Hyun-Ji Cho

Genetic variation at the perilipin locus is associated with changes in serum free fatty acids and abdominal fat following mild weight loss.

Objective:Perilipin (PLIN) is a class of protein-coating lipid droplets in adipocytes. We aimed to examine the association between common single-nucleotide polymorphisms (SNPs) at PLIN locus with circulating free fatty acid (FFA) and abdominal fat distribution in response to weight loss.Methods:Non-diabetic/overweight-obese Koreans (n=177) participated in a 12-week calorie restriction (−300kcal/day) program. Seven SNPs (6209T>C, 10076C>G, 10171A>T, 11482G>A, 13042A>G, 13048C>T and 14995A>T), abdominal fat areas (visceral/subcutaneous fat areas at 1st lumbar and 4th lumbar levels), serum lipids, glucose, insulin, FFA, oxidized low-density lipoprotein (LDL) and urinary 8-epi-prostaglandin F2α (PGF2α) were examined.Results:Single-nucleotide polymorphisms 10076C>G/10171A>T showed the strongest positive linkage disequilibrium (LD) (D′=0.923, R 2=0.839, P<0.001) and SNPs11482G>A/14995A>T showed moderate positive LD (D′=0.824, R 2=0.578, P<0.001). Calorie restriction induced 4.6% weight loss with significant abdominal fat reduction. In response to weight loss, subjects with nCA/nCA haplotypes at SNPs 10076C>G/10171A>T showed greater reduction in FFA levels than those with CA/CA haplotype (CA/CA: C/C at SNP 10076 and A/A at SNP 10171, nCA: non-CA haplotype carrier). On the other hand, subjects with nGA/nGA haplotype at SNPs 11482G>A/14995A>T had increased FFA levels with a rapid loss in abdominal fat, whereas GA/GA haplotype carriers had reduction in FFA levels. These results still remained significant after adjusting for age, gender and BMI. Prostaglandin F2α and oxidized LDL were also more reduced in GA/GA haplotype carriers than in nGA haplotype carriers. This effect remained significant after adjusting for baseline level, age, gender and BMI. Paradoxically, nGA haplotype carriers had increased levels of urinary PGF2α after weight reduction.Conclusion:Fasting plasma FFA changes following a modest weight loss in overweight-obese subjects are influenced by the genetic variability at the PLIN locus. Furthermore, circulating FFA changes rather than body fat itself may determine changes in lipid peroxides such as urinary PGF2α and oxidized LDL.

The frequency and risk of preclinical coronary artery disease detected using multichannel cardiac computed tomography in patients with ischemic stroke.

Background: Atherosclerosis is a systemic disease. Many ischemic stroke patients may have concomitant coronary artery disease (CAD). Detection and treatment of preclinical CAD in stroke patients may improve long-term outcome and survival because CAD is a major cause of death during follow-up in stroke patients. However, association between coronary and cerebral artery atherosclerosis in stroke patients has not fully been investigated. This study aimed at examining the frequency and high-risk groups of CAD in ischemic stroke patients. Methods: Consecutive patients who were admitted due to acute ischemic stroke between July 2006 and June 2010 were prospectively enrolled in this study. A total of 1,304 patients who underwent MSCT coronary angiography and cerebral angiography were included in this study. By using 64-multislice computed tomography coronary angiography, we investigated the frequency of CAD and association between coronary and cerebral artery atherosclerosis in terms of location and burden (severity and extent) in stroke patients. We also sought to identify high-risk groups for CAD among stroke patients. Results: The frequency of significant (≧50%) CAD was 32.3% and the frequency of any degree of CAD was 70.1%. Diabetes mellitus, serum levels of total cholesterol, high-density lipoprotein cholesterol and triglyceride, and significant stenosis of the extracranial carotid, intracranial vertebral and basilar arteries were independently associated with CAD. However, no association was found between CAD and significant stenosis of the anterior, middle and posterior cerebral arteries. The association between CAD and cerebral atherosclerosis was stronger with increased severity and extent of cerebral atherosclerosis. When compared to patients with <2 risk factors and without significant cerebral atherosclerosis, those with multiple (≧2) risk factors and atherosclerosis in both the carotid and the vertebrobasilar arteries had very high risks of CAD [odds ratio (OR) 8.36; 95% confidence interval (CI) 4.15–16.87]. The risk was also high in patients with multiple risk factors and atherosclerosis in either the carotid or the vertebrobasilar artery (OR 4.13; 95% CI 2.62–6.51), and in those with <2 risk factors but atherosclerosis in both the carotid and the vertebrobasilar arteries (OR 3.40; 95% CI 1.22–9.47). Conclusions: A substantial portion of stroke patients had preclinical CAD, and there was a clear relationship between coronary and cerebral artery atherosclerosis in terms of location and burden. The risk of CAD was particularly high in stroke patients with multiple risk factors and atherosclerosis of the carotid and/or vertebrobasilar arteries.

