Plasma Homocysteine Levels Research Articles

Plasma Homocysteine and Prognosis of Patients with Recanalization after Acute Basilar Artery Occlusion: An Analysis from the Acute Basilar Artery Occlusion Study (BASILAR) Nationwide Prospective Registry.

Few studies have investigated the association between plasma Homocysteine (Hcy) levels in patients with recanalization after acute Basilar Artery Occlusion (BAO). This study investigated the predictive value of Hcy on the clinical prognosis of patients with recanalization after acute BAO. Altogether, 829 participants were recruited from the standard medical treatment plus endovascular treatment group of the Acute Basilar Artery Occlusion Study (BASILAR). Hcy levels were measured the morning after admission. The primary outcome was a combination of death and major disability (modified Rankin Scale score 4-6) at 90 days, and the secondary outcome was the mortality of patients with recanalization after acute BAO within 90 days. We used multivariable logistic regression modeling to estimate the association between Hcy and prognosis in our participants at 90 days. Altogether, 647 patients were assessed, and 302 patients were included in this study. The median was 12.88 μmol/L, and the mean Hcy concentration was 15.49 μmol/L. Elevated plasma Hcy levels (Hcy >12.88 μmol/L) were associated with poor functional outcomes (adjusted odds ratio 1.922, 95% confidence interval (CI) 1.048-3.528, P=0.035), but not with mortality (adjusted odds ratio 1.605, 95% CI 0.986-2.489, P=0.058). In further subgroup analysis, the conclusion was consistent in all predefined subgroups. Our analysis suggests that elevated plasma Hcy levels have a predictive value for functional outcomes in patients with recanalization after acute BAO during the 90-day follow-up period, but not for mortality.

CRIF1 Deficiency Increased Homocysteine Production by Disrupting Dihydrofolate Reductase Expression in Vascular Endothelial Cells.

Elevated plasma homocysteine levels can induce vascular endothelial dysfunction; however, the mechanisms regulating homocysteine metabolism in impaired endothelial cells are currently unclear. In this study, we deleted the essential mitoribosomal gene CR6 interacting factor 1 (CRIF1) in human umbilical vein endothelial cells (HUVECs) and mice to induce endothelial cell dysfunction; then, we monitored homocysteine accumulation. We found that CRIF1 downregulation caused significant increases in intracellular and plasma concentrations of homocysteine, which were associated with decreased levels of folate cycle intermediates such as 5-methyltetrahydrofolate (MTHF) and tetrahydrofolate (THF). Moreover, dihydrofolate reductase (DHFR), a key enzyme in folate-mediated metabolism, exhibited impaired activity and decreased protein expression in CRIF1 knockdown endothelial cells. Supplementation with folic acid did not restore DHFR expression levels or MTHF and homocysteine concentrations in endothelial cells with a CRIF1 deletion or DHFR knockdown. However, the overexpression of DHFR in CRIF1 knockdown endothelial cells resulted in decreased accumulation of homocysteine. Taken together, our findings suggest that CRIF1-deleted endothelial cells accumulated more homocysteine, compared with control cells; this was primarily mediated by the disruption of DHFR expression.

Association of folate and vitamin B12 deficiency with vasovagal syncope: a case-control study

