Hyperhomocysteinemia as a Risk Factor for Saccular Intracranial Aneurysm: A Cohort Study in a Chinese Han Population.

BACKGROUND: We evaluated the possible relationships between serum total homocysteine and folate and Vitamin B12 in patients with intracranial aneurysm. METHODS: We enrolled consecutive patients with intracranial aneurysm from the Han population who were admitted to the hospital, as well as control subjects who received medical examination on an outpatient basis. The serum total homocysteine, folate, and Vitamin B12 levels were measured in patients with intracranial aneurysm and the control group, and the associations between those factors were analyzed using multivariate logistic analysis. RESULTS: A total of 140 patients with intracranial aneurysm and 140 control subjects were enrolled from July 2014 to December 2015. The mean serum total homocysteine level in the patient group (19.98 ± 10.84 µmol/L) was significantly higher than that in the control group (15.13 ± 5.55 µmol/L, P < .001). The serum total homocysteine level was negatively correlated with folate and Vitamin B12 levels (r = -.349, P < .001; r = -.531, P < .001, respectively) in the patient group. Homocysteine had an adjusted odds ratio of 2.196 (95% confidence interval: 1.188-4.057, P = .012) for the development of intracranial aneurysm. CONCLUSIONS: The present study provides evidence regarding the association between serum total homocysteine and folate and Vitamin B12 in patients with intracranial aneurysm. Hyperhomocysteinemia is an independent risk factor for intracranial aneurysm, and folate and Vitamin B12 are protective against intracranial aneurysm due to their roles in regulating the metabolism of homocysteine.

Hyperhomocysteinaemia is an independent risk factor for peripheral arterial disease in a Chinese Han population.

BACKGROUND AND AIMS: Hyperhomocysteineamia (HHcy) has long been suggested as a risk factor for atherosclerosis. However, the association between HHcy and peripheral arterial disease (PAD) is still controversial. There is a lack of research on this topic in the Chinese population. This study aims to provide further results. METHODS: 240 PAD patients and 240 control subjects were evaluated for both serum total homocysteine levels and ankle brachial indexes (ABIs). Multivariable logistic regression models were used to estimate the association between HHcy and the risk of developing PAD. Interaction and stratified analyses were conducted according to age, sex, smoking status, drinking status, and histories of chronic disease. RESULTS: The multivariate logistic regression analyses revealed that the risk of PAD was significantly associated with serum homocysteine levels. The interaction analysis showed no interactive role in the association between HHcy and PAD, indicating that homocysteine was associated with PAD independently of classical vascular risk factors. CONCLUSIONS: In conclusion, HHcy is an independent risk factor for PAD in the Chinese Han population. A prospective and randomized clinical trial of homocysteine lowering therapy in the Chinese population is needed to assess the causal nature of the relationship.

Hyperhomocysteinaemia is an independent risk factor of abdominal aortic aneurysm in a Chinese Han population.

The associations between hyperhomocysteinaemia (HHcy), methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, and abdominal aortic aneurysm (AAA) remain controversial, with only few studies focused on these associations within the Chinese population. We performed subgroup and interaction analyses in a Chinese Han population to investigate these associations. In all, 155 AAA patients and 310 control subjects were evaluated for serum total homocysteine levels and MTHFR C677T polymorphisms. Multiple logistic regression models were used to evaluate the aforementioned associations. Interaction and stratified analyses were conducted according to age, sex, smoking status, drinking status, and chronic disease histories. The multiple logistic analyses showed a significant association between HHcy and AAA but no significant association between MTHFR C677T polymorphism and AAA. The interaction analysis showed that age and peripheral arterial disease played an interactive role in the association between HHcy and AAA, while drinking status played an interactive role in the association between MTHFR C677T polymorphism and AAA. In conclusion, HHcy is an independent risk factor of AAA in a Chinese Han population, especially in the elderly and peripheral arterial disease subgroups. Longitudinal studies and clinical trials aimed to reduce homocysteine levels are warranted to assess the causal nature of these relationships.

Genetic variants of SLC17A1 are associated with cholesterol homeostasis and hyperhomocysteinaemia in Japanese men.

