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

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.

[1]  A. Quyyumi,et al.  Effects of Physiological Levels of Estrogen on Coronary Vasomotor Function in Postmenopausal Women , 1994 .

[2]  M. Walsh,et al.  Noninvasive quantitation of myocardial blood flow in human subjects with oxygen-15-labeled water and positron emission tomography. , 1989, Journal of the American College of Cardiology.

[3]  E L Bolson,et al.  A new digital electronic caliper for measurement of coronary arterial stenosis: comparison with visual estimates and computer-assisted measurements. , 1984, The American journal of cardiology.

[4]  P. Poole‐Wilson,et al.  Acute effect of 17 beta-estradiol on rabbit coronary artery contractile responses to endothelin-1. , 1992, The American journal of physiology.

[5]  A. Quyyumi,et al.  Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women. , 1994, Circulation.

[6]  Susan R. Johnson,et al.  Effects of Estrogen or Estrogen/ Progestin Regimens on Heart Disease Risk Factors in Postmenopausal Women: The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial , 1995 .

[7]  S. Reis,et al.  Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women. , 1994, Circulation.

[8]  P. Puddu,et al.  Vasotonic angina: a spectrum of ischemic syndromes involving functional abnormalities of the epicardial and microvascular coronary circulation. , 1993, Journal of the American College of Cardiology.

[9]  P. Poole‐Wilson,et al.  17-beta-Estradiol therapy lessens angina in postmenopausal women with syndrome X. , 1996, Journal of the American College of Cardiology.

[10]  Murota Seiitsu,et al.  Stimulation of prostacyclin biosynthetic activity by estradiol in rat aortic smooth muscle cells in culture , 1980 .

[11]  F. Klocke,et al.  Measurements of coronary flow reserve: defining pathophysiology versus making decisions about patient care. , 1987, Circulation.

[12]  N. Reichek,et al.  Abnormal myocardial phosphorus-31 nuclear magnetic resonance spectroscopy in women with chest pain but normal coronary angiograms. , 2000, The New England journal of medicine.

[13]  H. Sox.  Noninvasive testing in coronary artery disease. Selection of procedures and interpretation of results. , 1983, Postgraduate medicine.

[14]  P. Poole‐Wilson,et al.  Endothelium‐independent relaxation of rabbit coronary artery by 17β‐oestradiol in vitro , 1991, British journal of pharmacology.

[15]  D. Harder,et al.  Estrogen receptors and effects of estrogen on membrane electrical properties of coronary vascular smooth muscle , 1979, Journal of cellular physiology.

[16]  S. Higano,et al.  Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. , 1998, Circulation.

[17]  W. C. Elliott,et al.  The anginal syndrome with normal coronary arteriography. , 1967, Transactions of the Association of American Physicians.

[18]  U. Gleichmann,et al.  Improvement in coronary flow reserve determined by positron emission tomography after 6 months of cholesterol-lowering therapy in patients with early stages of coronary atherosclerosis. , 1999, Circulation.

[19]  J. Murabito,et al.  Prognosis After the Onset of Coronary Heart Disease An Investigation of Differences in Outcome Between the Sexes According to Initial Coronary Disease Presentation , 1993, Circulation.

[20]  T. Lehtimäki,et al.  Coronary Flow Reserve Is Reduced in Young Men With IDDM , 1998, Diabetes.

[21]  P. Yock,et al.  Mechanisms of estrogen-induced vasodilation: in vivo studies in canine coronary conductance and resistance arteries. , 1995, Journal of the American College of Cardiology.

[22]  E. Barrett-Connor,et al.  Prospective study of endogenous sex hormones and fatal cardiovascular disease in postmenopausal women , 1995, BMJ.

[23]  N Reichek,et al.  The Women's Ischemia Syndrome Evaluation (WISE) study: protocol design, methodology and feasibility report. , 1999, Journal of the American College of Cardiology.

[24]  O. Ylikorkala,et al.  Regulation of prostacyclin and thromboxane production by human umbilical vessels: the effect of estradiol and progesterone in a superfusion model. , 1982, Prostaglandins, leukotrienes, and medicine.

[25]  A. Quyyumi,et al.  Imipramine in patients with chest pain despite normal coronary angiograms. , 1994, The New England journal of medicine.

[26]  Michael V. Green,et al.  Left ventricular dysfunction in patients with angina pectoris, normal epicardial coronary arteries, and abnormal vasodilator reserve. , 1985, Circulation.

[27]  B. Sobel,et al.  Increased myocardial perfusion at rest and diminished perfusion reserve in patients with angina and angiographically normal coronary arteries. , 1990, Journal of the American College of Cardiology.

[28]  J. Viikari,et al.  Early impairment of coronary flow reserve in young men with borderline hypertension. , 1998, Journal of the American College of Cardiology.