first IHD diagnosis (hazard ratio [HR] = 18.2, 95% confidence interval [CI] = 11.6 to 28.6) or to die (HR = 2.3, 95% CI = 1.3 to 4.1). Patients with chest pain commonly had a history of gastro-oesophageal reflux disease (GORD; odds ratio [OR] = 2.0, 95% CI = 1.5 to 2.7) or went on to be diagnosed with GORD (risk ratio 4.5, 95% CI = 3.1 to 6.4).
Patients with chest pain but without established IHD were found to have an increased risk of being diagnosed with IHD. Chest pain in patients without established IHD was also commonly associated with GORD.
PMCID: PMC2648936  PMID: 19275827
chest pain; gastro-oesophageal reflux disease; mortality; myocardial ischaemia; primary healthcare
14.  Possible angina detected by the WHO angina questionnaire in apparently healthy men with a normal exercise ECG: coronary heart disease or not? A 26 year follow up study 
Heart  2004;90(6):627-632.
Objective: To determine whether men with possible angina (from their responses to the World Health Organization angina questionnaire) but a normal exercise ECG differ in long term rates of coronary heart disease events from men with no symptoms of angina.
Design: During 1972–75, 2014 apparently healthy men aged 40–59 years underwent an examination programme including case history, clinical examination, exercise ECG to exhaustion, and various other tests. All men completed the WHO angina questionnaire.
Subjects: Of 2014 men, 68 had possible angina, 1831 had no symptoms of angina, and 115 were excluded because they had definite angina or pathological exercise ECGs. All 68+1831 had normal exercise ECGs and none developed chest pain during the exercise test.
Results: At 26 years, men with possible angina had a coronary heart disease mortality of 25.0% (17/68) v 13.8% (252/1831) among men with no symptoms of angina (p < 0.013). They also had a higher incidence of coronary artery bypass grafting (CABG) (p < 0.0004) and acute myocardial infarction (p < 0.026). The excess coronary heart disease mortality among men with possible angina only started after 15 years, whereas differences in CABG/acute myocardial infarction started early. Multivariate analysis including well recognised coronary heart disease risk factors showed that possible angina was an independent risk factor (relative risk 1.79, 95% confidence interval 1.26 to 2.10).
Conclusions: Men with possible angina, even with a normal exercise test, have a greater risk of dying from coronary heart disease, having an acute myocardial infarct, or needing a CABG than age matched counterparts with no symptoms of angina.
PMCID: PMC1768281  PMID: 15145862
WHO angina questionnaire; coronary heart disease; mortality
15.  A novel prediction model for all cause emergency department visits in ischemic heart disease 
Ischemic heart disease (IHD) is the main cause of morbidity and mortality worldwide, and a considerable part of these patients attend to emergency departments, which increases the burden to these busy departments. The aim of this study was to develop a prediction model enabling prediction of all cause emergency department (ED) visits in patients with documented coronary stenosis in a derivation set, and then to determine its accuracy in a validation set.
In a prospective study at outpatient setting of Baqiyatallah hospital, Tehran, Iran, 502 patients with IHD were followed for 6 months for observing the outcome of ED visits for all causes. They were divided in two random groups of derivation set (n = 335) and validation set (n = 167). In the derivation set, to achieve an all cause ED visits prediction model, a prediction model was reached by entering demographic data, clinical variables, somatic comorbidity (Ifudu index), level of anxiety and depression (Hospital Anxiety Depression Scale (HADS) questionnaire), and angina grade (WHO Rose Angina) to a logistic regression. Then in the validation set, the sensitivity, specificity, and the accuracy of that model was tested.
A novel model for prediction of all cause ED visits in IHD patients in six months was presented with gender, anxiety, WHO angina grade and somatic comorbidity as inputs. Sensitivity, specificity, and accuracy of the model were 63.0%, 68.6%, and 67.7%, respectively.
Testing and using the achieved model is suggested to health care providers in other settings.
PMCID: PMC3214331  PMID: 22091242
Emergency Hospital Services; Office Visit; Coronary Artery Disease; Ischemic Heart Disease
16.  Angina (chronic stable) 
Clinical Evidence  2008;2008:0213.
Stable angina is usually caused by coronary atherosclerosis, and affects up to 16% of men and 10% of women aged 65–74 years in the UK. Risk factors include hypertension, elevated serum cholesterol levels, smoking, physical inactivity, and overweight. People with angina are at increased risk of other cardiovascular events and mortality compared with people without angina. Among people not thought to need coronary artery revascularisation, annual mortality is 1–2% and the annual non-fatal myocardial infarction (MI) rate is 2–3%.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are effects of long-term drug treatment for stable angina? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found nine systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the long-term effectiveness and safety of the following interventions: beta-blockers, calcium channel blockers, long-acting nitrates, potassium channel openers, combinations of these anti-anginal drug treatments and the use of these anti-anginal drug treatment as an adjunct to existing therapies.
