Efficacity of in-hospital multidimensional interventions of secondary prevention after acute coronary syndrome : a systematic review and meta-analysis

RAPPORT DE SYNTHÈSE : Contexte Les programmes de prévention cardiovasculaire secondaire après un événement coronarien aigu ont pu démontrer leur efficacité dans le contexte des soins ambulatoires. L'hospitalisation pour une maladie aiguë peut être considérée comme un «instant charnière», particulièrement adapté à un changement de comportement de santé et où des interventions de prévention secondaire, telle l'éducation du patient, pourraient être particulièrement efficaces. De plus, la prescription de médicaments de prévention cardiovasculaire durant l'hospitalisation semble augmenter la proportion des patients traités selon les recommandations sur le long terme. Récemment, plusieurs études ont évalué l'efficacité de programmes de prévention ayant pour but l'éducation des patients et/ou une augmentation du taux de prescription de médicaments prouvés efficaces par les médecins en charge. L'article faisant l'objet du travail de thèse synthétise la littérature existante concernant l'efficacité en termes de mortalité des interventions multidimensionnelles de prévention cardiovasculaire après un syndrome coronarien aigu, débutées à l'hôpital, centrées sur le patient et ciblant plusieurs facteurs de risque cardiovasculaire. MÉTHODE ET RÉSULTATS : En utilisant une stratégie de recherche définie à l'avance, nous avons inclus des essais cliniques avec groupe contrôle et des études avant-après, débutées à l'hôpital et qui incluaient des résultats cliniques de suivi en terme de mortalité, de taux de réadmission et/ou de récidive de syndrome coronarien aigu. Nous avons catégorisé les études selon qu'elles ciblaient les patients (par exemple une intervention d'éducation aux patients par des infirmières), les soignants (par exemple des cours destinés aux médecins-assistants pour leur enseigner comment prodiguer des interventions éducatives) ou le système de soins (par exemple la mise en place d'itinéraires cliniques au niveau de l'institution). Globalement, les interventions rapportées dans les 14 études répondant aux critères montraient une réduction du risque relatif (RR) de mortalité après un an (RR= 0.79; 95% intervalle de confiance (IC), 0.69-0.92; n=37'585). Cependant, le bénéfice semblait dépendre du type d'étude et du niveau d'intervention. Les études avant-après suggéraient une réduction du risque de mortalité (RR, 0.77; 95% IC, 0.66-0.90; n=3680 décès), tandis que le RR était de 0.96 (95% IC, 0.64-1.44; n=99 décès) pour les études cliniques contrôlées. Seules les études avant-après et les études ciblant les soignants et le système, en plus de cibler les patients, semblaient montrer un bénéfice en termes de mortalité à une année. CONCLUSIONS ET PERSPECTIVES : Les preuves d'efficacité des interventions de prévention secondaires débutées à l'hôpital, ciblant le patient, sont prometteuses, mais pas définitives. En effet, seules les études avant-après montrent un bénéfice en termes de mortalité. Les recherches futures dans ce domaine devraient tester formellement quels éléments des interventions amènent le plus de bénéfices pour les patients.

Improved three-dimensional free-breathing coronary magnetic resonance angiography using gadocoletic acid (B-22956) for intravascular contrast enhancement.

PURPOSE: To evaluate gadocoletic acid (B-22956), a gadolinium-based paramagnetic blood pool agent, for contrast-enhanced coronary magnetic resonance angiography (MRA) in a Phase I clinical trial, and to compare the findings with those obtained using a standard noncontrast T2 preparation sequence. MATERIALS AND METHODS: The left coronary system was imaged in 12 healthy volunteers before B-22956 application and 5 (N = 11) and 45 (N = 7) minutes after application of 0.075 mmol/kg of body weight (BW) of B-22956. Additionally, imaging of the right coronary system was performed 23 minutes after B-22956 application (N = 6). A three-dimensional gradient echo sequence with T2 preparation (precontrast) or inversion recovery (IR) pulse (postcontrast) with real-time navigator correction was used. Assessment of the left and right coronary systems was performed qualitatively (a 4-point visual score for image quality) and quantitatively in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), vessel sharpness, visible vessel length, maximal luminal diameter, and the number of visible side branches. RESULTS: Significant (P < 0.01) increases in SNR (+42%) and CNR (+86%) were noted five minutes after B-22956 application, compared to precontrast T2 preparation values. A significant increase in CNR (+40%, P < 0.05) was also noted 45 minutes postcontrast. Vessels (left anterior descending artery (LAD), left coronary circumflex (LCx), and right coronary artery (RCA)) were also significantly (P < 0.05) sharper on postcontrast images. Significant increases in vessel length were noted for the LAD (P < 0.05) and LCx and RCA (both P < 0.01), while significantly more side branches were noted for the LAD and RCA (both P < 0.05) when compared to precontrast T2 preparation values. CONCLUSION: The use of the intravascular contrast agent B-22956 substantially improves both objective and subjective parameters of image quality on high-resolution three-dimensional coronary MRA. The increase in SNR, CNR, and vessel sharpness minimizes current limitations of coronary artery visualization with high-resolution coronary MRA.

