Summary
Background
Cardiovascular disease is the primary cause of death in women. Prevention, screening and diagnosis are generally implemented at later stages and less frequently than in men, and provision of treatment is not optimal in women.
Aims
To assess the relevance of targeted screening for myocardial ischaemia in women with multiple risk factors, and to identify which specific factors target women more effectively.
Methods
We undertook a prospective observational study with retrospective data collection based on a cohort of symptomatic or asymptomatic women with multiple cardiovascular risk factors. All women underwent non-invasive diagnostic testing through the “Heart, arteries and women”, healthcare pathway available at Lille University Hospital, between 1 January 2013 and 30 June 2014.
Results
Screening was positive in 15.7% of the 287 participants. Thirty women had a coronary angiography: of these, 22 (73.3%) had no evidence of obstructive coronary artery disease. The independent predictive factors for positive screening were >5 years since menopause (odds ratio [OR] 3.9; P = 0.0016); high-density lipoprotein cholesterol ≤0.5 g/dL (OR 2.3; P = 0.0356); and body mass index ≥30 kg/m 2 (OR 3.7; P = 0.0009). Symptoms were predictive of positive screening ( P = 0.010), but were mostly atypical. Based on these observations, we developed a clinical coronary score to target screening more efficiently (area under the curve 0.733). Positive screening resulted in low rates of revascularization (16.6%), but a significant increase in the prescription of statins ( P = 0.002), antiplatelet agents ( P < 0.0001) and beta-blockers ( P = 0.024).
Conclusion
Screening for myocardial ischaemia among selected women at risk of cardiovascular disease can be useful to improve medical treatment.
Résumé
Contexte
Les maladies cardio-vasculaires restent la première cause de mortalité féminine. La prévention, le dépistage et les épreuves diagnostiques sont réalisés tardivement et moins fréquemment, et le traitement médical est sous-optimal chez la femme.
Objectifs
Evaluer la pertinence d’un dépistage ciblé de l’ischémie myocardique chez la femme à risque cardio-vasculaire et les facteurs susceptibles de mieux cibler le dépistage.
Méthodes
Nous avons réalisé une étude observationnelle prospective avec recueil rétrospectif des données chez 287 patientes à risque cardio-vasculaire, symptomatiques ou non, ayant bénéficié d’un test d’ischémie myocardique non invasif au sein du parcours de soin « Cœur, artères et femmes » au CHRU de Lille du 1 er janvier 2013 au 30 juin 2014.
Résultats
Le dépistage était positif chez 15,7 % des patientes. Parmi les 30 femmes qui ont eu une coronarographie, 22 (73,3 %) n’avaient pas d’obstruction coronaire significative. Les facteurs prédictifs indépendants d’un dépistage positif était : ménopause de plus de 5 ans (OR 3,9 ; P = 0,0016) ; HDL-C ≤ 0,5 g/dL (OR 2,3 ; P = 0,0356) ; et indice de masse corporelle ≥ 30 kg/m 2 (OR 3,7 ; P = 0,0009). Les symptômes étaient prédictifs d’un dépistage positif ( P = 0,010) mais majoritairement atypiques. Un score clinique coronaire a été développé pour cibler le dépistage (aire sous la courbe 0,733). Le dépistage positif a entrainé un faible taux de revascularisation (16,6 %), mais une optimisation de la prescription de statines ( P = 0,002), d’antiagrégant plaquettaires ( P < 0,0001) ou de bétabloquants ( P = 0,024).
Conclusion
Le dépistage de l’ischémie myocardique chez des femmes à risque cardio-vasculaire sélectionnées peut être utile pour améliorer la prise en charge médicale.
Background
Cardiovascular disease, particularly coronary artery disease (CAD), is the leading cause of death in women worldwide – and notably in developed countries – causing more deaths than all forms of cancer combined . Despite progress in the prevention and management of CAD, reductions in mortality are lower in women than in men . In younger women, an increased incidence of myocardial infarction has even been observed, with a higher risk of adverse outcomes . This major public health issue is frequently underestimated in women; prevention, screening and diagnosis typically occur at later stages and less frequently than in men, and provision of treatment is not optimal in women .