Key Points
Stable angina is a sensation of discomfort or pain in the chest, arm, or jaw brought on predictably by factors that increase myocardial oxygen demand, such as exertion, and relieved by rest or nitroglycerin. Stable angina is usually caused by coronary atherosclerosis, and affects up to 16% of men and 10% of women aged 65–74 years in the UK. Risk factors include hypertension, elevated serum cholesterol levels, smoking, physical inactivity, and overweight.People with angina are at increased risk of other cardiovascular events and mortality compared with people without angina.Among people not thought to need coronary artery revascularisation, annual mortality is 1–2% and annual non-fatal MI rates are 2–3%.We found no long-term, adequately powered RCTs of anti-anginal drugs versus placebo or comparing the use of a single anti-anginal drug versus combinations of anti-anginal drug classes. There is a consensus that monotherapy with beta-blockers, calcium channel blockers, nitrates, and potassium channel openers are effective for treating the symptoms of stable angina in the long term, although we found few studies to confirm this. There is also consensus that the concurrent use of two of these classes of drug has an additional beneficial effect on anginal symptoms and quality of life. It has not been established that this approach reduces cardiovascular events.Monotherapy with beta-blockers or calcium channel blockers seems equally effective at reducing angina attacks, and they are equally well tolerated in the long term. Adding a calcium channel blocker to existing anti-anginal drug treatments slightly reduces the need for coronary artery surgery, but has no effect on other cardiovascular events.Monotherapy with nitrates may be as effective as monotherapy with calcium channel blockers at reducing angina attacks and improving quality of life.We found no RCTs on the effects of long-term monotherapy with potassium channel openers in people with stable angina, but a large RCT of a potassium channel opener as an adjunct to existing anti-anginal drug treatments found a reduction the number of cardiovascular events compared with placebo.
PMCID: PMC2907993  PMID: 19445795
17.  Effects of α tocopherol and β carotene supplements on symptoms, progression, and prognosis of angina pectoris 
Heart  1998;79(5):454-458.
Objective—To evaluate the effects of α tocopherol and β carotene supplements on recurrence and progression of angina symptoms, and incidence of major coronary events in men with angina pectoris.
Design—Placebo controlled clinical trial.
Setting—The Finnish α tocopherol β carotene cancer prevention study primarily undertaken to examine the effects of α tocopherol and β carotene on cancer.
Subjects—Male smokers aged 50-69 years who had angina pectoris in the Rose chest pain questionnaire at baseline (n = 1795).
Interventions—α tocopherol (vitamin E) 50 mg/day, β carotene 20 mg/day or both, or placebo in 2 × 2 factorial design.
Main outcome measures—Recurrence of angina pectoris at annual follow up visits when the questionnaire was readministered; progression from mild to severe angina; incidence of major coronary events (non-fatal myocardial infarction and fatal coronary heart disease).
Results—There were 2513 recurrences of angina pectoris during follow up (median 4 years). Compared to placebo, the odds ratios for recurrence in the active treatment groups were: α tocopherol only 1.06 (95% confidence interval (CI) 0.85 to 1.33), α tocopherol and β carotene 1.02 (0.82 to 1.27), β carotene only 1.06 (0.84 to 1.33). There were no significant differences in progression to severe angina among the groups given supplements or placebo. Altogether 314 major coronary events were observed during follow up (median 5.5 years) and the risk for them did not differ significantly among the groups given supplements or placebo.
Conclusions—There was no evidence of beneficial effects for α tocopherol or β carotene supplements in male smokers with angina pectoris, indicating no basis for therapeutic or preventive use of these agents in such patients.

 Keywords: antioxidants;  angina pectoris;  prevention;  vitamin supplements
PMCID: PMC1728686  PMID: 9659191
18.  Incidence and prognosis of angina pectoris in South Asians and Whites: 18 years of follow-up over seven phases in the Whitehall-II prospective cohort study 
Whether the higher coronary mortality in South Asians compared with White populations is due to a higher incidence of disease is not known. This study assessed cumulative incidence of chest pain in South Asians and Whites, and prognosis of chest pain.
Over seven phases of 18-year follow-up of the Whitehall-II study (9775 civil servants: 9195 White, 580 South Asian), chest pain was assessed using the Rose questionnaire. Coronary death/non-fatal myocardial infarction was examined comparing those with chest pain to those with no chest pain at baseline.
