Environmental and genetic risk factors in early human atherogenesis: Lessons from the PDAY study

Abstract

A multi-institutional study 'Pathobiological Determinants of Atherosclerosis in Youth' (PDAY) was initiated to document the natural history of atherosclerosis, its relationship to risk factors, and pathobiology of lesion development in young subjects. Pathology laboratories in nine centers collected arteries and tissues from over 2000 persons from 15 through 34 years of age whose deaths were attributed to homicides, accidents, or suicides. Arteries were evaluated for lesions, and risk factors were analyzed in a central laboratory. Post-mortem risk factors included serum lipoproteins, serum thiocyanate (smoking), glycohemoglobin (diabetes), thickness of panniculus adiposus (obesity), small renal artery changes (hypertension) and apoprotein isoforms. This study documents the development of atherosclerosis at an early age. It also shows that the recognized risk factors for coronary heart disease are associated with lesion development in the arteries of these young subjects. The PDAY study has a counterpart in Japan where the development of atherosclerosis has been studied in young subjects. This Japanese study, in a population in which coronary heart disease has not yet become a major epidemic, has findings quite similar to the findings from the PDAY study. Studies of atherosclerosis in both Japan and the USA provide strong justification for reducing risk factors in young persons.