The Canadian Women's Heart Health Alliance ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 7: Sex, Gender, and the Social Determinants of Health.

Women vs men have major differences in terms of risk-factor profiles, social and environmental factors, clinical presentation, diagnosis, and treatment of cardiovascular disease. Women are more likely than men to experience health issues that are complex and multifactorial, often relating to disparities in access to care, risk-factor prevalence, sex-based biological differences, gender-related factors, and sociocultural factors. Furthermore, awareness of the intersectional nature and relationship of sociocultural determinants of health, including sex and gender factors, that influence access to care and health outcomes for women with cardiovascular disease remains elusive. This review summarizes literature that reports on under-recognized sex- and gender-related risk factors that intersect with psychosocial, economic, and cultural factors in the diagnosis, treatment, and outcomes of women's cardiovascular health.

Les profils de facteurs de risque, les facteurs sociaux et environnementaux, le tableau clinique, le diagnostic et le traitement des maladies cardiovasculaires montrent des différences importantes entre les femmes et les hommes. Il est plus probable que les femmes expérimentent des problèmes de santé complexes et multifactoriels, qui sont souvent en relation avec les disparités dans l'accès aux soins, la prévalence des facteurs de risque, les différences biologiques entre les sexes, les facteurs liés au genre et les facteurs socioculturels. De plus, la sensibilisation à la nature et à la relation intersectionnelles des déterminants socioculturels de santé, notamment les facteurs liés au sexe et au genre, qui influencent l'accès aux soins et les résultats cliniques des femmes atteintes d'une maladie cardiovasculaire demeure insaisissable. La présente revue résume la littérature qui porte sur les facteurs de risque liés au sexe et au genre peu reconnus qui se recoupent aux facteurs psychosociaux, économiques et culturels dans le diagnostic, le traitement et les résultats cliniques en lien avec la santé cardiovasculaire des femmes.

The Canadian Women's Heart Health Alliance Atlas on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 6: Sex- and Gender-Specific Diagnosis and Treatment.

This chapter summarizes the sex- and gender-specific diagnosis and treatment of acute/unstable presentations and nacute/stable presentations of cardiovascular disease in women. Guidelines, scientific statements, systematic reviews/meta-analyses, and primary research studies related to diagnosis and treatment of coronary artery disease, cerebrovascular disease (stroke), valvular heart disease, and heart failure in women were reviewed. The evidence is summarized as a narrative, and when available, sex- and gender-specific practice and research recommendations are provided. Acute coronary syndrome presentations and emergency department delays are different in women than they are in men. Coronary angiography remains the gold-standard test for diagnosis of obstructive coronary artery disease. Other diagnostic imaging modalities for ischemic heart disease detection (eg, positron emission tomography, echocardiography, single-photon emission computed tomography, cardiovascular magnetic resonance, coronary computed tomography angiography) have been shown to be useful in women, with their selection dependent upon both the goal of the individualized assessment and the testing resources available. Noncontrast computed tomography and computed tomography angiography are used to diagnose stroke in women. Although sex-specific differences appear to exist in the efficacy of standard treatments for diverse presentations of acute coronary syndrome, many cardiovascular drugs and interventions tested in clinical trials were not powered to detect sex-specific differences, and knowledge gaps remain. Similarly, although knowledge is evolving about sex-specific difference in the management of valvular heart disease, and heart failure with both reduced and preserved ejection fraction, current guidelines are lacking in sex-specific recommendations, and more research is needed.