In terms of pathogenesis, symptoms and prognosis, ischaemic heart disease (IHD) differs between women and men . The classic concept of CAD as myocardial ischaemia caused by obstruction of the major coronary arteries is not representative of all aspects of ischaemic disease in women. Myocardial ischaemia without obstruction of the major coronary arteries, described as microvascular dysfunction, is largely unknown , and yet is associated with high cardiovascular risk (CVR) . Symptoms are often atypical and misleading, causing late diagnosis and treatment . Initial presentation in women is more often acute, with a higher prevalence of sudden cardiac death and acute myocardial infarction without previous symptoms . Regardless of presentation, the prognosis of IHD is poorer in women than men, and cannot be explained by age and co-morbidities alone . There is, therefore, a strong rationale for screening in women. However, CAD appears to be more difficult to assess in women, because symptoms are often atypical, with lower functional capacity, higher mortality and more adverse outcomes, despite less significant obstructive CAD than in men . For a significant proportion of women, traditional disease management focusing on detecting a critical stenosis often fails to identify the women who are actually at risk. The pretest assessment that follows a male model is more difficult to interpret for women than for men, and should be adapted to the specific patterns of IHD in women .
Further research is needed to improve diagnostic and therapeutic approaches in women with CAD. The current public health challenge is to identify women at elevated risk of sudden cardiac death or acute myocardial infarction.
The primary objectives of our study were to evaluate the relevance of targeted screening for myocardial ischaemia in women with multiple risk factors, and to establish which factors would help in targeting women more efficiently. The secondary objectives were to evaluate the therapeutic outcomes of screening.
Methods
Study population
We undertook a prospective observational study with retrospective data collection based on a cohort of symptomatic or asymptomatic women with multiple CVR factors, followed through the “Heart, arteries and women” healthcare pathway that is available at Lille University Hospital, between 1 January 2013 and 30 June 2014. We selected all women who underwent non-invasive diagnostic testing. Women aged <40 years and >75 years were excluded, as were those with known CAD or an acute coronary syndrome ( Fig. 1 ).
Clinical data collected included CVR factors; history of cardiovascular events other than CAD; gynaecological history and menopausal status; cardiovascular symptoms; resting electrocardiogram; and lipid profile. Cardiovascular treatments at the time of consultation and after non-invasive stress testing were also documented.
Non-invasive cardiac stress testing
The indication and type of non-invasive diagnostic test was decided by one of the five consulting physicians, from exercise electrocardiogram; stress echocardiography (with exercise or dobutamine stress); stress myocardial perfusion imaging with single photon emission computed tomography (SPECT); and stress cardiovascular magnetic resonance imaging.
Exercise electrocardiogram treadmill testing was performed using the Bruce protocol or the modified Bruce protocol, according to estimated functional capacity. Significant ST-segment depression (≥1.0 mm horizontal or down-sloping depression, or ≥1.5 mm upsloping depression at 60 ms after the J point) with exercise electrocardiogram treadmill testing was considered positive for ischaemia .
For stress echocardiography and stress myocardial perfusion imaging, stress was induced by exercise on a cycle ergometer or a treadmill, or by injection of dobutamine if the patient was unable to exercise. Continuous electrocardiograms and blood pressure levels were recorded. The Bruce protocol was used for the exercise treadmill test, and a standardized protocol was used for exercise on the cycle ergometer. Dobutamine was administered by intravenous perfusion: initially 10 μg/kg/min, increasing by 10 μg/kg/min every 3 min up to a maximum of 40 μg/kg/min or until a stress endpoint was reached. Atropine was administered intravenously at a dose of 0.25 mg/min up to a maximum of 1.5 mg, while dobutamine perfusion was continued, to help patients achieve 85% of their age-predicted maximal heart rate.
During stress echocardiography, regional wall motion was recorded during rest, stress and recovery. Endocardial excursion and systolic thickening were assessed visually, for each segment, using a 17-segment model. A test was considered positive for ischaemia if a biphasic response or new worsening wall-motion abnormalities (hypokinesia, akinesia or dyskinesia) were observed in at least two contiguous non-overlapping segments .