Hypertoniebehandlung bei Nierenarterienstenose [Hypertension therapy in patients with renal artery stenosis].

Renovascular hypertension is due to reduced renal parenchymal perfusion. The correct diagnosis can be difficult. It is important to note that the demonstration of renal artery stenosis in a patient with hypertension does not necessarily constitute renovascular hypertension. Often, clinically nonsignificant and asymptomatic renal artery stenosis are found in patients with essential hypertension, or renal failure of other origin. Renovascular disease is a complex disorder with various clinical presentations. In patients with significant renovascular hypertension plasma renin is increased. For this reason the therapy aims to block the renin-angiotensin-aldosterone system. Bilateral renal artery stenosis causes renal sodium retention. In this situation a diuretic drug has to be added to the therapy. Endovascular or surgical therapy has to be considered in patients with flash pulmonary edema or fibromuscular dysplasia. The control of cardiovascular risk factors is important.

Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality

BACKGROUND: Data on the association between subclinical thyroid dysfunction and coronary heart disease (CHD) and mortality are conflicting. PURPOSE: To summarize prospective evidence about the relationship between subclinical thyroid dysfunction and CHD and mortality. DATA SOURCES: MEDLINE (1950 to January 2008) without language restrictions and reference lists of retrieved articles were searched. STUDY SELECTION: Two reviewers screened and selected cohort studies that measured thyroid function and then followed persons prospectively to assess CHD or mortality. DATA EXTRACTION: By using a standardized protocol and forms, 2 reviewers independently abstracted and assessed studies. DATA SYNTHESIS: Ten of 12 identified studies involved population-based cohorts that included 14 449 participants. All 10 population-based cohort studies examined risks associated with subclinical hypothyroidism (2134 CHD events and 2822 deaths), whereas only 5 examined risks associated with subclinical hyperthyroidism (1392 CHD events and 1993 deaths). In a random-effects model, the relative risk (RR) for subclinical hypothyroidism for CHD was 1.20 (95% CI, 0.97 to 1.49; P for heterogeneity = 0.14; I(2 )= 33.4%). Risk estimates were lower when higher-quality studies were pooled (RR, 1.02 to 1.08) and were higher among participants younger than 65 years (RR, 1.51 [CI, 1.09 to 2.09] for studies with mean participant age <65 years and 1.05 [CI, 0.90 to 1.22] for studies with mean participant age > or =65 years). The RR was 1.18 (CI, 0.98 to 1.42) for cardiovascular mortality and 1.12 (CI, 0.99 to 1.26) for total mortality. For subclinical hyperthyroidism, the RR was 1.21 (CI, 0.88 to 1.68) for CHD, 1.19 (CI, 0.81 to 1.76) for cardiovascular mortality, and 1.12 (CI, 0.89 to 1.42) for total mortality (P for heterogeneity >0.50; I(2 )= 0% for all studies). LIMITATIONS: Individual studies adjusted for different potential confounders, and 1 study provided only unadjusted data. Publication bias or selective reporting of outcomes could not be excluded. CONCLUSION: Subclinical hypothyroidism and hyperthyroidism may be associated with a modest increased risk for CHD and mortality, with lower risk estimates when pooling higher-quality studies and larger CIs for subclinical hyperthyroidism

Contribution of major cardiovascular risk factors to familial premature coronary artery disease : the GENECARD project

