Role of Blood Lipid Levels and Lipid-Lowering Therapy in Stroke Patients with Different Levels of Cerebral Artery Diseases: Reconsidering Recent Stroke Guidelines

Abstract

Hyperlipidemia is an important risk factor for ischemic stroke; the Stroke Prevention by Aggressive Reduction in Cholesterol Level and Treat Stroke to Target studies have shown that statins are beneficial for patients with stroke and that a low target for low-density lipoprotein cholesterol (LDL-C) concentration may maximize this benefit. Based on these results, recent guidelines have emphasized the application of “high-intensity statins” and “low LDL-C target” strategies in patients with stroke. However, it should be kept in mind that the role of blood lipids as a risk factor and benefit of lipid-lowering therapy are different among patients with different levels of cerebral arterial diseases. Studies have suggested that hypolipidemia, but not hyperlipidemia, is a risk factor for small vessel diseases (SVDs) such as intracerebral hemorrhages, microbleeds, white matter hyperintensities, and perhaps, lacunar infarction. Although lipid-lowering agents might benefit certain patients with SVD, high-intensity statin and low LDL-C target strategies cannot be applied. In contrast, these strategies are important in patients with extracranial atherosclerosis, such as internal carotid disease, considering ample evidence of the benefits of lipid-lowering agents. Imaging studies have shown that statins stabilize vulnerable plaques in these patients. Although lipid-lowering agents are likely to benefit patients with intracranial atherosclerosis, the degree of their benefit and appropriate target LDL-C level for these patients remain unclear. More studies are needed to elucidate the appropriate lipid-modifying strategies in patients with stroke with different levels of cerebral artery disease.

Association Between Intensity of Low-Density Lipoprotein Cholesterol Reduction With Statin-Based Therapies and Secondary Stroke Prevention

“…The heterogeneity of causes of index stroke, as well as recurrent stroke, may be 1 major factor associated with such a phenomenon. The benefits associated with LDL-C–lowering statin-based therapies vary among patients with stroke owing to the different causes, and there are concerns that such a strategy may not be universally beneficial to all patients with ischemic stroke . We found that more intensive LDL-C–lowering statin-based therapies were associated with a reduced risk of recurrent stroke only in trials with all patients having evidence of atherosclerosis.…”

“…One included trial performed in Japan comparing pravastatin, 10 mg daily, with placebo did not show a reduction in the risk of recurrent stroke . In the TST Trial, although the lower-target strategy was superior to the higher-target strategy in the French population, the benefit of the lower target was not shown for either major cardiovascular events or in recurrent stroke when South Korean patients were analyzed separately . Because the risk of recurrent stroke was not reduced by LDL-C–lowering statin-based therapies in randomized clinical trials of Asian populations, it is therefore not known whether the benefit associated with more intensive LDL-C–lowering statin-based therapies for secondary stroke prevention should be generalized to Asian populations.…”

The Underlying Role of the Glymphatic System and Meningeal Lymphatic Vessels in Cerebral Small Vessel Disease

“…The metabolic disturbance of blood lipids as well-established vascular factors seemed to have a potential role in small vessel disease, especially high-density lipoprotein [ 39 ]. Lipid-modifying therapies have shown benefits in the prevention of ischaemic small vessel disease and leukoaraiosis [ 50 ]. The apolipoprotein E(APOE) as the main carrier regulated the transport and metabolism of cholesterol in the periphery and CNS, and APOE polymorphism was strongly related to neurodegeneration and dementia [ 51 ].…”

Deep learning-based automatic classification of ischemic stroke subtype using diffusion-weighted images

“…Guidelines for secondary prevention of stroke underscore a tailored therapeutic approach based on stroke subtypes, 25,26 recommending strict blood pressure management for SVO strokes, 27 intensive antiplatelet and lipid-lowering therapy for LAA strokes, [28][29][30][31] and anticoagulant therapy for CE strokes. 32 However, a quarter of strokes are classified as embolic stroke with undetermined source (ESUS).…”