Intended for healthcare professionals

CCBYNC Open access
Research

Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study

BMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k3359 (Published 05 September 2018) Cite this as: BMJ 2018;362:k3359

Linked Editorial

Primary prevention with statins for older adults

Re: Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study

We are not surprised over the lack of statin benefit among most of the participants in the study by Ramos et al.[1] because in a previous meta-analysis of 19 cohort studies of elderly people (≥60 years) including more than 68,000 individuals we found that those with the highest LDL-cholesterol lived the longest; none of the studies found the opposite. In the largest study the authors had also compared longevity among the statin-treated and the non-treated and found that the non-treated lived the longest.[2]

It is not possible to know whether the benefit among the oldest diabetics in the study by Ramos et al. was due to statin treatment without knowing how many of the patients had withheld the treatment, because several studies have shown that more than half of statin-treated patients stop the treatment.[3-5]

We think that our study [2] explains the benefit among the diabetics age 75-84 years in the study by Ramos et al. because the number with hypercholesterolemia was much higher among those on statin treatment than among the non-treated (53.4% vs 21.8%). That the benefit was due to statin treatment is unlikely because many studies have shown lack of an association between total or LDL-C and cardiovascular disease in diabetic patients.[6-18] In accordance, a systematic review of clinical trials have shown that cholesterol-lowering have been unable to reduce CVD mortality, all-cause mortality and cardiovascular events in type 2 diabetics.[19]

The findings by Ramos et al. are also in accordance with two recent reviews showing that LDL-C is not the cause of atherosclerosis and CVD,[20] not even among individuals with familiar hypercholesterolemia.[21]

References

1. Ramos R, Comas-Cufí M, Martí-Lluch R et al. Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study. BMJ 2018; 362. doi.org/10.1136/bmj.k3359
2. 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
3. Roberts WC. The underused miracle drugs: The statin drugs are to atherosclerosis what penicillin was to infectious disease. Am J Cardiol 1996;78:377-8.
4. Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA 2002;288:462-7.
5. Wisniowska B, Skowron A. Evaluation of patients' adherence to statins in Poland. Curr Med Res Opin 2011;27:99-105
6. Uusitupa MI, Niskanen LK, Siitonen O et al. 5-year incidence of atherosclerotic vascular disease in relation to general risk factors, insulin level, and abnormalities in lipoprotein composition in non-insulin-dependent diabetic and nondiabetic subjects. Circulation 1990 ;82:27-36.
7. Jarrett RJ. Risk factors for coronary heart disease in diabetes mellitus. Diabetes 1992;41:Suppl 2:1-3.
8. Laakso M, Lehto S, Penttilä I, Pyörälä K. Lipids and lipoproteins predicting coronary heart disease mortality and morbidity in patients with non-insulin-dependent diabetes. Circulation 1993;88:1421-30.
9. Simons LA, McCallum J, Friedlander Y, Simons J. Diabetes, mortality and coronary heart disease in the prospective Dubbo study of Australian elderly. Aust N Z J Med 1996;26:66-74.
10. Niskanen L, Turpeinen A, Penttilä I, Uusitupa MI. Hyperglycemia and compositional lipoprotein abnormalities as predictors of cardiovascular mortality in type 2 diabetes: a 15-year follow-up from the time of diagnosis. Diabetes Care 1998;21:1861-9.
11. Östgren CJ, Lindblad U, Melander A, Råstam L. Survival in patients with type 2 diabetes in a Swedish community: Skaraborg hypertension and diabetes project. Diabetes Care 2002;25:1297-302.
12. Solfrizzi V, Panza F, Colacicco AM et al. Relation of lipoprotein(a) as coronary risk factor to type 2 diabetes mellitus and low-density lipoprotein cholesterol in patients > or =65 years of age (The Italian Longitudinal Study on Aging). Am J Cardiol 2002;89:825-9.
13. Roselli della Rovere G, Lapolla A, Sartore G et al. Plasma lipoproteins, apoproteins and cardiovascular disease in type 2 diabetic patients. A nine-year follow-up study. Nutr Metab Cardiovasc Dis 2003;13:46-51.
14. Liu J, Sempos C, Donahue RP et al. Joint distribution of non-HDL and LDL cholesterol and coronary heart disease risk prediction among individuals wal.ith and without diabetes. Diabetes Care 2005 ;28:1916-21.
15. Zoppini G, Targher G, Negri C et al. Usefulness of the triglyceride to high-density lipoprotein cholesterol ratio for predicting mortality risk in type 2 diabetes: role of kidney dysfunction. Atherosclerosis 2010;212:287-91. doi: 10.1016/j.atherosclerosis.2010.04.035.
16. Hero C, Svensson AM, Gidlund P et al. LDL cholesterol is not a good marker of cardiovascular risk in Type 1 diabetes. Diabet Med 2016;33:316-23. doi: 10.1111/dme.13007.
17. Sharif S, van der Graaf Y, Nathoe HM et al. HDL cholesterol as a residual risk factor for vascular events and all-cause mortality in patients with type 2 diabetes. Diabetes Care 2016;39:1424-30. doi: 10.2337/dc16-0155.
18. Feng Q, Wei WQ, Chung CP et al. Relationship between very low low-density lipoprotein cholesterol concentrations not due to statin therapy and risk of type 2 diabetes: A US-based cross-sectional observational study using electronic health records. PLoS Med 2018;15:e1002642. doi: 10.1371/journal.pmed.1002642.
19. de Lorgeril M, Hamazaki T, Kostucki W et al. Is the use of cholesterol-lowering drugs for the prevention of cardiovascular complications in type 2 diabetics evidence-based? A systematic review. Rev Recent Clin Trials 2012;7:150-7.
20. Ravnskov U, de Lorgeril, Diamond DM et al. LDL-C does not cause cardiovascular disease: a comprehensive review of current literature. Exp Rev Clin Pharm doi: 10.1080/17512433.2018.1519391
21. Ravnskov U, de Lorgeril M, Kendrick M, Diamond DM. Inborn coagulation factors are more important cardiovascular risk factors than high LDL-cholesterol in familial hypercholesterolemia. Med Hypotheses 2018;121:60-3. doi.org/10.1016/j.mehy.2018.09.019

Competing interests: No competing interests

03 October 2018
Uffe Ravnskov
MD, PhD, independent researcher
Prof Sherif AH Sultan MD FRCS PhD
Not affiliated to any institution
Magle Stora Kyrkogata 8, 22350 Lund, Sweden