Serum Homocysteine Levels and All-Cause and Cause-Specific Mortality in Korean Adult Men: A Cohort Study.

BACKGROUND: Hyperhomocysteinemia can increase the risk of cardiovascular disease (CVD), cancer, and neurological disorders; however, hypohomocysteinemia is generally not considered harmful. This study aimed to evaluate the relationship between all levels of homocysteine, both low and high homocysteine levels, and the risk of all-cause and cause-specific mortality in adult Korean men. METHODS: Adult Korean men (n = 221,356) were categorized into quintiles based on their homocysteine levels. The primary endpoints were all-cause, CVD, cancer, and dementia mortality. Hazard ratios were calculated using Cox proportional hazards models, and the dose-response relationship between homocysteine levels and mortality risk was further explored using restricted cubic spline models. RESULTS: Compared with the reference category (Q2, 8.8-9.9 µmol/L), there was a significant increase in all-cause mortality associated with both low and high levels after multivariable adjustment (Pinteraction = 0.002). Additionally, in spline regression, a U-shaped association between homocysteine levels and all-cause and CVD mortality was observed (inflection point = 9.1 µmol/L). This association was not observed in the vitamin supplementation subgroup. CONCLUSION: Among Korean adult men, both low and high homocysteine levels increased the risk of all-cause and CVD mortality, indicating a U-shaped relationship. However, this relationship was not statistically significant with vitamin supplementation, suggesting a potential protective role for vitamins.

Exploring the association of hyperhomocysteinemia with early pregnancy losses: A retrospective case-control study in a tertiary clinic in Türkiye.

A disturbance in the metabolism of homocysteine in both the mother and the fetus has been implicated in several placental vasculopathy-related disorders, including pregnancy loss. This study aimed to provide insights into the potential role of homocysteine, Vitamin B12, and folic acid in early pregnancy losses, with a specific focus on the Turkish population. The results of 93 pregnant women who experienced miscarriage between 5 and 14 gestational weeks and 93 healthy pregnant women at the same gestational weeks were compared. The demographic and pregnancy characteristics of all pregnant women were recorded. Vitamin B12, folic acid, and homocysteine levels were measured in serum samples obtained from the groups at similar gestational weeks. In addition, any associations between these biomarkers and different types of pregnancy loss, such as spontaneous abortion and missed abortion, were evaluated. Vitamin B12 and folic acid serum levels were significantly lower in women with miscarriages (P = .019, P < .001, respectively). Homocysteine levels were higher in the patient group (P < .001). Logistic regression analysis showed that a higher homocysteine level was the only predictive factor of miscarriage (P = .001, odds ratio = 0.596); however, folic acid and Vitamin B12 were not predictive factors. There was no significant difference in homocysteine and micronutrient levels between women with missed abortions and women with spontaneous abortions (P > .05). Our results support the continuing evidence of a link between maternal homocysteine levels and fetal loss. However, in exploring the shared pathways in the underlying mechanisms causing the 2 forms of pregnancy loss, maternal blood analysis showed no relationship.

Association of serum homocysteine with vitamin B12 and folate levels in women with pre-eclampsia in a tertiary health care center in Nepal.

BACKGROUND: Pre-eclampsia is a syndrome that chiefly includes the development of new-onset hypertension and proteinuria after 20 weeks of pregnancy. Pre-eclampsia is one of the major causes of mortality and morbidity in Nepal. Hyperhomocysteinemia may be a cause of the endothelial dysfunction provoked by oxidative stress in pre-eclampsia. This study was designed to evaluate the association of homocysteine with Vitamin B12 and folate in patients with pre-eclampsia. METHOD: An observational cross sectional study was performed in the Gynecology and Obstetrics Department of TUTH involving seventy two subjects with pre-eclampsia. Blood pressure, urinary protein levels, serum homocysteine, Vitamin B12 and folate levels were compared in both mild and severe forms of pre-eclampsia. Concentration of Vitamin B12 and folate were measured using Vitros ECI and homocysteine was measured using CLIA. SPSS 23.0 was used to analyze the data. Tests were performed with Mann Whitney Test and Spearman's rank correlation test. A p-value < 0.05 was considered statistically significant. RESULTS: This study showed no significant difference in age and weeks of gestation in both mild and severe forms of pre-eclampsia. Mean concentration of homocysteine was higher (13.1 ± 6.4 micromol/L) in severe Pre-eclampsia as compared to mild cases (7.6 ± 2.8 micromol/L). Mean concentration of folate was lower in severe cases (35.4 ± 24.1 micromol/L) when compared with mild cases of pre-eclampsia (57 ± 23.4 micromol/L). CONCLUSION: Homocysteine levels were increased in severe Pre-eclampsia when compared with mild pre-eclampsia and this finding can be used to predict and prevent complications in patients with pre-eclampsia.

Analysis of MTHFR C677T genotype and related factors in H-type hypertension in Tibet, China.

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.

Homocysteine, hopelessness, rumination, affective temperaments, and clinical course in patients with bipolar disorder-1.

