Risk Factor For Silent Brain Infarction Research Articles

Prevalence and Risk Factors of Silent Brain Infarction in Patients with Aortic Stenosis

Introduction: Silent brain infarction (SBI) is an independent risk factor for subsequent symptomatic stroke in the general population. Although aortic stenosis (AS) is also known to be associated with an increased risk of future symptomatic stroke, little is known regarding the prevalence and risk factors for SBI in patients with AS. Methods: The study population comprised 83 patients with severe AS with no history of stroke or transient ischemic attack and paralysis or sensory impairment (mean age 75 ± 7 years). All patients underwent brain magnetic resonance imaging to screen for SBI and multidetector-row computed tomography to quantify the aortic valve calcification (AVC) volume. Comprehensive transthoracic and transesophageal echocardiography were performed to evaluate left atrial (LA) abnormalities, such as LA enlargement, spontaneous echo contrast, or abnormal LA appendage emptying velocity (<20 cm/s), and complex plaques in the aortic arch. Results: SBI was detected in 38 patients (46%). Multiple logistic regression analysis indicated that CHA₂DS₂-VASc score and estimated glomerular filtration rate (eGFR) were independently associated with SBI (p < 0.05), whereas LA abnormalities and AVC volume were not. When patients were divided into 4 groups according to CHA₂DS₂-VASc score and eGFR, the group with a higher CHA₂DS₂-VASc score (≥4) and a lower eGFR (<60 mL/min/1.73 m²) had a greater risk of SBI than the other groups (p < 0.05). Conclusion: These findings indicate that AS is associated with a high prevalence of SBI, and that the CHA₂DS₂-VASc score and eGFR are useful for risk stratification.

Association between KCNQ2, TCF4 and RGS18 polymorphisms and silent brain infarction based on whole‑exome sequencing.

Silent brain infarction (SBI) is a cerebral infarction identified through brain imaging. In particular, studies have shown that the presence of SBI in elderly patients increases their risk of cognitive dysfunction, impairment and dementia. However, little research has been published on the relevance of SBI to these risks for the Korean population. The association between potassium voltage‑gated channel subfamilyQ member2 (KCNQ2), transcription factor4 (TCF4) and regulator of G‑protein signaling18 (RGS18) genotypes and SBI were investigated using whole‑exome sequencing and PCR restriction fragment length polymorphism (RFLP) analysis. The study population included 407patients with SBI (171males) and 401control subjects (172males). Genotyping was performed using PCR RFLP. Interestingly, TCF4 rs9957668T>C polymorphisms were associated with SBI prevalence [TTvs.CC: adjusted odds ratio(AOR), 1.815, 95% confidence intervals (CI), 1.202‑2.740; TT vs. TC+CC: AOR,1.492, 95%CI,1.066‑2.088; TT+TCvs.CC:AOR,1.454, 95%CI,1.045‑2.203]. The combination of KCNQ2 rs73146513A>G and TCF4 rs9957668T>C genotypes was associated with increasing SBI prevalence (AG/CC: AOR,3.719, 95%CI,1.766‑7.833; AA/CC: AOR,3.201, 95%CI,1.387‑7.387). The present study showed that TCF4 rs9957668T>C polymorphisms may be risk factors for SBI. Therefore, the TCF4 rs9957668T>C polymorphism may serve as a biomarker for increased risk of SBI in the Korean population.

Relationship of ocular microcirculation, measured by laser speckle flowgraphy, and silent brain infarction in primary aldosteronism.