Transoesophageal echocardiography in patients with acute stroke with sinus rhythm and no cardiac disease history

Background Transoesophageal echocardiography (TOE) is the gold standard for detecting potential cardiac sources of embolism (PCSE). However, the role of TOE in patients with ischaemic stroke with normal sinus rhythm (NSR) and no cardiac disease remains uncertain. Methods The authors retrospectively analysed 1833 consecutive patients with ischaemic stroke with NSR and no history of cardiac disease who were examined by TOE. The authors investigated the frequency of PCSE and aortic plaques detected in these patients. Determination of high- and medium-risk PCSE was based on the Trial of ORG 10172 in the Acute Stroke Treatment classification. The authors also determined how the proportions of stroke subtypes and treatment strategies based on current guidelines have been changed after TOE. Results PCSE and/or aortic plaques were detected in 753 (41.1%) of 1833 patients. After TOE, a total of 355 PCSE (45 high-risk PCSE and 310 medium-risk PCSE) were found in 323 patients (17.6%). Aortic plaques were found in 502 patients (27.4%). Among these, complex aortic plaques, which are significant sources of embolism, were found in 157 patients (8.5%). Changes in treatment strategies for secondary prevention based on the current guidelines would have been necessary in 63 patients (3.4 %) after TOE examination. Conclusion Potential embolic sources from the heart and aorta can be detected by TOE examination in many patients with stroke with NSR and no cardiac disease, which enables a better determination of stroke mechanisms.

Cortical thickness and hippocampal shape in pure vascular mild cognitive impairment and dementia of subcortical type

The progression pattern of brain structural changes in patients with isolated cerebrovascular disease (CVD) remains unclear. To investigate the role of isolated CVD in cognitive impairment patients, patterns of cortical thinning and hippocampal atrophy in pure subcortical vascular mild cognitive impairment (svMCI) and pure subcortical vascular dementia (SVaD) patients were characterized.

Comparison of the characteristics for in‐hospital and out‐of‐hospital ischaemic strokes

Background and purpose:  Patients who are being admitted to a hospital due to diseases other than stroke may develop a stroke (in‐hospital stroke; IHS).

The different infarct patterns between adulthood-onset and childhood-onset moyamoya disease

Background and purpose The pattern of infarctions based on the findings of diffusion-weighted image was assessed, and it was also investigated whether there are any age-specific differences in patients with moyamoya disease (MMD). Methods The subjects were 66 consecutive patients with MMD who had an acute cerebral infarction. Each ischaemic lesion was categorised into one of seven patterns (gyral, atypical territorial, honeycomb, classic territorial, multiple-dot, borderzone, deep lacunar) based on diffusion-weighted image findings. The patterns were compared between adulthood-onset MMD (A-MMD, ≥20 years old, 34 patients) and childhood/adolescent-onset MMD (C-MMD, <20 years old, 32 patients) according to their ages of infarct presentation. Results A total of 91 infarct patterns were observed from 66 patients. The gyral, atypical territorial, and honeycomb patterns, which are not usually seen in conventional stroke patients, were common in MMD (68.1%). Among all patterns, a gyral pattern was most common (40/91, 44.0%). Borderzone and deep lacunar patterns were infrequent. Gyral and borderzone patterns were more frequently seen in the C-MMD group, whereas a honeycomb pattern was not seen in young patients. Honeycomb pattern was more common at advanced vascular stages. Infarctions confined to the cortex were more common in the C-MMD group (26/32, 75.0%) than in A-MMD patients (14/34, 41.2%). Conclusions Moyamoya disease showed various characteristic and age-specific infarct patterns. Different infarct patterns between the A-MMD and C-MMD groups may be associated with age-specific vulnerability of the brain to ischaemia, stage of arteriopathy or changes of abnormal collateral pathways.

An FP-CIT PET comparison of the differences in dopaminergic neuronal loss between idiopathic Parkinson disease with dementia and without dementia.

