Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: Results from the NHLBI WISE study

doi:10.1067/mhj.2001.114198

American Heart Journal

Volume 141, Issue 5, May 2001, Pages 735-741

https://doi.org/10.1067/mhj.2001.114198 Get rights and content

Abstract

Background Chest pain in the absence of obstructive coronary artery disease (CAD) is common in women; it is frequently associated with debilitating symptoms and repeated evaluations and may be caused by coronary microvascular dysfunction. However, the prevalence and determinants of microvascular dysfunction in these women are uncertain. Methods We measured coronary flow velocity reserve (coronary velocity response to intracoronary adenosine) to evaluate the coronary microvasculature and risk factors for atherosclerosis in 159 women (mean age, 52.9 years) with chest pain and no obstructive CAD. All women were referred for coronary angiography to evaluate their chest pain as part of the Women’s Ischemia Syndrome Evaluation (WISE) study. Results Seventy-four (47%) women had subnormal (<2.5) coronary flow velocity reserve suggestive of microvascular dysfunction (mean, 2.02 ± 0.38); 85 (53%) had normal reserve (mean, 3.13 ± 0.64). Demographic characteristics, blood pressure, ventricular function, lipid levels, and reproductive hormone levels were not significantly different between women with normal and those with abnormal microvascular function. Postmenopausal hormone use within 3 months was significantly less prevalent among those with microvascular dysfunction (40% vs 60%, P =.032). Age and number of years past menopause correlated with flow velocity reserve (r = –0.18, P =.02, and r = –0.30, P <.001, respectively). No significant associations were identified between flow velocity reserve and lipid and hormone levels, blood pressure, and left ventricular ejection fraction. Conclusions Coronary microvascular dysfunction is present in approximately one half of women with chest pain in the absence of obstructive CAD and cannot be predicted by risk factors for atherosclerosis and hormone levels. Therefore, the diagnosis of coronary microvascular dysfunction should be considered in women with chest pain not attributable to obstructive CAD. (Am Heart J 2001;141:735-41.)

Section snippets

Methods

The Women’s Ischemia Evaluation (WISE) study is a 4-center study focused on developing new diagnostic techniques and advancing our understanding of pathophysiologic mechanisms for ischemic heart disease in women.⁵ Women referred for clinically indicated coronary angiography to evaluate chest pain were candidates for enrollment. As part of WISE, a subgroup of 159 women without obstructive CAD (<50% diameter stenosis in all coronaries) underwent invasive evaluation of the functional integrity of

Results

The 159 women, 85.5% of whom were white, had a mean age of 52.9 ± 10.6 years and were mostly postmenopausal (81.0%). The cohort had a maximum diameter coronary stenosis of 13.7% ± 18.2%. Of these women, 19.6% were current smokers, 17.1% had diabetes, 45.5% and 53.8% reported histories of hyperlipidemia and hypertension, respectively, and 43.6% of all women were using postmenopausal hormones (50.4% of postmenopausal women).

Discussion

Women with chest pain in the absence of obstructive coronary atherosclerosis pose both a diagnostic and a therapeutic challenge. Although many of these women are diagnosed with “noncardiac” chest pain, an alternative mechanism for their symptoms is coronary microvascular dysfunction. Identification of this disorder is important because known treatments provide effective symptom relief, and its diagnosis can limit the need for repeated evaluations of “noncardiac” chest pain.12, 13, 14 The