Abstract Background Studies demonstrated an association between vitamin B12 deficiency and vasovagal syncope (VVS) in pediatric patients. Moreover, some evidence suggested a pathophysiological role of plasma catecholamines elevation in VVS, which can arise from folate or vitamin B12 deficiency in terms of biochemical pathways. Purpose We aimed to evaluate the association of folate and vitamin B12 deficiency with VVS in adults. Methods In this case-control study, adult patients (18–70 years of age) with the diagnosis of VVS based on history and physical examination (2018 ESC guidelines) who underwent a head-up tilt test (HUTT) were included as the case group. The control group comprised age- and sex-matched individuals who participated in a population-based cohort study. The most important exclusion criteria were taking vitamin B12 or folate supplements, carbamazepine and phenobarbital, and a history of bariatric surgeries. Plasma levels of vitamin B12, folate, homocysteine, and thyroid-stimulating hormone (TSH), a possible confounder, were measured by Abbott Diagnostics chemiluminescence kits. We compared categorical variables and continuous variables by Chi-square and t-test, respectively. Logistic regression models were employed for adjusting for possible confounders, including age, sex, and TSH. Results From February 2020 to February 2021, we screened 157 patients with VVS, of whom 44 patients were included. After matching for age and sex, 44 healthy individuals without a history of syncope were examined as the control group. The mean age was 37.9 years in both groups, with 23 women (52.3%) in each group. Baseline characteristics were comparable across the study groups. There were no significant differences between serum levels of vitamin B12, folate, homocysteine, and TSH, as well as the prevalence of deficiency of folate and vitamin B12 between case and control groups (Table 1), even after adjusting for confounding variables. Serum levels of vitamin B12 were remarkably lower in patients with a lifetime syncopal episodes of ≥3 compared to patients with <3 lifetime attacks (Table 2, P=0.042). This correlation remained statistically significant after adjusting for possible confounders, including age, sex, and TSH by the logistic regression model (P=0.032). Conclusions In this study, we found that there is no significant difference between the prevalence of folate and vitamin B12 deficiency and serum levels of these vitamins in adult patients with VVS and healthy individuals; however, serum vitamin B12 was significantly lower in patients with recurrent VVS compared to patients with a lower burden of syncopal episodes. Future studies with larger sample sizes are recommended in the recurrent VVS subgroup. Therapeutic implications of these findings should be investigated in randomized-controlled trials. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Iran National Science Foundation Table 1Table 2

Association between plasma homocysteine levels and cognitive deficits in Han Chinese patients with schizophrenia across age groups

It was still unclear how homocysteine (Hcy) levels and cognitive deficits change in patients with schizophrenia of various ages. The present article attempts to assess the relationship between Hcy levels and cognitive deficits in patients with schizophrenia across age groups, especially in young people. Totals of 103 patients and 122 healthy controls were included. All participants were stratified into four groups according to their age: 18–29 years, 30–39 years, 40–49 years, and 50–59 years. Clinical data, plasma Hcy levels, and cognitive function score were collected. Cognitive function was evaluated using the MATRICS Consensus Cognitive Battery of tests assessing speed of processing, verbal learning and memory, visual learning and memory, working memory, and attention/vigilance. Compared with the healthy group, Hcy levels increased significantly, and all the measured cognitive function score were significantly lower in all age groups of patients with schizophrenia (p < 0.001). Hcy levels were negatively associated with speed of processing (SoP), working memory (WM), and visual learning and memory (Vis Lrng) score in 18–29 years. Further multiple regression analysis showed that SoP were independently associated with Hcy levels in patients with schizophrenia aged 18–29 years (B = 0.74, t = 3.12, p = 0.008). Based on our results, patients with schizophrenia performed worse on cognitive assessments and Hcy levels were more closely related to cognition in young patients.

Effect of vitamin B12, folate, and entacapone on homocysteine levels in levodopa-treated Parkinson's disease patients: A randomized controlled study

Previous studies have suggested a significant increase in plasma homocysteine (Hcy) levels in levodopa-treated Parkinson's disease (PD) patients, and vitamin B12 and folate supplementation may decrease Hcy levels. However, the effects of catechol-O-methyltransferase inhibitors on levodopa-induced increase in Hcy levels were conflicting. The aim of this study was to evaluate whether Hcy levels are increased in levodopa-treated PD patients and to evaluate the effects of vitamin B12 and folate or entacapone on Hcy levels in levodopa-treated PD patients.

Homocysteine as a Predictor Tool in Multiple Sclerosis.