Ce chapitre présente un résumé sur le diagnostic et le traitement des tableaux cliniques aigus/instables et non aigus/stables des maladies cardiovasculaires chez les femmes, et les différences propres à chacun des deux sexes. Les lignes directrices, les énoncés scientifiques, les revues systématiques/méta-analyses et les études de recherche originale sur le diagnostic et le traitement des coronaropathies, des maladies vasculaires cérébrales (AVC), des valvulopathies cardiaques et de l'insuffisance cardiaque chez les femmes ont été examinés. Les données probantes sont résumées sous forme narrative et, lorsqu'elles sont disponibles, des recommandations en matière de pratique et de recherche pour chacun des deux sexes sont présentées. Les tableaux cliniques du syndrome coronarien aigu et les délais d'attente à l'urgence sont différents selon qu'une femme ou un homme en est atteint. L'angiographie coronarienne reste l'examen de référence pour le diagnostic des coronaropathies obstructives. D'autres examens d'imagerie diagnostique (p. ex. la tomographie par émission de positons, l'échocardiographie, la tomographie d'émission à photon unique, la résonance magnétique cardiovasculaire, l'angiographie coronarienne par tomodensitométrie) se sont avérés utiles pour la détection des cardiopathies ischémiques chez les femmes. Le recours à ces modalités dépend de l'objectif de l'évaluation personnalisée et des ressources disponibles. La tomodensitométrie sans agent de contraste et l'angiographie par tomodensitométrie sont utilisées pour le diagnostic des AVC chez les femmes. Malgré les différences entre les sexes quant à l'efficacité des traitements de référence des divers tableaux cliniques du syndrome coronarien aigu, bon nombre des médicaments et des interventions cardiovasculaires qui ont fait l'objet d'essais cliniques n'avaient pas la puissance statistique nécessaire pour détecter des différences selon les sexes, de sorte que les connaissances restent fragmentaires sur ce sujet. De même, malgré l'évolution des connaissances sur les différences sexuelles quant à la prise en charge des valvulopathies cardiaques et de l'insuffisance cardiaque avec fraction d'éjection réduite ou préservée, on ne trouve pas de recommandations pour chaque sexe dans les lignes directrices actuelles, d'où la pertinence d'études supplémentaires portant sur cette question.

The Canadian Women's Heart Health Alliance Atlas on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 5: Sex- and Gender-Unique Manifestations of Cardiovascular Disease.

This Atlas chapter summarizes sex- and some gender-associated, and unique aspects and manifestations of cardiovascular disease (CVD) in women. CVD is the primary cause of premature death in women in Canada and numerous sex-specific differences related to symptoms and pathophysiology exist. A review of the literature was done to identify sex-specific differences in symptoms, pathophysiology, and unique manifestations of CVD in women. Although women with ischemic heart disease might present with chest pain, the description of symptoms, delay between symptom onset and seeking medical attention, and prodromal symptoms are often different in women, compared with men. Nonatherosclerotic causes of angina and myocardial infarction, such as spontaneous coronary artery dissection are predominantly identified in women. Obstructive and nonobstructive coronary artery disease, aortic aneurysmal disease, and peripheral artery disease have worse outcomes in women compared with men. Sex differences exist in valvular heart disease and cardiomyopathies. Heart failure with preserved ejection fraction is more often diagnosed in women, who experience better survival after a heart failure diagnosis. Stroke might occur across the lifespan in women, who are at higher risk of stroke-related disability and age-specific mortality. Sex- and gender-unique differences exist in symptoms and pathophysiology of CVD in women. These differences must be considered when evaluating CVD manifestations, because they affect management and prognosis of cardiovascular conditions in women.

Dans le présent chapitre d'Atlas sont récapitulés les aspects et les manifestations uniques, associés au sexe et certains associés au genre, des maladies cardiovasculaires (MCV) chez les femmes. Les MCV sont la cause principale de décès prématurés chez les femmes au Canada. De nombreuses différences quant aux symptômes et à la physiopathologie existent entre les sexes. Nous avons réalisé une revue de la littérature pour déterminer les différences entre les sexes dans les symptômes et la physiopathologie, et les manifestations uniques des MCV chez les femmes. Bien que les femmes atteintes d'une cardiopathie ischémique puissent éprouver des douleurs thoraciques, la description des symptômes, le délai entre l'apparition des symptômes et l'obtention de soins médicaux, et les symptômes prodromiques sont souvent différents de ceux des hommes. Les causes de l'angine et de l'infarctus du myocarde non liées à l'athérosclérose telles que la dissection spontanée de l'artère coronaire sont principalement observées chez les femmes. La coronaropathie obstructive et non obstructive, l'anévrisme aortique et la maladie artérielle périphérique montrent de plus mauvaises issues chez les femmes que chez les hommes. Des différences entre les sexes sont observées dans la cardiopathie valvulaire et les cardiomyopathies. Le diagnostic d'insuffisance cardiaque avec fraction d'éjection préservée est plus souvent posé chez les femmes qui présentent un meilleur taux de survie après un diagnostic d'insuffisance cardiaque. L'accident vasculaire cérébral (AVC) pourrait survenir tout au long de la vie des femmes, qui sont exposées à un risque plus élevé d'incapacités liées à l'AVC et de mortalité par âge. Il existe des différences uniques entre les sexes et les genres pour ce qui est des symptômes et de la physiopathologie des MCV chez les femmes. Lors de l'évaluation des manifestations des MCV, il faut tenir compte de ces différences puisqu'elles influencent la prise en charge et le pronostic des maladies cardiovasculaires chez les femmes.

