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Background: Cardiovascular disease (CVD) is a major global health concern with increasing incident cases and deaths. Homocysteine (Hcy) has been investigated for its potential association with CVD, researchers have debated the extent to which Hcy should be considered a risk factor for cardiovascular diseases, as only 50% of CVD can be explained by classical risk factors., Methods: We conducted a prospective cohort study using NHANES 1999-2006 data, analyzing 1,739 US patients aged at least 30 with CVD. Cox proportional hazards regression and restricted cubic splines were used to examine the relationship between Hcy levels and mortality, adjusting for covariates., Result: A total of 1,739 participants with cardiovascular disease (CVD) were enrolled, with a median follow-up period of 126 months. Among them, 1,194 participants died, including 501 deaths due to cardiovascular causes. After adjusting for covariates, the hazard ratios (HR) and 95% confidence intervals (CI) for CVD mortality at different levels of homocysteine (Hcy) (T1 (< 9.3), T2 (9.3-12.5), T3 (> 12.5)) were 1.26 (0.92, 1.73) (T2), and 1.69 (1.14, 2.51) (T3) (P for trend = 0.0086). The HR and 95% CI for all-cause mortality at different levels of Hcy were 1.22 (1.05, 1.42) (T2) and 1.64 (1.29, 2.09) (T3) (P for trend < 0.0001). Elevated Hcy levels were associated with increased risks of all-cause mortality and CVD deaths, even at levels below the conventional threshold. The nonlinear relationship was observed, with inflection points at 14.5 µmol/L for all-cause mortality and 14.6 µmol/L for CVD mortality. Subgroup analyses revealed interactions with age, serum vitamin B12, and smoking., Conclusion: Our study supports the notion that elevated Hcy levels are associated with higher all-cause and CVD mortality risks in CVD participants. The impact of Hcy on health outcomes can be observed at lower concentrations than previously thought., Competing Interests: Declarations Ethics approval and consent to participate The protocols of NHANES were approved by the institutional review board of the National Center for Health Statistics, CDC (https://www.cdc.gov/nchs/nhanes/). NHANES has obtained written informed consent from all participants. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Clinical trial number Not applicable., (© 2024. The Author(s).)

Background: We evaluated the diagnostic value of homocysteine (Hcy) levels combined with the Wells score and established a prediction model for venous thromboembolism (VTE) occurrence in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) based on the Hcy level and the Wells score., Patients and Methods: Clinical information from 914 patients with AECOPD was retrospectively collected in our hospital from June 2020 to October 2023. Receiver operating characteristic curves were plotted to evaluate the diagnostic ability of Hcy concentrations combined with Wells scores and the prediction ability of the model. Univariate and multivariate logistic regressions were used to explore the effects of Hcy levels and the Wells score on VTE occurrence. A nomogram was established for individual risk evaluation., Results: Hcy levels and Wells scores were significantly greater in the VTE group than in the non-VTE group (P < 0.001). The diagnostic ability of Hcy levels combined with the Wells score was greater than that Hcy levels or the Wells score alone. The AUC of the combined parameters was 0.935, with a sensitivity of 0.864 and a specificity of 0.855. Multivariate logistic regression indicated that elevated Hcy levels (OR:5.17, 95%CI: 3.76-7.09, P < 0.001) and Wells score (OR: 5.26, 95%CI: 3.22-8.59, P < 0.001) were independently associated with the risk of developing VTE in AECOPD patients. Decision curve analysis indicated that the net benefit of the nonadherence prediction nomogram was greater than that of the models adjusted for no or all variables, with a threshold of approximately 0.1-1.0., Conclusions: The established prediction model can be used to evaluate an individual's risk of developing VTE on the basis of the Hcy level, Wells score, and clinical parameters. AECOPD patients may benefit from the early intervention based on estimated risk probability., (© 2024. The Author(s).)

Background: Hyperhomocysteinemia can be due to various abnormalities of the complex interaction of methionine, folate and vitamin B12. It has been known to be a cardiovascular risk factor. This study aims to review the clinical presentation, underlying causes and clinical outcome in paediatric patients diagnosed with significant hyperhomocysteinemia in Malaysia., Design and Methods: Data were obtained from the medical records and the laboratory information system. Paediatric patients with significant hyperhomocysteinemia were identified from a selective high-risk screening of 96,721 patients, performed between 2010 and 2022. Inclusion criteria for the study were paediatric patients with significant hyperhomocysteinemia (>40 µmol/L)., Results: Sixteen patients were identified. The average total homocysteine (tHcy) and methionine were 269 µmol/L and 499 µmol/L in cystathionine β-synthase deficiency (CBS), 127 µmol/L and 29 µmol/L in patients with remethylation defects and 390 µmol/L and 4 µmol/L in congenital B12 deficiency. We found c.609G>A as the most prevalent mutation in MMACHC gene and possible novel mutations for CBS (c.402del, c.1333C>T and c.1031T>G) and MTHFR genes (c.266T>A and c.1249del). Further subclassification revealed CBS was 5/16 patients (31 %), remethylation defects was 9/16 (56 %) and congenital B12 deficiency was 2/16 (13 %). All patients received standard treatment and regular monitoring of the main biomarkers. The average age at the time of diagnosis were 9.2 years (CBS) and 1.2 years (remethylation defects). Congenital B12 deficiency had slight delay in milestones, remethylation defects had mild to moderate learning disabilities, CBS had variable degree of intellectual disability, delayed milestones, ophthalmological abnormalities, and thrombosis at an early adolescent/adulthood., Conclusions: The majority of significant hyperhomocysteinemia in Malaysian children was due to remethylation defects. Screening for hyperhomocysteinemia in Malaysian children is recommended for earlier treatment and improved clinical outcome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Homocysteine (Hcy) is a sulphur-containing nonessential amino acid derived from the intermediate metabolites of methionine. Methionine is obtained from dietary proteins, such as poultry, meat, eggs, seafood, and dairy products. Abnormalities in Hcy metabolic pathways, deficiencies in dietary methionine, folate, and vitamins B12, B6, and B2 and genetic defects, polymorphisms, or mutations in Hcy metabolism-related enzymes may lead to an increase in plasma Hcy levels. Generally, a plasma Hcy level higher than 10 or 15 μmol/L has been defined as hyperhomocysteinemia (HHcy). An individual with essential hypertension complicated with HHcy is considered to have H-type hypertension (HTH). Currently, HHcy is considered a novel independent risk factor for various cardiovascular diseases. To provide a useful reference for clinicians, the research progress on Hcy, HHcy, and HTH in recent years was systematically reviewed here, with a focus on the source and metabolic pathways of Hcy, plasma Hcy levels and influencing factors, detection methods for plasma Hcy levels, relationship between Hcy concentration and hypertension, pathogenesis of HTH, cardiovascular complications of HTH, and treatment of HTH., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: H-type hypertension is essential hypertension combined with high homocysteine, and both synergistically increase the risk of cardiovascular and cerebrovascular events. The aim of this study was to investigate the risk factors of H-type hypertension in Tibetan plateau population and correlation with MTHFR C677T gene., Methods and Results: A multi-stage cluster random sampling method was used to select the research subjects in Tibet Autonomous Region from June 2020 to November 2021. Among Tibetans, the incidence of H-type hypertension accounted for 84.31% of hypertensive patients. The logistic regression analysis demonstrated that age, uric acid (UA), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) were risk factors for the prevalence of H-type hypertension, the OR (95% CI) was 1.083(1.073-1.094), 1.002(1.001-1.004), 1.240(1.050-1.464) and 2.274(1.432-3.611), respectively. MTHFR C677T TT genotype patients with H-type hypertension OR (95% CI) was 1.629(1.004-2.643). Based on this, a nomogram model was established, and the reliability of the model was proved by area under ROC curve, Brier score and average absolute error. The model's results indicate that for every five years of age, the score increases by 6 points; for a 2mmol/L increase in TG, the score increases by 5.5 points; for a 1mmol/L increase in LDL-C, the score increases by 10 points; and individuals with the TT genotype receive 8 points. The higher the score, the greater the risk of disease., Conclusion: The MTHFR C677T TT genotype is a risk locus for Tibetan patients with H-type hypertension, with age, TG, and LDL-C were identified as risk factors for the disease., (© 2024. The Author(s).)

