The relationship between lipid-lowering medication and non-healthy status – Authors' reply
Authors: Tuija M Mikkola, Hannu Kautiainen, Johan G Eriksson
Journal: The Lancet Healthy Longevity (2024)

We thank Yangyan Wei and colleagues for their interest in our study.1Mikkola TM Kautiainen H von Bonsdorff MB et al.Healthy ageing from birth to age 84 years in the Helsinki Birth Cohort Study, Finland: a longitudinal study.Lancet Healthy Longev. 2023; 4: e499-e507Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar They commented on the finding that people experiencing healthy ageing were less likely to have used lipid-lowering medication in late midlife than those not experiencing health ageing. They state that “this result does not seem to be consistent with the protective effect of lipid-lowering drugs on patients with cardiovascular and cerebrovascular disease”. We fully agree that patients with a history of cardiovascular or cerebrovascular disease experience the protective effect of lipid-lowering drugs, and we agree with the comments by Wei and colleagues in the context of studies focusing on cardiovascular disease. However, our cohort did not consist of patients with cardiovascular or cerebrovascular disease. As our cohort study focused on a broad concept, healthy ageing, and not on specific diseases, the study was not designed to consider disease-specific confounders. Therefore, the finding that participants who used lipid-lowering drugs were more likely to be non-healthy than those not using lipid-lowering drugs can be explained by the fact that the users already had poor cardiovascular health in late midlife and were therefore prescribed lipid-lowering medication. We presented the finding as it appeared in our analysis, and we did not draw any conclusions on it in the published paper because that was not our main focus. The protective effect of low total cholesterol is not clear in older populations. The longitudinal Swedish AMORIS cohort study—which has a 35-year follow-up period—has shown that high total cholesterol is associated with reaching age 100 years.2Murata S Ebeling M Meyer AC Schmidt-Mende K Hammar N Modig K Blood biomarker profiles and exceptional longevity: comparison of centenarians and non-centenarians in a 35-year follow-up of the Swedish AMORIS cohort.Geroscience. 2023; (published online Sept 19.)https://doi.org/10.1007/s11357-023-00936-wGoogle Scholar Further, cross-sectional studies have shown that centenarians have lower total cholesterol than people aged around 70 years.3Barzilai N Atzmon G Schechter C et al.Unique lipoprotein phenotype and genotype associated with exceptional longevity.JAMA. 2003; 290: 2030-2040Crossref PubMed Scopus (502) Google Scholar However, biomarkers (including lipids) change with age, and drawing conclusions from cross-sectional studies is therefore difficult. We feel that our findings from a longitudinal study could also be supported by the findings from the Swedish AMORIS cohort study. Furthermore, total cholesterol is a rather crude measure, and does not take lipoprotein particle size into account. Increased particle sizes for both high-density and low-density lipoproteins has been associated with longevity.3Barzilai N Atzmon G Schechter C et al.Unique lipoprotein phenotype and genotype associated with exceptional longevity.JAMA. 2003; 290: 2030-2040Crossref PubMed Scopus (502) Google Scholar TMM has received research grants from Medicinska Understödsföreningen Liv och Hälsa. JGE has received funding for the submitted work from the Signe and Ane Gyllenberg Foundation, Samfundet Folkhälsan, Finska Läkaresällskapet, Medicinska Understödsföreningen Liv och Hälsa, the European Commission within the Seventh Framework Programme, the EU Horizon 2020 programme, and the Academy of Finland. HK declares no competing interests.