Predictive value of noninvasive measures of atherosclerosis for incident myocardial infarction: the Rotterdam Study.

BACKGROUND: Several noninvasive methods are available to investigate the severity of extracoronary atherosclerotic disease. No population-based study has yet examined whether differences exist between these measures with regard to their predictive value for myocardial infarction (MI) or whether a given measure of atherosclerosis has predictive value independently of the other measures. METHODS AND RESULTS: At the baseline (1990-1993) examination of the Rotterdam Study, a population-based cohort study among subjects age > or =55 years, carotid plaques and intima-media thickness (IMT) were measured by ultrasound, abdominal aortic atherosclerosis by x-ray, and lower-extremity atherosclerosis by computation of the ankle-arm index. In the present study, 6389 subjects were included; 258 cases of incident MI occurred before January 1, 2000. All 4 measures of atherosclerosis were good predictors of MI independently of traditional cardiovascular risk factors. Hazard ratios were equally high for carotid plaques (1.83 [1.27 to 2.62], severe versus no atherosclerosis), carotid IMT (1.95 [1.19 to 3.19]), and aortic atherosclerosis (1.94 [1.30 to 2.90]) and slightly lower for lower-extremity atherosclerosis (1.59 [1.05 to 2.39]), although differences were small. The hazard ratio for MI for subjects with severe atherosclerosis according to a composite atherosclerosis score was 2.77 (1.70 to 4.52) compared with subjects with no atherosclerosis. The predictive value of MI for a given measure of atherosclerosis was independent of the other atherosclerosis measures. CONCLUSIONS: Noninvasive measures of extracoronary atherosclerosis are strong predictors of MI. The relatively crude measures directly assessing plaques in the carotid artery and abdominal aorta predict MI equally well as the more precisely measured carotid IMT

Low prevalence of significant carotid artery disease in Iranian patients undergoing elective coronary artery bypass

BACKGROUND: Coronary artery bypass grafting ranks as one of the most frequent operations worldwide. The presence of carotid artery stenosis may increase the stroke rate in the perioperative period. Routine preoperative noninvasive assessment of the carotid arteries are recommended in many institutions to reduce the stroke rate. METHODS: 271 consecutive patients undergoing coronary artery bypass grafting at Shaheed Madani hospital of Tabriz, Iran (age, 58.5 Y; 73.1% male) underwent preoperative ultrasonography for assessment of carotid artery wall thickness. RESULTS: Plaque in right common, left common, right internal and left internal carotid arteries was detected in 4.8%, 7.4%, 43.2% and 42.1% of patients respectively. 5 patients (1.8%) had significant (<50%) and 3 (1.1%) patients had critical (<70%) stenosis in internal carotid arteries. Plaque formation in common carotid was not significantly different between two genders but the stenosis of left internal carotid was more frequently seen among men. Patients with plaques in right or left internal carotid arteries were significantly older. CONCLUSION: Consecutive Iranian patients undergoing elective coronary artery bypass surgery show a very low prevalence of significant carotid artery disease

Carotid intimal-media thickness as a surrogate for cardiovascular disease events in trials of HMG-CoA reductase inhibitors

BACKGROUND: Surrogate measures for cardiovascular disease events have the potential to increase greatly the efficiency of clinical trials. A leading candidate for such a surrogate is the progression of intima-media thickness (IMT) of the carotid artery; much experience has been gained with this endpoint in trials of HMG-CoA reductase inhibitors (statins). METHODS AND RESULTS: We examine two separate systems of criteria that have been proposed to define surrogate endpoints, based on clinical and statistical arguments. We use published results and a formal meta-analysis to evaluate whether progression of carotid IMT meets these criteria for HMG-CoA reductase inhibitors (statins). IMT meets clinical-based criteria to serve as a surrogate endpoint for cardiovascular events in statin trials, based on relative efficiency, linkage to endpoints, and congruency of effects. Results from a meta-analysis and post-trial follow-up from a single published study suggest that IMT meets established statistical criteria by accounting for intervention effects in regression models. CONCLUSION: Carotid IMT progression meets accepted definitions of a surrogate for cardiovascular disease endpoints in statin trials. This does not, however, establish that it may serve universally as a surrogate marker in trials of other agents

