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Association between low density lipoprotein and all cause and cause specific mortality in Denmark: prospective cohort study

BMJ 2020; 371 doi: (Published 08 December 2020) Cite this as: BMJ 2020;371:m4266

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High low-density-lipoprotein is beneficial

Dear Editor

In their study of the general population in Copenhagen, Johannesen et al. concluded that high levels of LDL-C were associated with an increased risk of all-cause mortality. They claim that “no previous study has examined the concentration of LDL-C associated with the lowest risk of all-cause mortality in a general population cohort.” [1] The fact is that the association between LDL-C and longevity in community-dwelling people has been examined in Spain, [2] Italy, [3,4] the USA, [5] Finland, [6] Korea [7] and China. [8] In two of these studies, the association between LDL-C and mortality was inverse; [2,3] in four of the others [4-7] it was nonsignificant. In an Iranian study, only CVD mortality was reported, and it was inversely associated with LDL-C. [9]

In the Chinese study, [8] which included more than five million statin-naïve young people, high LDL-C was associated with mortality, but those with the highest LDL-C who died, included only 0.076 percent of the population. Most likely they may have had familial hypercholesterolemia (FH), but that does not mean that the cause of death was high LDL-C. There is much evidence that premature mortality among subjects with FH is increased coagulation factors which a few of them have inherited as well. [10]

As the authors mention, several studies of elderly people with high cholesterol have shown that after the age of retirement, they live just as long or longer than elderly people with normal or low cholesterol. These studies are rejected by Johannesen et al. because they consider them conflicting and historical. However, they are in accord with the result of a review of 19 follow-up studies of elderly people, [11] and at least seven other studies from all over the world published during the last four years. [3-6,12-14] In the review, [11] CVD mortality was reported as well in seven of the 19 studies, and it was unassociated with LDL-C in six of them. Furthermore, eight more follow-up studies including young and middle-aged people or patients have found that high LDL-C is unassociated or inversely associate with mortality. [15-22]

In their review, Johannesen et al. claim that a recent study of young Korean people without statin-treatment has shown a U-shaped association between LDL-C and mortality. [25] This study of two cohorts included 347,971 and 182,943 individuals, respectively. In the first cohort, the association was U-shaped, but it was only statistically significant for the association between low LDL-C and mortality. In the other cohort, the association was also U-shaped, but not with statistical significance.

Johannesen et al. suggest that the association between low levels of LDL-C and an increased risk of all-cause mortality is explained by reverse causation. However, there is much evidence that low cholesterol predisposes both to infectious diseases [23] and to cancer. [24]

As CVD is the most common cause of death in most countries, these follow-up studies contradict the idea that high LDL-C causes CVD; an idea which is contradicted by many other types of studies as well. [25]


1. Johannesen CDL, Langsted A, Mortensen MB, Nordestgaard BG. Association between low density lipoprotein and all cause and cause specific mortality in Denmark: prospective cohort study. BMJ 2020;371:m4266 doi:10.1136/bmj.m4266
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Competing interests: No competing interests

17 December 2020
Uffe Ravnskov
Independent researcher
de Lorgeril M, Laboratoire Coeur et Nutrition, TIMC-CNRS, Université Grenoble-Alpes. Faculté de Médecine, 38056 La Tronche, France. Diamond D, Professor, Departments of Psychology, Molecular Pharmacology & Physiology, University of South Florida, Tampa, FL, 33620 US. Hama R, Director, Japan Institute of Pharmacovigilance, Osaka, Japan. ORCID ID 0000-0002-3802-6754 Hammarskjöld B, Assistant professor, Strömstads Academy, Östervåla, Sweden. Harcombe Z, Independent researcher, Cardiff, UK. Kendrick M, East Cheshire Trust, Macclesfield District General Hospital, Macclesfield, Cheshire, UK. McCully KS, Pathology and Laboratory Medicine Service, Veterans Affairs Boston Healthcare System. Associate Professor, Harvard Medical School, Boston, MA, Sultan S, Professor, Department of Vascular & Endovascular Surgery, National University of Ireland, Galway, Ireland. Sundberg R. Independent researcher, Stockholm, Sweden
no affiliation
22350 Lund, Sweden