Multiple sclerosis (MS) is a progressive and irreversible disease which affects the central nervous system (CNS) with still unknown etiology. Our study aimes to establish the homocysteine pattern that can predict the MS diseases progression and to identify a potential disease progression marker that can be easy to perform and non-invasive, in order to predict the diseases outcome. In order to achieve this goal, we included 10 adult RRMS subjects, 10 adult SPMS subjects and 10 age-matched healthy subjects. The homocysteine plasma level was measured using automated latex enhanced immunoassay and the cobalamin and folate measurements were performed using automated chemiluminescence immunoassay (CLIA). HCR was calculated by dividing the homocysteine plasma level by cobalamin plasma level. We found that the homocysteine level in plasma of both RRMS patients and SPMS group are significantly increased compared with the control group. There is a significantly higher concentration of homocysteine in SPMS group compared with the RRMS group. In addition, the HCR is significantly increased in SPMS compared with the RRMS group and is a very good index of disease severity.

Levels of plasma homocysteine dynamics speciality in the development of acute postresection hepatic failure

This study aims to evaluate the level of plasma homocysteine in patients with acute post-resection hepatic failure, depending on the degree of the disease. Materials and Methods. The article presents the results of a study of plasma homocysteine levels in 40 patients with c different classes of acute post-resection liver failure. Indications for liver resection were: primary liver cancer 11 (27%), metastatic liver lesions 21 (53%), parasitic liver diseases 3 (7%), benign liver formations 5 (13%). Patients were divided into 3 groups - Patients with Post hepatectomy liver failure (PHLF) class developed in the postoperative period A, B and C. Results. Analysis of the data showed that the initially normal level of plasma homocysteine before liver resection (surgical treatment) and after has different developmental options. Depending on the class of post-resection hepatic failure, the level of plasma homocysteine changes and has deviations from the reference values. In a comparative analysis of the average homocysteine values in the group of patients with post-resection hepatic insufficiency of class A, after surgical treatment, they were significantly lower than in patients with PHLF B and C. In particular, in patients with class B and C PNF, there is a significant trend towards an increase in homocysteine levels after surgery. Hyperhomocysteinemia may be a risk factor for the development of acute liver failure after surgical treatment for focal liver disease. Possibly, its adverse effect on the function and restoration of the liver parenchyma, which requires further targeted study.

Changes in Total Homocysteine and Glutathione Levels After Laparoscopic Sleeve Gastrectomy in Children with Metabolic-Associated Fatty Liver Disease.

Paediatric obesity is a well-known risk factor for metabolic-associated fatty liver disease (MAFLD). The aim of this study was to evaluate the effects of laparoscopic sleeve gastrectomy (LSG) on the levels of total homocysteine (tHcy) and total glutathione (tGSH) plasma levels in children with MAFLD. Twenty-four children with severe obesity who underwent LSG were included in the study. The metabolic parameters, systemic inflammatory markers, one-carbon metabolism products, ultrasound and histological improvement were evaluated at baseline (T0M) and after 12months from LSG (T12M). The patients exhibited a significant amelioration of several metabolic parameters at T12M. A significant reduction of steatosis was observed at ultrasound (from 72.7% of moderate-severe grade to 0% severe steatosis), accompanied by a statistically significant improvement of ballooning, portal and lobular inflammation and fibrosis. A statistically significant decrease of tumour necrosis factor circulating levels was also observed (T0M median = 290.3, IQR = 281.0-317.0pg/mL; T12M median = 260.4, IQR = 240.0-279.0pg/mL; p < 0.0001). After 12months from LSG, a significant increase of mean plasma levels of tHcy(T0M mean = 15.7 ± 4.1μmol/L; T12M mean = 21.1 ± 9.3μmol/L; p = 0.0146) was also observed. The increase of tHcy showed no causal link with the improvement of MAFLD-related inflammatory, metabolic and histological pattern. LSG in children with obesity induces an improvement of MAFLD-related metabolic derangement and liver damage, but also a mild hyperhomocysteinemia that should be avoided to prevent cardiovascular risk.

Plasma Levels of Homocysteine is Associated with Liver Fibrosis in Health Check-Up Population.

