TITLE:
Evidence that Low Density Lipoprotein Is the Primary Cause of Atherosclerotic Cardiovascular Disease: A Bradford-Hill Approach
AUTHORS:
David S. Schade, Deborah Helitzer, Philip Eaton
KEYWORDS:
Low Density Lipoprotein
JOURNAL NAME:
World Journal of Cardiovascular Diseases,
Vol.7 No.9,
September
19,
2017
ABSTRACT: Cardiovascular disease is the leading cause of death in the Westernized world. The costs in productive lives lost to individuals, families, and societyarestaggering. The epidemiology, pathogenesis, and preventativetreatmentare all clearly described. Why then, has this epidemic not been eradicated? One reason is the uncertainty about the primary cause of atherosclerotic cardiovascular disease. Low density lipoprotein (LDL) is a circulating lipid particle that deposits cholesterol into the arterial wallwhichsubsequently evolves into an atherosclerotic plaque and a life-threatening arterial thrombosis. The reason that LDL is not universally accepted as the cause of atherosclerosisis that there are no randomized controlled trials (RCT’s) providing this evidence. For ethical, financial, and scientificreasons, an RCT of sufficient duration to prove or disprove this hypothesismay never be initiated. We propose aunique approach to support the critical role of LDL in the pathogenesis of cardiovascular disease. Employing criteria based on those proposed by Sir Austin Bradford Hill, we describe the large body of scientific evidence supporting LDL as the primary cause of atherosclerosis. Sir Austin Bradford Hill was a British epidemiologist/statistician who lived in the 20thcentury. He acknowledged that the cause of a disease could not always be established by a randomized clinical trial. Therefore, he outlined nine criteria (now known as the Bradford-Hill criteria) that should be met if an etiological factor was likely the cause of a disease. The data in this manuscript are organized according to these nine criteria. These data strongly suggest that LDL is the primary cause of atherosclerotic cardiovascular disease and that sufficient LDL reduction (i.e., to mmol/L) will lead to atherosclerotic cardiovascular disease becoming a rare event.