The Canadian Women's Heart Health Alliance Atlas on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 4: Sex- and Gender-Unique Disparities: CVD Across the Lifespan of a Woman.

Women have unique sex- and gender-related risk factors for cardiovascular disease (CVD) that can present or evolve over their lifespan. Pregnancy-associated conditions, polycystic ovarian syndrome, and menopause can increase a woman's risk of CVD. Women are at greater risk for autoimmune rheumatic disorders, which play a role in the predisposition and pathogenesis of CVD. The influence of traditional CVD risk factors (eg, smoking, hypertension, diabetes, obesity, physical inactivity, depression, anxiety, and family history) is greater in women than men. Finally, there are sex differences in the response to treatments for CVD risk and comorbid disease processes. In this Atlas chapter we review sex- and gender-unique CVD risk factors that can occur across a woman's lifespan, with the aim to reduce knowledge gaps and guide the development of optimal strategies for awareness and treatment.

Les femmes présentent des facteurs de risque de maladies cardiovasculaires (MCV) uniques, liés au sexe et au genre, qui peuvent se manifester ou évoluer tout au long de leur vie. Les troubles médicaux associés à la grossesse, le syndrome des ovaires polykystiques et la ménopause peuvent augmenter le risque de MCV chez une femme. Les femmes sont plus exposées aux troubles rhumatologiques auto-immuns, qui jouent un rôle dans la prédisposition et dans la pathogenèse des MCV. L'influence des facteurs de risque traditionnels pour les MCV (par exemple, le tabagisme, l'hypertension, le diabète, l'obésité, la sédentarité, la dépression, l'anxiété et les antécédents familiaux) est plus importante chez les femmes que chez les hommes. Enfin, il existe des différences entre les sexes dans la réponse aux traitements du risque de MCV et des processus pathologiques comorbides. Dans ce chapitre de l'Atlas, nous passons en revue les facteurs de risque de MCV propres au sexe et au genre qui peuvent survenir tout au long de la vie d'une femme, dans le but de réduire les lacunes dans les connaissances et d'orienter l'élaboration de stratégies optimales de sensibilisation et de traitement.

Introducing the Canadian Women's Heart Health Alliance ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Diseases in Women.

Despite a global understanding that indicators and outcomes of cardiovascular disease (CVD) are known to differ between men and women, uptake of the recognition of sex and gender influences on the clinical care of women has been slow or absent. The Canadian Women's Heart Health Alliance (CWHHA) was established as a network of experts and advocates to develop and disseminate evidence-informed strategies to transform clinical practice and augment collaborative action on women's cardiovascular health in Canada. As an initial project, the CWHHA membership undertook an environmental scan of CVD in women in Canada from which a scientific statement could be developed to summarize critical sex- and gender-specific issues in CVD. This comprehensive review of the evidence focused on the sex- and gender-specific differences in comorbidity, risk factors, disease awareness, presentation, diagnosis, and treatment across the entire spectrum of CVD. In the process of creating the review, it was recognized that the team of CWHHA experts had also assembled an expansive collection of original research articles that were synthesized into detailed chapters reporting on the present state of the evidence unique to each cardiovascular condition in women. This work comprises an "ATLAS" on the epidemiology, diagnosis, and management of CVD in women. The overall goal of the ATLAS is to create a living document that will help clinicians and the public recognize the unique aspects of women's heart health care and provide policy makers with information they need to ensure equitable care for women with CVD.