Hyperuricaemia is an undisputed and highly predictive biomarker for cardiovascular risk. SLC17A1, expressed in the liver and kidneys, harbours potent candidate single nucleotide polymorphisms that decrease uric acid levels. Therefore, we examined SLC17A1 polymorphisms (rs1165196, rs1179086, and rs3757131), which might suppress cardiovascular risk factors and that are involved in liver functioning, via a large-scale pooled analysis of the Japanese general population in a cross-sectional study. Using data from the Japan Multi-Institutional Collaborative Cohort Study, we identified 1842 participants of both sexes, 35-69-years-old, having the requisite data, and analysed their SLC17A1 genotypes. In men, logistic regression analyses revealed that minor alleles in SLC17A1 polymorphisms (rs1165196 and rs3757131) were associated with a low-/high-density lipoprotein cholesterol ratio >2.0 (rs1165196: odds ratio [OR], 0.703; 95% confidence interval [CI], 0.536-0.922; rs3757131: OR, 0.658; 95% CI, 0.500-0.866), and with homocysteine levels of >10.0 nmol/mL (rs1165196: OR, 0.544; 95% CI, 0.374-0.792; rs3757131: OR, 0.509; 95% CI, 0.347-0.746). Therefore, these polymorphisms had dominant negative effects on cholesterol homeostasis and hyperhomocysteinaemia, in men, independent of alcohol consumption, physical activity, or daily energy and nutrition intake. Thus, genetic variants of SLC17A1 are potential biomarkers for altered cholesterol homeostasis and hyperhomocysteinaemia in Japanese men.

Ethnic differences in the prevalence of high homocysteine levels among low-income rural Kazakh and Uyghur adults in far western China and its implications for preventive public health.

OBJECTIVE: Homocysteine (Hcy) is a relevant biomarker of vascular disease: serum Hcy concentrations will increase the risk of systolic hypertension, whereas hyperhomocysteinemia (HHcy) has a synergistic effect with hypertension and increases the risk of cardiovascular disease. However, information has primarily been gathered from high-income and urban settings, and little is known regarding low-income rural settings. This study focused on a low-income rural and nomadic minority residing in far western China. Hcy levels were tested, and the prevalences of HHcy and H-type hypertension were investigated in this population. METHODS: This study used a stratified cluster random sampling method, selecting 2,180 individuals as subjects from Kazakh and Uyghur inhabitants (≥25 years old) of 18 villages in Xinjiang, China, which is approximately 4407 km from the capital, Beijing. Hcy levels were determined using a double reagent enzymatic cycling method. HHcy (Hcy > 10 µmol/L) was defined by the criteria of the American Heart Association. RESULTS: The Kazakh geometrical mean of Hcy was 13.34 µmol/L, and the Uyghur mean was 13.75 µmol/L; the mean values were higher in males than in females of both ethnicities (15.99 µmol/L vs. 11.63 µmol/L; 15.71 µmol/L vs. 11.91 µmol/L, respectively, p < 0.01). The serum levels of Hcy increased with increasing age in both ethnicities, and except for Kazakh individuals >65 years old, Hcy serum levels were higher in males than in females in all age groups of both ethnicities, with a p value less than 0.01. The Kazakh prevalence of HHcy was 80.0%, and the Uyghur prevalence was 78.2%; the male prevalence was higher than that in females for both ethnicities (93.5% vs. 69.6%; 90.8% vs. 64.6%, respectively, p < 0.05). Among the Kazakh, the prevalence of hypertension was 35.1%, and the prevalence was higher in males than in females (44.3% vs. 28.1%, p < 0.001); 87.6% of the Kazakh individuals had H-type hypertension, and the prevalence was higher in males than in females (95.0% vs. 80.0%, p < 0.05). In Uyghur, the prevalence of hypertension was 30.6%, and the prevalence was higher in males than in females (37.9% vs. 22.8%, p < 0.001); 88.0% of the Uyghur individuals had H-type hypertension, and the prevalence was higher in males than in females (93.9% vs. 79.1%, p < 0.05). CONCLUSIONS: HHcy was found to be common among the Kazakh and Uyghur. The prevalences of HHcy and H-type hypertension were high among both ethnicities and differed depending on gender and age. Community interventions should be conducted to improve public health conditions among the Kazakh and Uyghur in Xinjiang.

