Plasma levels of cyclic GMP and endothelin in postmenopausal women with unstable coronary artery disease

Abstract

Many women with typical anginal chest pain have normal coronary angiograms, which may be due to altered endothelial function. We evaluated the endothelial markers cyclic GMP (cGMP) and immunoreactive endothelin (ir-ET) regarding presence of coronary atherosclerosis in women with clinical signs of unstable coronary artery disease (CAD). Plasma levels of cGMP and ir-ET were determined in 118 patients and 84 controls. Ischaemia was evaluated at an exercise test. Of the patients 20% had normal vessels, 14% insignificant CAD and 66% significant stenosis at coronary angiography. Mean (95% CI) concentration of cGMP (nmol/l) was higher in patients than in controls (5.05 (4.53; 5.58) vs. 3.79 (3.34; 4.23)). Separating patients according to daily intake of nitroglycerin, only patients with this medication had significantly higher cGMP level (5.73 (4.88; 6.58)), whereas the difference between those without (4.35 (3.76; 4.94)) and controls disappeared. Patients with ischaemia at exercise test had higher cGMP level than those without (6.01 (5.13; 6.88) vs. 4.30 (3.66; 4.94)), even after adjusting for nitroglycerin treatment. ir-ET (pmol/l) was lower in patients with normal vessels than patients with coronary atherosclerosis (0.83 (0.78; 0.88) vs. 0.98 (0.92; 1.04)) and than the control group (0.91 (0.87; 0.94)). The difference between the control group and patients with atherosclerosis was also significant. Patients with unstable CAD and long-term nitroglycerin treatment have increased cGMP level. Patients with exercise-induced ischaemia have higher cGMP level than those without, irrespective of nitroglycerin treatment, which may reflect a general compensatory mechanism. Patients with normal vessels have low level of ir-ET, indicating different mechanisms for ischaemia/angina in these patients compared with patients with atherosclerosis.