Hyperhomocysteinemia independently causes and promotes atherosclerosis in LDL receptor-deficient mice

Background Hyperhomocysteine is an independent risk factor of coronary heart disease （CHD）. However, whether hyperhomocys teine affects the progression of atherosclerosis is unclear. In the present study, we examined the effect of hyperhomocysteine on the forma tion of atherosclerosis in low-density lipoprotein receptor-deficient （LDLr ） mice. Methods Forty-eight 7-week-old LDLr/ mice were assigned to the following groups： mice fed a standard rodent diet （control group）, mice fed a high-methionine diet （high-methionine group）, mice fed a high-fat diet （high-fat group）, and mice fed a diet high in both methionine and fat （high-methionine and high-fat group）. At the age of 19, 23, and 27 weeks, four mice at each interval in every group were sacrificed. Results At the end of the study, mice did not show atherosclerotic lesions in the aortic sinus and aortic surface until 27 weeks old in the control group. However, atherosclerotic lesions developed in the other three groups at 19 weeks. The amount of atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group （P 〈 0.001）. Atherosclerotic lesions on the aortic surface in the high-methionine and high-fat group were the most severe. The mean area of atherosclerotic lesions in the aortic sinus compared with atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group （P 〈 0.001）. Atherosclerotic lesions in the aortic sinus in the high-methionine and high-fat group were the most severe. Conclusions Homocysteinemia accelerates atherosclerotic lesions and induces early atherosclerosis independently in LDLrmice. Reducing the level of homocysteinemia may be beneficial for prevention and treatment of CHD.

Levels of serum homocysteine in depressive patients Self-correlation factor analysis and comparison with healthy subjects

BACKGROUND： Data indicate that the levels of serum homocysteine in depressive patients are higher than those in normal subjects. OBJECTIVE： To investigate the levels of serum homocysteine in patients with major depressive disorder, to determine whether serum homocysteine levels differ with sex, family history, or drug treatment, and to compare depressive patients with normal subjects. DESIGN： Non-randomized concurrent control trial. SETTING： Mental Heath Center of Shandong Province. PARTICIPANTS： Forty in-patients （23 males and 17 females, 18-63 years old） with major depressive disorder were selected from the Mental Health Center of Shandong Province from January to October 2006. All selected patients met the depressive diagnostic standard of Chinese Classification of Mental Disorder （3^rd Edition, CCMD-3）, and total scores evaluated by the 17-item Hamilton Rating Scale for Depression （HRSD） were ≥ 20. Meanwhile, 36 healthy subjects （20 males and 16 females, 18-60 years old） were enrolled as controls; their total 17-item HRSD scores were ≤ 7. All selected subjects provided consent, and the study was approved by the local ethics committee. METHODS： Fasting venous blood （3 mL） was drawn in both groups at 8：00 in the morning. The levels of serum homocysteine were determined by a fluorescence polarization immunoassay （FPIA）. The 17-item HRSD was also compiled from the patients when entering groups. The higher the scores were, the more severe the depression was. Enumeration data for both groups were compared by Chi-square test, measurement data were compared by t-test, and correlations were detected using Pearson and Spearman correlation analysis. MAIN OUTCOME MEASURES： ① Levels of serum homocysteine; ② incidence of hyperhomocysteinemia （HHcy）; ③ correlation between HRSD17 scores and levels of serum homocysteine in depressive patients. RESULTS： Forty depressive patients and 36 control subjects were included in the final analysis without any loss of participants. ① Levels of serum homocysteine and HHcy detection rate： the levels of serum homocysteine in the depressive patients were significantly higher than those in the control group （t = 4.377, P=0.000）. Hhcy detection rates were 42% （17/40） and 10% （4/36） in depressive group and control group, respectively. There was a significant difference between two groups （x^2 = 10.912, P = 0.001）. In the depressive group, there were no differences in serum homocysteine levels between males and females, before and after treatment, or between patients with positive or negative family histories of depression （t = 0.217-0.520, P 〉 0.05）. ② Correlation analysis： the HRSD17 scores in the depressive group were positively correlated with levels of serum homocysteine （r = 0.724, P = 0.000）. CONCLUSION： ① The increase in serum homocysteine levels may play an important role in the pathogenic mechanism of depressive disorder. ② The higher the levels of serum homocysteine are, the more severe the depressive disorder is. ③ There are no significant differences in serum homocysteine levels between patients of different sex or family history, or before and after drug treatment, among depressive patients.