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Pericardial fat volume is related to endothelial-mediated coronary blood flow in women with suspected coronary microvascular dysfunction. A report from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study
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Coronary microvascular dysfunction is prevalent in women with signs and symptoms of ischemia but no obstructive coronary artery disease (CAD) and is associated with an adverse prognosis. Elevated pericardial fat volume predicts adverse cardiac events, but mechanistic pathways of the association are not well understood.
118 women enrolled in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction study with suspected coronary microvascular dysfunction but no obstructive CAD underwent adenosine stress 1.5 T cardiovascular magnetic resonance imaging (CMR) imaging and invasive coronary reactivity testing. Semi-quantitative myocardial perfusion reserve index (MPR) index was derived from perfusion images. Pericardial fat volume was measured by manually contouring the cardiac margins and adjacent adipose tissue on a single trans-axial HASTE slice at the level of the left main coronary artery origin and indexed to body surface-area. Simple standard deviation analysis obtained for continuous variables and frequency (percent) for categorical variables. The relationships between pericardial fat volume and coronary reactivity testing parameters were examined by correlation and multivariable regression analyses.
Women with suspected coronary microvascular dysfunction had a mean age of 55 ± 10 years, body mass index (BMI) of 28 ± 7 kg/m², 44 % had a history of smoking, 63 % hypertension, 8 % diabetes, and 20 % dyslipidemia. CMR imaging-derived pericardial fat volume and coronary blood flow response to intracoronary acetylcholine (Δ CBF) were negatively correlated (r = −0.32, p = 0.0013). After adjustment for age, number of risk factors, high-density lipoprotein (HDL), and cold pressor diameter response, pericardial fat volume remained a significant predictor of Δ coronary blood flow (p = 0.04). There was no association with other coronary reactivity testing measures or CMRI derived MPR index.
Among women with suspected coronary microvascular dysfunction but no obstructive CAD, pericardial fat volume appears to be related in a hypothesized adverse direction to coronary microvascular endothelial function. These results support further work confirming and extending these results to investigate pericardial fat volume as mechanistic pathway and potential treatment target for coronary microvascular dysfunction-related adverse events.
Trial registration: clinicaltrials.gov NCT00832702.
Cardiovascular Imaging in Women
2024, Seminars in Nuclear Medicine
Multimodality cardiovascular imaging is a cornerstone diagnostic tool in the diagnosis, risk stratification, and management of cardiovascular diseases, whether those involving the coronary tree, myocardial, or pericardial diseases in general and particularly in women. This manuscript aims to shed some light and summarize the very features of cardiovascular disease in women, explore their unique characteristics and discuss the role of cardiovascular imaging in ischemic heart disease and cardiomyopathies. The role of four imaging modalities will be discussed including nuclear medicine, echocardiography, noninvasive coronary angiography, and cardiac magnetic resonance.
Sex Differences in Clinical Outcomes Associated With Quantitative Flow Ratio-Guided Percutaneous Coronary Intervention
2024, JACC: Asia
FAVOR III China (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) reported improved clinical outcomes in quantitative flow ratio (QFR) relative to angiography-guided percutaneous coronary intervention (PCI), but the clinical impact of QFR-guided PCI according to sex remains unknown.
The authors sought to compare sex differences in the 2-year clinical benefits of a QFR-guided PCI strategy and to evaluate the differences in outcomes between men and women undergoing contemporary PCI.
This study involved a prespecified subgroup analysis of the FAVOR III China trial, in which women and men were randomized to a QFR-guided strategy or a standard angiography-guided strategy. Sex differences in clinical benefit of the QFR guidance were analyzed for major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction, or ischemia-driven revascularization within 2 years.
A total of 1,126 women and 2,699 men were eligible and the occurrence of 2-year MACE was similar between women and men (10.3% vs 10.5%; P = 0.96). Compared with an angiography-guided strategy, a QFR-guided strategy resulted in a 7.9% and 9.7% reduction in PCI rates in men and women, respectively. A QFR-guided strategy resulted in similar relative risk reductions for 2-year MACE in women (8.0% vs 12.7%; HR: 0.62; 95% CI: 0.42-0.90) and men (8.7% vs 12.4%; HR: 0.69; 95% CI: 0.54-0.87) (P_interaction = 0.61). Furthermore, QFR values were not significantly different between men and women with various angiographic stenosis categories.
A QFR-guided PCI strategy resulted in improved MACE in both men and women at 2 years compared with an angiography-guided PCI strategy. The FAVOR III China Study [FAVOR III China]; (NCT03656848)
Sex, Gender, and Women's Heart Health: How Women's Heart Programs Address the Knowledge Gap
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This article aims to bridge existing knowledge gaps that impact clinical cardiovascular care and outcomes for women in Canada. The authors discuss various aspects of women’s heart health, emphasizing the efficacy of multidisciplinary care in promoting women’s well-being. The article also identifies the impact of national women’s heart health campaigns and the value of peer support in improving outcomes. The article addresses the particular risks that women face, such as pregnancy-related complications and hormone replacement therapy, all of which are associated with cardiovascular events, and highlights the differences in ischemic symptoms between men and women. Despite improvements in acute event outcomes, challenges persist in accessing timely ambulatory care, particularly for women. Canada has responded to these challenges by introducing Women Heart Programs, which offer tailored programs, support groups, and specialized testing. However, these programs remain few in number and are found only in urban settings. Overall, this review identifies sex and gender factors related to women’s heart health, underscoring the importance of specialized programs and multidisciplinary care in improving women’s cardiovascular health.