PurposeRecent studies have shown that the risk of cerebro- and cardiovascular events (CVEs) is higher in patients with primary aldosteronism (PA) than in those with essential hypertension (EH), and that silent brain infarction (SBI) is a risk factor and predictor of CVEs. Here, we evaluated the relationship between findings from laser speckle flowgraphy (LSFG), a recently introduced non-invasive means of measuring mean blur rate (MBR), an important biomarker of ocular blood flow, and the occurrence of SBI in patients with PA.Methods87 PA patients without symptomatic cerebral events (mean 55.1 ± 11.2 years old, 48 male and 39 female) were enrolled in this study. We measured MBR in the optic nerve head (ONH) with LSFG and checked the occurrence of SBI with magnetic resonance imaging. We examined three MBR waveform variables: skew, blowout score (BOS) and blowout time (BOT). We also recorded clinical findings, including age, blood pressure, and plasma aldosterone concentration.ResultsPA patients with SBI (15 of 87 patients; 17%) were significantly older and had significantly lower BOT in the capillary area of the ONH than the patients without SBI (P = 0.02 and P = 0.03, respectively). Multiple logistic regression analysis revealed that age and BOT were independent factors for the presence of SBI in PA patients (OR, 1.15, 95% CI 1.01–1.38; P = .03 and OR, 0.73, 95% CI 0.45–0.99; P = .04, respectively).ConclusionPA patients with SBI were older and had lower MBR BOT than those without SBI. Our analysis showed that age was a risk factor for SBI, and that BOT was a protective factor, in patients with PA. This suggests that BOT, a non-invasive and objective biomarker, may be a useful predictor of SBI and form part of future PA evaluations and clinical decision-making.

Abstract 2195: Early Menopause and the Risk of Silent Brain Infarction in Community-dwelling Elderly Subjects

Background and Purpose: Brain infarction is more common in men. Our previous study showed the male predominance of silent brain infarction (SBI), which was largely due to higher prevalence of alcohol habit and smoking in men than in women (Hypertens Res. 2010;33:748). However, early menopause could be a risk factor for SBI. Methods: We conducted a population-based analysis of brain magnetic resonance imaging (MRI) findings to examine whether early menopause contribute to SBI. The subjects (n=712) were living independently at home without apparent dementia. The National Hospital Organization Hizen Psychiatric Center Institutional Review Board approved the study, and written informed consent was obtained from all subjects. Participants underwent a structured clinical interview, a neurological examination, general hematology tests, biochemistry tests, and electrocardiograms. Natural menopause was considered to occur if a woman had ceased menstruating naturally for at least 1 year. Early menopause was defined as menopause before age 40. Women were also queried as to the cause of menopause (natural, surgical, other), whether a hysterectomy was performed, number of ovaries removed, the use of hormone replacement therapy, the total number of children, and the age at giving birth to her last child. T1-weighted, T2-weighted, and FLAIR images were obtained with a MRI (1.0T, Shimadzu Magnex XP). SBI was shown as low signal intensities on T1-weighted images, and their size was 5 mm or larger. The data were analyzed with the IBM SPSS Statistics 18 software for Windows (SPSS Japan Inc.). Results: Among 303 female subjects aged 60 years or older, the median age at menopause was 50 years, the median number of children was 3, and the median age at the last parity was 30 years. Early menopause (total or natural) was more frequent in subjects with SBI. Age at natural menopause, number of children, and age at the last parity were not significantly associated with SBI. In the 712 subjects (283 men and 429 women with a mean age of 67.1 years), SBI, DWMLs and PVHs were detected in 89 (12.5%), 240 (33.7%) and 154 (21.6%) of 712 participants, respectively. The prevalence of SBI was more frequent in men (15.5%) than in women (10.5%). In the forward stepwise method of logistic analysis, natural early menopause (OR 4.239, 95% CI1.060-16.960), age (OR 2.447/10y, 95% CI 1.849-3.240), hypertension (OR 4.045, 95% CI 2.413-6.780), alcohol intake (OR 2.091, 95% CI 1.230-3.553), and smoking (OR 2.936, 95% CI 1.520-5.671) were significant factors concerning SBI. Conclusions: The present study showed “natural” early menopause as one of the potential risk factors for SBI. Although the prevalence of natural early menopause was low (3.3% of 303 female subjects aged 60 years or older), natural menopause before the age of 40 years may be the basis for SBI or small vessel disease of the brain.