ObjectStudies have shown a link between homocysteine (Hcy) and heart diseases, kidney diseases, cerebrovascular diseases, liver diseases, and other pathological conditions. However, the relationship between Hcy and liver fibrosis (LF) is unclear. Here, we studied the link between plasma Hcy concentration and LF.MethodsWe determined and recorded the plasma Hcy concentration, general biochemical parameters, and liver stiffness measurement (LSM) in 1582 subjects, followed by statistical data analyses.ResultsDuring different stages of LF, we found a considerable difference (p <0.001 unless specified) in body mass index (BMI), sex, age, Hcy, the levels of alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT; P = 0.012), triglycerides (TG; P = 0.006), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBS), and platelet count (PLT). There was a strong association between the plasma Hcy concentration and the serum biomarkers of LF (P <0.001) and the values of LSM (P <0.001).ConclusionThe plasma Hcy concentration was substantially different among different stages of LF. The higher the plasma Hcy concentration, the more evident was the degree of LF.

The interaction of hypertension and homocysteine increases the risk of mortality among middle-aged and older population in the United States.

To investigate the interaction of hypertension and total plasma homocysteine (tHcy) levels on risk of all-cause and cardiovascular disease (CVD) mortality among middle-aged and older population. This observational cohort study analyzed data from the National Health and Nutrition Examination Survey database (1999-2002 survey cycle). A generalized additive model (GAM) based on Cox proportional hazards models was applied to estimate the relationship of tHcy level with all-cause and CVD mortality. Stratification analyses by sex and renal function were performed. Among 5724 individuals aged 40-85, 704 (12.3%) died, with 339 CVD deaths after a median follow-up period of 5.58 years. Mean age was 60.7 ± 13.4 years (49.6% men). In the fully adjusted model, we found that per 1 μmol/l increment of plasma tHcy was associated with 8% increased risk of all-cause mortality and 7% increased risk of CVD mortality in hypertensive participants. The adjusted hazard ratio (95% CIs) for all-cause and CVD mortality were 1.08 (1.06-1.10) and 1.07 (1.04-1.10), respectively. There were pronounced interactive effects between hypertension and tHcy levels on risk of all-cause mortality (P for interaction = 0.031). Hypertension and tHcy levels can interactively affect the risk of all-cause mortality among middle-aged and older population. Conceivably, hypertension may further enhance the ability of elevated tHcy to provoke the risk of all-cause mortality.

A Case-Control Study Investigating the Effect of MTHFR C677T Variant on Performance of Elite Athletes.

Increased level of plasma homocysteine (Hcy) is a potential risk factor for several multi-system diseases. The Methylenetetrahydrofolate reductase (MTHFR) gene C677T variant has been established as an important genetic determinant of hyperhomocysteinemia. There are conflicting reports about the effects of physical activity on plasma Hcy. Therefore, the main aim of this study was to investigate whether the MTHFR C677T variant affects elite athletic performance. This study was carried out on 214 individuals (114 elite athletes and 100 sedentary controls). Genotyping was performed using PCR- RFLP method. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. There was a significant difference between the athletes and the control group in genotype distribution and allele frequency of the MTHFR C677T variant. MTHFR C677T CC genotype and C allele were more prevalent in elite athletes than those in the sedentary controls (p =0.007, OR: 2.16, 95%:1.26-3.70; p=0.009, OR: 1.84, 95%:1.18-2.89, respectively). The control group had a higher MTHFR C677T CT genotype than the athletes (p=0.019, OR: 0.51, 95%:0.30-0.88). There was no deviation from HWE for the MTHFR C677T variant in the groups. Our findings support that there is an association between the MTHFR C677T C allele and athletic performance among the elite Turkish athletes.