South Asians had higher cumulative frequencies of typical angina by Phase 7 (17.0 versus 11.3%, P < 0.001) and exertional chest pain (15.4 versus 8.5%, P < 0.001) compared with Whites. Typical angina and exertional chest pain at baseline were associated with a worse prognosis compared with those with no chest pain in both groups (typical angina, South Asians: HR, 4.67 and 95% CI, 2.12–0.30; Whites: HR, 3.56 95% CI, 2.59–4.88). Baseline non-exertional chest pain did not confer a worse prognosis. Across all types of pain, prognosis was worse in South Asians.
South Asians had higher cumulative incidence of angina than Whites. In both, typical angina and exertional chest pain were associated with worse prognosis compared with those with no chest pain.
PMCID: PMC3159510  PMID: 21045007
circulatory disease; epidemiology; ethnicity
19.  Differences in admission rates and outcomes between men and women presenting to emergency departments with coronary syndromes 
Previous studies examining sex-related differences in the treatment of coronary artery disease have focused on patients in hospital. We sought to examine sex-related differences at an earlier point in care — presentation to the emergency department.
We collected data on ambulatory care and hospital admissions for 54 134 patients (44% women) who presented to an emergency department in Alberta between July 1998 and March 2001 because of acute myocardial infarction, unstable angina, stable angina or chest pain. We used logistic regression and Cox regression analyses to determine sex-specific associations between the likelihood of discharge from the emergency department or coronary revascularization within 1 year and 1-year mortality after adjusting for age, comorbidities and socioeconomic factors.
Following the emergency department visit, 91.3% of patients with acute myocardial infarction, 87.4% of those with unstable angina, 40.7% of those with stable angina and 19.8% of those with chest pain were admitted to hospital. Women were more likely than men to be discharged from the emergency department: adjusted odds ratio (and 95% confidence interval [CI]) 2.25 (1.75–2.90) for acute myocardial infarction, 1.71 (1.45–2.01) for unstable angina, 1.33 (1.15–1.53) for stable angina and 1.46 (1.36–1.57) for chest pain. Women were less likely than men to undergo coronary revascularization within 1 year: adjusted odds ratio (and 95% CI) 0.65 (0.57–0.73) for myocardial infarction, 0.39 (0.35–0.44) for unstable angina, 0.35 (0.29–0.42) for stable angina and 0.32 (0.27–0.37) for chest pain. Female sex had no impact on 1-year mortality among patients with acute myocardial infarction; it was associated with a decreased 1-year mortality among patients with unstable angina, stable angina and chest pain: adjusted hazard ratio (and 95% CI) 0.60 (0.46–0.78), 0.60 (0.46–0.78) and 0.74 (0.63–0.87) respectively.
Women presenting to the emergency department with coronary syndromes are less likely than men to be admitted to an acute care hospital and to receive coronary revascularization procedures. These differences do not translate into worse outcomes for women in terms of 1-year mortality.
PMCID: PMC2043078  PMID: 17984470
20.  The association of the ‘additional height index’ with atopic diseases, non-atopic asthma, ischaemic heart disease and mortality: a population-based study 
BMJ Open  2014;4(2):e003933.
Intrauterine growth has been associated with atopic conditions. Growth and adult height have been associated with cardiovascular disease, cancers and mortality but are highly genetic traits. The objectives of the study were as follows: first, to define a height measure indicating an individual's height below or above that which could be expected based on parental height (genetic inheritance) and growth charts. It was named ‘the additional height index’ (AHI), defined as (attained—expected) height; second, to investigate possible associations of AHI with atopic versus non-atopic health outcomes and with ischaemic heart disease (IHD) and IHD mortality.
General population-based study.
Research centre.
A random sample of 2656 men and women living in greater Copenhagen took part in the MONICA10 study (the Danish monitoring trends and determinants of cardiovascular disease). In total, 1900 participants with information of parental height were selected.
Outcome measures
Atopic sensitisation (serum IgE), questionnaire information of atopic dermatitis, rhinoconjunctivitis, asthma or wheezing, and registry-based diagnoses of IHD/IHD mortality from National Registries.
Increasing levels of AHI were inversely associated with non-atopic asthma, non-atopic wheezing, IHD and IHD mortality (IHD-all). For one SD increase of AHI, the OR or HR with CI in adjusted analyses was non-atopic asthma OR=0.52 (0.36 to 0.74), non-atopic wheezing OR=0.67 (0.51 to 0.89), and IHD-all HR=0.89 (0.78 to 1.01). The level of AHI was higher among individuals with atopic dermatitis, allergic rhinoconjunctivitis and atopic sensitisation (all p values <0.001) compared with individuals without those conditions; however, the associations were not confirmed in adjusted analyses.