Bien que l'on sache généralement que les indicateurs et les résultats des maladies cardiovasculaires (MCV) ne sont pas les mêmes chez les hommes et les femmes, la reconnaissance des différences entre les genres et les sexes dans la pratique clinique se fait lentement, voire pas du tout. L'Alliance nationale de la santé cardiaque des femmes (l'Alliance) est un réseau formé d'experts et d'intervenants ayant pour mission de formuler et de diffuser des stratégies fondées sur des faits afin de transformer la pratique clinique et de stimuler l'action concertée en matière de santé cardiovasculaire des femmes au Canada. Le premier projet des membres de l'Alliance a été de réaliser une analyse de la situation des femmes sur le plan des MCV au Canada, à partir de laquelle un énoncé scientifique pourrait être formulé pour résumer les différences entre les genres et les sexes en ce qui a trait aux MCV. Cette revue exhaustive des données probantes était axée sur les disparités entre les genres et les sexes sur les plans de la comorbidité, des facteurs de risque, des connaissances, des symptômes, du diagnostic et du traitement à l'égard de l'ensemble du spectre des MCV. Au cours des travaux nécessaires à cette revue, il est apparu que l'équipe des experts de l'Alliance avait aussi réuni une vaste collection d'articles sur la recherche de pointe, qui ont été synthétisés dans des chapitres détaillés faisant état des données actuelles sur la façon particulière dont chacune des maladies cardiovasculaires peut toucher les femmes. Un « atlas ¼ de l'épidémiologie, du diagnostic et de la prise en charge des MCV chez les femmes a donc été ainsi créé. L'objectif global était de concevoir un document évolutif pour aider les cliniciens et le grand public à reconnaître les aspects particuliers des soins de santé cardiaque des femmes et fournir aux décideurs les renseignements dont ils ont besoin afin d'assurer que les femmes atteintes d'une MCV reçoivent des soins équitables.

Sequential Right and Left Ventricular Assessment in Posttetralogy of Fallot Patients with Significant Pulmonary Regurgitation.

BACKGROUND: The natural history of right ventricular (RV) and left ventricular (LV) size and function among adults with tetralogy of Fallot (TOF) repair and hemodynamically significant pulmonary regurgitation (PR) is not known. The main aim of this study was to determine changes in RV and LV size and function over time in an adult population with TOF repair and hemodynamically significant pulmonary regurgitation. METHODS: Forty patients with repaired TOF and hemodynamically significant PR were included. These patients were identified on the basis of having more than one CMR between January 2008 and 2015. Patients with a prosthetic pulmonary valve or any cardiac intervention between CMR studies were excluded. Rate of progression (ROP) of RV dilation was determined for both indexed right ventricular end-systolic volume (RVESVi) and indexed right ventricular end-diastolic volume (RVEDVi), and calculated as the difference between the last and first volumes divided by the number of years between CMR#1 and CMR#2. Subjects were also divided into two groups based on the distribution of the ROP of RV dilation: Group I-rapid ROP (>50th percentile) and Group II-slower ROP (≤50th percentile). RESULTS: The interval between CMR#1 and CMR#2 was 3.9 ± 1.7 years (range 1-8 years). We did find a significant change in RVEDVi and RVESVi over this time period, although the magnitude of change was small. Nine patients (23%) had a reduction in right ventricular ejection fraction (RVEF) by greater than 5%, 13 patients (33%) had an increase in RVEDVi by greater than 10 mL/m2 and seven patients (18%) had an increase in RVESVi by greater than 10 mL/m2 . Median ROP for RVEDVi was 1.8 (range -10.4 to 21.8) mL/(m2 year); RVESVi 1.1 (range -5.8 to 24.5) mL/(m2 year) and RVEF -0.5 (range -8 to 4)%/year. Patients with a rapid ROP had significantly larger RV volumes at the time of CMR#1 and lower RVEF as compared to the slow ROP group. There was no overall significant change in LVEDVi, LVESVi, or LVEF over this time period. CONCLUSIONS: We have demonstrated, in a small population of patients with hemodynamically significant PR, that there is a small increase in RV volumes and decrease in RVEF over a mean 4-year period. We believe it to be reasonable practice to perform CMR at least every 4 years in asymptomatic patients with repaired TOF and hemodynamically significant PR. We found that LV volumes and function remained stable during the study period, suggesting that significant progressive LV changes are less likely to occur over a shorter time period. Our results inform a safe standardized approach to monitoring adults with hemodynamically significant PR post TOF repair and assist in planning allocation of this expensive and limited resource.

Adult Congenital Heart Disease Patients Experience Similar Symptoms of Disease Activity.