Association between high BMI and high homocysteine levels in Chinese patients with bipolar disorder

BackgroundBipolar disorder (BD) has been associated with an increased prevalence of weight gain and abnormally elevated plasma homocysteine (Hcy) levels. However, the relationship between BMI and Hcy in BD patients has not been investigated. This study aimed to explore this relationship in Chinese patients with BD. MethodsPlasma Hcy levels, socio-demographic parameters, clinical and anthropometric data were collected from 195 BD inpatients and 84 healthy controls. The level of plasma Hcy was determined by high-performance liquid chromatography. Body mass index (BMI) was calculated by body weight divided by the square of the height. The participants were divided into a high BMI group and a low BMI group using 24 kg/m2 as a threshold. ResultsThe prevalence of high BMI was slightly elevated in BD patients in comparison to healthy controls. Patients with elevated BMI had significantly higher Hcy levels than patients with low BMI. Hcy level was an independent contributor of the occurrence of high BMI in BD patients. The level of Hcy was positively correlated with BMI in BD patients. In addition, depressive episodes of BD were positively correlated with the prevalence of high BMI and married BD patients were more likely to have high BMI levels. ConclusionsThere is a close relationship between BMI and plasma Hcy levels in patients with BD, suggesting that Hcy may be an important indicator for BD-induced weight gain. This finding provides a new avenue for weight management of BD patients and to help avoid the potential risk of cardiovascular diseases.

The Impact of Homocysteine on the Risk of Hormone-Related Cancers: A Mendelian Randomization Study.

Background: Aberrant homocysteine level is associated with metabolic disorders and DNA damage, which may be involved in the carcinogenesis of hormone-related cancers, but clinical results of observational studies are controversial. In this study, we investigated the causal relationships between plasma homocysteine and breast cancer (BRCA), prostate cancer (PrCa), and renal cell carcinoma (RCC) using Mendelian randomization (MR) analyses.Design and Methods: To investigate the putative causal associations between homocysteine and the aforementioned three types of cancers, a two-sample MR study was employed for the study. The primary strategy for summary data analyses was the inverse-variance-weighted (IVW) approach. In our study, the single-nucleotide polymorphisms (SNPs) excluded confounding factors through Linkage Disequilibrium (LD). Phenoscanner tests were the instrumental variants (IVs), homocysteine was the exposure, and BRCA, PrCa, and RCC were the outcomes. Single-nucleotide polymorphisms associated with homocysteine were extracted from a large genome-wide association study (GWAS) meta-analysis of European participants (n = 44,147). Summary Statistics of BRCA were obtained from the latest and largest GWAS meta-analysis comprising of 82 studies from Breast Cancer Association Consortium (BCAC) studies, including women of European ancestry (133,384 cases and 113,789 controls); we obtained summary-level data from the GWAS meta-analysis of PrCa comprising 79,148 cases and 61,106 controls of European ancestry, and the dataset of RCC was a sex-specific GWAS meta-analysis comprising of two kidney cancer genome-wide scans for men (3,227 cases and 4,916 controls) and women (1,992 cases and 3,095 controls) of European ancestry. The MR-Egger and weight median analyses were applied for the pleiotropy test.Results: The results showed null associations between plasma homocysteine levels and overall BRCA (effect = 0.97, 95% CI: 0.90–1.06, P = 0.543), overall PrCa (effect = 1.01, 95% CI: 0.93–1.11, P = 0.774), RCC in men (effect = 0.99, 95% CI: 0.73–1.34, P = 0.929), and RCC in women (effect = 0.89, 95% CI: 0.61–1.31, P = 0.563).Conclusions: We found no putative causal associations between homocysteine and risk of BRCA, PrCa, and RCC.