Factors influencing ischemic cerebrovascular disease complicated by hyperhomocysteinemia

BACKGROUND： Hyperhomocysteinemia, as an important risk factor for ischemic cerebrovascular disease is receiving increasing attention. OBJECTIVE： To analyze whether differences of gender, age, cerebrovascular disease typing, and disease conditions exist when ischemic cerebrovascular disease occurs together with hyperhomocysteinemia. DESIGN： A controlled observation. SETTING： Department of Neurology, Tianjin Huanhu Hospital. PARTICIPANTS： A total of 601 acute ischemic cerebrovascular disease inpatients, comprising 386 males and 215 females, aged 33-90 years old, were admitted to the Department of Stroke, Tianjin Huanhu Hospital between August 2005 and April 2007, and were recruited for this study. All included patients consisted of 342 aged patients （≥ 60 years old） and 92 middle-aged and young patients （〈 60 years old）. Among these patients, 48 suffered from transient cerebral ischemic attack, 138 from lacunar cerebral infarction, 273 from atherosclerotic stroke, 38 from cardiogenic cerebral infarction, 44 from agnogenic ischemic stroke, and 6 from other factor-induced ischemic strokes. All included inpatients corresponded to the diagnosis criteria of acute ischemic cerebrovascular disease, formulated in the 4^th National Working Conference of Cerebrovascular Disease, and were confirmed as acute ischemic cerebral infarction by CT and/or MRI examinations. Informed consents of laboratory measurements were obtained from all subjects, and this study was approved by the Hospital＇s Ethics Committee. METHODS： Following admission, 2 mL venous blood was collected from each fasting patient on the third morning. Plasma homocysteine level was measured by an enzymatic cycling assay with a CX5 reader （Beckman, USA）. Plasma homocysteine levels ≥ 16μ mol/L were defined as hyperhomocysteinemia. Clinical neurological function deficit scoring was also performed for each ischemic stroke patient using Chinese stroke scales. Scores ranged from 0 45 （0-15： mild neurological function deficits, 16-30： moderate neurological deficits, and 31-45： severe neurological deficits）. The scores positively correlated with severity of stroke. MAIN OUTCOME MEASURES： Incidence of ischemic cerebrovascular disease patients complicated by hyperhomocysteinemia and the effects of patient age and gender; plasma homocysteine levels of each type of ischemic cerebrovascular disease; and effects of ischemic cerebrovascular disease conditions on plasma homocysteine levels. RESULTS： All 601 inpatients with acute ischemic cerebrovascular disease were included in the final analysis. The detection rate of homocysteine was significantly higher in aged patients than in middle-aged and young patients （ x^2 = 5.353 0, P 〈 0.05）. The incidence of hyperhomocysteinemia was significantly higher in male patients than in female patients （ x^2 = 9.484 4, P 〈 0.05）. There was no significant difference in the incidence of hyperhomocysteinemia among various types of ischemic cerebrovascular diseases （P 〉 0.05）. No significant difference in incidence of hyperhomocysteinemia existed between mild, moderate, and severe cerebrovascular disease patients （P 〉 0.05）. CONCLUSION： There is a greater chance of ischemic cerebrovascular disease complicated by hyperhomocysteinemia in older, male patients.

