Abstract
Excessive levels of low-density lipoprotein cholesterol (LDL-C) in the blood are a known risk factor for atherosclerosis, and a common target of treatment for primary and secondary prevention of cerebrocardiovascular disease. As lipid lowering agents including statins, ezetimibe and anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have shown good therapeutic results, the guidelines are constantly lowering the “optimal” LDL-C goals. However, old and new data point towards an association between low LDL-C and total cholesterol and intracerebral hemorrhage (ICH). In this review we aimed to shed light on this troubling association and identify the potential risk factors of such a potential adverse reaction. With respect to the data presented, we concluded that in patients with high risk of ICH, a cautious approach and individualized therapy strategy are advised when considering aggressive LDL reduction.
Highlights
Intracerebral hemorrhage (ICH), a sub-type of stroke, is a condition whereby a hematoma is formed within the brain parenchyma, and it is associated with a high mortality and disability rate [1,2,3]
It has been proposed that low cholesterol results in greater fragility of endothelial cells, which contributes to hematoma extension and slower repair of small intracerebral hemorrhages [4,5]
This review focused on the complex interplay between low levels of low-density lipoprotein (LDL) cholesterol and the risk of ICH, taking into account the need to lower LDL cholesterol for therapeutic purposes
Summary
Over the past two decades, several studies have examined the association between low levels of cholesterol and the risk of ICH. Lower LDL-C concentration was associated with a higher risk of hemorrhagic stroke (RR 0.62, 95% CI 0.41–0.92). A recent Korean study showed that both total cholesterol and LDL-C levels were lower in those with CMBs compared with those without such MRI findings [12]. Other prospective studies have not demonstrated the same association between low LDL-C and ICH or hemorrhagic stroke [13,14,15,16]. 9068 stroke-free participants aged ≥55 were followed for up to 20 years, demonstrated that low triglycerides were strongly associated with ICH, and with the presence of deep or infratentorial CMBs on MRI; no associations were found for HDL-cholesterol or LDL-C [13]. These studies were based on a single baseline LDL-C measurement, which could underestimate the association between LDL-C and ICH risk because of normal fluctuations and changes in LDL-C concentrations over time, due to the initiation of lipid-lowering therapy
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