BACKGROUND: There is a lack of objective data on the symptoms characterizing disease activity among adults with congenital heart disease (ACHD). The purpose of this study was to elicit the most important symptoms from patients across the spectrum of ACHD and to examine whether reported symptoms were similar across the spectrum of ACHD as a foundation for creating a patient-reported outcome measure(s). METHODS AND RESULTS: We constructed a 39-item survey using input from physicians specializing in ACHD to assess the symptoms patients associate with disease activity. Patients (n=124) prospectively completed this survey, and the results were analyzed based on underlying anatomy and disease complexity. A confirmatory cohort of patients (n=40) was then recruited prospectively to confirm the validity of the initial data. When grouped based on underlying anatomy, significant differences in disease-related symptom rankings were found for only 6 of 39 symptoms. Six symptoms were identified which were of particular significance to patients, regardless of underlying anatomy. Patients with anatomy of great complexity experienced greater overall symptom severity than those with anatomy of low or moderate complexity, attributable exclusively to higher ranking of 5 symptoms. The second patient cohort had symptom experiences similar to those of the initial cohort, differing in only 5 of 39 symptoms. CONCLUSIONS: This study identified 6 symptoms relevant to patients across the spectrum of ACHD and remarkable homogeneity of patient experience, suggesting that a single disease-specific patient-reported outcome can be created for quality and outcome assessments.

Right Ventricular Assessment in Adult Congenital Heart Disease Patients with Right Ventricle-to-Pulmonary Artery Conduits.

BACKGROUND: There is little data on right ventricular (RV) remodeling patterns in complex congenital heart disease (CHD) patients with right ventricle to pulmonary artery (PA) conduits, and novel RV imaging modalities have not been explored in this population. Knowledge of the RV remodeling process is an important first step to future understanding and tracking of the RV response to pressure and volume overload in this diverse population. Three-dimensional knowledge-based reconstruction (3DKBR) derived from two-dimensional transthoracic echocardiography (TTE-3DKBR) is a novel approach to RV assessment. The aims of this study were twofold: (1) to assess the feasibility and accuracy of 3DKBR in patients with CHD with RV to PA conduits and (2) to characterize the three-dimensional shape of the RV across the spectrum of CHD with RV to PA conduits. METHODS: Seventeen patients with tetralogy of Fallot, pulmonary atresia with ventricular septal defect, or truncus arteriosus (mean age, 29 ± 8 years; 24% women) and a conduit referred for cardiac magnetic resonance imaging (CMR) were prospectively recruited and underwent TTE-3DKBR. TTE-3DKBR echocardiographic image acquisition was performed using a standard ultrasound scanner linked to a Ventripoint Medical Systems unit. The surface RV volumetric reconstruction was performed by transmitting two-dimensional data points to an online database and comparing these with a lesion-specific catalog to derive the RV reconstruction. Parameters analyzed were end-diastolic volume (EDV), end-systolic volume, and ejection fraction. Intertechnique agreement was assessed using Pearson's correlation analysis, coefficients of variation, and Bland-Altman analysis. Three-dimensional shape comparisons of RV surface reconstructions were performed via automated validation testing of CMRs from 43 patients (mean age, 30 ± 8 years; 32% women) with RV to PA conduits (tetralogy of Fallot, n = 15; pulmonary atresia, n = 19; and truncus arteriosus, n = 9) distinct from patients in the 3DKBR comparison. RESULTS: There was good correlation and agreement between the two modalities: EDV, R = 0.77, P = .0004; end-systolic volume, R = 0.93, P < .0001; ejection fraction, R = 0.75, P < .0005. On Bland-Altman analyses, CMR EDV was slightly larger TTE-3DKBR, while EF was slightly higher by 3DKBR. Qualitative and quantitative assessment both demonstrated RV shape diversity based on surface reconstructions. CONCLUSION: This study demonstrates that TTE-3DKBR is an alternative technology that can be used to assess the RV in patients with complex CHD with a conduit. A novel method was used to compare RV shapes in this important population, and our results draw specific attention to the fact that the RV both within and outside diagnostic groups has very different unpredictable shapes and should not be treated equally. Our findings should set into motion future work focused on indices of RV shape and their impact on overall RV function and clinical outcomes, hence defining optimal timing of conduit revision, which at the current time is very unclear.

Pregnancy in women with heart disease: risk assessment and management of heart failure.

Heart disease, present in 0.5% to 3% of pregnant women, is an important cause of morbidity and the leading cause of death among pregnant women in the developed world. Certain heart conditions are associated with an increased risk of heart failure during pregnancy or the postpartum period; for these conditions, management during pregnancy benefits from multidisciplinary care at a center with expertise in pregnancy and heart disease. This article focuses on cardiac risks and management strategies for women with acquired and congenital heart disease who are at increased risk of heart failure during pregnancy.

Three-dimensional echocardiographic assessment of right ventricular volume and function in adult patients with congenital heart disease: comparison with magnetic resonance imaging.