Background and Purpose: Recent observational studies have reported that serum total homocysteine (tHcy) is associated with intracranial aneurysms (IAs). However, the causal effect of tHcy on IAs is unknown. We leveraged large-scale genetic association and real-world data to investigate the causal effect of tHcy on IA formation., Methods: We performed a two-sample Mendelian randomisation (MR) using publicly available genome-wide association studies summary statistics to investigate the causal relationship between tHcy and IAs, following the recommendations of the Strengthening the Reporting of Observational Studies in Epidemiology-MR statement. Furthermore, a propensity score matching (PSM) analysis was conducted to evaluate the detailed effects of tHcy on risk of IA formation by utilizing real-world multicentre data, including 9902 patients with and without IAs (1:1 matched). Further interaction and subgroup analyses were performed to elucidate how tHcy affects risk of IA formation., Results: MR analyses indicated that genetically determined tHcy was causally associated with IA risk (OR, 1.38, 95% CI 1.07 to 1.79; p=0.018). This is consistent with the more conservative weighted median analysis (OR, 1.41, 95% CI 1.03 to 1.93; p=0.039). Further sensitivity analyses showed no evidence of horizontal pleiotropy or heterogeneity of single nucleotide polymorphisms in causal inference. According to the PSM study, we found that, compared with low tHcy (≤15 µmol/L), moderate tHcy (>15-30 µmol/L) (OR 2.13, 95% CI 1.93 to 2.36) and high tHcy (>30 µmol/L) (OR 3.66, 95% CI 2.71 to 4.95) were associated with a higher IA risk (p trend <0.001). Subgroup analyses demonstrated significant ORs of tHcy in each subgroup when stratified by traditional cardiovascular risk factors. Furthermore, there was also a synergistic effect of tHcy and hypertension on IA risk (p interaction <0.001; the relative excess risk due to interaction=1.65, 95% CI 1.29 to 2.01)., Conclusion: Both large-scale genetic evidence and multicentre real-world data support a causal association between tHcy and risk of IA formation. Serum tHcy may serve as a biomarker to identify high-risk individuals who would particularly benefit from folate supplementation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Alzheimer disease (AD) is the most common cause of dementia worldwide. Its clinical manifestations include a progressive loss of memory and other cognitive domains, as well as brain atrophy. An elevated homocysteine level (&gt;15 µmol/L), known as hyperhomocysteinemia, is also an attributing risk factor for AD, vascular pathologies, and brain atrophy. Neuroimaging studies including T2-weighted magnetic resonance imaging scans revealed white matter hyperintensities in the periventricular and deep white matter, enlarged ventricles, widened sulci, and decreased white matter mass, which are features of aging, as well as cerebrovascular changes. This case series investigated changes in biochemical marker levels including serum homocysteine, folate, and vitamin B12, and the degree of atrophic variations in cortical-subcortical white matter in AD. The present study hypothesized that serum homocysteine levels might be used as a surrogate marker to screen for AD at an earlier stage.

Background: Combined methylmalonic acidemia (MMA) and hyperhomocysteinemia, cobalamin C (cblC) type, also named cblC deficiency is a rare autosomal recessive genetic metabolic disease. It progressively causes neurological, hematologic, renal and other system dysfunction. The clinical manifestations are relatively different due to the onset time of disease., Case Presentation: This report describes a rare case of a 26 year old man with cblC deficiency who developed life-threatening aortic dissection and acute kidney injury (AKI) and showed neuropsychiatric symptoms with elevated serum homocysteine and methylmalonic aciduria. After emergent operation and intramuscular cobalamin supplementation therapy, the male recovered from aortic dissection, neurological disorder and AKI. Finally, two previously published compound heterozygous variants, c.482G > A (p.R161Q) and c.658&#95;660del (p.K220del) in the MMACHC gene were detected in this patient and he was confirmed to have cblC deficiency., Conclusions: Poor cognizance of presenting symptoms and biochemical features of adult onset cblC disease may cause delayed diagnosis and management. This case is the first to depict a case of adult-onset cblC deficiency with aortic dissection. This clinical finding may contribute to the diagnosis of cblC deficiency., (© 2024. The Author(s).)

Background: Current guideline-recommended multiparameters used to assess the risk levels of pulmonary arterial hypertension (PAH) are invasive hemodynamic measurements or effort-dependent exercise tests. Serum natriuretic peptide is only one kind of effort-free biomarker that has been adopted for risk assessment. This study aimed to investigate the application of homocysteine as a non-invasive and effort-free measurement for the risk assessment of patients with PAH., Methods: Samples of 50 patients diagnosed with PAH via right heart catheterization were obtained, and the patients were divided into low-, intermediate- and high-risk groups for further analysis. Additionally, serum N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) and homocysteine levels of monocrotaline (MCT)-induced PAH rats were analyzed at each week with progressed severity of PAH, and they were sacrificed on day 28 with pathology being assessed., Results: Hyperhomocysteinemia was an independent predictor (odds ratio [OR]: 1.256; 95% confidence interval [CI]: 1.002-1.574) and showed a linear correlation with NT-proBNP. Hyperhomocysteinemia could discriminate between low/intermediate and high-risk levels in PAH with a cut-off value in 12 μmol/L. Moreover, the elevated homocysteine levels by weeks in MCT rats also demonstrated the association between homocysteine and the severity of PAH., Conclusions: Homocysteine can be a non-invasive and effort-free risk assessment for patients with pulmonary hypertension. Homocysteine level had a linear correlation with NT-proBNP level, and patients with hyperhomocysteinemia had a higher risk level, higher NT-proBNP level, and decreased lower diffusing capacity for carbon monoxide. The correlation between homocysteine level and PAH severity was also demonstrated in MCT rats.

