Women With Chest Pain and Normal Coronary Angiograms: No Longer a Benign Syndrome?
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PREVENTIVE CARDIOLOGY FALL 2006 190 I t is well established that chest pain in women is associated with a high rate of nonobstructive coronary artery disease (CAD) 1 and, in half or more of these patients, this symptom is unrespon- sive to therapy for CAD. 2 Symptoms have usually been attributed to noncardiac etiologies and, until recently, prognosis was considered benign. This view has been supported by early studies that reported angiography demonstrating normal or near-normal coronary arteries was associated with a long-term outlook similar to that of an actuarially normal population. 3,4 Continuing interest in this syndrome and appre- ciation of the phenomenon of myocardial ischemia in the absence of large vessel CAD have recently opened new vistas to this clinical dilemma. Of major concern is the finding that the clinical course is not always benign in women. 5 Factors implicated in the pathophysiology of cardiovascular events in this syndrome include coronary microvascular dys- function 2 and angiographically inapparent large- vessel CAD. 6 Findings from the Women’s Ischemia Syndrome Evaluation (WISE) 7 have enhanced our under- standing of this entity. In a recent publication that reflects their innovative approach, this group has extended our knowledge of the syndrome by further elucidating its prognostic implications and clinical factors predictive of events. 8 This study of 673 women (median age, 58 years; 20% minori- ties) with chest pain at baseline included patients with and without obstructive CAD on coronary angiography and those with and without persistent chest pain. This symptom was defined as “pain or discomfort above the waist” that continued to occur during the 12 months following enrollment in the program. Follow-up for a median of 5 years began 1 year after enrollment. Not surprisingly, women without significant CAD had a much lower event rate than those with significant CAD. In the women without obstructive CAD but with persistent chest pain (n=189), how- ever, the total cardiovascular event rate was more than 3 times that of the group characterized by neither obstructive CAD nor persistent chest pain (n=223). Specific events included nonfatal myo- cardial infarction (5.3% vs 1.6%), stroke (7.5% vs 2.0%), and heart failure (7.5% vs 3.7%); however, these differences were significant only for stroke; cardiovascular mortality did not differ significant- ly. After multivariate analysis of the entire cohort with and without significant CAD, persistent chest pain remained an independent predictor of cardio- vascular events together with diabetes, smoking, prolonged QT interval, and CAD severity. Several limitations of this provocative report require consideration. Although the follow-up interval was substantial, the number of patients in the important subgroups was small, and a sig- nificant difference in clinical outcome was found only for stroke. As acknowledged by the authors, the study population comprised an angiographic referral group, the results of which may not be generalizable. Although these findings require fur- ther investigation in larger study cohorts, they do suggest that persistent chest pain in women without obstructive CAD is a potential harbinger of major cardiovascular events. The WISE investigators have previously shown that coronary microvascular dysfunction is pres- ent in approximately half of women with this syndrome. 2 This finding has been demonstrated by invasive methodology 2 but, given its prevalence, a simple method to identify this physiologic abnor- mality and, thereby risk, is essential. In this regard, a recently developed noninvasive technique has shown considerable promise. 8 We can anticipate further advances in our understanding of the syn- drome of chest pain in women with nonobstructive Women With Chest Pain and Normal Coronary Angiograms: No Longer a Benign Syndrome? Melissa Robinson, MD; Ezra A. Amsterdam, MD, Editor in Chief EDITORIAL From the Division of Cardiovascular Medicine, Department of Internal Medicine, University of California, Davis, Sacramento, CA Address for correspondence: Ezra A. Amsterdam, MD, University of California, Davis, 4860 Y Street, Suite 2820, Ambulatory Care Center, Sacramento, CA 95817 E-mail: [email protected] www.lejacq.com ID: 6020 Preventive Cardiology® (ISSN 1520-037X) is published quarterly (Jan., April, July, Oct.) by Le Jacq, Three Parklands Drive, Darien, CT 06820-3652. Copyright ©2006 by Le Jacq. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publishers. The opinions and ideas expressed in this publication are those of the authors and do not necessarily reflect those of the Editors or Publisher. For copies in excess of 25 or for commercial purposes, please contact Sarah Howell at [email protected] or 203.656.1711 x106. ®
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Transcript of Women With Chest Pain and Normal Coronary Angiograms: No Longer a Benign Syndrome?
PREVENTIVE CARDIOLOGY FALL 2006190
It is well established that chest pain in women is associated with a high rate of nonobstructive
coronary artery disease (CAD)1 and, in half or more of these patients, this symptom is unrespon-sive to therapy for CAD.2 Symptoms have usually been attributed to noncardiac etiologies and, until recently, prognosis was considered benign. This view has been supported by early studies that reported angiography demonstrating normal or near-normal coronary arteries was associated with a long-term outlook similar to that of an actuarially normal population.3,4
Continuing interest in this syndrome and appre-ciation of the phenomenon of myocardial ischemia in the absence of large vessel CAD have recently opened new vistas to this clinical dilemma. Of major concern is the finding that the clinical course is not always benign in women.5 Factors implicated in the pathophysiology of cardiovascular events in this syndrome include coronary microvascular dys-function2 and angiographically inapparent large-vessel CAD.6
Findings from the Women’s Ischemia Syndrome Evaluation (WISE)7 have enhanced our under-standing of this entity. In a recent publication that reflects their innovative approach, this group has extended our knowledge of the syndrome by further elucidating its prognostic implications and clinical factors predictive of events.8 This study of 673 women (median age, 58 years; 20% minori-ties) with chest pain at baseline included patients with and without obstructive CAD on coronary angiography and those with and without persistent chest pain. This symptom was defined as “pain
or discomfort above the waist” that continued to occur during the 12 months following enrollment in the program. Follow-up for a median of 5 years began 1 year after enrollment.