English

Thrombosis of cerebral venous channel is a known complication of hypercoagulable states. Hyperhomocysteinaemia is a known hypercoagulable state. Obesity is a modern-day global epidemic. Disorders such as myocardial infarction (MI), stroke, and venous thromboembolism are on the rising trend and its increased morbidity and mortality is being associated with obesity. To date, however, the knowledge about the association between obesity and adult cerebral venous thrombosis (CVT) is sparse. We report a 44-year-old young morbidly obese metabolically unhealthy female who presented with headache, nausea, vomiting and giddiness. On evaluation, magnetic resonance venogram showed cerebral venous sinus thrombosis. On investigations, she had concomitant hyperhomocysteinaemia and metabolic syndrome. Cerebral venous sinus thrombosis causing stroke in young adults is uncommon with various conditions precipitating it.1,2,3 Severe headache (70 - 90 %), focal lateralized signs (25 % - 75 %), seizures (30 – 40 %) as well as behavioural symptoms such as delirium, amnesia, and disturbances in consciousness are the various associated clinical symptoms. The known inherited hypercoagulable risk factors that cause CVST are gain of function mutations in the genes encoding factor V (factor V Leiden) and prothrombin, Protein C, S and antithrombin III deficiency. Hyperhomocysteinaemia, is a known risk factor for causing venous thrombosis of the lower limbs. However, till date there is no data available showing its role in causing cerebral venous thrombosis. The interaction between genetic and acquired determinants result in high plasma levels of total homocysteine (tHcy).4,5,6 Vitamins such as folic acid, pyridoxine, and cobalamin are involved in the metabolic pathways of homocysteine and its deficiencies represent the acquired determinants. Venous thromboembolism (VTE) comprises of deep vein thrombosis of the leg and pulmonary embolism and obesity is now being recognised as one of the risk factors causing it. The risk of VTE is approximately increased to 2-fold in an individual with a body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 30 or more compared with a normal BMI (&lt; 25), and higher BMIs increase more risk with approximately 3 times higher risk in individuals with a BMI greater than 40.7, 8,9 Again obesity as a risk factor for CVST is less known.

Elevated Plasma Homocysteine Level Associated with Further Left Ventricular Structure and Function Damages in Type 2 Diabetic Patients: A Three-Dimensional Speckle Tracking Echocardiography Study.

Aims: The aims of this study were to explore the left ventricular (LV) structural remodeling and its risk factors in type 2 diabetes mellitus (T2DM) patients with or without hyperhomocysteinemia (hHcy) and to detect the accompanied LV dysfunction using three-dimensional speckle tracking echocardiography (3DSTE). Methods: There were totally 80 T2DM patients with undamaged LV ejection fraction (≥55%) in this study, 40 of whom were also diagnosed with hHcy as co-morbidity. Forty age- and gender-matched controls were also recruited. The risk factors and corresponding diagnostic values for LV remodeling (LVR) were, respectively, determined using logistic regression and area under the receiver operating characteristic curves (AUC). The 3DSTE was used to measure global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS). Results: The constituent ratio of LV geometry showed significant differences among the study populations (P = 0.01). Compared with the controls, three types of LVR accounted for larger proportion in the two T2DM groups, whereas LV hypertrophy was most prevalent in those with T2DM and hHcy. Glycosylated hemoglobin (HbA1c), total plasma homocysteine (tHcy), and HbA1c plus tHcy were all significant risk factors associated with LVR in T2DM patients (AUC values: 0.741, 0.746 and 0.851, respectively). The patients with T2DM alone had significantly lower GLS and GAS than the controls (both P < 0.05). The patients with T2DM and hHcy had significantly lower GLS, GCS, GAS, and GRS than the controls (all P < 0.001), and also had significantly lower GLS, GCS, and GRS than the patients with T2DM alone (all P < 0.05). Conclusions: The 3DSTE plus conventional echocardiography could be used as an effective supplement for detecting early and occult cardiac damages in T2DM patients with plasma homocysteine at normal or elevated levels.

Association between plasma homocysteine levels and pancreatic islet beta-cell function in the patients with type 2 diabetes mellitus: a cross-sectional study from China.