Hypertensive patients with snoring and elevated plasma homocysteine levels are common. When these factors are combined, the risk of coronary heart disease (CHD) is high. Herein, we developed and validated an easy-to-use nomogram to predict high-risk CHD in snoring hypertensive patients with elevated plasma homocysteine.Snoring patients (n = 1,962) with hyperhomocysteinemia and hypertension were divided into training (n = 1,373, 70%) and validation (n = 589, 30%) sets. We extracted CHD predictors using multivariate Cox regression analysis, then constructed a nomogram model. Internal validation using 1,000 bootstrap resampling was performed to assess the consistency and discrimination of the predictive model using the area under the receiver operating characteristic curve (AUC) and calibration plots.We constructed a nomogram model with the extracted predictors, including age, waist-height ratio, smoking, and low-density lipoprotein cholesterol levels. The AUCs of the training and validation cohorts at 80 months were 0.735 (95% CI: 0.678-0.792) and 0.646 (95% CI: 0.547-0.746), respectively. The consistency between the observed CHD survival and the probability of CHD survival in the training and validation sets was acceptable based on the calibration plots. A total of more than 151 points in the nomogram can be used in the identification of high-risk patients for CHD among snoring hypertensive patients with elevated plasma homocysteine.We developed a CHD risk prediction model for snoring hypertension patients with hyperhomocysteinemia. Our findings provide a useful clinical tool for the rapid identification of high-risk CHD at an early stage.

Hyperhomocysteinemia─a condition characterized by elevated levels of homocysteine in the blood─is associated with multiple health conditions including folate deficiency and birth defects, but there are no convenient, low-cost methods to measure homocysteine in plasma. A cell-free biosensor that harnesses the native homocysteine sensing machinery of Escherichia coli bacteria could satisfy the need for a detection platform with these characteristics. Here, we describe our efforts to engineer a cell-free biosensor for point-of-care, low-cost assessment of homocysteine status. This biosensor can detect physiologically relevant concentrations of homocysteine in plasma with a colorimetric output visible to the naked eye in under 1.5 h, making it a fast, convenient tool for point-of-use diagnosis and monitoring of hyperhomocysteinemia and related health conditions.

Thromboembolic manifestations are relatively frequent in patients with intermediate/severe hyperhomocysteinemia (>30 µmol/L) related to inherited disorders and deficiencies in vitamin B12 and folate. In contrast, moderate hyperhomocysteinemia (15-30 µmol/L) is a modest predictor of cardiovascular risk. The recognition of homocysteine as a cardiovascular risk factor has been challenged by some but not all randomized clinical trials. We reviewed the main data of this controversy and formulated conclusions to be translated in clinical practice.Homocysteine-lowering trials have been performed in cardiovascular subjects with moderate but not intermediate/severe hyperhomocysteinemia despite the dose-effect risk association. The first meta-analyses found no benefit and led cardiology societies not recommending homocysteine in the assessment of cardiovascular risk. This guideline challenged the need to diagnose and treat the nutritional and genetic causes of intermediate/major hyperhomocysteinemia and was not revised when larger meta-analyses concluded to a reduced risk of stroke. In a recent observational study, 84% of consecutive cardiovascular patients assessed for homocysteine had intermediate or major hyperhomocysteinemia, which was properly assessed in only half of the cases and related to B12 and/or folate deficiency and Addison/Biermer disease in 55% of these cases.In conclusion, revisiting observational studies and clinical trials suggests that cardiovascular patients should be screened for hyperhomocysteinemia, when no other risk factor is found. Patients with intermediate/major hyperhomocysteinemia should be properly assessed and treated for B vitamin deficiencies and inherited disorders according to current guidelines. Further trials are needed to assess the effect of lowering homocysteine according to hyperhomocysteinemia categories at baseline., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Hyperhomocysteinemia is associated with an increased risk for cardiovascular diseases. The influence of hyperhomocysteinemia on post-operative events, after coronary artery bypass surgery graft, is less studied., Methods: This cross-sectional study aimed to determine if hyperhomocysteinemia was associated with post-operative complications in patients < 50 years who underwent off-pump coronary artery bypass graft for coronary artery disease. A set of major post-operative complications were considered as primary outcome measures. The independent effect of hyperhomocysteinemia and other risk factors in the incidence of post-operative complications was determined by multivariate analysis., Results: The mean homocysteine levels among the study participants who had post-operative complications were significantly higher than those without post-operative complications (17.37 mmol/L vs. 12.84 mmol/L). On multivariate analysis, hyperhomocysteinemia, diabetes mellitus, and higher body mass index (> 25) were significant predictors of adverse events during the post-operative period., Conclusion: Hyperhomocysteinemia was a significant predictor of immediate post-operative adverse events after coronary artery bypass surgery graft. Necessary precautions and management strategies have to be evolved for these high-risk subsets.

Background: Increasing evidence points to hyperhomocysteinemia as an independent risk factor for coronary artery disease in addition to traditional cardiovascular risks, but few have studied the association between hyperhomocysteinemia and total coronary artery occlusion (TCAO). To understand the risk factors for TCAO, we investigated the potential relationship between hyperhomocysteinemia and TCAO, and the interactions between cardiovascular risk factors and hyperhomocysteinemia., Methods: A total of 890 adult patients from Southwest China participated in this cross-sectional study between February 2018 and February 2021. TCAO was defined as complete occlusion of more than one of the 15 coronary segments. Hyperhomocysteinemia was defined as serum homocysteine levels ≥15 μmol/L. Multivariable logistic regression models were used to determine the relationship between hyperhomocysteinemia and TCAO. The relationship between homocysteine as a continuous variable and TCAO was also analyzed. Subgroup analyses by sex, age, weight, smoking, hypertension, diabetes, and dyslipidemia were done, and interactions between subgroup variables and hyperhomocysteinemia were performed., Results: Individuals with hyperhomocysteinemia showed an increased risk for TCAO. The adjusted odds ratio for TCAO in individuals with hyperhomocysteinemia was 1.74 (95% confidence interval, 1.28-2.36). When analyzed as a continuous variable, homocysteine was associated with an increased risk for TCAO. Subgroup analysis showed that the association between hyperhomocysteinemia and TCAO was statistically significant in men, elderly, overweight, smokers, and non-diabetic people. Interaction analysis showed no significant interactions between hyperhomocysteinemia and group variables., Conclusions: In Southwest China, hyperhomocysteinemia was significantly associated with TCAO. This association was particularly significant in men, elderly, overweight, smokers, and non-diabetic people., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study investigated associations between serum homocysteine levels, body composition, and the probability of having nonalcoholic fatty liver disease (NAFLD) in Chinese healthcare workers., Patients and Methods: A total of 4028 healthcare workers were enrolled in this study, and all underwent a physical examination. Body composition was measured using multifrequency bioelectrical impedance analysis., Results: There were 1507 NAFLD patients (72.26% male, 27.74% female) and 2521 controls (39.83% male, 60.17% female). Body mass index (BMI), waistline, neck-circumference (NC), abdominal visceral fat area (AVFA), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), glucose (Glu), homocysteinemia (hcy) were higher in the NAFLD group than controls. Additionally, the skeletal-muscle was associated with a lower risk of NAFLD, whereas BMI, waistline, NC, hyperhomocysteinemia (HHcy) were associated with a higher risk of NAFLD. The best NC cut-off point for NAFLD was 34.45 cm (sensitivity 83.3% and specificity 83.9%) in women with HHcy, and the best skeletal-muscle content cut-off point for NAFLD was 41.335% (sensitivity 74.2% and specificity 65.6%) in men with HHcy., Conclusion: Interactions between skeletal-muscle content, NC, and HHcy may affect the incidence of NAFLD in healthcare workers. This may provide a novel approach for diagnosing NAFLD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hao, He, Tao and Wang.)