Brain cell apoptosis and enhancement of nervous excitability in pregnant rats with high plasma levels of homocysteine

Hyperhomocysteinemia is an important risk factor for preeclampsia-eclampsia. This study established a pregnant rat model of hyperhomocysteinemia, in which blood plasma homocysteine concentrations were twice or three times greater than that of normal pregnant rats. TUNEL revealed an increase in the number of apoptotic cells in the frontal cortex of pregnant rats with hyperhomocysteinemia. In addition, immunohistochemical staining detected activated nuclear factor-KB-positve cells in the frontal cortex. Reverse transcription-PCR detected that mRNA expression of the anti-apoptotic gene bcl-2 diminished in the frontal cortex. In situ hybridization and western blotting revealed that N-methyi-D- aspartate receptor 1 mRNA and protein expression was upregulated in the frontal cortex and hippocampus. These results indicate that hyperhomocysteinemia can induce brain cell apoptosis, increase nerve excitability, and promote the occurrence of preeclampsia in pregnant rats.

Hyperhomocysteinemia in ulcerative colitis is related to folate levels

AIM: To study the prevalence and clinical significance of hyperhomocysteinemia (hHcys), an independent factor for arterial and venous thrombosis, in a group of patients with ulcerative colitis (UC).METHODS: Fasting homocysteine (Hcys), folate, and vitamin B12 serum levels were measured in 40 UC patients and 50 healthy controls. Clinical data regarding UC were gathered.RESULTS: Median serum Hcys levels in UC patients were similar to those in controls (12.26 μmol/L vs 12.32 μmol/L), but the prevalence of hHcys was higher in UC patients than in controls (30% vs 10%, P= 0.028). UC significantly increased the risk of hHcys (adjusted odds ratio: 4.125;95% CI: 1.26-13.44). Multivariate regression analysis showed that male sex, folate and vitamin B12 deficiency or lower serum values were significant independent predictors of higher Hcys levels in UC patients (r2 = 0.4; P＜0.001).CONCLUSION: hHcys is common in UC patients and it is related to folate and vitamin B12 deficiency or lower serum values. It would be reasonable for patients with UC to receive folate and vitamin B complex supplements as a prophylactic measure.

Homocysteine, Vitamin B12 and Folic Acid in Children with Acute Glomerulonephritis

Homocysteine (Hcy) is an intermediate product of methionine formed by its demethylation. Hcy can be metabolized via remethylation to methionine or transsulfuration to cysteine which is dependent on several enzymes and cofactors. It is deleterious to blood vessel including glomeruli. Kidney is a major organ that metabolizes Hcy. More than 80% of patients with chronic renal disease develop hyperhomocysteinemia (hHcy). Accessible data of plasma Hcy in nephritic syndrome (NS) patients are controversial with increased, decreased and unchanged values reported. In renal patients, plasma Hcy concentration can be reduced by administration of folic acid. Absolute or relative deficiencies of folate, vitamin B6, or vitamin B12 may also play a role. Therefore, plasma Hcy, folic acid, vitamin B6, and vitamin B12 in children with acute glomerulonephritis (AGN) were accessed in this study. Hcy, folic acid vitamin B12, B6 and renal function such as blood urea nitrogen (BUN), creatinine (Cr) were analyzed 12 pediatric patients with AGN and 15 age and sex matched healthy children served as controls. The results revealed that a?significant increase in plasma Hcy in children with acute AGN when compared with controls. For simple regression analysis, Hcy was positively correlated with BUN, Cr, ferritin and uric acid but negatively correlated with serum glutathione. This research indicated hHcy suggests enhanced risks for inflammation and endothelial injury,?which lead to kidney disease. Folic acid has also been shown to improve endothelial function, suggesting an alternative explanation for the effect of folic acid on endothelial function. Careful considerations of not only dietary measures are necessary but also folate and vitamin B supplementation for reducing hHcy in AGN need to be investigated.

Evaluation of Plasma Homocysteine Levels in Type II Diabetes and Hypertensive Patients Attending University of Port Harcourt Teaching Hospital, Nigeria