During stress myocardial perfusion imaging, technetium-99m methoxyisobutylisonitril (99mTc-MIBI) was injected at peak stress and the next day at rest. Gated acquisitions were acquired. Semi-quantitative and quantitative visual interpretation were performed using a 17-segment model. A test was considered positive for ischaemia if a significant (≥10%) myocardial perfusion defect was observed . The perfusion defect size was quantified, and expressed as a percentage of the left ventricular myocardium.
Diagnosis of IHD
Coronary angiography diagnosed IHD when there was significant (>50%) obstructive stenosis in one or more coronary arteries or their major branches, and in symptomatic patients with a positive non-invasive test, but without significant obstructive CAD (<50% or no stenosis), probably attributable to microvascular disease .
Development of a clinical score to predict positive screening
When data were available, overall cardiovascular and coronary risk levels were assessed in non-diabetic women using the Framingham risk score , D’Agostino’s risk score and Systematic Coronary Risk Evaluation (SCORE; the European risk score, available at http://www.escardio.org/Education/Practice-Tools/CVD-prevention-toolbox/SCORE-Risk-Charts ) . Multivariable analysis and relative risk were used to develop a clinical coronary score based on independent predictive factors for a positive stress test. The reliability of CVR scores to predict a positive non-invasive stress test was then assessed.
Statistical analysis
First, descriptive analysis was performed to check and summarize the data: continuous variables are expressed as means ± standard deviations and nominal variables as percentages. Next, a comparative analysis was performed: Wilcoxon’s non-parametric test (two groups) and the Kruskal–Wallis test (three groups or more) were used to compare continuous variables. Categorical variables were compared using the χ 2 test or Fisher’s exact test when needed. Treatment regimens at initial visit and after non-invasive testing were compared using McNemar’s test. The ability of CVR scores to predict positive screening results among non-diabetic women was assessed using receiver operating characteristic (ROC) curves. To determine the subset of independent risk factors that could best explain a positive screening, a stepwise logistic regression was considered. However, the selection of a subset of variables can be strongly sample dependent. Bootstrap methods allow a more robust selection process, which reduces biases. All variables that were significantly ( P < 0.05) associated with a positive screening were then entered into a bootstrap logistic regression (500 samples). The subset of risk factors identified by the bootstrap procedure was used to build a score using logistic regression. A P value <0.05 was considered statistically significant. The statistical analysis was performed using SAS software, release 9.3 (SAS Institute, Cary, NC, USA).
Results
Baseline characteristics of the study population are summarized in Table 1 . The majority (93.7%) had at least one major modifiable CVR factor, 74.2% had two factors and 51.2% had three factors. Over half (63.6%) of the population had a body mass index >25 kg/m 2 . Cardiovascular symptoms were present in 49.1%.
| Variables | |
|---|---|
| Age (years) | 57 ± 8 |
| Body mass index (kg/m 2 ) | 29 ± 7 |
| Abdominal circumference (cm) | 102 ± 7 |
| Medical history | |
| Hypertension a | 213 (74.2) |
| Current smokers | 37 (12.9) |
| Diabetes mellitus b | 77 (26.8) |
| Dyslipidaemia c | 139 (48.4) |
| Family history of premature cardiovascular disease d | 82 (28.6) |
| Sleep apnoea syndrome | 34 (11.8) |
| Cerebrovascular diseases | 22 (7.7) |
| Peripheral arterial disease | 9 (3.1) |
| Preeclampsia or pregnancy-induced hypertension | 72 (25.1) |
| Gestational diabetes | 26 (9.1) |
| Menopausal status | |
| Menopausal women | 210 (73.1) |
| >5 years since menopause | 165 (57.5) |
| Current or previous hormone replacement therapy | 41 (14.2) |
| Cardiovascular symptoms | 141 (49.1) |
| Dyspnoea | 98 (34.1) |
| Chest pain | 86 (29.9) |
| Atypical angina | 32 (37.2) |
| Typical angina | 9 (10.4) |
| Non-anginal chest pain | 45 (52.4) |
| Abnormal resting electrocardiogram e | 52 (18.1) |
| LDL-C (g/L) | 1.23 ± 0.41 |
| HDL-C (g/L) | 0.59 ± 0.19 |
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