Hyperhomocysteinemia is a risk factor for Alzheimer's disease in an Algerian population.

BACKGROUND AND AIMS: There is growing evidence that increased blood concentration of total homocysteine (tHcy) may be a risk factor for Alzheimer's disease (AD). The present study was conducted to evaluate the association of serum tHcy and other biochemical risk factors with AD. METHODS: This is a case-control study including 41 individuals diagnosed with AD and 46 nondemented controls. Serum levels of all studied biochemical parameters were performed. RESULTS: Univariate logistic regression showed a significant increase of tHcy (p = 0.008), urea (p = 0.036) and a significant decrease of vitamin B12 (p = 0.012) in AD group vs. controls. Using multivariate logistic regression, tHcy (p = 0.007, OR = 1.376) appeared as an independent risk factor predictor of AD. There was a significant positive correlation between tHcy and creatinine (p <0.0001). A negative correlation was found between tHcy and vitamin B12 (p <0.0001). CONCLUSIONS: Our findings support that hyperhomocysteinemia is a risk factor for AD in an Algerian population and is also associated with vitamin B12 deficiency.

Serum homocysteine level is positively associated with chronic kidney disease in a Taiwan Chinese population.

BACKGROUND: Both hyperhomocysteinemia and chronic kidney disease (CKD) increase risk of cardiovascular disease. In this study, we investigated the association between serum homocysteine level and CKD. MATERIALS AND METHODS: A total of 1,581 participants were recruited from a health check-up center in a tertiary hospital in Taiwan between 2006 and 2008. Two groups were created based on serum homocysteine levels above or below 12.24 µmol/l. Estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease equation; we defined CKD as an eGFR below 60 ml/min/1.73 m(2). Multivariate logistic and linear regression analyses were used to estimate the associations between serum homocysteine levels and kidney function. RESULTS: Subjects with elevated homocysteine levels were older and had higher body mass index, blood pressures, fasting plasma glucose, total cholesterol, triglycerides, and eGFR than those with normal serum homocysteine level. Using multiple logistic regression analyses after adjustment for age, sex, lifestyle habits (smoking, alcohol consumption, and betel nut chewing) and chronic diseases (hypertension, diabetes, dyslipidemia), the odds ratio (95 % confidence interval) of having CKD was 5.76 (2.99-11.1) among subjects with elevated serum homocysteine levels compared to subjects with normal serum homocysteine levels. The significant increase in odds ratios for CKD in progressive homocysteine levels reveals a dose-response effect. After adjustment for confounders, at multiple linear regression analyses serum homocysteine level resulted significantly and negatively correlated to eGFR. CONCLUSIONS: Elevated serum homocysteine levels appear to be closely associated with CKD. Serum homocysteine levels are negatively associated with eGFR.

Association of polymorphisms on chromosome 9p21.3 region with increased susceptibility of abdominal aortic aneurysm in a Chinese Han population.

OBJECTIVE: Several studies have reported that polymorphisms on chromosome 9p21.3, near the CDKN2A/2B gene, are strongly associated with increased susceptibility to abdominal aortic aneurysm (AAA). However, no convincing data has been reported on a relationship between AAA and these variants in the Chinese Han population. The aim of this study was to evaluate the role of rs10757278 and rs1333049 in determining genetic susceptibility to AAA. METHODS: A total of 155 AAA patients and 310 controls, comparable in age and gender, were enrolled in this study. DNA samples were genotyped for rs10757278 and rs1333049 using the MassArray system. The association between these two single nucleotide polymorphisms and AAAs was tested using multivariate logistic regression. Stratified analysis was also performed by clinical and laboratory features. RESULTS: Single nucleotide polymorphisms rs10757278 and rs1333049 were significantly associated with increased risk of AAA. The frequencies of rs10757278-G and rs1333049-C in AAA patients were significantly higher than in control subjects (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.11-2.11; P = .01, and OR, 1.48; 95% CI, 1.07-2.05; P = .02). Multiple logistic regression analysis indicated that, after adjusting for smoking habits, drinking habits, and histories of other chronic diseases, homozygosity of the risk allele for rs10758278-G and rs1333049-C also increased the likelihood of AAA (OR, 2.31; 95% CI, 1.22-4.36, and OR, 2.14; 95% CI, 1.13-4.05). The frequency of the GC haplotype was significantly higher in AAA patients than in control subjects (OR, 1.44; P = .038). Stratification analysis of clinical and laboratory features revealed no association between polymorphisms and aortic diameters in AAA patients. There was a significantly high frequency of the rs10757278 GG genotype in AAA patients with high serum total homocysteine compared with those control subjects with high serum total homocysteine (OR, 2.71; 95% CI, 1.12-6.58; P = .03) indicating that the genotype GG of rs10757278 might interact with the homocysteine biological pathway to stimulate the presence of AAA. CONCLUSIONS: Present data demonstrate that rs10757278 and rs1333049 on chromosome 9p21.3 are significantly associated with increased risk of AAA in the Chinese population and emphasize the need to further study the role of these markers in AAA.

