Safeguarding Against Stroke Risk by Statins.

Whereas mighty prospective randomized trials—and meta-analyses of these—rightly command the data used to drive guidelines and daily clinical practice, careful long-term follow-up of closely monitored cohorts can generate crucial discoveries not anticipated in a 5-year study. As just one example, findings from lifelong follow-up in the American Framingham studies and the Whitehall cohorts in the United Kingdom show a strong association between blood pressure in middle years and dementia in later life. Such linkage was never expected when these ultra-long-term follow-up groups were recruited. In their excellent study of 6387 people aged 75 years and older, with up to 15-year follow-up, Lin and colleagues1Lin Z. Chen Y. Xiao Z. et al.Incremental benefit of lipid lowering in a large chinese population 75 years and older with established atherosclerotic cardiovascular disease.Mayo Clin Proc. 2023; 98: 1280-1296Google Scholar provide important insights of benefits—with one caveat—of long-term statin use in a Chinese population. Stroke is a much more common cause of death than myocardial infarction (MI) among older Chinese people. Indeed, in this study, 1518 strokes and 515 MIs occurred during the 15 years of follow-up. And among older people of every nation, a nonfatal MI may be an inconvenience, whereas a nonfatal stroke is often a catastrophe. So the present study by Lin et al provides important determinations with regard to the safety, benefit, and efficacy of statin therapy for individuals older than 75 years. The evidence for reduction in heart attack and cardiac death in younger individuals is robust and incontrovertible. Yet for primary prevention of heart attack and stroke in older people, the data are less secure. For example, in their 2022 statement, the US Preventive Services Task Force recommended statins for primary prevention—including stroke—for 40- to 75-year-old people but not for older populations.2Mangione C.M. Barry M.J. Nicholson W.K. et al.US Preventive Services Task ForceStatin Use for the Primary Prevention of Cardiovascular Disease in Adults: US Preventive Services Task Force Recommendation Statement.JAMA. 2022; 328: 746-753Crossref PubMed Scopus (40) Google Scholar In their JAMA publication, the authors state, “…current evidence is insufficient to assess the balance of benefits and harms of initiating a statin for the primary prevention of CVD events and mortality in adults 76 years and older.” Therefore, the study of Lin et al is particularly apposite, particularly because of the benefits in protection against stroke. Of the 6387 patients enrolled in the study, about 80% had overt cardiac disease and 20% prior stroke. The benefits of statin therapy in secondary prevention of atheromatous cardiac disease are well established, likewise for secondary prevention after ischemic stroke. What Lin’s study shows (Supplemental Figures 7 and 8) is that there was substantial protection against stroke in people without previous cerebrovascular disease. Indeed, the protection offered by more powerful lipid lowering was if anything greater among those who had not had a previous stroke. This is a crucial finding and, in my view, the most important result from this fine study. It cannot be determined, of course, whether the people with lower achieved cholesterol levels—presumably with more attendances at their physician—had better control of blood pressure and diabetes than patients with higher cholesterol levels. This likely would influence stroke events. Yet in a way this does not matter: if treating older people with lipid-lowering drugs means more visits to their physician, nurse, or pharmacist with a big reduction on stroke (and heart attack), then such a finding emphasizes the importance of follow-up with health care professionals. A less welcome finding from this survey was that very low achieved low-density lipoprotein (LDL) cholesterol levels below 40 mg/dL (to convert to mmol/L, multiply by 0.0259) seemed to increase the risk of hemorrhagic stroke. This was a small group of people, accounting for 6% of the study population, and so the authors suggest that a target LDL of about 40 to 75 mg/dL might be best. However, a large Danish study published very recently showed no evidence of elevated risks of a cerebral bleed at any level of statin intensity, and indeed there appeared to be protection from intracerebral hemorrhage with longer duration of therapy.3Boe N.J. Hald S.M. Jensen M.M. et al.Association between statin use and intracerebral hemorrhage location—a nested case-control registry study.Neurology. 2023; 100: e1048-e1061Crossref Scopus (1) Google Scholar Pragmatically, achieving ultralow LDL levels seems more difficult in Western populations than in Lin’s study population, so a target LDL between 40 and 80 mg/dL seems reasonable. For young people with premature coronary atheroma—all too commonplace in many societies—my view remains to treat cholesterol aggressively because even reaching the age of 75 years for such individuals would be an achievement. And what about dementia? In this survey, cognitive impairment developed in only about 10% of the study population (Supplemental Figure S3), and there appeared to be no benefit from more aggressive cholesterol lowering. Of course, there was no control group without statins to compare with, so we still do not know. We can still hope. So what does Lin’s study add? Treating cholesterol in a large older population has marked benefits, most especially against stroke in people without prior cerebrovascular disease. Should national and international guidelines consider recommending statins for healthy older people to prevent ischemic stroke? For those with high LDL, certainly. For everyone else—maybe. Incremental Benefit of Lipid Lowering in a Large Chinese Population Aged 75 Years and Older With Established Atherosclerotic Cardiovascular DiseaseMayo Clinic ProceedingsVol. 98Issue 9PreviewTo explore the optimal low-density lipoprotein cholesterol (LDL-C) level in patients aged 75 years and older with established atherosclerotic cardiovascular disease (ASCVD). Full-Text PDF