This study sought to investigate the association between plasma homocysteine (HCY) levels and pancreatic islet beta-cell function in type 2 diabetes mellitus (T2DM) patients. 430 hospitalized T2DM patients were enrolled in this cross-sectional study from December 2013 to December 2016. All participants were requested to complete a detailed questionnaire and undergo anthropometric measurements. Blood samples were collected from all participants. A 75-g oral glucose tolerance test (OGTT) was performed to diagnose T2DM in each individual, and an insulin releasing test (IRT) was used to calculate selected parameters for glucose, insulin, and C-peptide. Linear correlation and multivariate regression analyses were performed to assess the association between serum HCY concentration and these parameters. Patients were divided into the following subgroups based on quartiles of serum HCY levels: Group Q1: <17.03 µmol/L; Group Q2: 17.03-19.50 µmol/L; Group Q3: 19.5-24.7 µmol/L; and Group Q4: >24.7 µmol/L. The levels of fasting blood glucose (FBG), 2 h postprandial blood glucose (2hPBG), glycated hemoglobin A1c (HbA1c), fasting C-peptide and fasting insulin increased significantly as HCY levels increased (P<0.05). The area under the curves (AUCs) of serum glucose and insulin in IRT increased significantly and that of serum C-peptide decreased as HCY levels increased (P<0.05). The levels of Homeostasis Model Assessment-β (HOMA-β), Modified Beta-cell function Index (MBCI), Disposal Index (DI), C-peptide immunoreactivity (CPR), Insulinogenic Index 30 (IGI 30), and Secretory Units of Islets in Transplantation (SUIT) decreased as HCY levels increased. An inverse linear correlation was found between HOMA-β, MBCI, DI, CPR, IGI 30, SUIT 0 h, and HCY plasma concentration (R2, 0.539, 0.569, 0.500, 0.676, 0.579, and 0.588, respectively; P<0.001), and this association was independent of many confounders, such as age, gender, body mass index, glucose and insulin levels, and HbA1c. Serum HCY levels were inversely related to the parameters for pancreatic islet beta-cell function. Thus, the insulin releasing function of beta cells in the pancreas can be well elucidated by plasma HCY concentration.

Homocysteinemia-Induced Upper-Extremity Deep-Vein Thrombosis

Hyperhomocysteinemia is a rare condition which predisposes to arterial and venous thrombosis. Plasma homocysteine levels are influenced by many genetic factors and environmental factors. Increased levels of homocysteine at high-altitude areas (HAA) can predispose to upper-extremity deep-vein thrombosis (UEDVT). Therefore, awareness by the medical authorities regarding this entity at HAA as a sole cause of UEDVT needs to be established. Prompt reduction in the homocysteine level can be therapeutic as well as prophylactic in preventing the morbidity.

Homocysteine predicts vascular target organ damage in hypertension and may serve as guidance for first-line antihypertensive therapy.

Homocysteine is an independent risk factor for cardiovascular and cerebrovascular disease and has been proposed to contribute to vascular dysfunction. We sought to determine in a real‐world clinical setting whether homocysteine levels were associated with hypertension mediated organ damage (HMOD) and could guide treatment choices in hypertension. We performed a cross‐sectional analysis of prospectively collected data in 145 hypertensive patients referred to our tertiary hypertension clinic at Royal Perth Hospital and analyzed the association of homocysteine with HMOD, renin‐angiotensin‐aldosterone system (RAAS), and RAAS blockade. The average age of participants was 56 ± 17 years, and there was a greater proportion of males than females (89 vs. 56). Regression analysis showed that homocysteine was significantly associated with PWV (β = 1.99; 95% CI 0.99‐3.0; p < .001), albumin‐creatinine ratio (lnACR: β = 1.14; 95% CI 0.47, 1.8; p < .001), 24 h urinary protein excretion (β = 0.7; 95% CI 0.48, 0.92; p < .001), and estimated glomerular filtration rate (β = −29.4; 95% CI −36.35, −22.4; p < .001), which persisted after adjusting for potential confounders such as age, sex, 24 h BP, inflammation, smoking, diabetes mellitus (DM), and dyslipidemia. A positive predictive relationship was observed between plasma homocysteine levels and PWV, with every 1.0 µmol/L increase in homocysteine associated with a 0.1 m/s increase in PWV. Homocysteine was significantly associated with elevated aldosterone concentration (β = 0.26; p < .001), and with attenuation of ACEi mediated systolic BP lowering and regression of HMOD compared to angiotensin receptor blockers in higher physiological ranges of homocysteine. Our results indicate that homocysteine is associated with hypertension mediated vascular damage and could potentially serve to guide first‐line antihypertensive therapy.