Daily milk intake improves vitamin B-12 status in young vegetarian Indians: an intervention trial.

BACKGROUND: Asymptomatic Indian lacto vegetarians, who make up more than half of the Indian population in different geographic regions, have distinctly low vitamin B-12 concentrations than non- vegetarians. Vegetarians consume milk but it seems that the amount is not enough to improve vitamin B-12 status or vitamin B-12 concentration in milk itself may be low. The aim of this study was to determine if daily milk consumption can improve vitamin B-12 status. METHODS: Fifteen male and 36 female, young healthy post-graduate volunteers participated. Blood from ten participants (4 males and 6 females) was collected (day-1). They continued their regular diet for next fourteen days and on day-15, blood of all 51 participants was collected, plasma vitamin B-12 concentration was measured and were divided into two groups; Normal (vitamin B-12 >148 pmol/L, n = 22) and Vitamin B-12 deficient (<148 pmol/L, n = 29), the remaining plasma was stored. All participants consumed 600 ml. of non-enriched buffalo milk (200 × 3) during the day along with their usual diet. Next day blood was collected for plasma holotranscobalamin II measurement. Subjects from deficient group continued to drink 400 ml of milk daily for next 14 days and blood was collected on day-30. Plasma holotranscoabalamin II (day-1, 15, 16, 30), vitamin B-12, folate, total homocysteine, creatinine and hematoloical parameters (day-1, 15, 30), and milk vitamin B-12 concentrations (day-15, 16, 30) were measured. RESULTS: Fifty seven per cent of the participants were vitamin B-12 deficient and 65% were hyperhomocysteinemic. No significant difference in biomarkers was observed when there was no intervention. Plasma holotranscobalamin II concentration increased from 19.6 to 22.27 pmol/L (p < 0.0001) 24 hrs after milk load in the whole group. Plasma vitamin B-12 increased from 92.5 to 122 pmol/L and tHcy concentrations decreased from 31.9 to 24.9 µ mol/L (p < 0.0001 for both) 14 days after regular milk intake in vitamin B-12 deficient subjects. CONCLUSIONS: Regular intake of milk improved vitamin B-12 status of vitamin B-12 deficient vegetarians indicating a potential dietary strategy to improve the vitamin status.

Prevalence of hyperhomocysteinaemia and its major determinants in rural Chinese hypertensive patients aged 45-75 years.

