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Covid-19: a remote assessment in primary care

BMJ 2020; 368 doi: (Published 25 March 2020) Cite this as: BMJ 2020;368:m1182

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Cholesterol-lowering treatment may be a major cause of serious Covid-19 infections

Dear Editor

Most researchers consider the association between low cholesterol and infection as reverse causality, meaning that it is the microorganisms or the inflammation which lower cholesterol. However, there is much evidence that the explanation is that low cholesterol predisposes to infection because, as I have mentioned in a previous comment (1), there is solid evidence that LDL partakes in the immune system by adhering to and inactivating almost all kinds of microorganisms and their toxic products (2). In accordance is a study of hospitalized patients with various types of infectious diseases, where those with the lowest LDL-C measured previously had the largest risk of developing sepsis and where the risk was highest among those on statin treatment (3).

As mentioned by Matteo Pirro (4) the authors of several studies have claimed that patients who have been prescribed statin treatment have a lower risk of infectious diseases. However, these studies have a serious bias, because the authors have not investigated whether the patients have continued the treatment. Therefore, the benefit may instead have been due to their high cholesterol because several studies have found that 40-80% of all statin-treated patients stop their treatment by themselves probably because statin treatment may cause many serious side effects (6,7). Thus, in the papers mentioned by Pirro the authors have compared people who may have had high cholesterol most of their life with untreated people, most of whom may have had normal or low cholesterol.

As mentioned by Pirro as well, no one has studied whether people with familial hypercholesterolemia (FH) are protected against infections. However, in a review of eight preliminary cholesterol-lowering trials using a PCSK9-inhibitor as treatment of hypercholesterolemic people, many of whom had FH, common adverse events were nasopharyngitis, upper respiratory tract infections and influenza (8).

That high cholesterol may be protective is evident because in a meta-analysis of 19 studies where the authors had followed more than 68,000 elderly people for several years, most of those with the highest LDL-cholesterol lived the longest. None of the studies found the opposite and after the publication of this analysis, at least eight studies including almost 700,000 individuals have come up with the same result (10-17).

There are therefore good reasons to stop statin treatment of patients with severe Covid-9 infection, also because at least 20 statin trials have been unable to lower mortality with statistical significance (7) and because more than 20% of statin-treated people suffer from serious side effects (6,7).

1. Ravnskov U. Cholesterol-lowering treatment may worsen the outcome of a Covid-19 infection. BMJ 2020;368:m1182.
2. 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
3. Guirgis FW, Donnelly JP, Dodani S et al. Cholesterol levels and long-term rates of community-acquired sepsis. Crit Care. 2016;20:408
4. Pirro M. Cholesterol and cholesterol-lowering in COVID-19: why we should not let our guard down.
5. Diamond DM, de Lorgeril M, Kendrick M, Ravnskov U, Rosch PJ. Formal comment on “Systematic review of the predictors of statin adherence for the primary prevention of cardiovascular disease”. PLoS ONE 2019;14: e0205138. pone.0205138.
6. Diamond DM, Ravnskov U. How statistical deception created the appearance that statins are safe and effective in primary and secondary prevention of cardiovascular disease. Exp Rev Clin Pharmacol. 2015;8:201–210. doi: 10.1586/17512433.2015.1012494
7. Ravnskov U, de Lorgeril M, Diamond DM et al. LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature. Exp Rev Clin Pharm. 2018;11:959–970.
8. Farnier M, Gaudet D, Valcheva V, Minini P, Miller K, Cariou B. Efficacy of alirocumab in high cardiovascular risk populations with or without heterozygous familial hypercholesterolemia: Pooled analysis of eight ODYSSEY Phase 3 clinical program trials. Int J Cardiol 2016;223:750-7. doi: 10.1016/j.ijcard.2016.08.273.
9. 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
10. You S, Zhong C, Xu J et al. LDL-C/HDL-C ratio and risk of all-cause mortality in patients with intracerebral hemorrhage. Neurol Res. 2016;38:903-908. doi: 10.1080/01616412.2016.1204797
11. Park C H, Kang EW, Park JT et al. Association of serum lipid levels over time with survival in peritoneal dialysis patients. J Clin Lipidol. 2017;11(4):945-54. doi: 10.1016/j.jacl.2017.06.004.
12. Ahn C, Hwang Y, Park SK. Predictors of all-cause mortality among 514,866 participants from the Korean National Health Screening Cohort. PLoS One. 2017;12(9):e0185458. doi: 10.1371/journal.pone.0185458.
13. Zuliani G, Volpato S, Dugo M, Vigna GB, Morieri ML, Maggio M, et al. Combining LDL-C and HDL-C to predict survival in late life: The InChianti study. PLoS One. 2017;12(9): e0185307.
14. Orozco-Beltran D, Gil-Guillen VF, Redon J et al. Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: The ESCARVAL-RISK study. PLoS One. 2017;12:e0186196. doi: 10.1371/journal.pone.0186196. Berton 589
15. Wang M-C, Hu H-Y, Lin I-F, Chuang J-T. Plasma lipid concentrations and survival in
geriatric population. A retrospective cohort study. Medicine. 2019;98:49(e18154).
16. Yousufuddin M, Takahashi PY, Major B et al. Association between hyperlipidemia and mortality after incident acute myocardial infarction or acute decompensated heart failure: a propensity score matched cohort study and a meta-analysis. BMJ Open. 2019;9:e028638. doi:10.1136/bmjopen-2018-028638
17. Dégano IR, Ramos R, Garcia-Gil. Three-year events and mortality in cardiovascular disease patients without lipid-lowering treatment. Eur J Prev Cardiol. 2019 doi: 10.1177/2047487319862103
18. Ravnskov U, de Lorgeril M, Diamond DM et al. LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature. Exp Rev Clin Pharm. 2018;11:959–70.

Competing interests: No competing interests

04 May 2020
Uffe Ravnskov
independent researcher
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Magle Stora Kyrkogata 9, 22350 Lund, Sweden