Impact of homocysteine levels on mortality risk in patients with chronic limb-threatening ischemia undergoing revascularization

The current study aimed to reveal the clinical impact of plasma homocysteine levels in chronic limb-threatening ischemia (CLTI) patients undergoing revascularization. This was a sub-analysis of a prospective multicenter registry of CLTI patients, named the Surgical reconstruction versus Peripheral INtervention in pAtients with critical limb isCHemia (SPINACH) study. The current analysis included 192 non-dialysis-dependent CLTI patients who underwent revascularization for CLTI, and whose plasma homocysteine levels at baseline were available. The association of clinical characteristics with homocysteine levels was evaluated with the linear regression model. The association of homocysteine levels with the mortality risk was investigated using the Cox proportional hazards regression model. Cystatin C-based estimated glomerular filtration rate (eGFR) was independently associated with log-transformed homocysteine levels; the adjusted standardized regression coefficient (95% confidence interval) was − 0.432 (− 0.657 to − 0.253; P < 0.001). Homocysteine levels were significantly associated with the mortality risk in the univariate model (P = 0.017); the unadjusted hazard ratio was 1.71 (1.13–2.50) per twofold increase. The association was significantly attenuated when adjusted for cystatin C-based eGFR (P < 0.001); the hazard ratio adjusted for cystatin C-based eGFR was 1.28 (0.80–1.90; P = 0.29). An apparent association of homocysteine levels with an increased risk of mortality could be explained by renal dysfunction. Future studies will be needed to validate the current findings.

A Dietary Vitamin B12 Deficiency Impairs Balance and Coordination After Ischemic Injury to the Sensorimotor Cortex in Adult Male and Female Mice

ObjectivesThe majority of the world’s population is growing older, in 2000, 10% of the total population of the world was over 60 years old and is projected to increase to 21% by 2050. Brain vasculature is unique, and its aging has been scarcely investigated at the cellular, and molecular levels, as well as in the context of age-related comorbidities. Nutrition is a modifiable risk factor for stroke, as people age their ability to absorb some nutrients decreases. A primary example is vitamin B12, the majority of older adults are deficient in vitamin B12 because of changes in breakdown and absorption of the vitamin. Furthermore, a vitamin B12 deficiency results in elevated levels of homocysteine which is a risk factor for cardiovascular diseases, such as stroke. Using a mouse model system, the aim of this study was to understand the role of vitamin B12 deficiency in ischemic stroke outcome and investigate mechanistic changes in the brain. MethodsAt 10-weeks of age male and female C57Bl/6J mice were put on control (0.025 mg/kg of vitamin B12) or vitamin B12 deficient (0 mg/kg of vitamin B12) diets for 4-weeks prior to ischemic damage. At 14 weeks of age we induced ischemic stroke in the sensorimotor cortex using the photothrombosis model, all animals received damage. Animals continued on diets for 4 weeks after damage. At 18 weeks of age we assessed stroke outcome using the accelerating rotarod and forepaw placement task. After the collection of behavioral data, we euthanized animals and collected brain, blood, and liver tissue to assess histological and biochemical measurements. Plasma was used to measure total homocysteine and methylmalonic acid. ResultsAll animals maintained on the vitamin B12 deficient diet had increased levels of total homocysteine in plasma and liver tissue. Male and female mice maintained on a vitamin B12 deficient diet had impairments in balance and coordination on the accelerating rotarod compared to animals maintained on a control diet. ConclusionsVitamin B12 deficiency impacts motor function in older adult male and female mice. We are investigating damage volume and potential mechanisms within the damage brain tissue. Funding SourcesMidwestern University Start-Up Funds.