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Long term study backs statins for patients with high LDL and no other risk factors

BMJ 2017; 358 doi: https://doi.org/10.1136/bmj.j4171 (Published 07 September 2017) Cite this as: BMJ 2017;358:j4171

Re: Long term study backs statins for patients with high LDL and no other risk factors

In her comment about the follow-up study of the participants from the WOSCOPS trial by Vallejo-Vaz et al.(1 ), Jacqui Wise mentions that among the men initially allocated to the treatment group there were considerable reductions in the risk of coronary, cardiovascular and total mortality twenty years later, particular in those with the highest LDL-cholesterol (LDL-C)(2).

Apparently, Dr. Wise has not observed the serious error in the follow-up study, which is understandable since the 25 pages of study material and the 40 pages of supplementary material are extremely complicated. In our view, it is impossible to draw any conclusions from the follow-up study, because as mentioned in the supplementary material:

At 5 years after the completion of the randomised trial 38.7% and 35.2% of patients originally allocated to pravastatin and placebo arms, respectively, were taking statins (p<0.001). No later data on the proportion of individuals taking statin therapy were available for the subsequent years of follow-up.

It is well-known that many patients stop taking statins prematurely. In a study of over 140,000 elderly people, two thirds of those with a history of heart disease, and three quarters of those whose only “disease” was high cholesterol had discontinued the treatment after two years or less (3). The question is therefore, whether the benefit among those with high LDL-C is due to statin treatment or to their high LDL-C. The question is relevant because in a recent systematic review of 19 cohort studies including 30 cohorts with a total of 68,094 elderly people (≥60 years) followed for several years, an inverse association was found between all-cause mortality and LDL-C in 16 cohorts representing 92% of the total number of participants, and none of the other cohorts showed the opposite (4). In the largest study representing about 2/3 of the total number of participants, those with the highest LDL-C lived even longer than those taking statins (5). In two of nine cohorts, where cardiovascular mortality had been reported as well, mortality was highest in the lowest LDL-C quartile and with statistical significance; in seven cohorts, no association was found. One explanation is likely the little appreciated but well documented fact that LDL-C participates in immune system responses by complexing with and inactivating many types of microorganisms, and abundant evidence implicates infectious organisms in the pathogenesis of coronary heart disease (6,7).

1. Vallejo-Vaz A, Robertson M, Catapano A, et al. LDL-cholesterol lowering for the primary prevention of cardiovascular disease among men with primary elevations of LDL-cholesterol levels of 190 mg/dL or above: analyses from the WOSCOPS 5-year randomised trial and 20-year observational follow-up. Circulation 2017;(Sept). doi:10.1161/CIRCULATIONAHA.117.027966.
2. Wise J. Long term study backs statins for patients with high LDL and no other risk factors. BMJ 2017;358:j4171. doi: 10.1136/bmj.j4171.
3. Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA 2002;288:462-7.
4. Ravnskov U, Diamond DM, Hama R et al. Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review. BMJ Open 2016;6:e010401. doi: 10.1136/bmjopen-2015-010401.
5. Bathum L, Depont Christensen R, Engers Pedersen L, et al. Association of lipoprotein levels with mortality in subjects aged 50+ without previous diabetes or cardiovascular disease: a population-based register study. Scand J Prim Health Care 2013;31:172–80.
6. Ravnskov U, McCully KS. Vulnerable plaque formation from obstruction of vasa vasorum by homocysteinylated and oxidized lipoprotein aggregates complexed with microbial remnants and LDL autoantibodies. Ann Clin Lab Sci 2009;39:3–16.
7. Ravnskov U, McCully KS. Infections may be causal in the pathogenesis of atherosclerosis. Am J Med Sci 2012;344:391-4. doi: 10.1097/MAJ.0b013e31824ba6e0.

Competing interests: UR, RH, HO, and RS have written books with criticism of the cholesterol hypothesis. KSM has a US patent for a homocysteine-lowering protocol

21 September 2017
Uffe Ravnskov
Independent researcer
Rokura Hama, Björn Hammarskjöld, Malcolm Kendrick, Peter, Langsjoen, Kilmer S McCully, Harumi Okuyama, Paul Rosch, Tore Schersten, Sherif Sultan, Ralf Sundberg
Magle Stora Kyrkogata 9, 22350 Lund, Sweden