Résumé: Objectifs: Cette étude relève la prévalence des principaux facteurs de risque cardiovasculaire dans les coronaropathies précoces (P-CAD) familiales, survenant chez au moins deux frères et/ou soeurs d'une même fratrie. Méthodes: Nous avons recruté 213 survivants atteints de P-CAD, issus de 103 fratries, diagnostiqués avant l'âge de 50 ans chez les hommes et 55 ans chez les femmes. La présence ou non d'hypertension, d'hypercholestérolémie, d'obésité et de tabagisme a été documentée au moment de l'événement chez 163 de ces patients (145 hommes et 18 femmes). Chaque patient a été comparé à deux individus de même âge et sexe, chez qui un diagnostic de P-CAD «sporadique» (non familiale) était posé, et à trois individus choisis au hasard parmi la population générale. Résultats: En comparaison de la population générale, les patients atteints de P-CAD sporadique avaient une prévalence supérieure pour 1 'hypertension (29% vs. 14%, p<0.001), le cholestérol (54% vs. 33%, p<0.001), l'obésité (20% vs. 13%, p<0.001) et le tabagisme (76% vs. 39%, p<0.001). Ces facteurs de risque étaient de prévalences similaires, voire supérieures chez les patients atteints de P-CAD familiale (43% [p<0.05 vs. P-CAD sporadiques], 58% [p=0.07], 21% et 72%) respectivement). Seulement 7 (4%) des 163 patients atteints de P-CAD familiale et 22 (7%) des 326 patients atteints de P-CAD sporadique, ne présentaient aucun facteur de risque cardiovasculaire, comparés à 167 (34%) des 489 patients issus de la population générale. Conclusions: Les facteurs de risque cardiovasculaire classiques et réversibles ont une haute prévalence chez les patients atteints de P-CAD familiale. Ce fait rend improbable une contribution génétique prédominante, agissant en l'absence de facteurs de risque. Abstract: Objectives: This study was designed to assess the prevalence of major cardiovascular risk factors in familial premature coronary artery disease (P-CAD), affecting two or more siblings within one sibship. Background: Premature CAD has a genetic component. It remains to be established whether familial P-CAD is due to genes acting independently from major cardiovascular risk factors. Methods: We recruited 213 P-CAD survivors from 103 sibships diagnosed before age ?50 (men) or ?55 (women) years old. Hypertension, hypercholesterolemia, obesity, and smoking were documented at the time of the event in 163 patients (145 men and 18 women). Each patient was compared with two individuals of the same age and gender, diagnosed with sporadic (nonfamilial) P-CAD, and three individuals randomly sampled from the general population. Results: Compared with the general population, patients with sporadic P-CAD had a higher prevalence of hypertension (29% vs. 14%, p < 0.001), hypercholesterolemia (54% vs. 33%, p < 0.001), obesity (20% vs. 13%, p < 0.001), and smoking (76% vs. 39%, p < 0.001). These risk factors were equally or even more prevalent in patients with familial P-CAD (43% [p < 0.05 vs. sporadic P-CAD], 58% [p = 0.07], 21% and 72%, respectively). Overall, only 7 (4%) of 163 of patients with familial P-CAD and 22 (7%) of 326 of patients with sporadic P-CAD had none of these conditions, as compared with 167 (34%) of 489 patients in the general population. Conclusions: Classic, remediable risk factors are highly prevalent in patients with familial P-CAD. Accordingly, a major contribution of genes acting in the absence of these risk factors is unlikely

Genetic variants influencing circulating lipid levels and risk of coronary artery disease.

OBJECTIVE: Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. METHODS AND RESULTS: We combined genome-wide association data from 8 studies, comprising up to 17 723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37 774 participants from 8 populations and also in a population of Indian Asian descent. We also assessed the association between single-nucleotide polymorphisms (SNPs) at lipid loci and risk of CAD in up to 9 633 cases and 38 684 controls. We identified 4 novel genetic loci that showed reproducible associations with lipids (probability values, 1.6×10(-8) to 3.1×10(-10)). These include a potentially functional SNP in the SLC39A8 gene for HDL-C, an SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-C, and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with 1 or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (probability values, 1.1×10(-3) to 1.2×10(-9)). CONCLUSIONS: We have identified 4 novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-C, genetic loci mainly associated with circulating triglycerides and HDL-C are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk.

Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.

BACKGROUND: The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteine-lowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and risk of CAD. OBJECTIVE: We tested whether common genetic polymorphisms associated with variation in tHcy are also associated with CAD. DESIGN: We conducted a meta-analysis of genome-wide association studies (GWAS) on tHcy concentrations in 44,147 individuals of European descent. Polymorphisms associated with tHcy (P < 10(-8)) were tested for association with CAD in 31,400 cases and 92,927 controls. RESULTS: Common variants at 13 loci, explaining 5.9% of the variation in tHcy, were associated with tHcy concentrations, including 6 novel loci in or near MMACHC (2.1 Ã- 10(-9)), SLC17A3 (1.0 Ã- 10(-8)), GTPB10 (1.7 Ã- 10(-8)), CUBN (7.5 Ã- 10(-10)), HNF1A (1.2 Ã- 10(-12)), and FUT2 (6.6 Ã- 10(-9)), and variants previously reported at or near the MTHFR, MTR, CPS1, MUT, NOX4, DPEP1, and CBS genes. Individuals within the highest 10% of the genotype risk score (GRS) had 3-μmol/L higher mean tHcy concentrations than did those within the lowest 10% of the GRS (P = 1 Ã- 10(-36)). The GRS was not associated with risk of CAD (OR: 1.01; 95% CI: 0.98, 1.04; P = 0.49). CONCLUSIONS: We identified several novel loci that influence plasma tHcy concentrations. Overall, common genetic variants that influence plasma tHcy concentrations are not associated with risk of CAD in white populations, which further refutes the causal relevance of moderately elevated tHcy concentrations and tHcy-related pathways for CAD.

Transposition of great arteries and single coronary artery: a new surgical technique for the arterial switch operation.

A single coronary artery can complicate the surgical technique of arterial switch operations, impairing early and late outcomes. We propose a new surgical approach, successfully applied in a 2.1 kg neonate, aimed at reducing the risk of early and late compression and/or distortion of the newly constructed coronary artery system.

Free-breathing whole-heart coronary MRA with 3D radial SSFP and self-navigated image reconstruction.

Respiratory motion is a major source of artifacts in cardiac magnetic resonance imaging (MRI). Free-breathing techniques with pencil-beam navigators efficiently suppress respiratory motion and minimize the need for patient cooperation. However, the correlation between the measured navigator position and the actual position of the heart may be adversely affected by hysteretic effects, navigator position, and temporal delays between the navigators and the image acquisition. In addition, irregular breathing patterns during navigator-gated scanning may result in low scan efficiency and prolonged scan time. The purpose of this study was to develop and implement a self-navigated, free-breathing, whole-heart 3D coronary MRI technique that would overcome these shortcomings and improve the ease-of-use of coronary MRI. A signal synchronous with respiration was extracted directly from the echoes acquired for imaging, and the motion information was used for retrospective, rigid-body, through-plane motion correction. The images obtained from the self-navigated reconstruction were compared with the results from conventional, prospective, pencil-beam navigator tracking. Image quality was improved in phantom studies using self-navigation, while equivalent results were obtained with both techniques in preliminary in vivo studies.