We aimed to investigate the prevalence of hyperhomocysteinaemia (total plasma homocysteine (tHcy) ≥ 10 µmol/l) and its major determinants in rural Chinese hypertensive patients. A cross-sectional investigation was carried out in Lianyungang of Jiangsu province, China. This analysis included 13 946 hypertensive adults. The prevalence of hyperhomocysteinaemia was 51.6 % (42.7 % in women and 65.6 % in men). The OR of hyperhomocysteinaemia were 1.52 (95 % CI 1.39, 1.67) and 2.32 (95 % CI 2.07, 2.61) for participants aged 55-65 and 65-75 v. 45-55 years; 1.27 (95 % CI 1.18, 1.37) for participants with a BMI ≥ 25 v. < 25 kg/m²; 1.14 (95 % CI 1.06, 1.23) for participants with v. without antihypertensive treatment; 1.09 (95 % CI 1.00, 1.18) for residents inland v. coastal; 0.89 (95 % CI 0.82, 0.97) and 0.83 (95 % CI 0.74, 0.92) for participants with moderate and high v. low physical activity levels; 1.54 (95 % CI 1.41, 1.68) and 2.47 (95 % CI 2.17, 2.81) for participants with a glomerular filtration rate 60-90 and < 60 v. ≥ 90 ml/min per 1.73 m²; and 1.20 (95 % CI 1.07, 1.35) and 3.81 (95 % CI 3.33, 4.36) for participants with CT and TT v. CC genotype at methylenetetrahydrofolate reductase 677C>T polymorphism, respectively. Furthermore, higher tHcy concentrations were observed in smokers of both sexes (men: geometric mean 12.1 (interquartile range (IQR) 9.2-14.5) v. 11.9 (IQR 9.-14.) µmol/l, P= 0.005; women: geometric mean 10·3 (IQR 8.3-13.0) v. 9.6 (IQR 7.8-11.6) µmol/l, P= 0.010), and only in males with hypertension grade 3 (v. grade 1 or controlled blood pressure) (geometric mean 12.1 (IQR 9.2-14.4) v. 11.7 (IQR 9.2-14.0), P= 0.016) and in male non-drinkers (yes v. no) (geometric mean 12.3 (IQR 9.4-14.8) v. 11.7 (IQR 9.1-13.9), P= 0.014). In conclusion, there was a high prevalence of hyperhomocysteinaemia in Chinese hypertensive adults, particularly in the inlanders, who may benefit greatly from tHcy-lowering strategies, such as folic acid supplementation and lifestyle change.

Folate and vitamin B12 deficiency and hyperhomocysteinemia promote oxidative stress in adult type 2 diabetes.

OBJECTIVE: The purpose of this study was to examine the status of folate and vitamin B12 (B12) in relation to serum homocysteine (HCY) and oxidative stress indices in patients with type 2 diabetes (T2DM). METHODS: This case-control study involved 100 Omani adults (50 patients newly diagnosed with T2DM and 50 age- and gender-matched healthy controls). Several parameters were investigated, including dietary intake and biochemical assessments of folate, B12, HCY, oxidative stress markers (glutathione and total antioxidant status), and antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase). RESULTS: Low serum levels of folate, B12, and hyperhomocysteinemia were prevalent in patients with T2DM compared with controls. Oxidative stress was evident in patients with T2DM as indicated by low serum levels of glutathione, total antioxidant status, and impaired antioxidant enzymatic activities (superoxide dismutase, glutathione peroxidase, and catalase). CONCLUSION: The low intake of folate and B12 is associated with low serum levels of these two nutrients and hyperhomocysteinemia in Omani adults with T2DM.

Serum folate, total homocysteine levels and methylenetetrahydrofolate reductase 677C>T polymorphism in young healthy female Japanese.

Environmental and genetic factors influence serum total homocysteine (tHcy), a risk factor for vascular diseases. The gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) is reported to be a genetic factor for influencing tHcy. However, it is not clear whether MTHFR polymorphism influences tHcy in the younger generation. To investigate the influence of MTHFR polymorphism on vascular disease risks in young Japanese females, we determined dietary intakes, serum folate and tHcy, and examined the influence of MTHFR 677C>T polymorphism in healthy junior and high school students (n=192, 12-18y). The relationships between MTHFR polymorphism and folate intake, serum folate or tHcy were investigated by dividing participants into CC, CT and TT types. Among individuals with the TT genotype, folate and tHcy levels were significantly lower (p<0.05) or higher (p<0.0001), respectively, than in those with the other genotypes; although there were no significant differences in the intake of folate among genotypes. In addition, a significant inverse correlation between folate and tHcy (p<0.05) was noted in all genotypes, even in young females, so far not examined in Asian populations. Therefore, MTHFR genotypes were proven to be a significant determinant for folate and tHcy concentrations. However, the association of increased folate intake with lower tHcy concentration, even in cases of the mutation TT type, indicates the importance of folate intake in young Japanese females for early detection of risk, as well as the prevention of vascular diseases.

