Relationship and prognostic value of coronary artery calcification by electron beam computed tomography to stress-induced ischemia by single photon emission computed tomography.

BACKGROUND: Stress single photon emission computed tomography (SPECT) is commonly performed in patients with abnormal electron beam computed tomography (EBCT) to define risk stratification, but the published prognostic data for patients undergoing both SPECT and EBCT are limited. The objective of the study was to examine the association and prognostic value between EBCT, coronary artery calcium score (CACS), and stress SPECT imaging. METHODS: We identified 835 patients (age 54.8 +/- 10.0 years, 77% male) who underwent EBCT and stress SPECT within a 3-month period. Coronary artery calcium score was categorized as normal (0), minimal (1-10), mild (11-100), moderate (101-400), and severe (>400). Single photon emission computed tomography summed stress score (SSS) was categorized as normal, low risk, intermediate risk, and high risk per Cedar Sinai criteria. Average follow-up was 4.8 +/- 3.2 years. End points were all-cause death, death/myocardial infarction (MI), and death/MI/late revascularization. RESULTS: The correlation of CACS to SSS was weak but statistically significant (r = +0.19, P < .001). The percentage of high-risk SSS increased with higher CACS scores; 4% of patients with normal EBCT and 18% with severe CACS had high-risk SSS. Coronary artery calcium score (chi2 = 11.4, P < .001), diabetes mellitus (chi2 = 4.6, P = .031), and chest pain class (chi2 = 8.7, P = .003) were independently associated with high-risk SPECT. The SSS (chi2 = 6.9, P = .009) and CACS (chi2 = 7.8, P = .005) were independently associated with mortality, as well as with both secondary end points of death/MI and death/MI/late revascularization. Only CACS predicted mortality in the 408 asymptomatic patients (chi2 = 5.2, P = .02), but these patients had an annual mortality of only 0.4% over the next 5 years. CONCLUSIONS: In selected patients undergoing both EBCT and SPECT, CACS is weakly correlated with SPECT SSS, likely reflecting the different information provided by EBCT and SPECT. Coronary artery calcium score is independently associated with high-risk SPECT after adjustment for clinical variables. Coronary artery calcium score and SSS are complementary for the prediction of mortality in symptomatic patients. Only CACS predicted mortality in the asymptomatic patients, but they had a low annual mortality.

Evaluation and clinical implications of aortic valve calcification measured by electron-beam computed tomography.

BACKGROUND: Electron-beam computed tomography (EBCT) is used to measure coronary calcification but not for aortic valve calcification (AVC). Its accuracy, association with aortic stenosis (AS) severity, and diagnostic and prognostic value with respect to AVC are unknown. METHODS AND RESULTS: In 30 explanted aortic valves, the AVC score by EBCT (1125+/-1294 Agatston units [AU]) showed a strong linear correlation (r=0.96, P<0.0001) with valvular calcium weight (653+/-748 mg) by pathology that allowed estimation of calcium weight as AVC score/1.7, with a small standard error of the estimate (53 mg). In 100 consecutive clinical patients, we measured AVC by EBCT and AS severity by echocardiographic aortic valve area (AVA). The AVC score was 1316+/-1749 AU (range 0 to 7226 AU). Intraobserver and interobserver variabilities were excellent (4+/-4% and 4+/-10%, respectively). AVC and AVA were strongly associated (r=0.79, P<0.0001) but had a curvilinear relationship that suggested that AVC and AVA provide complementary information. AVC score > or =1100 AU provided 93% sensitivity and 82% specificity for diagnosis of severe AS (AVA <1 cm2), with a receiver operator characteristic curve area of 0.89. AVC assessment by echocardiography was often more severe than by EBCT (P<0.0001). During follow-up, 22 patients either died, developed heart failure, or required surgery. With adjustment for age, sex, symptoms, ejection fraction, and AVA, the AVC score was independently predictive of event-free survival (risk ratio 1.06 per 100-AU increment [1.02 to 1.10], P<0.001), even after adjustment for echocardiographic calcifications. CONCLUSIONS: AVC is accurately and reproducibly measured by EBCT and shows a strong association and diagnostic value for severe AS. The curvilinear relationship between AVC and AVA suggests these measures are complementary, and indeed, AVC provides independent outcome information. Thus, AVC is an important measurement in the evaluation of patients with AS.