Structure-Based Predictive Models for Allosteric Hot Spots

In allostery, a binding event at one site in a protein modulates the behavior of a distant site. Identifying residues that relay the signal between sites remains a challenge. We have developed predictive models using support-vector machines, a widely used machine-learning method. The training data set consisted of residues classified as either hotspots or non-hotspots based on experimental characterization of point mutations from a diverse set of allosteric proteins. Each residue had an associated set of calculated features. Two sets of features were used, one consisting of dynamical, structural, network, and informatic measures, and another of structural measures defined by Daily and Gray [1]. The resulting models performed well on an independent data set consisting of hotspots and non-hotspots from five allosteric proteins. For the independent data set, our top 10 models using Feature Set 1 recalled 68–81% of known hotspots, and among total hotspot predictions, 58–67% were actual hotspots. Hence, these models have precision P = 58–67% and recall R = 68–81%. The corresponding models for Feature Set 2 had P = 55–59% and R = 81–92%. We combined the features from each set that produced models with optimal predictive performance. The top 10 models using this hybrid feature set had R = 73–81% and P = 64–71%, the best overall performance of any of the sets of models. Our methods identified hotspots in structural regions of known allosteric significance. Moreover, our predicted hotspots form a network of contiguous residues in the interior of the structures, in agreement with previous work. In conclusion, we have developed models that discriminate between known allosteric hotspots and non-hotspots with high accuracy and sensitivity. Moreover, the pattern of predicted hotspots corresponds to known functional motifs implicated in allostery, and is consistent with previous work describing sparse networks of allosterically important residues

Risk factors for progression of atherosclerosis measured at multiple sites in the arterial tree - The Rotterdam Study

Background and Purpose - Studies investigating determinants of atherosclerotic disease progression are relatively rare. Moreover, although atherosclerotic disease can be assessed noninvasively in different vascular beds, previous studies have not considered progression of atherosclerosis at >1 site. The present study was designed to identify risk factors for progression of atherosclerosis measured at multiple sites in the arterial tree. Methods - The Rotterdam Study is a population-based cohort study of 7983 men and women greater than or equal to 55 years of age. Carotid plaques and intima-media thickness were assessed by ultrasound, aortic atherosclerosis by x-ray, and lower-extremity atherosclerosis by the ankle-arm index. Data on progression of atherosclerosis over an average period of 6.5 years were available for 3409 participants. Associations of established cardiovascular risk factors with mild, moderate, and severe progression of atherosclerosis were investigated through multinomial regression analysis. Results - Age, smoking, total cholesterol, and systolic blood pressure and/or hypertension were strong, independent predictors of moderate and severe progression of atherosclerosis at multiple sites. Diabetes mellitus predicted only severe progression of atherosclerosis. Associations of sex with progression of atherosclerosis were remarkably modest. Conclusions - Age, smoking, total cholesterol, and systolic blood pressure and/or hypertension strongly predict progression of extracoronary atherosclerosis in the elderly, but sex remarkably does not. These results emphasize the need for prevention of progression of extracoronary atherosclerotic disease in men and women alike

The association between coronary calcification assessed by electron beam computed tomography and measures of extracoronary atherosclerosis - The Rotterdam Coronary Calcification Study

OBJECTIVES The present study was designed to examine the associations of coronary calcification assessed by electron beam computed tomography (CT) with measures of extracoronary atherosclerosis. BACKGROUND Although measures of extracoronary atherosclerosis have been used to predict coronary events, it is not yet known to what extent those measures reflect coronary atherosclerosis. METHODS The Rotterdam Coronary Calcification Study is a population-based study in subjects age 55 years and over. Participants of the study underwent an electron beam CT scan. Coronary calcification was quantified according to the Agatston calcium score. Measures of extracoronary atherosclerosis included common carotid intima media thickness (IMT), carotid plaques, ankle-arm index (AAI) and aortic calcification. We used the first 2,013 participants for the present analyses. Age-adjusted geometric mean calcium scores were computed for categories of extracoronary measures using analyses of variance. RESULTS Graded associations with coronary calcification were found for the carotid and aortic measures. Associations were strongest for carotid plaques and aortic calcification; coronary calcification increased from the lowest category (no plaques) to the highest category 9-fold and 11-fold in men and 10-fold and 20-fold in women, respectively. A nonlinear association was found for AAI with an increase in coronary calcification only at lower levels of AAI. CONCLUSIONS In this population-based study, graded associations were found between coronary calcification and common carotid IMT, carotid plaques and aortic calcification. A nonlinear association was found between coronary calcification and the AAI. (C) 2002 by the American College of Cardiology Foundation