Recent development in the effects of statins on cardiovascular disease through Rac1 and NADPH oxidase.

Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), are important lipid-lowering agents. After two decades of laboratory and clinical studies, their pleiotropic effects appear well-established. One of these effects is through the regulation of Rac1 and NADPH oxidases. Relatively few human trials have been carried out with regards to the action of statins on Rac1 and NADPH oxidases, but similar positive effects were also observed in blood vessels and myocardium of participants in the trials. Besides, more specific biomarkers for the antioxidation effects of statins have been developed in the recent two years; both monitoring of the progress of disease and the effects of medical therapy will be possible. Further development of the potency and specificity of statin may enhance their therapeutic potential on cardiovascular disease.

Incremental prognostic value of exercise single-photon emission computed tomographic (SPECT) thallium 201 imaging in patients with ST-T abnormalities on their resting electrocardiograms.

BACKGROUND: The incremental prognostic value of thallium 201 imaging in patients with nonspecific ST-T abnormalities on the resting electrocardiogram (ECG) may be different from those with a normal resting ECG. METHODS: Nine hundred thirty-nine consecutive patients with nonspecific ST-T abnormalities on their resting ECG who had undergone exercise 201 Tl imaging were followed for a median duration of 7.0 y (94% complete). The Cox proportional hazards regression model was used in a stepwise fashion to generate (1) a clinical (Cl) model, (2) a clinical and exercise (Cl + Ex) model, (3) and a clinical, exercise, and thallium (Cl + Ex + Tl) model, for the prediction of cardiac death. RESULTS: Age, sex, and diabetes composed the Cl model (chi2 = 63, P < .0001). The Duke treadmill score added to the Cl + Ex model (chi2 = 71, P < .0001). Increased lung uptake (P < .0001) added significantly and summed reversibility score ( P = .03) added modestly to the Cl + Ex + Tl model (chi2 = 96, P < .0001). On the basis of the Cl + Ex + Tl model, the low-, intermediate-, and high-risk groups had a 7-y survival free of cardiac death of 99%, 88%, and 58%, respectively (P < .0001). Using the Cl + Ex + Tl model, only a small number of low-risk and high-risk patients by the Cl + Ex model were reclassified. However, 48% of the 230 patients in the intermediate-risk group by the Cl + Ex model were reclassified as low risk or high risk. CONCLUSIONS: 201 Tl imaging has incremental prognostic value in patients with nonspecific abnormalities on their resting ECG. However, patients classified as low risk or high risk by exercise testing using the Cl + Ex model do not require 201 Tl imaging. Intermediate-risk patients should be further risk-stratified by 201 Tl imaging.

Prognostic value of the Duke treadmill score in the elderly.

OBJECTIVES: The purpose of this study was to test the hypothesis that the Duke treadmill score works less well for risk stratification in patients age 75 years or above. BACKGROUND: Although the Duke treadmill score is generally effective for risk stratification, its prognostic value in the elderly may be limited because they have a higher prevalence of coronary artery disease (CAD), more severe CAD and a lower exercise tolerance. METHODS: The study population consisted of 247 patients age 75 years or above, and the control population consisted of 2,304 patients below 75 years of age. All patients were symptomatic, had undergone exercise thallium testing between 1989 and 1991 and were followed for a median of >6.5 years. The Cox regression model was used to test the association of the Duke score (utilized both as a continuous variable and using previously published risk group cutoffs) with outcomes (cardiac death, nonfatal myocardial infarction [MI], late revascularization). RESULTS: Using the Duke score to risk-stratify the elderly, 26% were in the low risk group, 68% were in the intermediate risk group and 6% were in the high risk groups; seven-year cardiac survival was 86%, 85% and 69%, respectively (p = 0.45). There was also no significant association between these Duke score risk groups and all other outcome end points in the elderly. The Duke score as a continuous variable did not predict cardiac death (p = 0.43) or cardiac death or MI (p = 0.42), but did predict total cardiac events (which included late revascularization) (p = 0.0027). For the control population, more patients (55%) were in the low risk group, and the Duke score (as a continuous variable or in risk groups) was highly predictive of all end points (p = 0.0001). CONCLUSIONS: The Duke score predicted cardiac survival in younger patients but not in patients age 75 years or above. The majority of the elderly were classified as intermediate risk by the Duke score. Only a minority of the elderly were classified as low risk, but this group still had an annual cardiac mortality of 2%/year.