Retinal arterial occlusions in the young: systemic associations in Indian population.

PURPOSE: To determine the systemic associations in retinal arterial occlusions (RAO) in young Indian individuals less than 40 years of age. MATERIALS AND METHODS: Case records of 32 patients (35 eyes) of less than 40 years, with non-traumatic RAO were analysed. All patients underwent detailed ophthalmic and systemic evaluation including hemogram, lipid profile, coagulation profile, vasculitis screening, carotid Doppler, echocardiogram. RESULTS: In the study 21 were males and 11 were females. The age ranged from 11-39 years (Mean 27.6 ± 8.43). Nine (28%) patients were below 20 years of age. Among 35 eyes, 28 (80%) had central retinal artery occlusion (CRAO), three (8.6%) had branch retinal artery occlusion (BRAO), two (5.7%) each had cilio-retinal (CLAO) and hemi-retinal artery occlusion (HRAO). Vision ranged from no perception of light to 20/20. On systemic evaluation, in 21 (65.6%) patients a hypercoagulable state was responsible for the RAO. Conditions leading to a hypercoagulable state included hyperhomocysteinemia (21.9%), hyperlipidemia (15.6%), anticardiolipin antibody (6.2%), antiphospholipid antibody (6.2%), polycythemia, thrombocytosis, protein S deficiency, use of oral contraceptives and renal disorder (3.1% each). Six (18.7%) patients had cardiac valvular defects. Vasculitis screening was positive in three (9.4%) patients. Two (6.2%) had isolated systemic hypertension. In two (6.2%) patients no abnormality could be detected. CONCLUSION: The systemic associations of RAOs in the Indian population were distinctly different from those reported in the Western population. Hyperhomocysteinemia was the commonest association found. Whereas associations reported in the Western population such as cardiac abnormalities, coagulation disorders, hemoglobinopathies and oral contraceptive use were uncommon.

The incidence of raised procoagulant factors and hyperhomocysteinaemia in Chinese patients with chronic venous insufficiency.

BACKGROUND: For reasons that are poorly understood, there appear to be differences in the prevalence of chronic venous insufficiency (CVI) and venous thromboembolism between Caucasians and Asians. OBJECTIVES: To compare levels of procoagulant factors and homocysteine (Hcy) in Hong Kong (HK) Chinese and United Kingdom (UK) Caucasian populations of patients with CVI (patients of CEAP clinical stages C4 - C6). METHODS: HK Chinese and UK Caucasian patients with CEAP clinical grade 4-6 venous disease were enrolled. Patients with conditions known to be associated with thrombophilia (TP) were excluded. UK and HK patients were matched by gender, age (within 5 years) and by CEAP clinical grade. All subjects underwent clinical examination, venous duplex ultrasound, and measurement of Hcy and factors (F) VIII, IX and XI. RESULTS: 63 Patients were enrolled in each group: Mean age 64y (HK group); 67y (UK group). 37% were female; 19% had active venous ulceration. One-third of patients in each group had deep venous reflux. High Hcy, FIX and FXI were significantly more common in the UK group. Multiple TP was more common in the UK group: raised levels of >or=2 factors in 26 vs. 14 patients (P = 0.022, chi(2)). Median Hcy (14.3 vs. 10.8 micromol/L; P < 0.0005, Wilcoxon signed rank [WSR]), FIX (131 vs. 115%; P = 0.048), and FXI (114 vs. 97%; P = 0.002) were significantly higher in the UK group. There was no significant difference in FVIII levels. CONCLUSIONS: Raised procoagulant factors were more common in Caucasians compared with Chinese patients with CVI in this study. As with the inherited thrombophilias, the pattern of raised procoagulant factors in Chinese patients appears to differ from that in Caucasians.

Asymptomatic Mongolian middle-aged women with high homocysteine blood level and atherosclerotic disease.

