Effect of intensive versus standard lipid-lowering treatment with atorvastatin on the progression of calcified coronary atherosclerosis over 12 months: a multicenter, randomized, double-blind trial.

BACKGROUND: Recent clinical trials have suggested that intensive versus standard lipid-lowering therapy provides for additional benefit. Electron-beam computed tomography provides the opportunity to quantify the progression of coronary artery calcification (CAC) in serial measurements. METHODS AND RESULTS: In a multicenter, randomized, double-blind trial, 471 patients (age 61+/-8 years) who had no history of coronary artery disease and no evidence of high-grade coronary stenoses (>50% diameter reduction) were randomized if they had > or =2 cardiovascular risk factors and moderate calcified coronary atherosclerosis as evidenced by a CAC score > or =30. Patients were assigned to receive 80 mg or 10 mg of atorvastatin per day over 12 months. Progression of CAC volume scores could be analyzed in 366 patients. After pretreatment with 10 mg of atorvastatin for 4 weeks, 12 months of study medication reduced LDL cholesterol from 106+/-22 to 87+/-33 mg/dL in the group randomized to receive 80 mg of atorvastatin (P<0.001), whereas levels remained stable in the group randomized to receive 10 mg (108+/-23 at baseline, 109+/-28 mg/dL at the end of the study, P=NS). The mean progression of CAC volume scores, corrected for the baseline CAC volume score, was 27% (95% CI 20.8% to 33.1%) in the 80-mg atorvastatin group and 25% (95% CI 19.1% to 30.8%) in the 10-mg atorvastatin group (P=0.65). CAC progression showed no relationship with on-treatment LDL cholesterol levels. CONCLUSIONS: We did not observe a relationship between on-treatment LDL cholesterol levels and the progression of calcified coronary atherosclerosis. Over a period of 12 months, intensive atorvastatin therapy was unable to attenuate CAC progression compared with standard atorvastatin therapy. The possibility remains that the time window was too short to demonstrate an effect.

Effects of lifestyle modification on the progression of coronary atherosclerosis, autonomic function, and angina--the role of GNB3 C825T polymorphism.

BACKGROUND: Given the multimodal medical and interventional treatment options in coronary artery disease, the additional value of intensified lifestyle modification is unclear. We have therefore examined the effects of lifestyle modification on top of current treatment and also associated with the GNB3 C825T polymorphism, which has established association to sympathetic activation and the precipitation of angina. METHODS: One hundred one patients with established coronary artery disease were randomized to a 1-year lifestyle modification group (lifestyle group [LG]) or an advice group. Risk factors, coronary calcification (electron beam tomography), heart rate variability, baroreflex sensitivity, anginal symptoms, and quality of life (QOL) were assessed on entry and after 1 year. RESULTS: Patients in LG had excellent program adherence, but lifestyle modification had no impact on metabolic risk factors and coronary calcification. Changes in heart rate, heart rate variability, and blood pressure were only slightly favoring LG. Baroreflex sensitivity increased by 2 (0.79-3.13) ms/mm Hg in the LG but decreased by -0.10 (-1.11 to 0.92) in the advice group (P = .013). Lifestyle modification led to improved physical QOL, reductions of anginal attacks (-54% vs 11%, P = .01), and dose reductions in 30% of anti-ischemic medications (P = .004). *825T allele carriers had a more pronounced reduction of heart rate and improvement of angina and QOL. The beneficial effect on reduction of medication was seen in *825T allele carriers only. CONCLUSIONS: In the presence of modern treatments, comprehensive lifestyle modification provides no additional benefits on progression of atherosclerosis but improves autonomic function, angina, and QOL with concomitant reduced need of medication. These responses are more pronounced in GNB3*825T allele carriers.

[Assessment of the natural history of coronary artery calcification and identification of its determinants. Rationale of the 2nd part of the Heinz Nixdorf Recall Study]. / Analyse des natürlichen Verlaufs der Koronargefässverkalkung und Identifizierung ihrer Determinanten. Rationale des 2. Teils der Heinz Nixdorf Recall Studie.