Cardiovascular Risk Prediction with Ultrasound

This paper addresses primary care physicians, cardiologists, internists, angiologists and doctors desirous of improving vascular risk prediction in primary care. Many cardiovascular risk factors act aggressively on the arterial wall and result in atherosclerosis and atherothrombosis. Cardiovascular prognosis derived from ultrasound imaging is, however, excellent in subjects without formation of intimal thickening or atheromas. Since ultrasound visualises the arterial wall directly, the information derived from the arterial wall may add independent incremental information to the knowledge of risk derived from global risk assessment. This paper provides an overview on plaque imaging for vascular risk prediction in two parts: Part 1: Carotid IMT is frequently used as a surrogate marker for outcome in intervention studies addressing rather large cohorts of subjects. Carotid IMT as a risk prediction tool for the prevention of acute myocardial infarction and stroke has been extensively studied in many patients since 1987, and has yielded incremental hazard ratios for these cardiovascular events independently of established cardiovascular risk factors. However, carotid IMT measurements are not used uniformly and therefore still lack widely accepted standardisation. Hence, at an individual, practicebased level, carotid IMT is not recommended as a risk assessment tool. The total plaque area of the carotid arteries (TPA) is a measure of the global plaque burden within both carotid arteries. It was recently shown in a large Norwegian cohort involving over 6000 subjects that TPA is a very good predictor for future myocardial infarction in women with an area under the curve (AUC) using a receiver operating curves (ROC) value of 0.73 (in men: 0.63). Further, the AUC for risk prediction is high both for vascular death in a vascular prevention clinic group (AUC 0.77) and fatal or nonfatal myocardial infarction in a true primary care group (AUC 0.79). Since TPA has acceptable reproducibility, allows calculation of posttest risk and is easily obtained at low cost, this risk assessment tool may come in for more widespread use in the future and also serve as a tool for atherosclerosis tracking and guidance for intensity of preventive therapy. However, more studies with TPA are needed. Part 2: Carotid and femoral plaque formation as detected by ultrasound offers a global view of the extent of atherosclerosis. Several prospective cohort studies have shown that cardiovascular risk prediction is greater for plaques than for carotid IMT. The number of arterial beds affected by significant atheromas may simply be added numerically to derive additional information on the risk of vascular events. A new atherosclerosis burden score (ABS) simply calculates the sum of carotid and femoral plaques encountered during ultrasound scanning. ABS correlates well and independently with the presence of coronary atherosclerosis and stenosis as measured by invasive coronary angiogram. However, the prognostic power of ABS as an independent marker of risk still needs to be elucidated in prospective studies. In summary, the large number of ways to measure atherosclerosis and related changes in human arteries by ultrasound indicates that this technology is not yet sufficiently perfected and needs more standardisation and workup on clearly defined outcome studies before it can be recommended as a practice-based additional risk modifier.

Partial cricotracheal resection for congenital subglottic stenosis in children: the effect of concomitant anomalies.

OBJECTIVE: To review the surgical outcomes of partial cricotracheal resection in children with severe congenital subglottic stenosis and define the effect of concomitant anomalies or syndromes affecting outcome. METHODS: Forty-one children with subglottic stenosis of congenital and mixed (acquired on congenital) etiologies who underwent partial cricotracheal resection were identified from a prospectively collected database. Children with congenital subglottic stenosis and concomitant anomalies/syndromes were compared to children with congenital subglottic stenosis with no syndromes or concomitant anomalies. Operation-specific decannulation rates and complication rates were the primary outcome measures. We performed a two-sample test of proportion using the STATA-10 software for categorical variables to detect differences in proportions. Significance was set at p value<0.05. RESULTS: Twenty-seven (66%) of 41 children had concomitant anomalies/syndromes and 14 (34%) had congenital subglottic stenosis without concomitant anomalies/syndromes. Four patients needed revision surgery in the concomitant anomaly group and two patients needed revision surgery in the non concomitant anomaly group before achieving decannulation. The operation-specific decannulation rate in the concomitant anomaly group was 85% and 86% in the non anomaly group. When compared to children without concomitant anomaly, children with concomitant anomalies were more likely to have delayed decannulation following partial cricotracheal resection. However, this difference was not found to be statistically significant. The complication and operation-specific decannulation rates after partial cricotracheal resection were comparable to children without concomitant anomalies. Mortality rate was 11% (three of 27 patients) in the group with associated congenital anomalies or syndromes. Two patients succumbed to the primary pathology and one patient died due to tracheostomy-tube obstruction. There was no post-operative death in the non anomaly group. CONCLUSION: Partial cricotracheal resection can be done safely and effectively in children with concomitant anomalies/syndromes to achieve decannulation. The post-operative course may be prolonged but the decannulation and the complication rates are comparable to those children with congenital subglottic stenosis without concomitant anomalies.