Growing numbers of studies have shown that hyperhomocysteinemia is an independent, modifiable risk factor for cardiovascular diseases. Hyperhomocysteinemia has been found to be negatively associated with the vitamin B group, especially folate and cobalamin. Because of the relative scarcity of fruits and vegetables in Mongolian foods, and the high cardiovascular diseases rate in Mongolia, we examined homocysteine level and its relation with atherosclerotic change in middle-aged Mongolian women. This cross-sectional study included 79 female asymptomatic residents of Ulaanbaatar, Mongolia. Besides analysis of homocysteine and chemistry tests, participants were interviewed and underwent physical and Doppler ultrasound examination of extracranial vessels. The mean homocysteine level was 9.87 +/- 3.6 micromol/l, and the 2.5th and 97.5th percentiles were 2.2 micromol/l and 19.9 micromol/l. Participants with abnormal Doppler ultrasound finding had significantly higher homocysteine levels (12.8 +/- 4.5 micromol/l vs 8.7 +/- 2.3 micomol/l, P < 0.001) and homocysteine was significantly associated with having atherosclerotic change (odds ratio 2.2, 95% confidence interval = 1.42-3.49, P < 0.001) after adjustment for age, low-density lipoprotein, diastolic blood pressure, and body mass index. Hyperhomocysteinemia was found to be significantly associated with atherosclerotic change in female Mongolian adults. Further studies are necessary to determine factors associated with homocysteine elevation among the Mongolian population.

Ethnicity and risk factors for change in the ankle-brachial index: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: The aim of this study was to determine the risk factors for conversion from a normal to either a low or high ankle-brachial index (ABI). METHODS: Participants in the Multi-Ethnic Study of Atherosclerosis who had two separate measurements of the ABI over a 3-year time period were assessed. RESULTS: At baseline, the mean age was 62 years and 50% were women, 28% African American, 12% Chinese, 22% Hispanic and 38% non-Hispanic White. Of the 5514 participants with a baseline ABI between 0.90 and 1.40, 89 (1.6%) had an ABI < or = 0.90 ("low ABI group") and 71 (1.3%) had an ABI > or = 1.40 ("high ABI group") 3 years later. On multivariable analysis, the odds for having progressed into the low ABI group were significantly increased for higher baseline age, hypertension, diabetes, greater pack-years of cigarette smoking, and homocysteine levels. The odds for progression into the high ABI group were increased for male gender and higher body mass index. Compared with non-Hispanic Whites, African Americans had a significantly higher odds for progression to the low ABI group (odds ratio [OR]: 2.24, 95% confidence interval [CI]: 1.29-3.88) while having a reduced odds for progression to the high ABI group (OR: 0.50, 95% CI: 0.24-1.00). Neither Chinese nor Hispanic ethnicity was significantly associated with progression to either ABI group. CONCLUSIONS: The risk factors for progression to a low or high ABI were distinct and African Americans were at increased risk for progression to a low ABI but at decreased risk for progression into the high ABI group.

Homocystine levels, polymorphisms and the risk of ischemic stroke in young Asian Indians.

BACKGROUND: Homocysteine has been for a fairly long time been debated to be a risk factor for stroke. Opinions are divided as to whether raised levels of homocysteine seen in stroke patients are the cause or consequence of stroke. A large number of studies have been conducted in the Caucasian as well as on the Oriental population, which tend to suggest contradictory findings at many times. However, there have been no reports forthcoming from the Asian Indian population, which is a genetically different population than the previously studied populations. SUBJECTS AND METHODS: In our present study, we looked at homocysteine levels and four commonly seen polymorphisms of homocysteine metabolizing enzymes and their respective prevalence in 120 acute onset ischemic stroke patients compared with an equal number of age and gender matched healthy population. We also tested the influence of folic acid dosage (5 mg OD) on the levels of homocysteine and the allied vitamin supplements, vitamin B12 and folate in smaller groups selected from the larger group. RESULTS AND CONCLUSIONS: We found homocysteine levels to be significantly raised in the stroke population compared with healthy controls [patients: 12 micromol/L (range: 5.3-39.1 micromol/L), controls: 11.2 micromol/L (range: 6.2-14.2 micromol/L); P =0.001]. There was an almost total response to folic acid dosage as all hyperhomocysteinemic patients showed lowering of homocysteine levels in response to the dosage. The MTHFR 677 C > T polymorphisms showed association with both homocysteine levels as well as stroke (P < 0.001). Nutritional deficiency plays a dominant role in hyperhomocysteinemic conditions in our stroke population, however. Genetic determinants of homocysteine level may also have some part in determining hyperhomocysteinemic conditions in the Asian Indian populations.

