Oxidative stress and paraoxonase 1 status in acute ischemic stroke patients.

OBJECTIVE: The connection of oxidative stress with dyslipidemia creates a newly-emerging atherosclerosis risk factor involved in acute ischemic stroke development. This study analyzed the influence of oxidative stress on structural changes of high-density lipoprotein (HDL) particles connected with modification in protective paraoxonase 1 (PON1) activity. METHODS: This study used 185 patients with acute ischemic stroke and 185 apparently healthy controls. Oxidative stress status, PON1 status, lipids and high-sensitivity C-reactive protein (hsCRP) were determined. In isolated HDL lipoprotein fraction we determined selected markers of oxidative stress (malondialdehyde, MDA) and the content of total sulfhydryl (SH) groups. The capability of oxidative and PON1 status parameters to discriminate patients according to survival status was evaluated. RESULTS: Stroke patients had lower HDL-cholesterol than controls and a remarkable fall in PON1 activity (control group-227U/L, survivors-42U/L, lethal outcome group-61U/L, p < 0.001), along with more prominent inflammation. Pronounced oxidative stress and impaired antioxidative protection was present among patients. HDL fraction analysis revealed a significant decrease of SH groups content (control group vs. patients, p < 0.05) and increased in MDA content in patients (lethal outcome vs. control group, p < 0.05). According to logistic regression analysis, the best predictor of disease outcome was oxidative stress marker - prooxidative-antioxidative balance (PAB). CONCLUSIONS: Pronounced oxidative stress in this group of acute ischemic stroke patients probably led to HDL structural changes, which could further cause an alteration or decrease of PON1 activity. Evidence of increased prooxidant level associated with decreased protective, antioxidative factors suggests their mutual involvement in this complex pathology.

LDL and HDL subclasses in acute ischemic stroke: prediction of risk and short-term mortality.

OBJECTIVE: Small, dense low-density lipoprotein (sdLDL) and small-sized high-density lipoprotein (HDL) particles are established risk factors for ischemic heart disease. However, their clinical significance for acute ischemic stroke (AIS) is uncertain. This study evaluates associations of LDL and HDL particle sizes and subclasses with AIS risk and short-term mortality after AIS. METHODS: Two hundred AIS patients hospitalised for first-in-a-lifetime stroke and 162 apparently healthy controls were included in the study. LDL and HDL particles were separated by gradient gel electrophoresis and serum lipid parameters were measured by standard laboratory methods. Baseline characteristics of LDL and HDL particles were evaluated for the prediction of AIS and short-term mortality after AIS. RESULTS: AIS patients had significantly more LDL III and IVb, but less LDL I and II particles. They also had significantly smaller HDL size, more HDL 3a, 3b and 3c and less HDL 2b subclasses. The relative content of both sdLDL and small-sized HDL particles was significantly increased in patients (P<0.001 and P<0.001, respectively). In addition, sdLDL was significantly higher in AIS fatalities (n=25) compared with survivors (n=175, P<0.05). Increased sdLDL was a significant predictor of AIS (OR=4.31; P<0.001) and in-hospital mortality after AIS (OR=5.50; P<0.05). The observed relationships persisted after adjustment for conventional risk factors. CONCLUSIONS: AIS is associated with adverse distributions of LDL and HDL subclasses. In addition, short-term mortality after AIS is associated with increased sdLDL particles. Our results indicate that sdLDL is an independent predictor of both AIS onset and consecutive short-term mortality.