Dysfonction microvasculaire et ischémie du myocarde [Microvascular dysfunction and myocardial ischemia]

Une lésion fonctionnelle ou structurale des artérioles intramurales influence le seuil ischémique du myocarde. Le diagnostic de dysfonction microvasculaire est retenu en présence d'une diminution du flux coronaire maximal et de coronaires angio-graphiquement normales ou presque normales. Un trouble de la microcirculation peut traduire une dysfonction endothéliale chez le sujet diabétique ou hyperlipidémique, ou une lésion structurale ou fonctionnelle dans le cadre de la cardiomyopathie hypertrophique, la sténose aortique ou l'hypertension artérielle. Après recanalisation de l'artère responsable d'un infarctus, la mesure de la fonction microcirculatoire permet d'estimer la qualité de la reperfusion myocardique. L'appréciation de la fonction microvasculaire est un enjeu majeur dans l'évaluation de l'ischémie du myocarde en l'absence de sténose coronaire. Functional or structural lesions in intramural arterioles influence the ischemic threshold of the myocardium. Microvascular dysfonction is evidenced by a decrease in coronary blood flow during maximum hyperemia in the presence of angiographically normal or near-normal coronary arteries. Microvascular dysfonction may reflect endothelial dysfonction in diabetic or hyperlipidemic patients, as well as structural and functional changes in patients with hypertrophic cardiomyopathy, aortic stenosis or hypertension. Assessing microvascular fonction after thrombolysis or primary angioplasty for acute myocardial infarction allows to estimate the quality of myocardial reperfusion. Assessing microvascular fonction is a major component of the evaluation of myocardial ischemia in the absence of coronary artery stenoses.

Relation between plaque type, plaque thickness, blood shear stress, and plaque stress in coronary arteries assessed by X-ray Angiography and Intravascular Ultrasound

Purpose: Atheromatic plaque progression is affected, among others phenomena, by biomechanical, biochemical, and physiological factors. In this paper, the authors introduce a novel framework able to provide both morphological (vessel radius, plaque thickness, and type) and biomechanical (wall shear stress and Von Mises stress) indices of coronary arteries. Methods: First, the approach reconstructs the three-dimensional morphology of the vessel from intravascular ultrasound(IVUS) and Angiographic sequences, requiring minimal user interaction. Then, a computational pipeline allows to automatically assess fluid-dynamic and mechanical indices. Ten coronary arteries are analyzed illustrating the capabilities of the tool and confirming previous technical and clinical observations. Results: The relations between the arterial indices obtained by IVUS measurement and simulations have been quantitatively analyzed along the whole surface of the artery, extending the analysis of the coronary arteries shown in previous state of the art studies. Additionally, for the first time in the literature, the framework allows the computation of the membrane stresses using a simplified mechanical model of the arterial wall. Conclusions: Circumferentially (within a given frame), statistical analysis shows an inverse relation between the wall shear stress and the plaque thickness. At the global level (comparing a frame within the entire vessel), it is observed that heavy plaque accumulations are in general calcified and are located in the areas of the vessel having high wall shear stress. Finally, in their experiments the inverse proportionality between fluid and structural stresses is observed.

Effect of hormone replacement therapy on vasomotor function of the coronary microcirculation in post-menopausal women with medically treated cardiovascular risk factors.

Aims The aim of this study was to evaluate the effect of hormone replacement therapy (HRT) on coronary vasomotor function in post-menopausal women (PM) with medically treated cardiovascular risk factors (RFs) in a cross-sectional and a longitudinal follow-up (FU) study. Methods and results Myocardial blood flow (MBF) response to cold pressor testing (CPT) and during pharmacologically induced hyperaemia was measured with positron emission tomography in pre-menopausal women (CON), in PM with HRT and without HRT, and repeated in PM after a mean FU of 24 +/- 14 months. When compared with CON at baseline, the endothelium-related change in MBF (DeltaMBF) to CPT progressively declined in PM with HRT and without HRT (0.35 +/- 0.23 vs. 0.24 +/- 0.20 and 0.16 +/- 0.12 mL/g/min; P = 0.171 and P = 0.021). In PM without HRT and in those with HRT at baseline but with discontinuation of HRT during FU, the endothelium-related DeltaMBF to CPT was significantly less at FU than at baseline (0.05 +/- 0.19 vs. 0.16 +/- 0.12 and -0.03 +/- 0.14 vs. 0.25 +/- 0.18 mL/g/min; P = 0.023 and P = 0.001), whereas no significant change was observed in PM with HRT (0.19 +/- 0.22 vs. 0.23 +/- 0.22 mL/g/min; P = 0.453). Impaired hyperaemic MBFs when compared with CON were not significantly altered from those at baseline exam. Conclusion Long-term administration of oestrogen may contribute to maintain endothelium-dependent coronary function in PM with medically treated cardiovascular RFs.