Background: Homocysteine is an important non-protein amino acid, very useful in all methylation reactions occurring in the body as the precursor of the sole methyl group donor S-Adenosyl-methionine (SAM). However, elevated plasma homocysteine levels have been reported to contribute to epithelial damage leading to coronary artery disease and other metabolic syndromes. This study was aimed at evaluating the concentration of plasma homocysteine in diabetics and hypertensive patients in Port Harcourt, Nigeria. Methods: The study population included 60 Type II diabetes mellitus and Hypertensivesubjectsas group (I), 60 Type II diabetes mellitus and Normotensive subjects as group (II), 60 Hypertensive subjects as group (III), and 60 healthy subjects as control group within the age range of 30 - 70 years. An enzyme-linked immunosorbent assay (ELISA) method was used to quantitatively measure homocysteine in the serum sample, glycated haemoglobin were determined quantitatively using sandwich immunodetection and blood pressure was determined using mercury sphygnanometer. Statistics: The statistical analysis was done using GraphPad Prism version 9.4.1, and statistical significance was determined by a P Results: The results showed significantly higher plasma homocysteine levels in diabetics and hypertensive comorbidity patients when compared to healthy controls, P Conclusion: Our result shows an increase in plasma homocysteine levels in diabetics and hypertensives when compared to controls, and comorbidity instigates a higher increase in plasma levels when compared with the single morbidity.

Association between Hyperhomocysteinemia and Microangiopathic Complications (Neuropathy and Nephropathy) in Subjects with Type 1 and Type 2 Diabetes

This prospective case-control study aimed to assess the prevalence of hyperhomocysteinemia and explore its potential correlation with microangiopathic complications, specifically nephropathy and neuropathy, in a cohort of both type 1 and type 2 diabetic patients. Conducted at the Marc Sankalé Center of Abass Ndao Hospital in Dakar from June to September 2018, the study enrolled a total of 106 diabetic patients, comprising 93 type 2 diabetics and 13 type 1 diabetics, who were matched with control subjects free from clinically detectable pathologies, based on sex and age ± 2 years. The mean age of type 1 and type 2 diabetic patients was 24.46 ± 8.41 years and 57.28 ± 11.28 years, respectively. Our findings revealed a statistically significant elevation in mean homocysteine levels among patients when compared to controls (12.63 vs. 9.88;p < 0.0001). Hyperhomocysteinemia was observed in 24.5% of the patients, exclusively among those with type 2 diabetes. Within the hyperhomocysteinemia subgroup, 58% were male, and 42% were female. The analysis of neuropathy and nephropathy frequencies among type 2 diabetic patients, stratified by homocysteine concentrations, demonstrated a notably higher prevalence of diabetic nephropathy in patients with hyperhomocysteinemia compared to those with normohomocysteinemia (23.07% vs. 8.75%;p = 0.052). Similarly, diabetic neuropathy exhibited a significantly greater frequency in patients with hyperhomocysteinemia as opposed to normohomocysteinemia (80.76% vs. 50%;p = 0.005). Furthermore, our results established a significant positive correlation between homocysteine concentrations and both age (r = 0.402;p < 0.0001) and creatinine levels (r = 0.461;p < 0.0001). Bivariate logistic regression analysis indicated that patients with hyperhomocysteinemia faced 3 times and 6 times higher risks of developing neuropathy (OR = 3.5;p = 0.061) and diabetic nephropathy (OR = 6.092;p = 0.014), respectively.

Homocysteine is associated with the progression of non-culprit coronary lesions in elderly acute coronary syndrome patients after percutaneous coronary intervention

Background The influence of homocysteine （Hcy） on the migration and proliferation of vascular smooth muscle cells has been well established. However, the impact of Hcy levels on the progression of non-culprit coronary lesions （NCCLs） is controversial. This study aims to evaluate whether the plasma level of Hcy is related to the progression of NCCLs after percutaneous coronary stent implantation in elderly patients with acute coronary syndrome （ACS）. Methods A total of 223 elderly patients （〉 65 years old） with ACS undergoing stent im- plantation and follow-up coronary angiography were enrolled. Laboratory determination comprised of blood sample evaluation for Hcy was carried out before baseline coronary intervention. The patients were classified into two groups according to the blood Hcy tertiles （〉 15 mmol/L or 〈 15 mmol/L）. Patients were followed up for 12.2 months. NCCL progression was assessed by three-dimensional quantitative coronary angiography. Results A significantly higher ratio of NCCL progression was observed in the group with baseline Hcy concentrations above 15 mmol/L compared to the group with concentrations below 15 mmol/L （41/127, 32.3% vs. 14/96, 14.6%, P = 0.002）. Multivariate Cox regression analysis showed that Hcy and diabetes mellitus were independent risk factors for NCCL progression. The crude haz- ard ratio （HR） of NCCL progression for Hcy level was 1.056 （95% CI： 1.01-1.104, P = 0.015）. The adjusted HR of NCCL progression for Hcy level was 1.024 （95% CI： 1.007-1.042, P = 0.007）. The adjusted HR of NCCL progression for diabetes mellitus was 1.992 （95% CI： 1.15-3.44, P = 0.013）. Conclusions Hcy is an independent risk factor for NCCL progression after 12 months of follow-up in elderly patients with ACS who has undergone percutaneous coronary stenting.