Elevated total plasma homocysteine (hyperhomocysteinemia) is a marker of cardiovascular, thrombotic, and neuropsychological disease. It has multiple causes, including the common nutritional vitamin B12 or folate deficiency. However, some rare but treatable, inborn errors of metabolism (IEM) characterized by hyperhomocysteinemia can be missed due to variable presentations and the lack of awareness. The aim of this study is to identify undiagnosed IEM in adults with significantly elevated homocysteine using key existing clinical data points, then IEM specific treatment can be offered to improve outcome. We conducted a retrospective study with data mining and chart review of patients with plasma total homocysteine >30 μmol/L over a two-year period. We offer biochemical and genetic testing to patients with significant hyperhomocysteinemia without a clear explanation to diagnose IEM. We identified 22 subjects with significant hyperhomocysteinemia but no clear explanation. Subsequently, we offered genetic testing to seven patients and diagnosed one patient with classic homocystinuria due to cystathionine beta-synthase deficiency. With treatment, she lowered her plasma homocysteine and improved her health. This study stresses the importance of a thorough investigation of hyperhomocysteinemia in adults to identify rare but treatable IEM. We propose a metabolic evaluation algorithm for elevated homocysteine levels., (© 2022 Wiley Periodicals LLC.)

A male patient presented with a sudden visual decline in the right eye (OD). Fundus revealed bilateral vasculitis; OD also showed an occluded inferior retinal vein and a wedge-shaped retinal opacification of the inferior macula and nasal retina. Fluorescein angiography revealed occlusive retinal vasculitis, while optical coherence tomography showed paracentral acute middle maculopathy (PAMM) in the OD. A thorough systemic evaluation revealed hyperhomocysteinemia and a positive Mantoux test. A diagnosis of PAMM with occlusive retinal vasculitis in presumed intraocular tuberculosis and hyperhomocysteinemia was made. Retinal vasculitis improved with oral corticosteroid, intravitreal anti-vascular endothelial growth factor and laser photocoagulation. However, the patient declined antitubercular therapy despite recommendations. This unique report indicates that PAMM may complicate tubercular retinal vasculitis, especially in the presence of systemic hypercoagulable states., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Homocysteine is a sulfur-containing amino acid formed in the intermediary metabolism of methionine. Amino acid metabolism and heme biosynthesis pathways are complexly intertwined. Plasma homocysteine elevation, hyperhomocysteinemia (HHcy), has been reported in patients with acute hepatic porphyria (AHP), a family of rare genetic disorders caused by defects in hepatic heme biosynthesis., Areas Covered: This article summarizes published case series in which givosiran, a subcutaneously administered small interfering RNA approved for AHP treatment, appeared to exacerbate dysregulated homocysteine metabolism in patients with AHP. A comprehensive exploratory analysis of ENVISION trial data demonstrated that on a population level, givosiran increased homocysteine but with wide interpatient variations, and there is no proof of correlations between HHcy and changes in efficacy or safety of givosiran., Expert Opinion: The strong correlation and co-increase of homocysteine and methionine suggest that HHcy associated with givosiran is likely attributable to the impaired trans-sulfuration pathway catalyzed by cystathionine β-synthase, which uses vitamin B6 as a cofactor. Data-based consensus supports monitoring total plasma homocysteine and vitamin B6, B12, and folate levels before and during givosiran treatment; supplementing with pyridoxine/vitamin B6 in patients with homocysteine levels >100 μmol/L; and involving patients with homocysteine levels >30 μmol/L in decisions to supplement.

Background: Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease. Total serum homocysteine (tHcy) status varies greatly with ethnicity and gender. Here, we studied the tHcy status by investigating concentration of tHcy and calculating prevalence of HHcy according to different age groups and genders., Methods: This is a cross-sectional study of 10,258 participants (7,248 males and 3,010 females) above 19 years old from Henan Province, northern China. tHcy levels were determined enzymatically. HHcy was defined as a tHcy level higher than 15 μmol/L., Results: In the whole population, the median value of tHcy was 13.56 (11.50, 16.50) μmol/L, and the HHcy prevalence was 34.61%. Males had much higher tHcy levels than females: 14.51 (12.58, 17.71) μmol/L vs. 11.23 (9.75, 12.97) μmol/L, p < 0.001. Also, males had much higher HHcy prevalence than females (44.33% vs. 11.20%, p < 0.001, OR = 6.33, 95% CI: 5.59 - 7.14). HHcy prevalence and tHcy levels increased greatly for both genders above 60 years old., Conclusions: Our results demonstrated that prevalence of HHcy is very high in northern China. Implementation of tHcy-lowering strategies is needed.

Homocysteine (Hcy) is a sulfhydryl-containing amino acid, which is not acquired through the diet, but rather synthesized as an intermediate metabolite in the methionine cycle. Hcy is present in plasma, with normal levels between 5 and 15 μmol/L, a slightly elevated level between 15 to 30 μmol/L, moderate from 30 to 100 μmol/L and a value > 100 μmol/L classified as severe hyperhomocysteinemia (HHcy). HHcy has been associated with inflammation and atherosclerosis and is considered an independent risk factor for cardiovascular diseases (CVD). Here, we review the main evidence showing the association and the possible involvement of HHcy in the most common CVD.

BACKGROUND Hyperhomocysteinemia (HHcy) and metabolic syndrome (MS) are established cardiovascular risk factors of stroke and are frequently associated with hypertension. However, studies on the association between HHcy combined with MS and stroke risk in hypertensive patients were absent. MATERIAL AND METHODS In 14 059 selected participants with elevated blood pressure, we assessed the prevalence of the MS and stroke. We defined HHcy as plasma total homocysteine >15 μmol/L. MS was defined according to the Chinese Diabetes Society (CDS) criterion. Multivariable analysis was used to examine the association of HHcy or (and) MS with stroke risk in different models. RESULTS The prevalence rates of HHcy and MS were 49.96% and 42.21%, respectively. Patients with stroke had higher plasma total homocysteine levels and a higher prevalence of MS (P<0.001). Multivariable analyses indicated that HHcy and MS are independently associated with higher prevalence of stroke (adjusted-odds ratio (OR): 1.36, 95% CI 1.17 to 1.58, P<0.001; adjusted-OR: 1.68, 95% CI 1.44 to 1.96, P<0.001, respectively). Those with combined HHcy and MS had higher odds of stroke than those with isolated HHcy or MS (adjusted-OR: 1.78, 95% CI 1.47 to 2.15, P<0.001; adjusted-OR: 1.39, 95% CI 1.13 to 1.70, P=0.002, respectively). CONCLUSIONS HHcy combined with MS was associated with higher prevalence of stroke in Chinese adults with elevated blood pressure.