Cet article vise à répondre aux incertitudes actuelles qui se répercutent sur les soins cardiovasculaires et les issues cliniques chez les femmes au Canada. Les auteurs abordent différents aspects de la santé cardiaque des femmes, mettant l’accent sur l’efficacité des soins multidisciplinaires pour améliorer le bien-être des femmes. L’article présente également l’effet des campagnes nationales sur la santé cardiaque des femmes et l’importance de l’entraide entre collègues pour améliorer les résultats. L’article traite des risques particuliers touchant les femmes, comme les complications liées à la grossesse et l’hormonothérapie substitutive, qui sont toutes associées à des événements cardiovasculaires, et il souligne les différences entre les hommes et les femmes pour ce qui est des symptômes ischémiques. Bien que des améliorations aient été observées quant à l’issue des événements aigus, des difficultés persistent sur le plan de l’accès rapide à des soins ambulatoires, surtout pour les femmes. Le Canada a répondu à ces difficultés en créant des programmes pour la santé cardiaque des femmes, qui offrent des services adaptés, des groupes de soutien et des analyses spécialisées. Cependant, ils sont encore peu nombreux et accessibles seulement en milieu urbain. Dans l’ensemble, cette analyse définit les facteurs liés au sexe et au genre qui interviennent dans la santé cardiaque des femmes, soulignant l’importance de mettre en place des programmes spécialisés et des soins multidisciplinaires pour améliorer la santé cardiovasculaire des femmes.
The Importance of Nontraditional and Sex-Specific Risk Factors in Young Women With Vasomotor Nonobstructive vs Obstructive Coronary Syndromes
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Heart disease is the leading cause of premature death for women in Canada. Ischemic heart disease is categorized as myocardial infarction (MI) with no obstructive coronary artery disease (MINOCA), ischemia with no obstructive coronary arteries (INOCA), and atherosclerotic obstructive coronary artery disease (CAD) with MI (MI-CAD) or without MI (non-MI-CAD). This study aims to study the prevalence of traditional and nontraditional ischemic heart disease risk factors and their relationships with (M)INOCA, compared to MI-CAD and non-MI-CAD in young women.
This study investigated women who presented with premature (at age ≤ 55 years) vasomotor entities of (M)INOCA or obstructive CAD confirmed by coronary angiography, who are currently enrolled in either the Leslie Diamond Women’s Heart Health Clinic Registry (WHC) or the Study to Avoid Cardiovascular Events in British Columbia (SAVEBC). Univariable and multivariable regression models were applied to investigate associations of risk factors with odds of (M)INOCA, MI-CAD, and non-MI-CAD.
A total of 254 women enrolled between 2015 and 2022 were analyzed, as follows: 77 with INOCA and 37 with MINOCA from the registry, and 66 with non-MI-CAD and 74 with MI-CAD from the study. Regression analyses demonstrated that migraines and preeclampsia or gestational hypertension were the most significant risk factors, with a higher likelihood of being associated with premature (M)INOCA, relative to obstructive CAD. Conversely, the presence of diabetes and a current or previous smoking history had the highest likelihood of being associated with premature CAD.
The risk factor profiles of patients with premature (M)INOCA, compared to obstructive CAD, have significant differences.
Au Canada, la cardiopathie est la principale cause de décès prématuré chez les femmes. La cardiopathie ischémique est catégorisée comme suit : infarctus du myocarde (IM) en l’absence de coronaropathie obstructive (MINOCA), ischémie sans obstruction des artères coronaires (INOCA) et athérosclérose coronaire obstructive accompagnée d’un IM ou sans IM. La présente étude vise à examiner la prévalence des facteurs de risque classiques et non classiques de cardiopathie ischémique et leurs liens avec le (M)INOCA, comparativement à l’athérosclérose coronaire obstructive accompagnée d’un IM ou sans IM chez les femmes jeunes.
Cette étude portait sur des femmes qui avaient prématurément (55 ans ou moins) souffert d’un (M)INOCA ou d’une coronaropathie obstructive confirmés par coronarographie et qui étaient inscrites au registre de la Leslie Diamond Women’s Heart Health Clinic (WHC) ou qui participaient à l’étude visant à éviter les événements cardiovasculaires en Colombie-Britannique (Study to Avoid Cardiovascular Events in BC; SAVEBC). Des modèles de régression univariés et multivariés ont été utilisés pour explorer les associations entre les facteurs de risque et les probabilités de (M)INOCA, ainsi que d’athérosclérose coronaire obstructive accompagnée ou non d’un IM.
Au total, 254 femmes inscrites de 2015 à 2022 ont été recensées, soit 77 présentant une INOCA et 37, un MINOCA selon le registre WHC, et 66 présentant une athérosclérose coronaire obstructive sans IM et 74, une athérosclérose coronaire obstructive accompagnée d’un IM selon l’étude SAVEBC. Les analyses de régression ont démontré que les migraines et la prééclampsie ou l’hypertension gestationnelle étaient les facteurs de risque les plus importants associés à une probabilité la plus élevée de (M)INOCA comparativement à une coronaropathie obstructive. En revanche, la présence d’un diabète et d’un tabagisme actuel ou passé était associée à la probabilité la plus élevée de coronaropathie prématurée.
Il existe d’importantes différences pour ce qui est des profils de facteurs de risque des patientes ayant prématurément souffert d’un (M)INOCA en comparaison d’une coronaropathie obstructive.
Global Longitudinal Strain as Predictor of Inducible Ischemia in No Obstructive Coronary Artery Disease in the CIAO-ISCHEMIA Study
2024, Journal of the American Society of Echocardiography
Global longitudinal strain (GLS) is a sensitive marker for identifying subclinical myocardial dysfunction in obstructive coronary artery disease (CAD). Little is known about the relationship between GLS and ischemia in patients with myocardial ischemia and no obstructive CAD (INOCA).
To investigate the relationship between resting GLS and ischemia on stress echocardiography (SE) in patients with INOCA.
Left ventricular GLS was calculated offline on resting SE images at enrollment (n = 144) and 1-year follow-up (n = 120) in the CIAO-ISCHEMIA (Changes in Ischemia and Angina over One year in International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial screen failures with no obstructive CAD on computed tomography [CT] angiography) study, which enrolled participants with moderate or severe ischemia by local SE interpretation (≥3 segments with new or worsening wall motion abnormality and no obstructive (<50% stenosis) on coronary computed tomography angiography.
Global longitudinal strain values were normal in 83.3% at enrollment and 94.2% at follow-up. Global longitudinal strain values were not associated with a positive SE at enrollment (GLS = –21.5% positive SE vs GLS = –19.9% negative SE, P = .443) or follow-up (GLS = –23.2% positive SE vs GLS = –23.1% negative SE, P = .859). Significant change in GLS was not associated with positive SE in follow-up (P = .401). Regional strain was not associated with colocalizing ischemia at enrollment or follow-up. Changes in GLS and number of ischemic segments from enrollment to follow-up showed a modest but not clinically meaningful correlation (β = 0.41; 95% CI, 0.16, 0.67; P = .002).
In this cohort of INOCA patients, resting GLS values were largely normal and did not associate with the presence, severity, or location of stress-induced ischemia. These findings may suggest the absence of subclinical myocardial dysfunction detectable by echocardiographic strain analysis at rest in INOCA.