Comparison of acute and chronic antioxidant interventions in experimental renovascular disease.

Reactive oxygen species (ROS) can modulate renal hemodynamics and function both directly, by leading to vasoconstriction, and indirectly, by inducing renal inflammation and tissue growth. The involvement of oxidative stress in the pathogenesis of renovascular disease (RVD) is increasingly recognized, but the relative contribution of long-term tissue injury to renal dysfunction remains unclear. We hypothesized that functional and structural alterations elicited by oxidative stress in RVD would be more effectively modulated by chronic than by acute antioxidant intervention. Renal hemodynamics and function were quantified in vivo in pigs using electron-beam computed tomography at baseline and after vasoactive challenge (ACh and sodium nitroprusside); after 12 wk of RVD (simulated by concurrent hypercholesterolemia and renal artery stenosis, n = 7); RVD acutely infused with the SOD-mimetic tempol (RVD+tempol, n = 7); RVD chronically supplemented with antioxidant vitamins C (1 g) and E (100 IU/kg; RVD+vitamins, n = 7); or control (normal, n = 7). Renal tissue was studied ex vivo using immunoblotting and immunohistochemistry. Basal renal blood flow (RBF) and glomerular filtration rate were similarly decreased in all RVD groups. ACh-stimulated RBF remained unchanged in RVD, increased in RVD+tempol, but further increased (similarly to normal) in RVD+vitamins (P < 0.05 vs. RVD). Furthermore, RVD+vitamins also showed a decreased presence of superoxide anion, decreased NAD(P)H-oxidase and nitrotyrosine expression, increased endothelial nitric oxide synthase expression, and attenuated renal fibrosis. Chronic antioxidant intervention in early RVD improved renal hemodynamic responses more effectively than acute intervention, likely due to increased nitric oxide bioavailability and decreased structural injury. These suggest that chronic tissue changes play an important role in renal compromise mediated by oxidative stress in RVD.

Long-term antioxidant intervention improves myocardial microvascular function in experimental hypertension.

Hypertension increases oxidative stress, which can impair myocardial microvascular function and integrity. However, it is yet unclear whether long-term antioxidant intervention in early hypertension would preserve myocardial perfusion and vascular permeability responses to challenge. Pigs were studied after 12 weeks of renovascular hypertension without (n=8) or with daily supplementation of antioxidants (100 IU/kg vitamin E and 1 g vitamin C, n=6), and compared with normal controls (n=7). Myocardial perfusion and microvascular permeability were measured in vivo by electron beam computed tomography before and after 2 cardiac challenges (intravenous adenosine and dobutamine). Basal left ventricular muscle mass was also obtained. Mean arterial pressure was significantly increased in both groups of hypertensive animals (without and with antioxidants, 123+/-9 and 126+/-4 mm Hg, respectively, versus normal, 101+/-4 mm Hg; both P<0.05), but muscle mass was not different among the groups. The impaired myocardial perfusion response to adenosine observed in hypertensives (normal, +51+/-14%; P<0.05 versus baseline; hypertension, +14+/-15%; P=0.3 versus baseline) was preserved in hypertensive pigs that received antioxidants (+44+/-15%; P=0.01 compared with baseline). Long-term antioxidant intervention also preserved subendocardial microvascular permeability responses in hypertension. On the other hand, antioxidant intervention had little effect on the hypertension-induced myocardial vascular dysfunction observed in response to dobutamine. This study demonstrates that the impaired myocardial perfusion and permeability responses to increased cardiac demand in early hypertension are significantly improved by long-term antioxidant intervention. These results support the involvement of oxidative stress in myocardial vascular dysfunction in hypertension and suggest a role for antioxidant strategies to preserve the myocardial microvasculature.