Introduction: Paracentral acute middle maculopathy (PAMM) is a tomographic finding of a retinal occlusive vascular disorders with different aetiologies. Despite the well documented triple association among hyper-homocysteine, retinal vein occlusion and PAMM, up to date no reports exist on the development of PAMM in young patients affected by ulcerative colitis (UC)., Case Description: A multimodal imaging study, including fundus photographs, optical coherence tomography (OCT) B-scans, OCT angiography (OCT-A) and fluorescein and indocyanine green angiography, was performed in a 32-years-old male complaining of acute-onset paracentral scotoma in the right eye. Fundus images demonstrated the typical dark gray area of retinal capillary ischemia, corresponding on OCT B-scans to the hyper-reflective plaques in the INL, and consistent with PAMM lesions.The deep capillary plexus (DCP) was normal on OCT-A. Fluorescein angiography revealed a concurrent branch retinal vein preocclusion and showed capillary drop out parafoveally. Patient's anamnesis was negative except for a 15-years history of UC and use of acetylsalicylic acid (ASS). At the time of presentation, UC was quiescent, but new blood tests revealed concomitant high values of homocysteinemia requiring oral vitamin B12 and folate supplementation. Two months later PAMM lesions had disappeared on OCT B-scans and a retinal thinning at the level of the inner nuclear layer (INL) was visible. The DCP on OCT-A remained unchanged without any sign of capillary ischemia., Conclusions: Although no definitive evidence directly links UC with PAMM, the latter should be suspected in young patients affected by IBD with coexisting hyper-homocysteinemia and unexplained visual symptoms.

Folate metabolism disorders are known to have a potential involvement in the pathophysiology of mitochondrial diseases. Many researchers suggest that profound systemic folate deficiency may contribute to mitochondrial folate deficiency. Folic acid metabolism is closely related to vitamin B 1 2 and homocysteine. Considering that hereditary optic neuropathies (HON) are mitochondrial diseases, it is important to study the folate status, the content of vitamin B 1 2 and homocysteine in patients with this pathology., Objective: To compare the content of folic acid, vitamin B 1 2 and homocysteine in the blood serum of patients with Leber's hereditary optic neuropathy (LHON) and autosomal recessive optic neuropathy (ARON), optic neuropathy of other genesis, and the comparison group., Material and Methods: The study involved 58 patients with LHON and ARON, the control group of 49 patients with ischemic, inflammatory, traumatic and compressive optic neuropathies, and the comparison group of 20 healthy volunteers., Results: A decrease in blood folic acid levels was revealed (4.0±1.6 ng/mL) in patients with HON compared to the control group ( p =1.3·10 -8 ) and the comparison group ( p =1·10 -17 ). The content of vitamin B 1 2 in patients with HON was 380.8±168.1 pg/mL, which was significantly lower than in the comparison group ( p =0.0001). The homocysteine content was 14.1±5.6 μmol/L in patients with HON, which was significantly higher than in the control group ( p =0.0007) and the comparison group ( p =0.000003). At the same time, an increase in homocysteine level of more than 10 µmol/L was revealed in 75% of patients with HON. Similar metabolic disorders were found in groups with various mutations in mitochondrial and nuclear DNA., Conclusion: Patients with HON showed marked decrease in the levels of folic acid and vitamin B 12 , as well as hyperhomocysteinemia. It is very important to identify the causes of metabolic disorders in order to determine the role of folate deficiency in the development of HON, as well as the possibility of its pharmacological treatment.

Background: The relationship between serum homocysteine levels and carotid artery damage in subjects with newly diagnosed type 2 diabetes mellitus remains unclear. The effect of hyperhomocysteinemia (HHCY) on carotid artery damage in patients with different cholesterol levels needs to be further investigated. Methods: In total 456 newly diagnosed type 2 diabetes from Beijing Chaoyang Hospital were recruited into the study. Patients were divided into four groups according to the levels of serum homocysteine and cholesterol. Carotid artery damage was defined as thickened intima-media and/or plaque formation. Results: In all the subjects, 80.2% patients had HHCY. The incidence of carotid artery injury was significantly lower in diabetic patients with normal homocysteine levels and nonhypercholesterolemia. Spearman correlation analysis showed homocysteine was positively correlated with free fatty acid and negatively correlated with glucose metabolism parameters. Logistic regression showed HHCY was correlated with carotid artery injury after adjusting for traditional cerebrovascular risk factors in type 2 diabetes without hypercholesterolemia (odds risk = 3.197, P  = 0.022). Whereas HHCY was not associated with carotid artery injury in either total study population or hypercholesterolemia subgroup. Conclusions: HHCY was correlated with carotid artery damage in newly diagnosed type 2 diabetic subjects without hypercholesterolemia. How to improve the adverse vascular outcomes mediated by HHCY for diabetic patients needed further investigation.

A nationwide survey was conducted from October 2018 to September 2019 to assess the prevalence of hyperhomocysteinemia (Hhcy) and its influencing factors in China. A standardized questionnaire was used to collect information. Hhcy was defined as the level of serum homocysteine (HCY) ⩾ 15.0µmol/L. The H-type hypertension (HHYP) was defined as hypertension with an elevated serum HCY 15.0µmol/L). Finally, 110 551 residents ⩾ 40 years of age from 31 provinces in the mainland of China were included. Overall, the median serum HCY level was 10.9µmol/L (interquartile range 7.9-15.1). A total of 28 633 participants (25.9%) were defined as Hhcy. The Hhcy prevalence ranged from 7.9% in Shanghai to 56.8% in Tianjin. The data showed that serum HCY levels were associated with age, male gender, cigarette smoking, hypertension, diabetes, ethnicity, endurance in exercise (inverse), and fruit and vegetable intake (inverse). In addition, 15 486 participants were defined as HHYP, and the rate was 14.0%. HHYP was an independent predictor of stroke with an adjusted odds ratio of 1.752 (95% CI 1.338-2.105). The geographical distribution pattern of the Hhcy epidemic reflects dynamic differences, and national strategies should be carried out to further improve the care of patients with Hhcy across China., (© 2021. Higher Education Press.)

This study investigated the outcomes and major adverse cardiovascular events (MACEs) incurred by acute myocardial infarction (AMI) patients comorbiding with hypertension and hyperhomocysteinemia (HHcy) during hospitalization and 1-year follow-up. 648 consecutive AMI patients were divided into four categories: (1) hypertension with Hcy ≥ 15 µmol/L; (2) hypertension with Hcy < 15 µmol/L; (3) no-hypertension with Hcy ≥ 15 µmol/L; (4) no-hypertension with Hcy < 15 µmol/L. Information taken from these case files included gender, past medical history, vital signs, laboratory examination, electrocardiogram, coronary angiography, cardiac ultrasound, and medicine treatment. The primary endpoints were duration of coronary care units (CCU) stay, duration of in-hospital stay, and MACEs during follow-up. Our data show that hypertension and HHcy have a synergistic effect in AMI patients, AMI comorbiding with hypertension and HHcy patients had more severe multi-coronary artery disease and more frequent non-culprit coronary lesions complete clogging, had a higher prevalence of pro-brain natriuretic peptide, and significant decreases in the left ventricular ejection fraction. These patients had significant increases in the duration of CCU stay and in-hospital stay, had significant increase in the rate of MACEs, had significant decreases in the survival rate during follow-up., (© 2021. The Author(s).)