The Heinz Nixdorf Recall Study, which was inaugurated in 2000, is an ongoing population-based study to evaluate the prediction of cardiovascular events by integrating new imaging and nonimaging modalities in risk assessment. A focus is the additional prognostic value of coronary artery calcification (CAC). Currently used risk stratification algorithms often describe the individuals' risk based on few established risk factors only inaccurately. Using noninvasive quantification of CAC progression, the natural history of atherosclerosis with its repetitive, frequently subclinical plaque ruptures, may detect an unstable course of the disease long before the disease irreversibly manifests in sudden death or myocardial infarction. While the independent additional prognostic value of CAC quantification has been shown in asymptomatic patients at intermediate risk, only few studies provided evidence for an independent prognostic value of serial CAC measurements. In the Heinz Nixdorf Recall Study, the impact of established and new risk factors, e.g., the metabolic syndrome, psychosocial and environmental risk factors, or genetic variables, can be assessed. Further, the association of CAC progression with the incidence of other cardiovascular diseases such as heart failure or aortic or aortic valve calcification can be described. Since April 2006, the participants of the study return to the study center 5 years after baseline recruitment to assess health status and to determine the risk factor profile. Based on recently published data, serial CAC measurements have been granted allowing for (1) characterization of the natural history of CAC progression, and (2) identification of its determinants. The rationale of serial CAC quantification is discussed in this article.The Heinz Nixdorf Recall Study will contribute to the appraisal of new imaging modalities in risk stratification.

Coronary atherosclerosis and cardiovascular risk in masters male marathon runners. Rationale and design of the "marathon study".

BACKGROUND: Regular physical exercise is recommended to reduce cardiovascular mortality. And yet, atherosclerosis is the main cause of exercise-associated death in persons beyond age 35. The need for risk stratification in marathon runners is under discussion. The predictive value of modern imaging- and non-imaging-based markers of risk that can be used for risk stratification in masters endurance athletes still deserves exploration. METHODS: Male runners > 50 years who have completed at least five marathon races during the preceding 3 years and do not suffer from coronary artery disease, angina nor diabetes mellitus are studied to assess the predictive value of established and modern imaging- based and biochemical cardiovascular risk factors. Laboratory parameters including clinical chemistry, hematology and hormone measurements are determined. Lifestyle-related risk factors, psychosocial and socioeconomic variables are explored using standardized questionnaires. Coronary, carotid, femoral and aortic atherosclerosis is measured using electronbeam computed tomography and ultrasound. In addition, a resting ECG, a bicycle stress test and heart rate variability are performed. Myocardial morphology and function are assessed using echocardiography and magnetic resonance imaging. Participants are invited to compete in a marathon race to quantify the association of coronary atherosclerosis with marathon-related changes of cardiac troponin levels and the extent of marathon-induced inflammation. At the cellular level, the effect on the amount of circulating progenitor cells (EPCs) is determined by FACS analysis. Changes in laboratory parameters and hormone levels are also studied. Annual long-term follow-up including hospital records and death certificates is performed. Data are compared with those from a general unselected cohort from the Heinz Nixdorf Recall Study. CONCLUSION: This study should contribute to cardiovascular risk assessment in the growing number of masters marathon runners with a focus on assessing the predictive value of modern imaging techniques and biochemical markers for comprehensive risk stratification.

Scimitar syndrome in an adult: diagnosis and surgical treatment.

A 51-year-old woman, presenting with increasing dyspnoea on exertion was admitted for surgery of a right sided partial anomalous pulmonary venous return. Contrast enhanced electron-beam tomography (EBT) presented a hypoplastic right lower lobe and confirmed the diagnosis of a so-called scimitar syndrome. Surgery consisted of creation of an atrial septal defect, transposition of the anomalous vein and reocclusion of the artificial septal defect with a Dacron patch. One year after surgery, the patient's physical strength increased to a normal level without dyspnoea, while three-dimensional imaging reconstructed from EBT demonstrated an intact operative situs.

[Noninvasive computed tomographic coronary angiography as a complement to coronary calcium quantification in symptomatic patients]. / Nichtinvasive computertomographische Koronarangiographie als Ergänzung zur Koronarkalkquantifizierung bei symptomatischen Patienten.