Not surprisingly, women without significant CAD had a much lower event rate than those with significant CAD. In the women without obstructive CAD but with persistent chest pain (n=189), how-ever, the total cardiovascular event rate was more than 3 times that of the group characterized by neither obstructive CAD nor persistent chest pain (n=223). Specific events included nonfatal myo-cardial infarction (5.3% vs 1.6%), stroke (7.5% vs 2.0%), and heart failure (7.5% vs 3.7%); however, these differences were significant only for stroke; cardiovascular mortality did not differ significant-ly. After multivariate analysis of the entire cohort with and without significant CAD, persistent chest pain remained an independent predictor of cardio-vascular events together with diabetes, smoking, prolonged QT interval, and CAD severity.
Several limitations of this provocative report require consideration. Although the follow-up interval was substantial, the number of patients in the important subgroups was small, and a sig-nificant difference in clinical outcome was found only for stroke. As acknowledged by the authors, the study population comprised an angiographic referral group, the results of which may not be generalizable. Although these findings require fur-ther investigation in larger study cohorts, they do suggest that persistent chest pain in women without obstructive CAD is a potential harbinger of major cardiovascular events.
The WISE investigators have previously shown that coronary microvascular dysfunction is pres-ent in approximately half of women with this syndrome.2 This finding has been demonstrated by invasive methodology2 but, given its prevalence, a simple method to identify this physiologic abnor-mality and, thereby risk, is essential. In this regard, a recently developed noninvasive technique has shown considerable promise.8 We can anticipate further advances in our understanding of the syn-drome of chest pain in women with nonobstructive
Women With Chest Pain and Normal Coronary Angiograms: No Longer a Benign Syndrome?Melissa Robinson, MD; Ezra A. Amsterdam, MD, Editor in Chief
EDITORIAL
From the Division of Cardiovascular Medicine, Department of Internal Medicine, University of California, Davis, Sacramento, CAAddress for correspondence: Ezra A. Amsterdam, MD, University of California, Davis, 4860 Y Street, Suite 2820, Ambulatory Care Center, Sacramento, CA 95817E-mail: [email protected]
www.lejacq.com ID: 6020
Preventive Cardiology® (ISSN 1520-037X) is published quarterly (Jan., April, July, Oct.) by Le Jacq, Three Parklands Drive, Darien, CT 06820-3652. Copyright ©2006 by Le Jacq. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publishers. The opinions and ideas expressed in this publication are those of the authors and do not necessarily reflect those of the Editors or Publisher. For copies in excess of 25 or for commercial purposes, please contact Sarah Howell at [email protected] or 203.656.1711 x106.
®
FALL 2006 PREVENTIVE CARDIOLOGY 191
CAD as well as investigation of this problem in men, in whom it is a less frequent but nonetheless equally challenging problem.
REFERENCES 1 Sullivan AK, Holdright DR, Wright CA, et al. Chest pain
in women: clinical, investigative, and prognostic features. BMJ. 1994;308:883–886.
2 Reis SE, Holubkov R, Conrad Smith AJ, et al. Coronary micro-vascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study. Am Heart J. 2001;141:735–741.
3 Kemp HG, Elliott WC, Gorlin R. The anginal syn-drome with normal coronary arteriography. Trans Assoc Am Physicians. 1967;80:59–70.
4 Likoff W, Segal BL, Kasparian H. Paradox of normal selective coronary arteriograms in patients considered to have unmistakable coronary heart disease. N Engl J Med. 1967;267:1063–1066.
5 Bugiardini R, Manfrini O, Pizzi C, et al. Endothelial func-tion predicts future development of coronary artery disease: a study of women with chest pain and normal coronary angiograms. Circulation. 2004;109:2518–2523.
6 Erbel R, Ge J, Bockisch A, et al. Value of intracoronary ultra-sound and Doppler in the differentiation of angiographically normal coronary arteries: a prospective study in patients with angina pectoris. Eur Heart J. 1996;17:880–889.
7 Bairey Merz CN, Shaw LJ, Reis SE, et al, for the WISE Investigators. Insights from the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) Study: Part II: gen-der differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of athero-sclerosis and macrovascular and microvascular coronary disease. J Am Coll Cardiol. 2006;7(3 suppl):S21–S29.
8 Johnson BD, Shaw LJ, Pepine CJ, et al. Persistent chest pain predicts cardiovascular events in women without obstruc-tive coronary artery disease: results from the NIH-NHLBI-sponsored Women’s Ischemia Syndrome Evaluation (WISE) study. Eur Heart J. 2006;27:1408–1415.
Preventive Cardiology® (ISSN 1520-037X) is published quarterly (Jan., April, July, Oct.) by Le Jacq, Three Parklands Drive, Darien, CT 06820-3652. Copyright ©2006 by Le Jacq. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publishers. The opinions and ideas expressed in this publication are those of the authors and do not necessarily reflect those of the Editors or Publisher. For copies in excess of 25 or for commercial purposes, please contact Sarah Howell at [email protected] or 203.656.1711 x106.
®
