Intended for healthcare professionals


Taking a longer term view of cardiovascular risk: the causal exposure paradigm

BMJ 2014; 348 doi: (Published 21 May 2014) Cite this as: BMJ 2014;348:g3047
  1. Allan D Sniderman, professor of medicine1,
  2. Peter P Toth, professor of clinical medicine2,
  3. George Thanassoulis, assistant professor of medicine34,
  4. Michael J Pencina, professor of biostatistics and bioinformatics5,
  5. Curt D Furberg, professor emeritus of public health sciences6
  1. 1Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health Centre, Room H7.22, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, QC H3A 1A1 Canada
  2. 2Department of Family and Community Medicine, University of Illinois School of Medicine, Peoria, IL
  3. 3CGH Medical Center, Sterling, IL, USA
  4. 4Cardiology Division, Department of Medicine, Royal Victoria Hospital, McGill University Health Centre, Montreal, Canada
  5. 5Duke Clinical Research Institute, Durham, NC, USA
  6. 6Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
  1. Correspondence to: A D Sniderman allansniderman{at}

Allan D Sniderman and colleagues argue that many people already have advanced arterial damage when they are identified to be at high risk of a cardiovascular event and that a better approach would be to prevent the damage by earlier intervention against the treatable causes of cardiovascular disease

The decision to treat a healthy person with statins to prevent cardiovascular disease remains challenging. All the major cholesterol guidelines recommend that, except for people with diabetes and very high low density lipoprotein (LDL) cholesterol concentrations, the decision is principally based on the patient’s risk of a cardiovascular event over the next 10 years.1 2 3 4 However, the instruments they use to quantify this risk, the threshold of risk that activates statin treatment, and the emphasis they allocate to LDL cholesterol all differ.

Age is by far the strongest predictor of cardiovascular risk. This is not because age causes cardiovascular events but because progressive and incessant injury to the arterial wall over time from LDL cholesterol, blood pressure, and smoking cause the advanced, complex atherosclerotic lesions that are the precursors of cardiovascular events.5 Since clinical risk cannot rise until advanced, extensive, intramural disease is present, many, or perhaps most, of those who become eligible for primary prevention with statins based on 10 year risk already have at least moderately advanced, diffuse atherosclerosis. It therefore makes sense to identify and treat the known causes of vascular disease earlier. The causal exposure paradigm aims to prevent advanced disease by assessing the treatable causes of vascular disease and projecting their clinical consequences over 20-30 years in order to identify those who would gain most from earlier pharmacological intervention.

Limitations of using 10 year risk

A 40 year old non-smoking American man with a LDL cholesterol level of 4.16 mmol/L (160 mg/dL, the 90th centile of the American population), …

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