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^☆: Supported by contracts from the National Heart, Lung, and Blood Institute, contracts N01-HV-68161, N01-HV-68162, N01-HV-68163, and N01-HV-68164 and grants from the Gustavis and Louis Pfeiffer Research Foundation; the Women’s Guild, Cedars-Sinai Medical Center; Ladies Hospital Aid Society of Western Pennsylvania, University of Pittsburgh; and qmed, Inc.

^☆☆: Reprint requests: Steven E. Reis, MD, c/o WISE Coordinating Center, 127 Parran Hall, 130 DeSoto St, Pittsburgh, PA 15261. E-mail: [email protected]

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Acute Ischemic Heart DiseaseCoronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: Results from the NHLBI WISE study☆,☆☆

Abstract

Section snippets

Methods

Results

Discussion

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Prostaglandins Leukot Mediat

Noninvasive testing in coronary artery disease: selection of procedures and interpretation of results

Postgrad Med

The anginal syndrome with normal coronary arteriography

Trans Assoc Am Physicians

Left ventricular dysfunction in patients with angina pectoris, normal epicardial coronary arteries, and abnormal vasodilator reserve

Circulation

The Women’s Ischemia Syndrome Evaluation (WISE) study: protocol design, methodology and pilot phase report

J Am Coll Cardiol

Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial

JAMA

Prospective study of endogenous sex hormones and fatal cardiovascular disease in postmenopausal women

Lancet

Measurements of coronary flow reserve: defining pathophysiology versus making decisions about patient care

Circulation

Acute Ischemic Heart Disease
Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: Results from the NHLBI WISE study☆,☆☆