BACKGROUND: Invasive, selective coronary angiography remains the "gold standard" of direct visualization of epicardial coronary arteries. Technical advances in recent years and improvements in image quality in both electron beam computed tomography (EBT) and multislice spiral/helical computed tomography (MSCT) brought along an increasing interest in the potential clinical role of noninvasive computed tomographic coronary angiography (CTCA). POTENTIAL AND LIMITATIONS: Measurement of coronary calcification permits quantitative estimation of overall coronary plaque burden and thereby allows assessment of cardiovascular risk and likelihood of the presence of a significant stenosis. However, the precise site and degree of stenoses cannot be measured. Contrast-enhanced CTCA lumenography permits visualization of epicardial coronary artery stenoses with a sensitivity and specificity of about 90%. Noncalcified plaques may also be detected in individual cases, but very few data are available on this aspect of CTCA. Image artifacts due to rapid motion, especially in the distal segments of the right and circumflex coronary arteries, may preclude reliable assessment of 20-30% of these segments. Also, in-stent restenoses and distal bypass anastomoses will, in the foreseeable future, remain difficult to confidently diagnose by CTCA. Combined assessment of calcified plaque burden and CTCA may enhance diagnostic accuracy especially in patients with low or moderate calcium scores. In the presence of heavy calcifications, stenoses may be masked. INDICATIONS: Noninvasive CT-based evaluation of coronary arteries seems useful in patients with a low to intermediate pretest likelihood for significant coronary artery disease (CAD). This holds for several ACC/AHA class II indications described for invasive, selective coronary angiography and for few class I indications. Further prospective studies are required to establish the clinical value of combined assessment of coronary calcium quantification and CTCA.

[Noninvasive plaque imaging using contrast-enhanced cardiac computed tomography]. / Nichtinvasive Darstellung koronarer Plaques mittels kontrastgestützter kardialer Computertomographie.

Recent technical advances in both multislice spiral computed tomography (MSCT) and electron-beam computed tomography (EBT) renewed the clinicians' interest in the potentials of CT-based, contrast-enhanced, noninvasive coronary angiography. Despite the fact that invasive, selective coronary angiography remains the "gold standard", cardiac CT lumenography permits visualization of flow-limiting coronary stenosis with a sensitivity and specificity of about 90%. The method is, nevertheless, limited by imaging artifacts which are due to extensive coronary calcifications, or, especially in the right coronary and circumflex artery, to rapid coronary motion. Moreover, the clinical value for the exclusion of obstructive coronary artery disease is not yet established, and further prospective studies are required. On the other hand, cardiac CT permits reliable estimation of coronary calcification and quantification of overall coronary plaque burden and thereby allows risk assessment to predict the individual cardiovascular risk. Diagnostic accuracy may be enhanced by combining assessment of calcified plaque burden and contrast imaging. The newer MSCT technology also allows for differentiation of coronary lesion configuration, especially of noncalcified plaques. However, very few data are currently available on this aspect, and the future clinical relevance of this promising technique remains to be proven. The purpose of this article is to describe the principles and potentials of contrast-enhanced coronary CT imaging and to summarize the practical limitations with the currently available scanning equipment.

Radiation exposure during cardiac CT: effective doses at multi-detector row CT and electron-beam CT.

PURPOSE: To measure the effective radiation doses delivered at electron-beam computed tomography (CT) and multi-detector row spiral CT of coronary arteries and to compare these doses with those delivered at catheter coronary angiography. MATERIALS AND METHODS: An anthropomorphic phantom equipped with 66 thermoluminescent dosimeters was imaged at cardiac CT. Four protocols for unenhanced coronary artery calcium scoring were simulated: one with electron-beam CT and three with multi-detector row CT. Four similar protocols for coronary CT angiography were simulated. All multi-detector row spiral CT protocols were performed with retrospective electrocardiographic triggering. Biplane catheter coronary angiography also was simulated. Radiation doses to organs were measured, and effective doses were calculated according to guidelines published in International Commission on Radiological Protection Publication 60. RESULTS: Coronary artery calcium scoring with electron-beam CT yielded effective radiation doses of 1.0 and 1.3 mSv for male and female patients, respectively. The radiation doses at calcium scoring with multi-detector row CT were 1.5-5.2 mSv for male patients and 1.8-6.2 mSv for female patients. Electron-beam CT coronary angiography yielded effective doses of 1.5 and 2.0 mSv for male and female patients, respectively. The highest effective doses were delivered at multi-detector row CT angiography: 6.7-10.9 mSv for male patients and 8.1-13.0 mSv for female patients. Catheter coronary angiography yielded effective doses of 2.1 and 2.5 mSv for male and female patients, respectively. CONCLUSION: Higher radiation doses are delivered at multi-detector row cardiac CT compared with the doses delivered at electron-beam CT and catheter coronary angiography.