Lipid Paradox in Statin-Naïve Acute Ischemic Stroke But Not Hemorrhagic Stroke

Something is important in here but I have no clue. 

Lipid Paradox in Statin-Naïve Acute Ischemic Stroke But Not Hemorrhagic Stroke 

Kai-Hung Cheng^1,2, Jr-Rung Lin³, Craig S. Anderson^4,5, Wen-Ter Lai^1,2, Tsong-Hai Lee^6* and the SRICHS Group^†

• ¹Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
• ²Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
• ³Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Taoyuan, Taiwan
• ⁴Neurological and Mental Health Division, The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia
• ⁵Neurology Department, Royal Prince Alfred Hospital, Sydney, NSW, Australia
• ⁶Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan

Background: Low lipid level is associated with better cardiovascular outcome. However, lipid paradox indicating low lipid level having worse outcomes could be seen under acute injury in some diseases. The present study was designed to clarify the prognostic significance of acute-phase lipid levels within 1 day after admission for stroke on mortality in first-ever statin-naïve acute ischemic stroke (IS) and hemorrhagic stroke (HS).

Methods: This observational study was conducted using the data collected from Stroke Registry In Chang-Gung Healthcare System (SRICHS) between 2009 and 2012. Patients with recurrent stroke, onset of symptoms >1 day, and history of the use of lipid-lowering agents prior to index stroke were excluded. Stroke was classified into IS and hypertension-related HS. The primary outcomes were 30-day and 1-year mortality identified by linkage to national death registry for date and cause of death. Receiver operating characteristic (ROC) curve analysis and multivariate Cox proportional hazard models were used to examine the association of lipid profiles on admission with mortality.

Results: Among the 18,268 admitted stroke patients, 3,746 IS and 465 HS patients were eligible for analysis. In IS, total cholesterol (TC) <163.5 mg/dL, triglyceride (TG) <94.5 mg/dL, low-density lipoprotein (LDL) <100 mg/dL, non-high-density lipoprotein cholesterol (non-HDL-C) <130.5 mg/dL, and TC/HDL ratio <4.06 had significantly higher risk for 30-day/1-year mortality with hazard ratio (HR) of 2.05/1.37, 1.65/1.31, 1.68/1.38, 1.80/1.41, and 1.58/1.38, respectively, compared with high TC, TG, LDL, non-HDL-C, and TC/HDL ratio (p < 0.01 in all cases). In HS, lipid profiles were not associated with mortality, except HDL for 30-day mortality (p = 0.025) and high uric acid (UA) concentrations for 30-day and 1-year mortality (p = 0.002 and 0.012, respectively). High fasting glucose and high National Institute of Health Stroke Scale (NIHSS) score at admission were associated with higher 30-day and 1-year mortality in both IS and HS and low blood pressure only in IS (p < 0.05). Synergic effects on mortality were found when low lipids were incorporated with high fasting glucose, low blood pressure, and high NIHSS score in IS (p < 0.05).

Conclusions: Lipid paradox showing low acute-phase lipid levels with high mortality could be seen in statin-naïve acute IS but not in HS. The mortality in IS was increased when low lipids were incorporated with high fasting glucose, low blood pressure, and high NIHSS score.

Introduction

The concept of “the lower the cholesterol, the better the outcome” is suggested for the prevention of cardiovascular events (1); however, there is inconsistent or weak association in the metabolic significance of lipids with stroke. Statin can lower cholesterol concentrations and help to reduce stroke risk in high-risk populations and in patients with non-cardioembolic stroke or transient ischemic attack (2). If statin therapy is discontinued between 3 and 6 months after an index ischemic stroke (IS), there is an increased risk of recurrent stroke within 1 year after statin discontinuation (3). High serum total cholesterol (TC) levels represent a risk factor of IS in Western countries, but it was found to be a risk factor mainly for large-artery occlusive infarction in Japanese men and not for lacunar or embolic infarction in either sex (4). The epidemiological studies in Eastern Asians have shown significantly inverse association between serum cholesterol and the risk of intracerebral hemorrhage (5–10). A recent community study in Japan found that high-density lipoprotein (HDL) levels had an inverse relationship with the incidence of lacunar infarction but a positive association with the risk of hemorrhagic stroke (HS), mainly in women (11). Lipid levels may be different between HS patients and non-HS controls, but a decline in serum TC and low-density lipoprotein (LDL) levels can be found within 6 months prior to primary HS, independent of statin treatment (12). These alterations in serum lipid trends may suggest a biological pathway to induce HS occurrence. However, the study of acute-phase lipid on stroke outcome is rare, and it is advised that further studies are needed to confirm the level of acute-phase lipid as a potential biomarker for brain injury.

The plasma concentration of LDL may increase with age, mainly as the result of reduced clearance of LDL and reduced conversion of cholesterol to bile acids with age (13), so it is likely that lipids may have more influence on the elderly than on young patients. Also, our previous study (14) has shown that the stroke etiology is different between young and elderly patients, and strokes of other determined etiology and undetermined etiology are the most common types among young stroke patients. As lipids may be involved in the progression of atherosclerosis, which is the most common stroke etiology in elderly patients, it is likely that lipids may play a more significant role in elderly stroke patients.

Reverse epidemiology or risk factor paradox has been mentioned in the case of body mass index, serum cholesterol, and blood pressure in elderly population (15, 16). However, there are limited outcome studies of acute-phase lipid in cerebrovascular and cardiovascular diseases. The present study intends to determine the association of acute-phase lipid levels within 1 day after admission for stroke, with short-term and long-term mortality in statin-naïve elderly Han-Chinese stroke patients with first-ever acute IS and HS.