Homocysteine (Hcy) is a non-protein, sulfur-containing amino acid, which is recognized as a possible risk factor for coronary artery and other pathologies when its levels in the blood exceed the normal range of between 5 and 12 μmol/L (hyperhomocysteinemia). At present, standard procedures in laboratory medicine, such as high-performance liquid chromatography (HPLC), are commonly employed for the quantitation of total Hcy (tHcy), i.e., the sum of the protein-bound (oxidized) and free (homocystine plus reduced Hcy) forms, in biological fluids (particularly, serum or plasma). Here, the response of Aerosol Jet-printed organic electrochemical transistors (OECTs), in the presence of either reduced (free) and oxidized Hcy-based solutions, was analyzed. Two different experimental protocols were followed to this end: the former consisting of gold (Au) electrodes' biothiol-induced thiolation, while the latter simply used bare platinum (Pt) electrodes. Electrochemical impedance spectroscopy (EIS) analysis was performed both to validate the gold thiolation protocol and to gain insights into the reduced Hcy sensing mechanism by the Au-gated OECTs, which provided a final limit of detection (LoD) of 80 nM. For the OECT response based on Platinum gate electrodes, on the other hand, a LoD of 180 nM was found in the presence of albumin-bound Hcy, with this being the most abundant oxidized Hcy-form (i.e., the protein-bound form) in physiological fluids. Despite the lack of any biochemical functionalization supporting the response selectivity, the findings discussed in this work highlight the potential role of OECT in the development of low-cost point-of-care (POC) electronic platforms that are suitable for the evaluation, in humans, of Hcy levels within the physiological range and in cases of hyperhomocysteinemia.

Background: The prevalence of coronary artery disease (CAD) continues to increase among young Chinese adults. Current smoking has been recognized as a major risk factor for premature CAD, and hyperhomocysteinaemia (HHcy) has also been suggested to be associated with CAD progression. However, the combined effect of current smoking and HHcy on the severity of coronary artery stenosis in young adults is still uncertain., Methods: We consecutively collected young patients (18-35 years of age), diagnosed with CAD and underwent coronary angiography (CAG) at Anzhen Hospital between January 2013 and May 2020. HHcy was defined as serum homocysteine (Hcy) level > 15 µmol/L. The severity of coronary artery stenosis was evaluated by Gensini Score. The co-effect of current smoking and HHcy on CAD severity as well as the relationship between plasma Hcy, pack-years of smoking and CAD severity were assessed by multivariate linear regression analysis., Results: A total of 989 participants (mean age, 33 years; 96.2% male) fulfilling the criteria were enrolled in this study. Patients with both HHcy and current smoking accounted for 39.1% of all the subjects. Multivariate liner analysis indicated both serum Hcy levels (β 0.302; 95% CI 0.141-0.462; P < 0.001) and pack-years of smoking (β 0.523; 95% CI 0.265-0.781; P < 0.001) were independently associated with the severity of coronary artery stenosis after adjusting for other traditional confounders. In addition, serum Hcy levels were correlated with pack-years of smoking in young CAD patients (r = 0.116, P = 0.001). Moreover, combination of HHcy and current smoking was suggested to have higher risk for CAD severity (β 17.892; 95% CI 11.314-24.469; P < 0.001), compared with HHcy (β 7.471; 95% CI 0.009-14.934; P = 0.048) or current smoking (β 7.421; 95% CI 0.608-14.233; P = 0.033) alone., Conclusion: Combination of HHcy and smoking is independently associated with the severity of CAD in young patients ≤ 35 years of age., (© 2021. The Author(s).)

Background: Homocysteine (Hcy) is considered to be a risk factor for cardiovascular and cerebrovascular diseases. Few studies have evaluated the distribution of Hcy on a large-scale health examination. Accordingly, this study aimed to investigate the level and distribution of Hcy in the population with healthy physical examination and the correlation with other biomarkers, and analyzed for cardiovascular and other diseases., Methods: Measurements of serum Hcy, TC, TG, LDL-c, HDL-c, ALT, ALP, γ-GT, TBIL, GLU, urea, Cr, UA, and related metabolic risk factors were selected for analysis from 8063 medical examination samples collected from February 2017 to April 2020. The relationship between Hcy and other biochemical indicators were evaluated with the multivariate regression model of age, gender, smoking, drinking, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP)., Results: Among 8063 cases, the age, BMI, SBP, and DBP of the high-Hcy group were higher than those of the low-Hcy group, the difference was statistically significant (P < 0.001), and the proportion of males, smoking, and drinking were higher than the low-Hcy group, the difference was statistically significant (P < 0.001); Hcy of the abnormal GLU group is higher than the normal GLU group (P = 0.002) and the Hcy of abnormal TG and HDL is higher than that of the normal blood lipid group (P < 0.001); Hcy of people with abnormal UA and Urea was higher than that of people with normal renal function (P < 0.001, P = 0.007). In multivariate analysis, lnHDL-C was negatively correlated with lnHcy (β = - 0.038, SE = 0.016, P = 0.019), lnCr was positively correlated with lnHcy (β = 0.055, SE = 0.016, P < 0.001), lnUA and lnHcy were positive correlated (β = 0.043, SE = 0.019, P = 0.022)., Conclusion: Hcy is closely related to HDL-c, Cr, and UA, which indicates that Hcy may affect the metabolism of HDL-c and UA, and can also be used as an auxiliary diagnostic index for kidney injury., (© 2021. The Author(s).)

The present study was designed to evaluate the strength of association of raised plasma homocysteine concentration as a risk factor for coronary heart disease independent of conventional risk factor. It was a case control study conducted at Punjab Institute of Cardiology Lahore. A total of 210 subjects aged 25 to 60 years comprising of 105 newly admitted patients of CHD as cases and 105 age and sex matched healthy individuals with no history of CHD as control were recruited for the study. Fasting blood samples were obtained from cases and controls. Plasma homocysteine was analyzed by fluorescence polarization immunoassay (FPIA) method on automated immunoassay analyzer (Abbott IMX). Total cholesterol, triglyceride and HDL cholesterol were analyzed using calorimetric kit methods. The concentration of LDL cholesterol was calculated using Friedewald formula. The patients were also assessed for traditional risk factors such as age, sex, family history of CVD, hypertension, smoking and physical activity, and were compared with control subjects. The collected data was entered in SPSS version 24 for analysis and interpretation.The mean age in controls and experimental groups were 43.00± 8.42 years and 44.72± 8.59 years with statistically same distribution (p- value= 0.144). The mean plasma homocysteine for cases was 22.33± 9.22 µmol/L where as it was 12.59±3.73 µmol/L in control group. Highly significant difference was seen between the mean plasma level of homocysteine in cases and controls (p˂0.001).Simple logistic regression indicates a strong association of coronary heart disease with hyperhomocysteinemia (OR 7.45), which remained significantly associated with coronary heart disease by multivariate logistic regression (OR 7.10, 95%C1 3.12-12.83, p=0.000). The present study concludes that elevated levels of Plasma homocysteine is an independent risk factor for coronary heart disease independent of conventional risk factors and can be used as an indicator for predicting the future possibility for the onset of CVD.

[Figure: see text].