Association between serum homocysteine and arterial stiffness in elderly： a community-based study

Background Arterial stiffness and homocysteine are both powerful predictors of cardiovascular disease, especially in older popula tions. Previous studies have investigated the association of homocysteine with arterial stiffness in human subjects, while the relationship between homocysteine and arterial stiffness in the elderly is still indefinite. The current study examined the association of homocysteine with arterial stiffness in Chinese community-based elderly persons. Methods We related serum levels of homocysteine to two measures of arte- rial stiffness （carotid-femoral pulse wave velocity （PWV） and carotid-radial PWV） in 780 participants （46.3% men, mean age 71.9 years （ranging 65-96 years old）） from two communities of Beijing, China. Arterial stiffness were measured within two days of the time of bio- marker measurement. Results In multiple-adjusted models, homocysteine levels was strongly associated with the carotid-femoral PWV （standardized 13 = 0.13, P 〈 0.001）, even after adjustment for classical risk factors of cardiovascular disease. The association is also stronger when the carotid-femoral PWV is elevated above normal, whereas no significant association with homocysteine was observed for ca-rotid-radial PWV. Conclusions In Chinese elderly persons, serum homocysteine levels are associated with alterations of aortic stiffness.

Association Between Homocysteine Level and Methylenetetrahydrofolate Reductase Gene Polymorphisms in Type 2 Diabetes Accompanied by Dyslipidemia

Objective To investigate the association between total homocysteine(tHcy)level in plasma and methylenetetrahydrofblate reductase(MTHFR)C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus(T2DM)accompanied by dyslipidemia.Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively.Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C.Plasma tHcy and lipid levels were measured as well.The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test.Plasma tHcy level ofT2DM patients who carried the different genotypes was compared by Student's t test.Results Finally,82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study.There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism inT2DM patients(t=2.27,P=0.02).Moreover,the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677TT genotype was significantly higher than that in those with CT+CC genotype(13.62+6.97 vs.10.95+3.62pmol/L,t=2.2O,P=0.03);while for patients without dyslipidemia,comparison of the tHcy level between those who carried the above two alleles showed no significantly difference(13.34±6.03 vs.12.04±5.09μmol/L,t=1.08,P=0.29).Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.

Plasma Homocysteine and Gene Polymorphisms Associated with the Risk of Hyperlipidemia in Northern Chinese Subjects

