Large Artery Atherosclerotic Research Articles

Polymorphisms of DNA Repair Pathway Genes and Cigarette Smoking in Relation to Susceptibility to Large Artery Atherosclerotic Stroke among Ethnic Chinese in Taiwan

Cigarette-smoking induced oxidative DNA damage to endothelial cells has been reported to play an etiological role in atherosclerosis development. Individual vulnerability to oxidative stress through smoking exposure and the ability to repair DNA damage, which plays a critical role in modifying the risk susceptibility of large artery atherosclerotic (LAA) stroke, is hypothesized. Thus, we examined the effect of genetic polymorphisms of DNA repair pathway genes and cigarette smoking in relation to risk susceptibility of LAA stroke. We enrolled 116 LAA stroke patients and 315 healthy controls from the Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan. Genotyping of polymorphisms of the OGG1 (Ser326Cys), XRCC1 (Arg399Gln), ERCC2 (Lys751Gln), and ERCC5 (Asp1104His) genes was performed and used to evaluate LAA stroke susceptibility. Of those non-synonymous polymorphisms, the ERCC2 Lys751Gln variant was found to be associated with LAA stroke risk (OR: 1.69, 95%CI: 1.02-2.86), and this association was more pronounced in smokers, manifesting a 2.73-fold increased risk of LAA stroke (p=0.027). A joint effect on risk elevation of LAA stroke was seen in those patients with OGG1 and ERCC2 polymorphisms (OR: 2.75, 95%CI: 1.26-6.00). Moreover, among smokers carrying the OGG1 Ser326Cys polymorphism, there was a tendency toward an increased risk of LAA stroke in those patients who had a greater number of high-risk genotypes of XRCC1, ERCC2, and ERCC5 polymorphisms (p(trend)=0.010). The susceptible polymorphisms of DNA repair pathway genes may have a modifying effect on the elevated risk of LAA stroke in smokers among ethnic Chinese in Taiwan.

Elevated serum lipoprotein(a) as a potential predictor for combined intracranial and extracranial artery stenosis in patients with ischemic stroke

Objectives Despite compelling evidence of lipoprotein(a) [Lp(a)] as a risk factor for ischemic stroke, its underlying mechanism remains unclear. Our aim is to investigate whether serum Lp(a) level is associated with the extent and location of cerebral steno-occlusive lesions, and with large artery atherosclerotic (LAA) stroke in Korean patients. Methods We analyzed data prospectively collected over a 3-year period on consecutive patients with stroke or TIA. Based on an angiographic study, a total of 1012 patients were classified into four subtypes: non-cerebral stenosis ( n = 654), intracranial stenosis ( n = 198), extracranial carotid stenosis ( n = 86), and combined intracranial and extracranial carotid stenosis ( n = 74). Independent associations of Lp(a) levels with the extent and location of cerebral stenosis were evaluated, and Lp(a) levels of subtypes by the TOAST criteria were compared. Results Lp(a) levels of LAA stroke were significantly higher than those of the other four stroke mechanisms. Patients with more advanced intracranial ( p = 0.001) and extracranial carotid stenoses ( p = 0.001) tended to have higher Lp(a) levels. In multiple regression analysis, the third Lp(a) quartile was the strongest risk factor for isolated intracranial (OR 3.36, 95% CI 1.77–6.37) or extracranial stenosis (OR 4.82, 95% CI 1.96–11.88), whereas the fourth Lp(a) quartile was the most powerful predictor for combined intracranial and extracranial carotid stenosis (OR 4.98, 95% CI 1.92–12.91). Conclusions Our results indicate that greatly elevated Lp(a) levels are associated with LAA stroke and extensive burden of cervicocerebral steno-occlusive lesions, which might offer indirect evidence of proatherothrombogenic role of Lp(a) in ischemic stroke.

Impact of metabolic syndrome on distribution of cervicocephalic atherosclerosis: Data from a diverse race-ethnic group

BackgroundVascular localization of symptomatic large artery atherosclerotic (LAA) stroke differs for unknown reasons by race-ethnicity. The metabolic syndrome (MetSD) is associated with higher atherosclerotic stroke risk and comprises abnormal risk factors that can vary by race. Thus, we investigated whether MetSD may contribute to race-ethnic differences in LAA stroke by examining the association of MetSD with symptomatic intra- and extracranial atherosclerosis among a diverse race-ethnic group. MethodWe analyzed data prospectively collected over a 4-year period on subjects with ischemic stroke/TIA. Independent vascular risk factor associations with intracranial and extracranial LAA vs. non-LAA mechanism were evaluated in two groups stratified by race-ethnicity; whites and non-whites (Hispanics, African-American, and Asian-American). Results1167 patients met study criteria. Intracranial LAA was more prevalent in non-whites vs. whites (20.4% vs. 9.6%, P<0.001), while extracranial LAA had a more frequent point value in whites compared to non-whites (10.7% vs. 7.5%, P=0.267). The presence of MetSD was more prevalent in both intracranial and extracranial LAA group than in non-LAA group: no significant differences were observed in the prevalence of MetSD between intra vs. extracranial LAA or whites vs. non-whites. However, with increasing numbers of abnormal metabolic components, whites were more likely to have experienced extracranial LAA, whereas non-whites were more likely to have experienced intracranial LAA. After adjusting for covariates, MetSD was associated with extracranial LAA in whites (OR, 1.98; 95% CI, 1.13–3.45), while there was a tendency that intracranial LAA was associated with MetSD in non-whites (OR, 1.80; 95% CI, 0.97–3.32). No association was found between MetSD and extracranial LAA in non-whites and between this syndrome with intracranial LAA in whites. ConclusionsOur results showed that the impact of MetSD on the distribution of cervicocephalic atherosclerosis differed by race-ethnicity. This finding may in part explain the well-known differences in race-ethnic predilection to intracranial or extracranial atherosclerosis.

Association of serum lipid indices with large artery atherosclerotic stroke

Low-density lipoprotein cholesterol (LDL) is the primary lipid target for vascular risk reduction in stroke patients, but emerging data suggest that other lipid indices may better predict vascular hazard. We evaluated the relationship between several measures of the classically obtained serum lipid panel and the occurrence of large artery atherosclerotic stroke. Data prospectively collected over a 4-year period on subjects admitted with ischemic stroke or TIA to a university medical center were analyzed. Independent associations of fasting serum lipid indices with large artery atherosclerotic (LAA) stroke mechanism were evaluated. Of 1,049 patients, 247 (23.5%) were classified with LAA, 224 (21.4%) were classified with small vessel disease (SVD), and 578 (55%) were non-LAA, non-SVD subtype. Lipid levels were similar between LAA and SVD patients. Total cholesterol, triglycerides, LDL, non-high-density lipoprotein cholesterol (HDL), and triglyceride:HDL ratio were significantly higher in LAA vs non-LAA, non-SVD patients. After adjustment for age, hypertension, diabetes, smoking, body mass index, and premorbid statin use, significant odds ratios (ORs) for LAA compared with all other ischemic stroke subtypes for patients in the uppermost lipid quartiles (vs lowest) were triglycerides (OR 2.69, 95% CI 1.44 to 5.02) and non-HDL (OR 2.39, 95% CI 1.40 to 4.11). LDL was not associated with LAA. Compared with all other ischemic stroke subtypes, elevated levels of serum triglycerides and non-high-density lipoprotein, but not low-density lipoprotein (LDL), are associated with large artery atherosclerotic stroke. These non-LDL lipid measures may have utility in delineating atherosclerotic stroke risk.