Endothelial nitric oxide synthase gene polymorphisms and the risk of silent brain infarction

Silent brain infarction (SBI), a unique cerebrovascular disorder, is frequently detected on magnetic resonance imaging (MRI) of apparently healthy elderly persons, and it is known to increase the risk of stroke and other related diseases. Although detailed mechanisms of SBI pathogenesis have yet to be determined, recent studies suggest that SBI is significantly influenced by genetic factors. In this study, we investigated polymorphisms in the endothelial nitric oxide synthase (eNOS) gene (i.e., -786T>C, 4a4b and 894G>T) as possible risk factors for SBI. We enrolled 269 patients with SBI and 234 control subjects and examined their fasting plasma homocysteine and folate levels, and analyzed for eNOS polymorphisms and haplotypes. The prevalence of SBI was shown to be significantly higher in patients with the eNOS 894GT genotype (OR, 2.00; 95% CI, 1.30-3.08) and 894GT+TT genotype (OR, 2.05; 95% CI, 1.34-3.16), compared with the 894GG genotype. However, in the case of -786T>C and 4a4b polymorphisms, no significant difference was observed between SBI patients and normal subjects. Interestingly, we found that the prevalence of SBI can increase twice as high when either -786T>C or 4a4b polymorphism was combined with 894G>T polymorphism, -786TC+CC/894GT+TT (OR, 3.83; 95% CI, 1.24-11.80) and 4a4b+4a4a/894GT+TT (OR, 4.08; 95% CI, 1.34-12.40), respectively. According to haplotype analysis, we found that three haplotypes (-786T-4b-894G, -786T-4b-894T and -786C-4a-894T) were shown to be significantly different between SBI patients and control subjects. These results indicate that eNOS polymorphisms and haplotypes serve as risk factors for SBI, and three different polymorphic loci in the eNOS gene play interactively, thereby leading to synergistic effects for the generation of SBI.

Evaluation of genetic risk factors for silent brain infarction.

Silent brain infarction (SBI) is often found with white matter hyperintensity. A recent genetic study on elderly twins indicated that the susceptibility to white matter hyperintensity was largely determined by genetic factors, implying the existence of genetic susceptibility for SBI as well. We therefore studied 3 genetic polymorphisms in SBI, the deletion/insertion polymorphism of angiotensin-converting enzyme (ACE) gene, the apolipoprotein(a) [apo(a)] size polymorphism, and the T677C polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene, by a case-control study. By MRI, 147 subjects with SBI and 214 without cerebral infarctions (control group) were selected from participants of a health examination of the brain. Seventy-four patients with symptomatic subcortical infarction (SSI) from the same area were also included in the study. In addition to the control group, 2 more reference populations were recruited. Typing of the apo(a) size polymorphism was done by Western blotting with the use of an anti-apo(a) antibody. Genotypes of ACE and MTHFR were determined by polymerase chain reaction amplification of the genomic DNA and subsequent restriction enzyme digestion. The ACE polymorphism was not associated with either SBI or SSI. In contrast, the small apo(a) was associated with both SSI and SBI. The MTHFR polymorphism was associated only with SSI. The association of MTHFR and apo(a) was greater in the younger subjects. Among the 3 genetic polymorphisms studied, only the apo(a) size polymorphism is a risk factor for SBI.

4.Apoprotein(a)phenotype:ラクナ梗塞の遺伝的危険因子

Silent brain infarction (SBI) is often found with white matter hyperintensity (WMH). A recent genetic study on elderly twins indicated that the susceptibility to WMH was largely determined by genetic factors, implying the existence of genetic susceptibility for SBI as well. We therefore studied three genetic polymorphisms in SBI, the D/I polymorphism of angiotensin-converting enzyme (ACE) gene, the apolipoprotein (a) [apo (a)] phenotype and the T677C polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene, by a case-control study.By MRI, 147 subjects with SBI [SBI group] and 214 without cerebral infarctions [Control group] were selected from participants of a health examination of the brain. Eighty-five patients with symptomatic subcortical infarction (SSI group) from the same area were also included in the study. In addition to the Control, two more reference populations were recruited.Typing of the apo (a) phenotype was done by western blotting using an anti-apo (a) antibody. Genotypes of ACE and MTHFR were determined by PCR amplification of the genomic DNA and subsequent restriction enzyme digestion.The ACE polymorphism was not associated either with SBI or with SSI. In contrast, the small-sized apo (a) was associated both with SSI and SBI. The MTHFR polymorphism was associated only with SSI. The association of MTHFR and apo (a) was greater in the younger subjects. Among the three genetic polymorphisms studied, only the apo (a) phenotype is a risk factor for SBI.