Previous studies have demonstrated a decreased density of dopamine transporters (DAT) in basal ganglia in patients with idiopathic Parkinson disease (IPD) using 123I-n-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane (FP-CIT), and the reductions in striatal DAT levels were inversely correlated with the severity of motor dysfunction in IPD. However, there has been no study on the correlation of DAT levels between IPD patients with and without cognitive dysfunction. Thus, we evaluated the differences in regional DAT density in the brain of patients with IPD without dementia and those with dementia using FP-CIT positron emission tomography. We recruited 24 consecutive patients with IPD, including 7 with IPD without dementia and 17 with IPD with dementia, and 18 healthy controls. FP-CIT positron emission tomography scans were acquired 90 and 210 minutes after the FP-CIT injection. The DAT density did not differ in the caudate nucleus or the putamen between patients with IPD without dementia and those with dementia. However, the DAT density between the 2 groups with IPD demonstrated a significantly decreased density compared with that of healthy controls in the putamen. We cautiously suggest that there is no relationship between DAT density and cognitive severity because there were no significant differences in the DAT density between IPD with dementia and those without dementia.

Comprehensive evaluation of coronary artery disease and aortic atherosclerosis in acute ischemic stroke patients: usefulness based on Framingham risk score and stroke subtype.

Background: Evaluation of coronary artery disease (CAD) and aortic atherosclerosis has been performed in patients with acute ischemic stroke. We investigated the usefulness of a dual-source CT (DSCT) protocol enabling the comprehensive evaluation of CAD and aortic atherosclerosis. The clinical characteristics of those patients who would benefit more from this protocol were investigated based on vascular risk factors, Framingham Risk Score (FRS), and stroke subtype. Methods: Of 469 patients with acute ischemic stroke, the 274 who had no history of CAD and had undergone DSCT were analyzed. Predictors of CAD (≧50% stenosis) or complicated aortic plaque (CAP) were evaluated based on vascular risk factors, FRS and stroke subtype. Results: Of the 274 patients analyzed, asymptomatic CAD (≧50% stenosis) was found in 61 (22.3%) and CAP in 58 (21.2%). Furthermore, the severity of CAD or aortic atherosclerosis was correlated with FRS (CAD, r = 0.291, p < 0.001 and aortic atherosclerosis, r = 0.297, p < 0.001). Additionally, severe CAD and aortic atherosclerosis were independent predictors of each other: CAP for the presence of CAD (≧50% stenosis) [odds ratio (OR), 5.71; 95% confidence interval (CI), 1.94–16.87]; CAD (≧50% stenosis) for the presence of CAP (OR, 4.20; 95% CI, 1.82–9.72). Specific stroke subtypes as well as large-artery atherosclerosis (OR, 5.25; 95% CI, 2.24–12.31) and cardioembolism (OR, 5.22; 95% CI, 1.75–15.60) were associated with the presence of CAP. Conclusions: A comprehensive evaluation protocol for CAD and aortic atherosclerosis may be useful in acute ischemic stroke patients, especially in those with higher FRS or specific stroke subtypes.

Failure of complete recanalization is associated with poor outcome after cardioembolic stroke.

Background:  Recanalization is strongly associated with outcomes after thrombolytic treatment. Cardiac emboli are known as better response to fibrinolytic agents because they are fibrin‐rich; however, cardioembolic stroke itself is associated with poor outcomes and high mortality. Completeness of recanalization may therefore affect the outcome of cardioembolic stroke. We investigated whether degree of recanalization influences outcomes following fibrinolytic therapy in cardioembolic stroke.

Perforator territory infarction in the lenticulostriate arterial territory: mechanisms and lesion patterns based on the axial location.

Background: We hypothesized that perforator territory infarcts in the lenticulostriate territory (pLSAIs) may have heterogeneous lesion patterns and stroke mechanisms. Methods: We reviewed prospectively collected patients who developed pLSAIs within 72 h after stroke onset. Lesion patterns were analyzed based on the six axial levels. Based on MR angiography, stenosis of the middle cerebral artery (MCA) was classified into 3 groups. White matter hyperintensities were assessed by Fazeka’s scale of periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH). Results: Of 221 patients, 159 were normal, 44 had mild stenosis, and 18 had severe stenosis of the MCA. Larger infarct volume was correlated with the severity of MCA disease (r = 0.289, p < 0.001). Lower lesion patterns were correlated with the severity of MCA disease (r = –0.294, p < 0.001). A higher lesion pattern was correlated with the severity of DWMH or PVH scores (r = 0.205, p = 0.002 in DWMH, and r = 0.137, p = 0.042 in PVH). Conclusions: Patients with MCA disease have larger and lower lesion patterns beginning from the proximal territory of the lenticulostriate artery (LSA). Patients with severe white matter changes have smaller and higher lesion patterns in the distal territory of the LSA.