Objective: To investigate the predictive value of hyperhomocysteinaemia (HHcy) for obstructive coronary artery disease (CAD) in an Asian population in northern China., Methods: This retrospective study enrolled patients at their first cardiac assessment and assigned them to an obstructive CAD group or a non-obstructive CAD group according to the coronary angiography results. HHcy was defined as a homocysteine (Hcy) level > 15 µmol/l., Results: This study enrolled 2987 participants: 1172 in the non-obstructive CAD group and 1815 in the obstructive CAD group. Hcy level in the obstructive CAD group was significantly higher than in the non-obstructive CAD group. The proportion of patients with HHcy in the obstructive CAD group was significantly greater than in the non-obstructive CAD group. Multivariate logistic regression analysis demonstrated that HHcy was independently correlated with obstructive CAD in both young (aged ≤ 55 years) and old patients (aged > 55 years). HHcy showed a higher sensitivity (93.1%), specificity (86.1%) and accuracy (90.0%) for obstructive CAD. The odds ratio for HHcy was 84.2. The Kappa value (0.8) showed substantial agreement between obstructive CAD and HHcy., Conclusions: HHcy was associated with obstructive CAD and may be a potentially independent risk factor for obstructive CAD with good predictive value.

Background: Homocysteine (Hcy) is considered as a modifiable risk factor for vascular disease. This study was aimed to explore the association between serum concentration and the severity of primary chronic venous disease (CVD)., Methods: Clinical data of 582 patients diagnosed with primary CVD were collected and analyzed retrospectively. The Clinical Etiology Anatomy Pathophysiology classification system was used to grade the severity of chronic venous disease. Patients were divided into 2 groups (group A: C1-C3; group B: C4-C6). The association between serum homocysteine levels and the severity of primary chronic venous disease was investigated using rank sum test and logistic regression., Results: The difference between the level of homocysteine in each grade has statistical significance. Group A has higher median Hcy concentrations than Group B (15.40 μmol/L vs. 14.05 μmol/L, P< 0.01). Further binary logistic regression showed no statistical significance among the level of Hcy (11.00-14.75 μmol/L [OR 0.66, 95% CI 0.40-1.11, P= 0.12], 14.75-20.38μmol/L [OR 0.97, 95% CI 0.59-1.69, P = 0.89], ≥20.38 μmol/L [OR 0.67, 95% CI 0.41-1.10, P = 0.11]), but age (OR 1.03, 95% CI 1.01-1.04, P< 0.01) and female (OR 0.41, 95% CI 0.28-0.59, P< 0.01) are associated with more severe stages of CVD., Conclusions: Higher level of Hcy is associated with more severe stages of CVD, but it not an independent risk factor. However, Advanced age and female are risk factors for CVD development based on logistic regression analysis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Our study aimed to determine the association between homocysteine levels and cardiovascular disease (CVD) risk in middle-aged and elderly adults in a community in northern Taiwan., Methods: Participants in our study included adults aged 50 to 85 years old during community health examinations in 2019. A total of 396 people were enrolled, the ethnicity of all participants is Chinese. We divided participants according to tertiles of ln[homocysteine] level (low, middle and high groups). The CVD risk was calculated by the Framingham cardiovascular risk score (FRS). An FRS ≥ 20% indicated high CVD risk. Pearson correlation coefficients were calculated between homocysteine level and other cardio-metabolic risk factors while adjusting for age. Multivariate logistic regression analysis was used to determine the association of high and middle ln[homocysteine] groups with high CVD risk after adjusting age, sex, uric acid, creatinine, and body mass index (BMI). The Youden index and receiver operating characteristic (ROC) curves were performed to determine the optimized cut-off value., Results: There were 396 people enrolled for analysis; 41.4% of participants were male, and the average age was 64.79 (± 8.76). In our study, we showed a positive correlation of homocysteine with FRS. In the logistic regression models, higher ln[homocysteine] levels was associated with higher CVD risk with a odds ratio (OR) of 2.499 and 95% confidence interval (CI) of 1.214 to 5.142 in the high homocysteine level group compared with the low homocysteine group after adjusting for traditional CVD risk factors. The area under the ROC curve was 0.667, and a ln[homocysteine] cut-off value of 2.495 µmol/L was determined., Conclusions: Middle-aged and elderly people with increased homocysteine levels were associated with higher FRSs in this Taiwan community. Furthermore, homocysteine was an independent risk factor for high CVD risk in this study.

Background: Evidence linking homocysteine (Hcy) with cardiovascular diseases (CVD) or its risk factors are limited in a sub-Saharan black population., Objective: We set out to evaluate the association between Hcy and hypertension and other CVD risk factors in a population of adult Nigerians., Methods: Data of 156 adults aged 18-70 years was accessed from the North Central study site of the REmoving the MAsk on Hypertension (REMAH) study. Homocysteine, blood glucose and lipid profile in whole blood/serum were measured using standard laboratory methods. Hypertension was diagnosed if average of 5 consecutive blood pressure (BP) measurements obtained using a mercury sphygmomanometer was equal to or higher than 140 systolic and/or 90 mmHg diastolic or the individual is on antihypertensive medication. Hyperhomocysteinemia (HHcy) was defined as Hcy > 10 µmol/L., Results: Of the 156 participants, 72 (43.5%) were hypertensive, of whom 18 had HHcy. Subjects with HHcy were significantly (p < 0.05) older (41.5 vs. 40.6yrs), had lower HDL-cholesterol (0.6 vs. 0.8 mmol/L) and higher systolic (145.5 vs. 126.0 mmHg) and diastolic BP (92.9 vs. 79.6 mmHg), compared to those without HHcy. Intake of alcohol and a 1 yr increase in age were respectively and significantly (p < 0.05) associated with a 1.54 and 0.10 µmol/L increase in Hcy. In a multivariable model adjusted for age, sex and body mass index, a 1 µmol/L increase in Hcy, was associated with a 1.69 mmHg and 1.34 mmHg increase in systolic and diastolic pressure (p < 0.0001) respectively; and a 0.01 mmol/L decrease in HDL-cholesterol (p < 0.05)., Conclusion: HHcy occurs among hypertensive Nigerians and it is independently associated with age, HDL-cholesterol, systolic and diastolic BP.

Our meta-analysis focused on the relationship between homocysteine (Hcy) level and the incidence of aneurysms and looked at the relationship between smoking, hypertension and aneurysms. A systematic literature search of Pubmed, Web of Science, and Embase databases (up to March 31, 2020) resulted in the identification of 19 studies, including 2,629 aneurysm patients and 6,497 healthy participants. Combined analysis of the included studies showed that number of smoking, hypertension and hyperhomocysteinemia (HHcy) in aneurysm patients was higher than that in the control groups, and the total plasma Hcy level in aneurysm patients was also higher. These findings suggest that smoking, hypertension and HHcy may be risk factors for the development and progression of aneurysms. Although the heterogeneity of meta-analysis was significant, it was found that the heterogeneity might come from the difference between race and disease species through subgroup analysis. Large-scale randomized controlled studies of single species and single disease species are needed in the future to supplement the accuracy of the results.