Objective To examine the relationship between occurrence of hyperlipidemia, plasma homocysteine and polymorphisms of methylenetetra hydrofolate reductase （MTHFR） gene and methionine synthase （MS） gene. Methods A total of 192 hyperlipidemia patients were selected and divided into hypercholesterolemia group, hypertriglyceridemia group, and combined hyperlipidemia group. Another 208 normal individuals were selected as control. Total plasma homocysteine （tHcy） concentration was measured by high-performance liquid chromatography （HPLC）. Lipid profiles were measured for all subjects The polymorphisms of MTHFR gene C677T and MS gene A2756G were analyzed by PCR-RFLP. Results The tHcy concentration in the combined hyperlipidemia patients was significantly higher than that in the control （15.95μmol/L vs 13.43 μmol/L, P〈0.05）. The prevalence of hyperhomocysteinemia （HHcy） in the combined hyperlipidemia group was significantly higher than that in the control （42.2% vs 23.0%, P=0.015）, with the odds ratio （OR） of 3.339 （95%CI： 1.260-8.849）. The hyperlipidemia patients with HHcy had a higher concentration of total cholesterol （TC） than that in the normal tHcy patients （5.67±0.95 mmol/L vs 5.47±0.92 retool/L, P=0.034）. There was no significant difference in genotype or allele frequencies of MTHFR C677T between the hyperlipidemic and control groups. The hyperlipidemia patients with MTHFR CT/TT genotype had a higher concentration of triglyceride （TG） than those with CC genotype （2.24±1.75 mmol/L vs 1.87±0.95 mmol/L, P〈0.05）. Individuals with CT/TT genotype had a higher concentration of tHcy than those with 677CC genotype both in the hyperlipidemia group （12.61±1.24μmol/L vs 11.20±1.37 μmol/L, P〈0.05） and in the control group （14.04±1.48 μmol/L vs 12.61±1.24 μmol/L, P〈0.05）. The percentage of MS 2756 GG/AG genotype in the combined hyperlipidemia group was significantly higher than that in the control （26.7% vs 13.0%, P=0.012）, with the OR of 3.121 （95%C1： 1.288-7.65/）. The hyperlipidemia patients with MS 2756AG/GG genotype had a higher concentration of TC （5.87±0.89 mmol/L vs 5.46±0.93 retool/L, P〈0.05） and LDL-C （3.29±0.81 mmol/L vs 2.94±0.85 retool/L, P〈0.05） than those with AA genotype. However, individuals with 2756AG/GG genotype showed no significant difference in tHcy among those with AA genotype. Conclusion HHcy and MS A2756G mutation may be the risk factors for combined hyperlipidemia. Further study is needed to confirm the role of HHcy and MS A2756G mutation in the development of hyperlipidemia.

Association between Serum Homocysteine and Oxidative Stress in Elderly Patients with Obstructive Sleep Apnea/hypopnea Syndrome

Objective Elderly patients with obstructive sleep apnea/hypopnea syndrome （OSAHS） has a higher risk of cardiovascular and cerebrovascular disease. However, changes of homocysteine （Hey） as markers of cardiovascular and eerebrovascular disease associated with OSAHS and their mechanism have not been elucidated so far. This study aims to investigate the changes of both serum Hcy and oxidative stress and their possible links with OSAHS in elderly patients. Methods Based on polysomnogram （PSG） and age, 83 patients with OSAHS were recruited and divided into elderly-OSAHS （n=32） and non-elderly OSAHS groups （n=51）. Fifty two subjects without OSAHS were divided into elderly control （n=29） and non-elderly control groups （n-23）. A total of 135 subjects were included in the present study. All subjects were recorded for PSG variables and the contents of homocysteine （Hcy）, malonaldehyde （MDA）, and glutathione （GSH） which were detected after sleep. Serum homocysteine was measured by cyclophorase. MDA and GSH were measured by speetrophotometer. Results （1） The serum levels of Hcy showed significant difference among the four groups （P〈0.05）. The concentrations of Hcy in elderly OSAHS patients were higher than in other groups, while those in the elderly control group were higher than in the non-elderly control; the concentrations in the non-elderly OSAHS group were higher than in the non-elderly control. （2） The concentrations of MDA and GSH changed at an equal pace with Hcy in the four groups. （3） Multielement linearity regression analysis indicated a statistically significant relationship between Hcy concentration and age, MDA, GSH, and apnea hypopnea index （AHI）. Conclusions （1） The concentrations of Hcy and oxidative stress have increased with advancing age. （2） The concentrations of Hcy and oxidative stress have further increased in the elderly patients with OSAHS. （3） Oxidative stress might cause high-level serum Hcy in the elderly patients with OSAHS.

