This is a contribution from a member of THINCS,
The International Network of Cholesterol Skeptics


Letter to the editor of New England Journal of Medicine submitted April 2008 by Uffe Ravnskov. Read also the editor´s answer below.

Why enhanced cholesterol lowering is ineffective in familial hypercholesterolemia
Kastelein and coworkers had several explanations to the lack of effect of a more intensive cholesterol lowering in the ENHANCE trial (April 3 issue), but they did not consider that the concentration of cholesterol seems to have little importance in familial hypercholesterolemia. For instance, several studies, including two with Kastelein as co-author (1,2), have shown that neither the incidence (1) or the prevalence (2) of cardiovascular disease are associated with the lipid levels.
      A possible cause of cardiovascular disease in familial hypercholesterolemia may be inborn errors of the coagulation system. In cohorts of people with familial hypercholesterolemia, plasma fibrinogen and factor VIII were significantly higher in those with coronary heart disease than in those without (3), whereas total and LDL cholesterol did not differ significantly; and recently Kasteleins group found that polymorphism in the prothrombin gene is strongly associated with cardiovascular risk in people with this disorder (4). The reason why statin treatment is of benefit in familial hypercholesteromemia may therefore be their well-known antithrombotic effects, not their effect on cholesterol.  

1. Jansen AC, van Aalst-Cohen ES, Tanck MW, Trip MD, Lansberg FJ, Liem AH et al. The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolaemia: data in 2400 patients. J Intern Med 2004;256:482-90
de Sauvage Nolting PR, Defesche JC, Buirma RJ, Hutten BA, Lansberg PJ, Kastelein JJ. Prevalence and significance of cardiovascular risk factors in a large cohort of patients with familial hypercholesterolaemia. J Intern Med 2003;253:161-8.
3. Sugrue DD, Trayner I, Thompson GR, Vere TV, Dimeson J, Stirling Y, et al. Coronary artery disease and haemostatic variables in heterozygous familial hypercholesterolaemia. Br Heart J 1985;53:265-8.

Jansen AC, van Aalst-Cohen ES, Tanck MW, Cheng S, Fontecha MR, Li J, et al. Genetic determinants of cardiovascular disease risk in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 2005;25:1475-81.

The editors answer:

Dear Dr. Ravnskov,

I am sorry that we will not be able to print your recent letter to the editor regarding the Kastelein article of April 3.  The space available for correspondence is very limited, and we must use our judgment to present a representative selection of the material received.  Many worthwhile communications must be declined simply for lack of space.

Sincerely yours,

Gregory D. Curfman, M.D.
Executive Editor
New England Journal of Medicine




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