Effective risk stratification using exercise myocardial perfusion SPECT in women: Gender-related differences in prognostic nuclear testing

AbstractObjectives. This study was designed to evaluate the incremental prognostic value over clinical and exercise variables of rest thallium-201/exercise technetium-99m sestamibi single-photon emission computed tomography (SPECT) in women compared with men and to determine whether this test can be used to effectively risk stratify patients of both genders.Background. To minimize the previously described gender-related bias in the evaluation of coronary artery disease in women, there is a need to identify a noninvasive testing strategy that is able to accurately and effectively risk stratify women.Methods. We identified 4,136 consecutive patients (2,742 men, 1,394 women) who underwent dual-isotope SPECT. The incremental value of nuclear testing was determined using both a stepwise Cox proportional hazards model and Kaplan-Meier survival analysis. Receiver operating characteristic curve analysis was performed to determine test discrimination for high risk patients in men and women.Results. The patient population was followed up for 20 ± 5 months for events (cardiac death or nonfatal myocardial infarction). During this time, 63 myocardial infarctions and 32 cardiac deaths occurred in the men, and 31 myocardial infarctions and 14 cardiac deaths occurred in the women. Nuclear testing significantly stratified both men and women irrespective of their rest electrocardiogram. Cox proportional hazards analysis revealed that nuclear testing added incremental prognostic value in both men and women after inclusion of the most predictive clinical and exercise variables (overall chi-square 89 in men vs. 120 in women, p < 0.005). Kaplan-Meier survival analysis demonstrated that nuclear testing further stratified men and women with both intermediate to high and low prescan likelihoods of coronary artery disease (p < 0.005 for all). Receiver operating characteristic curve analysis demonstrated superior discrimination for the nuclear scan results in identifying high risk women than men (area under the curve: 0.84 ± 0.03 vs. 0.71 ± 0.03 in men, p < 0.0005). The odds ratio comparing event rates in patients with abnormal versus those with normal scan results was greater in women than in men, suggesting superior stratification using nuclear testing in women.Conclusions. Dual-isotope myocardial perfusion imaging yields incremental prognostic value in both men and women. This modality identifies low risk women and men equally well but relatively high risk women more accurately than relatively high risk men and, thus, is able to stratify women more effectively than men

The actions of the cannabinoid receptor antagonist, SR 141716A, in the rat isolated mesenteric artery

1. The actions of the cannabinoid receptor antagonist, SR 141716A, were examined in rat isolated mesenteric arteries. At concentrations greater than 3 μM, it caused concentration-dependent, but endothelium-independent, relaxations of both methoxamine- and 60 mM KCl-precontracted vessels. 2. SR 141716A (at 10 μM, but not at 1 μM) inhibited contractions to Ca(2+) in methoxamine-stimulated mesenteric arteries previously depleted of intracellular Ca(2+) stores. Neither concentration affected the phasic contractions induced by methoxamine in the absence of extracellular Ca(2+). 3. SR 141716A (10 μM) caused a 130 fold rightward shift in the concentration-response curve to levcromakalim, a K(+) channel activator, but had no effect at 1 μM. 4. SR 141716A (10 μM) attenuated relaxations to NS 1619 (which activates large conductance, Ca(2+)-activated K(+) channels; BK(Ca)). The inhibitory effect of SR 141716A on NS 1619 was not significantly different from, and was not additive with, that caused by a selective BK(Ca) inhibitor, iberiotoxin (100 nM). SR 141716A (1 μM) did not effect NS 1619 relaxation. 5. SR 141716A (10 μM) had no effect on relaxations to the nitric oxide donor S-nitroso-N-acetylpenicillamine, or relaxations to carbachol in the presence of 25 mM KCl. 6. The results show that, at concentrations of 10 μM and above, SR 141716A causes endothelium-independent vasorelaxation by inhibition of Ca(2+) entry. It also inhibits relaxations mediated by K(+) channel activation. This suggests that such concentrations of SR 141716A are not appropriate for investigation of cannabinoid receptor-dependent processes