Background: The prevalence of acute coronary syndrome (ACS) continues to increase among young Chinese adults. Homocysteine (HCY) has been suggested as a promoter of atherosclerosis leading to coronary artery disease (CAD). Yet, it remains uncertain whether HCY is associated with the ACS and the severity of coronary artery stenosis in young adults., Methods: Young patients (18-35 years of age) diagnosed with ACS who underwent coronary angiography (CAG) at Anzhen Hospital between January 2013 and June 2019 were assigned to the ACS group. As confirmed by CAG during the same period, an equivalent age-matched population without CAD was assigned to the non-CAD group. A serum HCY level > 15 µmol/L was defined as hyperhomocysteinemia (HHCY). The Gensini score assessed the severity of coronary artery stenosis., Results: A total of 1103 participants, including 828 ACS patients and 275 non-CAD subjects, were enrolled in this study. Young ACS patients had higher level of serum HCY and greater prevalence of HHCY compared with non-CAD subjects [for HCY, 16.55 (11.93-29.68) vs 12.50 (9.71-17.42), P < 0.001; for HHCY prevalence, 62.08% vs 26.18%, P < 0.001]. Multivariate logistic regression analysis with the stepwise method indicated that HHCY was an independent predictor associated with the presence of ACS, after adjusting for traditional confounders (OR, 4.561; 95% CI, 3.288-6.327; P < 0.001). Moreover, young ACS patients with HHCY had increased prevalence of ST-segment elevation myocardial infarction (STEMI) (P = 0.041), multi-vessel disease (P = 0.036), and decreased value of left ventricular ejection fraction (LVEF) (P = 0.01). Also, the HCY level was significantly correlated with Gensini Score in ACS patients (r = 0.142, P < 0.001)., Conclusion: HHCY is significantly associated with the presence of ACS and the severity of coronary artery stenosis in young adults ≤ 35 years of age.

Aim: To clarify the risk factors for adult moyamoya disease (MMD) in patients from South China., Material and Methods: We prospectively studied adult patients who were diagnosed angiographically with MMD. The demographic profiles, medical history and clinical characteristics were compared between adult MMD and non-MMD stroke patients. Logistic regression analysis was used to determine the risk factors associated with adult MMD., Results: A total of 35 adult MMD patients and 202 adults patients with non-MMD stroke were included. Of the 35 MMD patients, bilateral MMD occurred in 48.6% and bypass surgery was performed in 28.6%; these figures were significantly lower than those reported in patients from Korea and the United States (p < 0.05). After adjusting for baseline demographics and potential confounders, multivariate logistic regression analysis was conducted, which showed that the plasma homocysteine level (odds ratio [OR]: 1.10; 95% confidence interval [CI]: 1.06?1.14) and occupation as a technological worker (OR: 4.23; 95% CI: 1.65?10.89) were independently associated with adult MMD., Conclusion: Hyperhomocysteinemia and type of occupation were found to be independent risk factors for adult MMD in patients from South China. However, there is still a need for further research to clarify the pathogenesis of MMD. Given the lack of understanding about the risk factors and prevention measures for MMD, we suggest bypass surgery be used for MMD treatment in clinical practice in China to achieve more desirable effects in the management of the disease.

Hyperhomocysteinemia (HHcy) has been considered a risk factor for different diseases, including cardiovascular disease (CVD), inflammation, neurological diseases, cancer, and many other pathological conditions. Likewise, arachidonic acid (AA) metabolism is implicated in both vascular homeostasis and inflammation, as shown by the development of CVD, following the imbalance of its metabolites. This review summarizes how homocysteine (Hcy) can influence the metabolism of AA. In silico literature searches were performed on PubMed and Scopus as main sources. Several studies have shown that altered levels of Hcy, through AA release and metabolism, can influence the synthesis and the activity of prostaglandins (PGs), prostacyclin (PGI2), thromboxane (TXA), epoxyeicosatrienoic acids (EETs), and hydroxyeicosatetraenoic acids (HETEs). It is believed that by targeting Hcy in the AA pathways, novel compounds with better pharmacological and pharmacodynamics benefits may be obtained and that this information is valuable for a dietician to manipulate diets to improve health., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To identify hyperhomocysteinemia and to assess its possible association with the course and other markers of endothelial damage in multiple sclerosis., Material and Methods: Analysis of blood serum for homocysteine, for the content of adhesion molecules sPECAM-1, matrix metalloproteinase 9, blood plasma test for von Willebrand factor antigen in patients with multiple sclerosis. The values of these indicators were analyzed depending on the course and activity of the demyelinating process, the severity of neurological disorders, as also depending on the therapy received., Results: Hyperhomocysteinemia was found in more than half of patients with multiple sclerosis. A significantly higher homocysteine level was found in male patients, and hyperhomocysteinemia was associated with the activity of the process in patients with highly active multiple sclerosis., Conclusion: The results of the study suggest a possible association of hyperhomocysteinemia with high process activity and disease progression, as well as with mechanisms of neurodegeneration. Determination of homocysteine concentration may be one potential marker for predicting the course of the disease.

Background & Objective: Homocysteine is possibly associated with cerebral small vessel diseases such as leukoaraiosis, silent brain infarction and cerebral microbleeds, which are in turn associated with cognitive dysfunction. We aimed to examine the relationships between cerebral microbleeds (CMBs) and plasma total homocysteine (tHcy) level, methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and cognitive function., Methods: A total of 819 patients with memory disturbance who visited a dementia clinic consecutively were included in this study. We retrospectively collected demographic, clinical and laboratory data including tHcy level, MTHFR C677T polymorphism and Mini-Mental State Examination (MMSE). All patients underwent brain MRI including fluid attenuated inversion recovery (FLAIR) image and T2*-weighed gradient-echo (GRE) image. Logistic regression analysis was performed to test the association between risk factors and the presence of microbleeds., Results: One hundred and sixty-one (19.7%) patients had CMBs, of whom 88 (54.7%) had CMBs in the lobar region. CMBs were more common in older hypertensive male patients with hyperhomocysteinemia. In multivariable analysis, plasma tHcy remained an independent predictor of the presence of CMBs after adjusting other confounders (OR: 1.035, 95% CI: 1.009-1.062, p = 0.009). Higher plasma tHcy level was also associated with number of CMBs, TT MTHFR genotype, and lower MMSE scores., Conclusions: Elevated plasma tHcy level is related to high prevalence of CMBs and cognitive dysfunction. Lowering plasma tHcy could be helpful in cognitively impaired patients who have CMBs or the MTHFR TT genotype., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Aims: Homocysteine (Hcy) level has been increasingly linked with stroke and ischemic stroke (IS). However, a dose-response meta-analysis of prospective cohort studies of the association is lacking. We aimed to explore the quantitative dose-response association of Hcy level with stroke and IS in a meta-analysis of prospective cohort studies., Methods and Results: We performed a systematic search of PubMed, Embase and Web of Science databases up to April 25, 2019 for prospective cohort studies assessing the association of Hcy level with stroke and IS. We used random-effect models to estimate the pooled relative risk (RRs) (with 95% confidence intervals [CIs]) for the association of Hcy with risk of stroke and IS. Restricted cubic splines were used to evaluate possible linear or nonlinear association of Hcy level with stroke and IS. We included 10 prospective cohort studies (7 articles) with 11,061 participants in the meta-analysis. Hcy level was associated with increased risk of stroke (RR = 1.58, 95% CI 1.25-2.00, I 2  = 39.5%) and IS (RR = 1.54, 95% CI 1.21-1.97, I 2  = 36.4%) for the highest versus the lowest categories. We found a linear association between Hcy level and stroke (P nonlinearity  = 0.660) and IS (P nonlinearity  = 0.981). For each 1-μmol/L increase in Hcy, the pooled RR was 1.06 (95% CI 1.01-1.12, I 2  = 59.0%) for stroke and 1.05 (95% CI 1.00-1.11, I 2  = 58.6%) for IS., Conclusion: This meta-analysis indicated that elevated Hcy level was associated with increased risk of stroke and IS., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)