PURPOSE: This study aimed to explore the associations between homocysteine, rumination, affective temperaments, clinical features, and hopelessness in bipolar disorder-1 (BD-1). MATERIALS AND METHODS: In total, 57 euthymic patients with BD-1 and 57 healthy controls were included. The Beck Hopelessness Scale (BHS), Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A), and Ruminative Responses Scale Short Form (RRS-SF) were administered. Homocysteine, folate, and vitamin B12 levels were measured. RESULTS: The BHS total (p = 0.047), TEMPS-A irritable (p = 0.007), and TEMPS-A cyclothymic (p= 0.001) scores were significantly higher than the control group in the BD-1 group. Hyperhomocysteinemia (HHcy) was found in 33.3% of the patients (n = 19). In the HHcy group, age of onset of disease (p = 0.020) was significantly lower than the non-HHcy group in patients. Previous suicide attempt number was significantly correlated with scores of reflective pondering, brooding, and global rumination in BD-1 (p Ë‚ 0.05). Except for hyperthymic temperament, all types of affective temperaments were correlated with the scores of RRS-SF brooding (p Ë‚ 0.05) in the BD-1 group. The RRS-SF brooding scores significantly correlated with the BHS total scores (r = 0.263, p < 0.05); the TEMPS-A hyperthymic (ß = -0.351, p = 0.001) and TEMPS-A irritable (ß = 0.536, p < 0.001) scores significantly predicted the BHS total scores in the BD-1 group. CONCLUSIONS: The findings may lead clinical efforts and future clinical trials to explore and intervene in related sources and presentations of BD-1's adverse consequences.

Vitamin B12 status and hyperhomocysteinemia in patients with Rheumatoid arthritis treated with methotrexate and folic acid.

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory arthritis in which the immune system targets synovial joints. Methotrexate serves as the mainstay of treatment for RA due to its efficacy. However, patients treated with methotrexate are uniquely at risk for vitamin B12 deficiency and hyperhomocysteinemia due to coincident disease risk factors and the fact that methotrexate use is associated with malabsorption. The objective of this study was to assess for vitamin B12 deficiency among patients with RA treated with methotrexate and folic acid. METHODS: This cross-sectional study included 50 patients with RA treated with methotrexate and folic acid and 49 patients with RA treated with other therapies. Patients were matched by age, sex, race, renal function, and disease activity. We compared plasma vitamin B12, methylmalonic acid, and homocysteine levels between these two groups utilizing quantitative and categorical analyses. RESULTS: Thirty-seven (74%) RA patients on methotrexate and folic acid had elevated plasma homocysteine levels compared with only 27 (55%) RA patients receiving other therapies (P < 0.05). The proportion of patients with low vitamin B12 and high methylmalonic acid levels did not differ between the two groups. CONCLUSIONS: Our data show high plasma homocysteine levels among RA patients treated with methotrexate and folic acid. While plasma vitamin B12 levels were similar between the two groups, high plasma homocysteine is also a sensitive marker of vitamin B12 deficiency. Additional studies should evaluate for the presence of clinical features of vitamin B12 deficiency and hyperhomocysteinemia among RA patients treated with methotrexate and folic acid.

Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy).

BACKGROUND: While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes. METHODS: This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment. RESULTS: The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0-1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2-1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering. CONCLUSIONS: This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg. GOV IDENTIFIER: NCT03472508 (Registration Date: March 21, 2018).

Folic acid and plasma lipids: Interactions and effect of folate supplementation.

Dyslipidaemia and hyperhomocysteinemia are known risk factors for cardiovascular disease. While it is evident that optimization of plasma lipid is associated with low risk of cardiovascular disease in the general population, it is not yet fully clear whether reduction of homocysteinemia is associated with an improvement in risk in all subjects. The aim of our narrative review is to highlight eventual effects of folate supplementation on LDL-C levels, LDL-C oxidation and atherosclerosis-related complications. A comprehensive literature search was done in electronic database, including PubMed, Web of Science, Cochrane, and Scopus from inception up to January 2024. Based on the available evidence, epidemiological data, pathophysiological observations and meta-analyses of randomized clinical trials suggest that folic acid supplementation may modestly but significantly improve plasma lipid levels, lipid atherogenicity, and atherosclerosis-related early vascular damage, and that folic acid supplementation may significantly reduce the risk of cerebrovascular disease. Considering the low-cost and high safety profile of folic acid, its long-term supplementation could be considered for dyslypidaemic patients in secondary prevention for cardiovascular disease.

The effect of metabolic factors on the association between hyperuricemia and chronic kidney disease: a retrospective cohort mediation analysis.

