A newly published scientific statement from the American Heart Association (AHA) focuses on the impact of aggressive low-density lipoprotein cholesterol (LDL-C) lowering on the risk for dementia and hemorrhagic stroke.
“The brain is the body’s most cholesterol-rich organ, and some have questioned whether aggressive LDL-C lowering induces abnormal structural and functional changes,” the writing group, led by Larry Goldstein, MD, chair, Department of Neurology, University of Kentucky, Lexington, points out.
The 39-page AHA scientific statement, titled “Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke,” was published online September 14 in the journal Arteriosclerosis, Thrombosis, and Vascular Biology.
Their objective was to evaluate contemporary evidence that either supports or refutes the conclusion that aggressive LDL-C lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment or dementia or hemorrhagic stroke.
The eight-member writing group used literature reviews, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize the latest evidence and identify gaps in current knowledge.
They reached four main conclusions.
First, the available data “consistently” show that LDL-C lowering reduces the risk of atherosclerotic cardiovascular disease-related events in high-risk groups.
Second, although some older retrospective, case-control, and prospective longitudinal studies suggest that statins and LDL-C lowering are associated with cognitive impairment or dementia, the “preponderance” of observational studies and data from randomized trials do not support this conclusion, at least among trials with median follow-up of up to 6 years. The group says additional studies are needed to ensure cognitive safety over longer periods of time. For now, contemporary guidelines recommending the risk-stratified attainment of lipid-lowering goals are “reasonable,” they conclude.
Third, the risk for hemorrhagic stroke associated with statin therapy in patients without a history of cerebrovascular disease is “small and consistently nonsignificant.” They found no evidence that PCSK9 inhibitors or ezetimibe (Zetia) increases bleeding risk. Further, there is “no indication” that patients or populations with lifelong low LDL-C have enhanced vulnerability to hemorrhagic stroke, and there is “little evidence” that achieving very low levels of LDL-C increases that risk. What is clear, the writing group says, is that lower LDL-C levels correlate with lower risk of overall stroke and stroke recurrence, mostly related to a reduction in ischemic stroke. “Concern about hemorrhagic stroke risk should not deter a clinician from treating LDL-C to guideline-recommended risk-stratified targets,” the writing group says.
Fourth, the group notes that data reflecting the risk of hemorrhagic stroke with statin therapy among patients with a history of hemorrhagic stroke are not robust. PCSK9 inhibitors have not been adequately tested in patients with prior ICH. Lipid lowering in these populations requires more focused study.
The research had no commercial funding. A list of disclosures for the writing group is available with the original article.
Arterioscler Thromb Vasc Biol. Published online September 14, 2023. Abstract