Distinct risk profiles of early and advanced atherosclerosis: prospective results from the Bruneck Study

J Willeit, S Kiechl, F Oberhollenzer… - … , and vascular biology, 2000 - Am Heart Assoc
J Willeit, S Kiechl, F Oberhollenzer, G Rungger, G Egger, E Bonora, M Mitterer, M Muggeo
Arteriosclerosis, thrombosis, and vascular biology, 2000Am Heart Assoc
Most epidemiological surveys on risk factors of atherosclerosis were cross-sectional in
design and did not consider the existence of pathologically distinct processes. The Bruneck
Study is a prospective survey in the general community (age range, 40 to 79 years). The
baseline examination and first reevaluation were performed in the summers of 1990 and
1995 (participation, 92%; follow-up, 96%). Carotid atherosclerosis was monitored with high-
resolution duplex ultrasound. Early (incidence and/or extension of nonstenotic lesions) and …
Abstract
—Most epidemiological surveys on risk factors of atherosclerosis were cross-sectional in design and did not consider the existence of pathologically distinct processes. The Bruneck Study is a prospective survey in the general community (age range, 40 to 79 years). The baseline examination and first reevaluation were performed in the summers of 1990 and 1995 (participation, 92%; follow-up, 96%). Carotid atherosclerosis was monitored with high-resolution duplex ultrasound. Early (incidence and/or extension of nonstenotic lesions) and advanced (incidence and/or progression of stenosis >40%) stages of atherogenesis were differentiated. The risk profile of early atherogenesis consists of traditional risk factors, such as hypertension, hyperlipidemia, and cigarette smoking (pack-years), supplemented by a variety of less well-established risk conditions, including high body iron stores, hypothyroidism, microalbuminuria, and high alcohol consumption. In contrast, the risk profile of advanced atherogenesis includes markers of enhanced prothrombotic capacity, attenuated fibrinolysis, and clinical conditions known to interfere with coagulation: high fibrinogen, low antithrombin, factor V Leiden mutation, lipoprotein(a) >0.32 g/L, high platelet count, cigarette smoking, and diabetes. Hyperlipidemia and hypertension were of only minor relevance. These findings, along with the epidemiological features of advanced atherogenesis and emergence of an elevated fibrin turnover, suggest atherothrombosis to be a key mechanism in the development of advanced stenotic atherosclerosis. Supplementary 6-category logistic regression models illustrate the changing association between major risk predictors and atherosclerosis of increasing severity and substantiate appropriateness of the 40% threshold applied for the definition of advanced stenotic atherosclerosis. Atherosclerosis is a heterogeneous process that subsumes etiologically and epidemiologically distinct disease entities. The multifactorial etiology of atherosclerosis, which goes far beyond the traditional risk factors, has not yet achieved adequate attention in clinical practice and disease prevention.
Am Heart Assoc