Increased levels of homocysteine in patients with ulcerative colitis

AIM: To investigate serum levels of homocysteine (Hcys) and the risk that altered levels carry for thrombosis development in ulcerative colitis (UC) patients. METHODS: 55 UC patients and 45 healthy adults were included. Hcys, vitamin B12 and folic acid levels were measured in both groups. Clinical history and thrombo- embolic events were investigated. RESULTS: The average Hcys level in the UC patients was 13.3 ± 1.93 μmmol/L (range 4.60-87) and was higher than the average Hcys level of the control group which was 11.2 ± 3.58 μmmol/L (range 4.00-20.8) (P < 0.001). Vitamin B12 and folic acid average values were also lower in the UC group (P < 0.001). Whenmultivariate regression analysis was performed, it was seen that folic acid deficiency was the only risk factor for hyperhomocysteinemia. Frequencies of thromboembolic complications were not statistically significantly different in UC and control groups. When those with and without a thrombosis history in the UC group were compared according to Hcys levels, it was seen that there were no statistically significant differences. A negative linear relationship was found between folic acid levels and Hcys. CONCLUSION: We could not find any correlations between Hcys levels and history of prior thromboembolic events.

Elevated Homocysteine and C-reactive Protein Levels Independently Predict Worsening Prognosis after Stroke in Chinese Patients

Increased plasma total homocysteine (tHcy) and high sensitivity C-reactive protein (hsCRP) levels are independent risk factors for cardiovascular disease.However, the predictive value of tHcy in combination with hsCRP in patients with stroke is not known.To determine the relationship between tHcy and hsCRP, we enrolled 291 patients with first-onset stroke (196 ischemic and 95 hemorrhagic).Plasma tHcy and hsCRP levels were measured and subsequent vascular events and deaths were determined over a 5-year period.Using the arbitrary cutoff for tHcy (【18 μmol/L and ≥18 μmol/L) and hsCRP (【1 mg/L, 1-3 mg/L and 】3 mg/L), the patients were divided into 6 groups.Survival analysis showed that the probability of death or new vascular events during a 5-year follow-up increased according to tHcy and hsCRP levels (P【0.01).The relative risk (RR) of death or new vascular events was 4.67 (95% CI, 1.96 to 11.14, P=0.001) in patients with high tHcy (≥18 μmol/L) and hsCRP (】3 mg/L) compared with those with low tHcy (【18 μmol/L) and hsCRP (【1 mg/L).The increased tHcy level (≥18 μmol/L) combined with increased hsCRP level (】3 mg/L) was still significantly associated with the risk of death or new vascular events (RR, 4.10, 95% CI, 1.61 to 10.45, P=0.003) even when adjusted for other risk factors at inclusion.The combination of increased tHcy and hsCRP levels had a stronger predictive value than increased hsCRP alone or increased tHcy level alone.Further studies are required to evaluate the potential decrease in risks associated with lowering both Hcy and hsCRP levels in patients that present with both increased tHcy and hsCRP.

Effect of advanced age on plasma homocysteine levels and its association with ischemic stroke in non-valvular atrial fibrillation

Background Elevated homocysteine （Hcy） has been reported to be associated with cardiovascular events in atrial fibrillation （AF） pa- tients, while the age-related expression pattern of plasma Hcy in AF remains unknown. The study was aimed to investigate the effect of ad- vanced age on plasma Hcy levels and its association with ischemic stroke in non-valvular AF patients. Methods A total of 2562 consecu- tive patients with non-valvular AF and 535 controls were enrolled and divided into six age groups. Plasma Hcy levels were analyzed among different age groups, and the effect of advanced age on Hcy was investigated. Results Plasma Hcy levels did not show any difference among groups aged below 65 years, while it increased sharply in patients aged 65-74 years and aged over 75 years （15.7 ±4.6 μmol/L, 17.1 ±4.9 μmol/L, both P 〈 0.01 compared with the first four age groups）. Hcy was much higher in AF patients than in controls at the same age group （all P 〈 0.05）. The proportion of patients with hyperhomocysteinemia increased gradually with age from 32.3%, 29.2%, 31.2%, 32.4%, 45.9%, to 51.4% in six age groups. The concentration of Hcy in AF patients with ischemic stroke increased progressively with age, and was higher than those without stroke at the same age. Logistic regression analysis demonstrated that age 65-74 years [odds ratios （OR）： 1.742, 95% confidence interval （CI）： 1.223-2.482, P = 0.002] and age ≥ 75 years （OR： 2.637, 95% CI： 1.605-4.335, P 〈 0.001） were significantly independent predictors of elevated plasma Hcy levels. Conclusions Advanced age was significantly associated with elevated Hcy levels, which may provide a possible explanation for the progressive increase in ischemic stroke especially in elderly AF patients.

