International nifedipine trial on anti-atherosclerotic therapy (INTACT) - methodologic implications and results of a coronary angiographic follow-up study using computer-assisted film analysis

Animal experiments demonstrated a significant suppressive effect of various calcium channel blockers on the formation of atherosclerotic lesions. Therefore, a prospective, placebo-controlled, randomized, double blind multicenter study was performed to investigate the inhibitory influence of the calcium channel blocker nifedipine (80 mg/day) on the progression of coronary artery disease in man. Study endpoints were changes of coronary morphology documented by coronary angiography with particular respect to the formation of new coronary stenoses. In 348 out of 425 patients included in the study, coronary angiograms were repeated after three years. The angiograms were standardized by induction of a maximal coronary vasodilation with high doses of nitrates and by using absolutely identical angiographic projections. Quantitative analysis of coronary cineangiograms was performed with the computer-assisted contour detection system CAAS. Parameters were mean and minimal diameter of all segments and minimal stenosis diameter, percent diameter stenosis, length and plaque area of all stenoses. Continuous intake of study medication was registered in 282 patients, 134 on nifedipine and 148 patients on placebo. In these patients, a total of 3808 coronary segments with 893 stenoses (≥ 20% diameter reduction in at least one angiographic projection) were compared on the baseline and follow-up cineangiograms. The changes in all angiographic parameters analyzed averaged over all patients by considering all angiographic projections analyzed, indicated significant progression of the disease (p < 0.006). The average changes in all parameters were even about three times more profound, when in the individual patients only the respective projections indicating the maximal changes were considered for the calculation (p < 0.001). However, with neither of these two analysis modes, the differences in progression between the treatment groups were statistically significant. In the follow-up angiograms, a total of 196 new coronary lesions (185 stenoses, 11 occlusions) were found at previously normal arterial sites. In patients on nifedipine, an average of only 0.58 new lesions per patient were detected versus 0,80 lesions per patient on placebo (-27%; p=0.031). INTACT is the first prospective angiographic trial on the progression of coronary artery disease using computer-assisted quantitative coronary angiography in such a high number of patients. All parameters analyzed indicated significant progression of coronary artery sclerosis. Nifedipine had no influen

Usefulness of quantitative and qualitative angiographic lesion morphology, and clinical characteristics in predicting major adverse cardiac events during and after native coronary balloon angioplasty

Major, adverse cardiac events (death, myocardial infarction, bypass surgery and reintervention) occur in 4 to 7% of all patients undergoing coronary balloon angioplasty. Prospectively collected clinical data, and angiographic quantitative and qualitative lesion morphologic assessment and procedural factors were examined to determine whether the occurrence of these events could be predicted. Of 1,442 patients undergoing balloon angioplasty for native primary coronary disease in 2 European multicenter trials, 69 had major, adverse cardiac procedural or in-hospital complications after ≥1 balloon inflation and were randomly matched with patients who completed an uncomplicated in-hospital course after successful angioplasty. No quantitative angiographic variable was associated with major adverse cardiac events in univariate and multivariate analyses. Univariate analysis showed that major adverse cardiac events were associated with the following preprocedural variables: (1) unstable angina (odds ratio [OR] 3.11; p 45 ° (OR 2.34; p 45 ° (OR 2.87; p 45 ° (OR 2.54; p < 0.006) were independent predictors of major adverse cardiac events

Effects of Cyclic Strain and Growth Factors on Vascular Smooth Muscle Cell Responses

Under physiological and pathological conditions, vascular smooth muscle cells (SMC) are exposed to different biochemical factors and biomechanical forces. Previous studies pertaining to SMC responses have not investigated the effects of both factors on SMCs. Thus, in our research we investigated the combined effects of growth factors like Bfgf (basic fibroblast growth factor), TGF-β (transforming growth factor β) and PDGF (platelet-derived growth factor) along with physiological cyclic strain on SMC responses. Physiological cyclic strain (10% strain) significantly reduced SMC proliferation compared to static controls while addition of growth factors bFGF, TGF-β or PDGF-AB had a positive influence on SMC growth compared to strain alone. Microarray analysis of SMCs exposed to these growth factors and cyclic strain showed that several bioactive genes (vascular endothelial growth factor, epidermal growth factor receptor, etc.) were altered upon exposure. Further work involving biochemical and pathological cyclic strain stimulation will help us better understand the role of cyclic strain and growth factors in vascular functions and development of vascular disorders