Individuals with childhood conditions that led them to attain tallness higher than expected from their parents’ height may be at lower risk of non-atopic asthma/wheeze and IHD/IHD mortality but possibly at higher risk of atopic conditions. The measure of tallness below or above the expected height could be a sensitive alternative to normal height in epidemiological analyses.
PMCID: PMC3939652  PMID: 24583759
21.  Ischemic heart disease, factor predisposing to Barrett’s adenocarcinoma: A case control study 
AIM: To define the significance of ischemic heart disease (IHD) (stable angina to infarction) co-existance in Barrett esophagus (BE) patients and patients with esophageal adenocarcinoma (AdE).
METHODS: All BE/AdE patients in Blackpool-Wyre-Fylde area and Trikala prefecture identified from medical records. Patient clinical details were obtained from hospital and General Practitioner records. Additional information was gathered from validated questionnaire.
RESULTS: Forty (33%) AdE and 83 (19%) BE patients had IHD (P = 0.002). Eighteen (15%) AdE and 34 (8%) BE patients had suffered a myocardial infarction (P = 0.03). Three (3%) AdE and 7 (2%) BE patients had severe heart failure (P = 0.82). Thirty-nine (47%) BE with IHD and 8 (20%) AdE patients with IHD consumed aspirin daily (P = 0.004). Seventh-seven (93%) BE patients with IHD and 36 (90%) AdE patients with IHD were on statins (P = 0.86). Logistic regression analysis: AdE was more frequent in the elderly, with long term reflux, long BE and concurrent IHD (odds ratio: 2.086, P = 0.001) not consuming statins. Eighteen (22%) BE patients with IHD [16 (84%) with myocardial infarction] vs 33 (10%) without IHD died from non-neoplastic causes within 24 mo from BE diagnosis (P = 0.005).
CONCLUSION: IHD is more prevalent in AdE than BE patients. Increased prevalence of AdE is related with the presence of myocardial infarction but not severe heart failure, possibly because patients with BE and severe IHD have low life expectancy.
PMCID: PMC4133444  PMID: 25133047
Barrett esophagus; Esophageal adenocarcinoma; Ischemic heart disease; Myocardial infarction; Non-steroidal anti-inflammatory drugs
22.  Ischaemic Heart Disease in Young Women* 
British Medical Journal  1974;4(5939):253-259.
The mortality rate from ischaemic heart disease (I.H.D.) has increased in young women by about 50% in 12 years, and it is now possible to report the findings in 150 women who developed symptoms and signs of I.H.D. under the age of 45. Data obtained from 145 of these women form the basis of this report: 81 presented with myocardial infarction and 64 with angina. In the remaining five there was a definite nonatherosclerotic cause for the premature onset of I.H.D.
Hypercholesterolaemia, hypertension, or excessive cigarette smoking each occurred in a large minority, and more than one of these major risk factors was present in most patients. Hypercholesterolaemia was the commonest factor. In women in whom lipoprotein typing was undertaken the type II pattern was more frequent than type IV. The prevalence of hypercholesterolaemia and hypertension was the same in those with myocardial infarction and in those with angina.
Excessive cigarette smoking was more common in women with myocardial infarction than in those with angina. The latter did not differ in their cigarette smoking habits from the normal population.
A premature menopause had occurred in 20% of these women, but there was no relation between the early onset of I.H.D. with age at menarche, parity, or the incidence of abortion. Oral contraceptives did not increase the risk of myocardial infarction unless one of the major risk factors was also present.
Altogether 75% of patients with angina or myocardial infarction survived 12 years. Coexisting hypertension worsened the prognosis. The prognosis after myocardial infarction was similar in these women to that previously described for men under the age of 40.
PMCID: PMC1612268  PMID: 4425852
23.  The Association of Angina Pectoris with Heart Disease Mortality Among Men and Women by Diabetes Status: The Rancho Bernardo Study 
Journal of Women's Health  2010;19(8):1433-1439.
To study the sex-specific association of angina pectoris with mortality in community-dwelling older adults with and without diabetes.
Baseline prevalence of angina was evaluated in 822 men and 1184 postmenopausal women aged 50–89 years at the 1984–1987 Rancho Bernardo Study clinic visit, when an oral glucose tolerance test (OGTT) and the Rose angina questionnaire were administered. All-cause and coronary heart disease (CHD) mortality were assessed after an average follow-up period of 13.2 years. Sex-specific Cox proportional hazard models were used to examine the independent association of angina with mortality by glucose tolerance category.