High Prevalence and Factors Contributing to Hyperhomocysteinemia, Folate Deficiency, and Vitamin B_(12) Deficiency among Healthy Adults in Shanghai, China

Elevated plasma or serum total homocysteine (tHcy) level has been established as a risk factor for cardiovascular disease[1], as well as dementia and cognitive decline[2]. Plasma or serum folate and vitamin B12 influence homocysteine (Hcy) metabolism as a co-substrate and cofactor respectively, so that low concentrations of folate and vitamin B12 are also associated with high Hcy levels[1]. However, not much information is available describing serum tHcy, folate, and vitamin B12 status in Shanghai adults, especially in a healthy population. Therefore, we hypothesize that low serum folate and vitamin B12 is associated with high Hcy in healthy adults in Shanghai. The aim of this study was to determine the status of serum tHcy, folate, and vitamin B12, and the prevalence and factors contributing to HHcy, folate deficiency, and vitamin B12 deficiency among healthy adults in Shanghai, China.

Endogenous hydrogen sulfide and ERK1/2-STAT3 signaling pathway may participate in the association between homocysteine and hypertension

Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical data of primary hypertensive patients admitted to our hospital.Secondly,we explored a rat model to study the effect of Hcy on blood pressure and the role of H2S.An hyperhomocysteinemia(HHcy)rat model was induced to explore the effect of Hcy on blood pressure and the possible mechanism.We carried out tissue histology,extraction and examination of RNA and protein.Finally,we conducted cell experiments to determine a likely mechanism through renin-angiotensin-aldosterone system(RAAS)and extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway.Results In primary hypertensive inpatients with HHcy,blood pressure was significantly higher as compared with inpatient counterparts lacking HHcy.In the rat model,blood pressure of the Wistar rats was significantly increased with increases in serum Hcy levels and decreased after folate treatment.Angiotensin converting enzyme 1(ACE1)expression in the Wistar Hcy group was enhanced comparing to controls,but was decreased in the Wistar folate group.Angiotensin II receptor type 1(AGTR1)levels in the kidney tissue increased in the Wistar folate group.Both serum H2S and kidney cystathionineγ-lyase decreased with elevated levels of serum Hcy.In vitro,increased concentrations and treatment times for Hcy were associated with increased expression of collagen type 1 and AGTR1.This dose and time dependent response was also observed for p-STAT3 and p-ERK1/2 expression.Conclusion Endogenous H2S might mediate the process of altered blood pressure in response to changes in serum Hcy levels,in a process that is partly dependent on activated RAAS and ERK1/2-STAT3 signaling pathway.

Association between serum homocysteine and arterial stiffness：role of anti-hypertensive drugs

To the Editor I read the article of Zhang, et al. with great interest. They investigated the association of homocysteine with arterial stiffness in Chinese community-based elderly persons. The carotid-femoral pulse wave velocity （PWV） was significantly higher in the high homocyteine group than in the normal one, however, there was no differences in carotid-radial PWV between the high homocyteine group and the normal one. Homocysteine levels were strongly associated with the carotidfemoral PWV even after adjustment for classical risk factors of cardiovascular disease. I congratulate the authors for this important study. However, I want to make minor criticism for this study from the methodological aspect.

Study on the Relationship between Plasma Homocysteine and Acute Cerebral Vascular Disease

The levels of plasma homocysteine were determined by using high-performance liquid chromatographic method. It was found that plasma homocysteine levels were significantly higher in the patients with stroke than that in the controls. There was no correlation between plasma homocys- teine levels and hypertension, smoking, concentrations of blood glucose or hypertriglyceridesemia. It was suggested that hyperhomocysteinemia may be an independent risk factor for acute cerebral vascu- lar disease.