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Managing dyslipidaemia for the primary prevention of cardiovascular disease

BMJ 2018; 360 doi: (Published 23 March 2018) Cite this as: BMJ 2018;360:k946

Rapid Response:

Is it wise to lower cholesterol?

Ryan et al. (1) correctly mention that the risk factors with the lowest hazard ratios are obesity and the lipid profile. A relevant question is if high cholesterol (tC) or LDL-cholesterol (LDL-C) is a risk factor at all, because more than 20 cohort studies of elderly individuals from many countries have shown that tC is inversely associated with total mortality and either unassociated or inversely associated with cardiovascular mortality (2); and a systematic review of 19 studies including more than 68,000 individuals have shown that elderly people with the highest LDL-C values live longer than elderly people with low values (3). In the largest study those with the highest LDL-C lived even longer than those on statin treatment (4). The reason why most studies have shown that high tC is a risk factor for young and middle age people may be that working people are more stressed than senior citizens; that mental stress is able to raise cholesterol (5,6), and that stress may cause CVD by other ways (7-10). Furthermore, a recent study including more than 300,000 adult individuals of all ages from Asia, Australia and New Zealand found that high tC was not a risk factor for CVD among those who had no other risk factors (11).
It is well established that high LDL-cholesterol is a risk factor for CVD in familial hypercholesterolemia (FH). However, FH individuals may have inherited more important risk factors as well, because in five of six cohorts in four studies published before the introduction of statin treatment, LDL-cholesterol of those with and without CVD, none of whom had received any lipid-lowering treatment, did not differ with statistical significance (12-15). Furthermore, except from apheresis no randomized, controlled cholesterol-lowering trial including FH individuals only has succeeded with lowering the risk of CVD. Most of them have been very short, but in two trials with a duration of two years and in one with a duration of ten years, the number of CVD events increased in the groups whose LDL-C was lowered the most (16-18). The reason why apheresis is beneficial may be because apheresis removes not only blood lipids, but also various factors that promote coagulation (19,20).

1. Ryan A, Heath S, Cook P. Managing dyslipidaemia for the primary prevention of cardiovascular disease. BMJ 2018;360:k946. doi: 10.1136/bmj.k946.
3. 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
4. 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.
5. Frideman M, Rosenman RH, Carroll V. Changes in the serum cholesterol and blood clotting time in men subjected to cyclic variation of occupational stress. Circulation 1958;17:852-61.
6. Muldoon MF, Herbert TB, Patterson SM, et al. Effects of acute psychological stress on serum lipid levels, hemoconcentration, and blood viscosity. Arch Intern Med 1995;155:615-20.
7. Chrousos GP. The role of stress and the hypothalamic–pituitary–adrenal axis in the pathogenesis of the metabolic syndrome: neuro-endocrine and target tissue-related causes. Internat J Obes 2000;24:S50-S55.
8. Bachen EA, Muldoon MF, Matthews KA, Manuck SB. Effects of hemoconcentration and sympathetic activation on serum lipid responses to brief mental stress. Psychosom Med 2002;64:587-94.
9. Dimsdale JE. Psychological stress and cardiovascular disease. J Am Coll Cardiol 2008;51:1237–46.
10. Björntorp P. Heart and Soul: Stress and the Metabolic Syndrome, Scand Cardiovasc J 2009;35:3:172-7.
11. Peters SAE, Wang X, Lam TH, et al. Clustering of risk factors and the risk of incident cardiovascular disease in Asian and Caucasian populations: results from the Asia Pacific Cohort Studies Collaboration. BMJ Open 2018;8:e019335. doi:10.1136/bmjopen-2017-019335
12. Yamashita S, Kawamoto T, Ueyama Y et al. Relationship between LDL receptor activity and development of coronary heart disease in Japanese cases with heterozygous familial hypercolesterolemia. Artery 1987;15:24-43.
13. Seed M, Hoppichler F, Reaveley D et al. Relation of serum lipoprotein(a) concentration and apolipoprotein(a) phenotype to coronary heart disease in patients with familial hypercholesterolemia. N Engl J Med 1990;322:1494-9.
14. Hill JS, Hayden MR, Frohlich J, Pritchard PH. Genetic and environmental factors affecting the incidence of coronary heart disease in heterozygous familial hypercholesterolemia. Arterioscl Thromb 1991;11:290-7.
15. Tato F, Keller C, Schuster H et al. Relation of lipoprotein(a) to coronary heart disease and duplexsonographic findings of the carotid arteries in heterozygous familial hypercholesterolemia. Atherosclerosis 1993;101:69-77.
16. Kojima S, Harada-Shiba M, Toyota Y et al. Changes in coagulation factors by passage through a dextran sulfate cellulose column during low-density lipoprotein apheresis. Int J Artif Organs 1992;15:185-90.
17. Hovland A, Hardersen R, Nielsen EW et al. Hematologic and hemostatic changes induced by different columns during LDL apheresis. J Clin Apher 2010;25:294-300.
18. Koivisto P, Miettinen TA. Long-term effects of ileal bypass on lipoproteins in patients with familial hypercholesterolaemia . Circulation 1984;70:290-6.
19. Kastelein JJ, van Leuven SI, Burgess L et al. Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolaemia . N Engl J Med 2007;356:1620-30.
20. Kastelein JJ, Akdim F, Stroes ES et al. Simvastatin with or without ezetimibe in familial hypercholesterolaemia . N Engl J Med 2008;358:1431-43.

Competing interests: No competing interests

28 March 2018
Uffe Ravnskov
MD, PhD; independent researcher
Magle Stora Kyrkogata 9, 22350 Lund, Sweden