At baseline, average age was 71 years for both sexes; 61 men (7.4%) and 142 women (12.0%) had angina. Overall, 129 men (15.9%) and 130 women (11.0%) had type 2 diabetes; 228 men (27.7%) and 357 women (30.2%) had impaired glucose tolerance (IGT). During follow-up, 485 men (59%) and 557 women (47%) died, of whom 103 men (21.2%) and 104 women (18.7%) had fatal CHD. Women with diabetes and angina had a 3–4-fold greater risk of dying from CHD than women with diabetes but without angina, independent of covariates. Women with angina and IGT had twice the risk of CHD mortality compared with women with IGT but without angina. A smaller increased risk of fatal CHD in men was not statistically significant.
Angina was associated with an increased risk of dying from CHD among women, especially among those who also had IGT or diabetes.
PMCID: PMC2941406  PMID: 20629575
24.  Chest pain and subsequent consultation for coronary heart disease: a prospective cohort study 
Chest pain may not be reported to general practice but could be an important first sign of coronary heart disease (CHD).
To determine whether self-reported chest pain predicts future consultation for CHD in those with no history of consultation for CHD.
Design of study
Population-based study, with 7 year's follow up by GP record linkage.
General practice in North Staffordshire.
A survey, including the Rose angina questionnaire, was mailed to 4002 adults. Linked GP records used to identify responders with no record of CHD (G3 Read code or British National Formulary code for nitrate use) in the 32 months before the survey to form the sample for a 7-year prospective study. ‘Survival’ was compared in those with and without self-reported chest pain up to the earliest date of GP diagnosis of CHD, death, or end of the study period.
The survey response was 65% and 2348 participants gave permission to access their GP records. Of these, 2229 had no prior consultation for CHD. From the questionnaire, 558 reported chest pain of which 186 reported exertional pain and 103 met the criteria for angina. When followed prospectively, incidence of CHD consultations was higher in those with any chest pain definition, compared with no pain, and continued to be so for 7 years subsequently. Although these associations were strongly age related, self-reported symptoms were found to be an independent risk factor for future consultation for CHD.
This study highlighted that self-reported chest pain is a marker of future CHD. The usefulness of early identification of people with this symptom remains to be established.
PMCID: PMC2032699  PMID: 17244423
angina; chest pain; coronary disease; epidemiology; referral and consultation; screening
25.  Helicobacter pylori infection: relation with cardiovascular risk factors, ischaemic heart disease, and social class. 
British Heart Journal  1995;74(5):497-501.
OBJECTIVE--To determine whether Helicobacter pylori infection is associated with the development of ischaemic heart disease and whether such infection can explain the social class inequality in ischaemic heart disease. DESIGN--Cardiovascular risk factor levels, prevalence of ischaemic heart disease (Rose questionnaire angina, and/or a history of myocardial infarction), and serum antibodies to H pylori (enzyme linked immunosorbent assay) were assessed in a cross sectional population based survey. SETTING--Belfast and surrounding districts, Northern Ireland. PARTICIPANTS--1182 men and 1198 women aged 25-64 years randomly selected from the Central Services Agency's general practitioner lists. MAIN OUTCOME MEASURES--The relation of H pylori infection with cardiovascular risk factors and ischaemic heart disease. The association of social class with ischaemic heart disease. RESULTS--Systolic and diastolic blood pressure, plasma viscosity, and total cholesterol were not associated with H pylori infection. A weak negative association existed between H pylori infection and fibrinogen (mean (SE) difference in fibrinogen between infected and uninfected individuals -0.09 (0.04) g/l, P = 0.02) and between infection in women and high density lipoprotein (HDL) cholesterol (mean (SE) difference in HDL cholesterol between infected and uninfected individuals -0.06 (0.02) mmol/l, P = 0.006). A potentially important association was demonstrated between H pylori infection and ischaemic heart disease but this did not reach statistical significance (odds ratio (95% confidence interval (CI) 1.51 (0.93 to 2.45), P = 0.1). Social class was associated with ischaemic heart disease independently of cardiovascular risk factors and H pylori infection (odds ratio, manual v non-manual (95% CI) 1.82 (1.14 to 2.91), P = 0.01). CONCLUSION--H pylori may be independently associated with the development of ischaemic heart disease but if this is so the mechanism by which this effect is exerted is not through increased concentration of plasma fibrinogen. H pylori infection does not explain the social class inequality in ischaemic heart disease which exists independently of known cardiovascular risk factors.
PMCID: PMC484068  PMID: 8562233

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