BACKGROUND: The aim of this study was to evaluate the accuracy of three-dimensional (3D) ultrasound compared with the standard magnetic resonance imaging method in determining right ventricular (RV) volumes and function in adult patients with congenital heart disease and chronic, severe pulmonary regurgitation (PR). METHODS: Twenty-five patients with severe PR secondary to either pulmonary valvotomy or tetralogy of Fallot repair were evaluated using 3D ultrasound and MRI. RESULTS: The mean RV ejection fractions were 42 +/- 8% on 3D ultrasound and 44 +/- 7% on MRI (r = 0.89, P < .0001). The mean end-diastolic volumes were 249 +/- 66 and 274 +/- 82 mL and the mean end-systolic volumes 147 +/- 50 and 159 +/- 60 mL on 3D ultrasound and MRI, respectively. Similarly, there were strong correlations of both end-diastolic volume and end-systolic volume on 3D ultrasound and MRI (r = 0.88 and r = 0.89, respectively). CONCLUSIONS: Three-dimensional ultrasound was comparable with MRI in determining RV size and function in most patients with complex congenital heart disease. It will be important to study 3D US in a larger population of patients with TOF, which will be possible only through multi-center collaboration.

Real-time three-dimensional transesophageal echocardiography in the intraoperative assessment of mitral valve disease.

BACKGROUND: The aims of this study were to evaluate the feasibility of real-time 3-dimensional (3D) transesophageal echocardiography in the intraoperative assessment of mitral valve (MV) pathology and to compare this novel technique with 2-dimensional (2D) transesophageal echocardiography. METHODS: Forty-two consecutive patients undergoing MV repair for mitral regurgitation (MR) were studied prospectively. Intraoperative 2D and 3D transesophageal echocardiographic (TEE) examinations were performed using a recently introduced TEE probe that provides real-time 3D imaging. Expert echocardiographers blinded to 2D TEE findings assessed the etiology of MR on 3D transesophageal echocardiography. Similarly, experts blinded to 3D TEE findings assessed 2D TEE findings. Both were compared with the anatomic findings reported by the surgeon. RESULTS: At the time of surgical inspection, ischemic MR was identified in 12% of patients, complex bileaflet myxomatous disease in 31%, and specific scallop disease in 55%. Three-dimensional TEE image acquisition was performed in a short period of time (60 +/- 18 seconds) and was feasible in all patients, with optimal (36%) or good (33%) imaging quality in the majority of cases. Three-dimensional TEE imaging was superior to 2D TEE imaging in the diagnosis of P1, A2, A3, and bileaflet disease (P < .05). CONCLUSIONS: Real-time 3D transesophageal echocardiography is a feasible method for identifying specific MV pathology in the setting of complex disease and can be expeditiously used in the intraoperative evaluation of patients undergoing MV repair.

Assessment of novel risk factors in patients at low risk for cardiovascular events based on Framingham risk stratification.

BACKGROUND: Coronary heart disease (CHD) risk assessed by the Framingham risk score does not take into account the various "novel" markers that are of increasing interest. In this paper we examine a low-risk population to determine which novel markers may be of additive value to the Framingham assessment of CHD risk. METHODS: Levels of high-sensitivity C-reactive protein (hs-CRP), soluble vascular cell adhesion molecule (s-VCAM), soluble intercellular adhesion molecule (s-ICAM-1), endothelial selectin (e-selectin), homocysteine and von Willebrand factor (vWF) were measured in 53 apparently healthy subjects recruited from a risk-reduction referral clinic. Carotid intima medial thickness (IMT) and number of plaques were determined by ultrasonography. Brachial ultrasound flow-mediated dilation (FMD) was also measured. Framingham risk scores were calculated and univariate and multivariate analyses of the resulting percent CHD risk over 10 years and novel markers were undertaken. RESULTS: Abnormal carotid IMT and presence of plaques, hs-CRP, homocysteine, FMD and s-ICAM-1 were detected with a high frequency in this low-risk cohort. Average IMT, number of plaques and homocysteine were highly correlated with the calculated percent CHD whereas measures of hs-CRP, s-ICAM-1 and FMD were independent of the percent CHD calculation. CONCLUSIONS: FMD, as a reflection of the functional status of the vasculature, and hs-CRP and s-ICAM-1, as indicators of inflammatory processes, were independent of Framingham risk assessment in patients at low risk for cardiovascular disease.