Physicians' Academy for Cardiovascular Education

Low LDL-c and TG levels associated with risk of hemorrhagic stroke in women

Lipid levels and the risk of hemorrhagic stroke among women

Literature - Rist PM, Buring JE, Ridker PM, et al., - Neurology 2019. DOI:

Introduction and methods

Although hypercholesterolemia is a risk factor for ischemic stroke, a meta-analysis observed that total and LDL cholesterol levels were inversely associated with the risk of hemorrhagic stroke. No association was seen for HDL-c [1]. Moreover, a meta-analysis of statin trials revealed that a 1 mmol/L reduction in LDL-c was associated with a 15% increased risk of hemorrhagic stroke [2]. Other studies suggested that low triglyceride (TG) levels may also increase hemorrhagic stroke risk [3-5].

Several questions regarding these observations remain unanswered. For instance, no sex-stratified data have been presented due to low numbers of events among women. The burden of stroke is, however, considered to be higher in women than in men [6]. It is therefore important to identify risk factors for stroke in women. Moreover, the association between lipid levels and stroke were not specified by hemorrhagic stroke subtypes. Finally, no distinction was made between individuals with elevated lipid levels and those with optimal or near optimal lipid levels.

This study evaluated the association between lipid levels (total cholesterol [TC], LDL-c, TG and HDL-c) and risk of hemorrhagic stroke in the large, prospective Women’s Health Study (WHS) [7,8]. WHS is a randomized, double blind, placebo-controlled trial of low-dose aspirin and vitamin E for the primary prevention of CV disease and cancer among 39876 US female health professionals of at least 45 years old. Lipid levels were determined in a blood sample taken prior to randomization, in 27937 samples. Strokes were classified as ischemic, hemorrhagic and unknown types. Hemorrhagic stroke was further divided into intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) or intraventricular hemorrhage (IVH). During a mean of 19.3 years of follow-up, 137 incident hemorrhagic strokes were reported (ICH: 85, SAH: 43 and 3 IVH, combination ICH/SAH: 3 and 3 due to a procedure).

Main results


In a large, prospective cohort of middle-aged to elderly women, an increased risk of hemorrhagic stroke was seen among those with LDL-c <70 mg/dL and a potential increase in risk among those with LDL-c ≥160 mg/dL. Low TG levels were also associated with a higher risk of hemorrhagic stroke, specifically the subarachnoid subtype. Total and HDL cholesterol were not significantly linked to the risk of hemorrhagic stroke. These findings suggest that women with very low LDL-c or TG levels should be monitored for other modifiable risk factors for hemorrhagic stroke, such as hypertension and smoking, to minimize their overall risk of hemorrhagic stroke.


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