Commentary: Statins for secondary prevention after coronary artery bypass grafting: Pleiotropic effects and dementia risk

Abstract

Central MessageStatins are essential secondary prevention after CABG, but new research suggests we should investigate potential pleiotropic effects and their impact on the risk of dementia.See Article page 1875. In this issue, Pan and colleagues1Pan E. Nielsen S.J. Mennander A. Björklund E. Martinsson A. Lindgren M. et al.Statins for secondary prevention and major adverse events after coronary artery bypass grafting.J Thorac Cardiovasc Surg. 2022; 164: 1875-1886.e4Scopus (4) Google Scholar present a study using population-based data from the SWEDEHEART registry to report on the impact of statins on major adverse events after coronary artery bypass grafting (CABG). Their results demonstrate decisively that the use of statins is associated with a decreased risk of all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, the need for new revascularization or angiography, and, interestingly, dementia. These effects were observed in both men and women, and in those younger than and older than 75 years of age, and were not dependent on whether patients were taking high-, intermediate- or low-dose statins. The effect of statins is fundamentally based on their ability to inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A, reducing endogenous plasma cholesterol synthesis in the liver.2Stancu C. Sima A. Statins: mechanism of action and effects.J Cell Mol Med. 2001; 5: 378-387Crossref PubMed Scopus (531) Google Scholar What we commonly forget is that these drugs have many other pleiotropic effects; statins not only directly affect lipid metabolism but also complex intracellular signaling pathways. It is well-known they increase endothelial nitric oxide synthetase production, reduce multiple inflammatory processes, stabilize atherosclerotic plaques, and restore platelet activity and anticoagulation processes.2Stancu C. Sima A. Statins: mechanism of action and effects.J Cell Mol Med. 2001; 5: 378-387Crossref PubMed Scopus (531) Google Scholar,3Oesterle A. Laufs U. Liao J.K. Pleiotropic effects of statins on the cardiovascular system.Circ Res. 2017; 120: 229-243Crossref PubMed Scopus (584) Google Scholar Because of these effects, it is not surprising that, when tolerated, these medications will exert a very significant effect on major adverse cardiovascular events and survival for patients' cardiovascular disease, including those who have undergone CABG. In this case as in so many others, understanding the pharmacologic mechanisms using the tools of basic and translational science help inform our interpretations of clinical and registry database studies, and vice versa. Perhaps one of the most novel findings of the paper by Pang and colleagues1Pan E. Nielsen S.J. Mennander A. Björklund E. Martinsson A. Lindgren M. et al.Statins for secondary prevention and major adverse events after coronary artery bypass grafting.J Thorac Cardiovasc Surg. 2022; 164: 1875-1886.e4Scopus (4) Google Scholar was the finding of a negative association between statin use and dementia. This finding is interesting but must be interpreted with caution in the setting of this study and its methodology. Published studies have correlated cardiovascular health and neurocognitive impairment (dementia), and therefore it is reasonable to observe that drugs used for secondary prevention of cardiovascular events could also impact neurovascular health. However, at least one meta-analysis has failed to find significant evidence that statins reduce the risk of dementia.4McGuinness B. Craig D. Bullock R. Passmore P. Statins for the prevention of dementia.Cochrane Database Syst Rev. 2016; 1: CD003160Google Scholar This is an area that is in need of additional research, including basic science studies to more clearly elucidate the potential pleiotropic mechanisms of statins, and prospective clinical trials and retrospective registry studies to more clearly describe any associations with dementia and other neurocognitive impairments. In this instance, the results of a large study of the SWEDEHEART registry evaluating the secondary preventive effects of statins found an interesting association between statin use and a decreased risk of dementia, but the most relevant clinical information to be derived from this study is the tremendous benefits of statins for the secondary prevention after CABG and the need for surgeons, cardiologists, and primary care providers to ensure patients can be maintained on these essential medications to reap the long-term benefits. Statins for secondary prevention and major adverse events after coronary artery bypass graftingThe Journal of Thoracic and Cardiovascular SurgeryVol. 164Issue 6PreviewThe objective of this study was to evaluate the association of statin use after coronary artery bypass grafting (CABG) and long-term adverse events in a large population-based, nationwide cohort. Full-Text PDF Open Access