Brain MRI, apoliprotein E genotype, and plasma homocysteine in American Indian Alzheimer disease patients and Indian controls.

We obtained brain MRIs, plasma homocysteine levels and apolipoprotein E genotyping for 11 American Indian Alzheimer disease (AD) subjects and 10 Indian controls. We calculated white matter hyperintensity volume (WMHV), whole brain volume (WBV), and ratio of white matter hyperintensity volume to whole brain volume (WMHV/WBV). There were no significant differences between AD subjects and controls in gender, history of hypertension, diabetes, or history of high cholesterol, but hypertension and diabetes were more common among AD subjects. There was no difference between AD and control groups in age (range for all subjects was 61-89 years), % Indian heritage, waist size or body mass index. Median Indian heritage was 50% or greater in both groups. Range of education was 5-13 years in the AD group and 12-16 years in controls. Median plasma homocysteine concentration was higher in AD subjects (11 micromol/L vs. 9.8 micromol/L), but did not achieve statistical significance. Significantly more AD subjects had apolipoprotein Eepsilon4 alleles than did controls (63% vs.10%). Neuroimaging findings were not significantly different between the 2 groups, but AD subjects had greater WMHV (median 15.64 vs. 5.52 cc) and greater WMHV/WBV ratio (median 1.63 vs. 0.65 %) and a far greater range of WMHV. In combined AD subjects and controls, WBV correlated with BMI and age. WMHV and WMHV/WBV correlated inversely with MMSE scores (p = 0.001, 0.002, respectively). In addition, WMHV correlated positively with % Indian heritage (p = 0.047).

Exploratory study of plasma total homocysteine and its relationship to short-term outcome in acute ischaemic stroke in Nigerians.

BACKGROUND: Hyperhomocysteinemia is a potentially modifiable risk factor for stroke, and may have a negative impact on the course of ischaemic stroke. The role of hyperhomocysteinemia as it relates to stroke in Africans is still uncertain. The objective of this study was to determine the prevalence and short-term impact of hyperhomocysteinemia in Nigerians with acute ischaemic stroke. We hypothesized that Hcy levels are significantly higher than in normal controls, worsen stroke severity, and increase short-term case fatality rates following acute ischaemic stroke. METHODS: The study employed both a case-control and prospective follow-up design to study hospitalized adults with first - ever acute ischaemic stroke presenting within 48 hours of onset. Clinical histories, neurological evaluation (including National Institutes of Health Stroke Scale (NIHSS) scores on admission) were documented. Total plasma Hcy was determined on fasting samples drawn from controls and stroke cases (within 24 hours of hospitalization). Outcome at 4 weeks was assessed in stroke patients using the Glasgow Outcome Scale (GOS). RESULTS: We evaluated 155 persons (69 acute ischaemic stroke and 86 healthy controls). The mean age +/- SD of the cases was 58.8 +/- 9.8 years, comparable to that of controls which was 58.3 +/- 9.9 years (T = 0.32; P = 0.75). The mean duration of stroke (SD) prior to hospitalization was 43.5 +/- 38.8 hours, and mean admission NIHSS score was 10.1 +/- 7.7. Total fasting Hcy in stroke patients was 10.2 +/- 4.6 umol/L and did not differ significantly from controls (10.1 +/- 3.6 umol/L; P = 0.88). Hyperhomocysteinemia, defined by plasma Hcy levels > 90th percentile of controls (>14.2 umol/L in women and >14.6 umol/L in men), was present in 7 (10.1%) stroke cases and 11 (12.8%) controls (odds ratio 0.86, 95% confidence interval 0.31 - 2.39; P > 0.05). In multiple regression analysis admission NIHSS score (but not plasma Hcy) was a significant determinant of 4 week outcome measured by GOS score (P < 0.0001). CONCLUSION: This exploratory study found that homocysteine levels are not significantly elevated in Nigerians with acute ischaemic stroke, and admission Hcy level is not a determinant of short-term (4 week) stroke outcome.