BACKGROUND: Hyperuricemia, hyperglycemia, hypertension, hyperlipidemia, and hyperhomocysteinemia are all established risk factors for chronic kidney disease (CKD), and their interplay could exacerbate CKD progression. This study aims to evaluate the potential mediation effects of hyperglycemia, hypertension, hyperlipidemia, and hyperhomocysteinemia on the association between hyperuricemia (HUA) and chronic kidney disease (CKD). METHODS: We collected electronic medical record data from 2055 participants who underwent physical examinations at the Affiliated Hospital of Qingdao University. The data were utilized to investigate the mediating effect of various factors including systolic blood pressure (SBP), diastolic blood pressure (DBP), homocysteine (HCY), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), blood glucose (Glu), and hemoglobin A1c (HbA1c) on the relationship between HUA and CKD. RESULTS: Upon adjusting for confounding variables, mediation analysis indicated that only HCY acted as a mediator in the HUA-CKD relationship (p value < 0.05), exhibiting a statistically significant mediation effect of 7.04%. However, after adjustment for multiple testing, none of these variables were statistically significant. CONCLUSIONS: Considering the observed associations between hyperuricemia, hyperglycemia, hypertension, hyperlipidemia, and CKD, none of the factors of interest remained statistically significant after adjusting for multiple testing as potential mediators of hyperuricemia on CKD.

Homocysteine Facilitates the Formation of Carotid Atherosclerotic Plaque Through Inflammatory and Noninflammatory Mechanisms.

Background: Elevated homocysteine (Hcy) was considered a significant risk factor in the development and progression of carotid atherosclerosis (CAS), which involves a combination of inflammatory and noninflammatory mechanisms. However, epidemiological surveys have presented conflicting results. In this study, we aim to offer an epidemiological viewpoint on how elevated Hcy impacts CAS and its potential mechanisms. Methods: Levels of high-sensitivity C-reactive protein (hsCRP) were measured to assess the inflammatory status. The estimation of CAS events was performed by assessing carotid intima-media thickness using Doppler ultrasonography. Univariate analysis was conducted to investigate the variations in biochemical parameters among three groups: normal, carotid atherosclerotic thickening (CAT), and carotid atherosclerotic plaque (CAP) formation. Logistic regression analysis was conducted to identify the risk factors associated with the progression of CAT and CAP. In addition, multivariate linear regression analysis was conducted to identify the independent factors that correlated with hsCRP levels. Results: The study encompassed 3897 participants, with 2992 (76.8%) being males and 905 (23.2%) being females. The incidence of CAT and CAP rose with higher Hcy levels, with an overall odds ratio (OR) of 2.04 [95% confidence intervals (CI) 1.69-2.40] for CAT and 2.68 (95% CI 2.32-3.05) for CAP. After adjusting for gender, age, and blood markers, the OR for CAT and CAP decreased, with an overall OR of 1.05 (95% CI 0.81-1.28) and OR of 1.24 (95% CI 1.02-1.46), respectively. CAP risk independently increased when Hcy level exceeded 19.7 µmol/L (P = 0.030), but not CAT risk (P = 0.299). The impact of hsCRP on CAS events is similar to that of Hcy, and a multiple linear analysis found a significant independent correlation between hsCRP and Hcy (P = 0.001). Conclusions: Elevated Hcy levels can facilitate the formation of CAP through both inflammatory and noninflammatory processes, but it does not independently influence CAT.

Homocysteine, hyperhomocysteinemia, and H-type hypertension.

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.

Folate, vitamin B12, and homocysteine status in the Korean population: data from the 2013-2015 Korea National Health and Nutrition Examination Survey.

OBJECTIVES: We aimed to assess the serum folate, vitamin B12, and homocysteine status in Korean adolescents and adults using national data. METHODS: Blood samples were collected from participants aged ≥10 years in the Korea National Health and Nutrition Examination Survey 2013-2015. The stored serum samples were used to measure folate, vitamin B12, and homocysteine concentrations. A total of 8,016 participants were included in this analysis. Unweighted descriptive statistics and adjusted geometric means of the B vitamins and homocysteine concentrations were estimated. RESULTS: Females had higher serum folate and vitamin B12 concentrations and lower serum homocysteine concentrations than males. Folate deficiency (<6.8 nmol/L) and hyperhomocysteinemia (>15 µmol/L) were found in 8.6% and 11.8% of males, respectively. Approximately 3% of males had low or marginally low vitamin B12 status (≤221 pmol/L). Folate and vitamin B12 deficiencies and hyperhomocysteinemia were found in <2% of females. Suboptimal folate status was prevalent among adolescents and young adults, while suboptimal vitamin B12 status and hyperhomocysteinemia were relatively higher in older adults. Adjusted mean homocysteine concentrations were sharply decreased from the first to second decile of serum folate in males. CONCLUSIONS: In the Korean population, the proportion of males who achieved desirable folate and homocysteine concentrations were lower than those of females. Although most Koreans have adequate vitamin B12, a suboptimal folate status is common, particularly among adolescents and young adults. These findings could establish a foundation for public health initiatives aimed at improving folate levels in the Korean population.

Elevated Homocysteine Level and Brain Atrophy Changes as Markers to Screen the Alzheimer Disease: Case Series.

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 (>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.

Association Between Hyperhomocysteinemia Combined with Metabolic Syndrome and Higher Prevalence of Stroke in Chinese Adults Who Have Elevated Blood Pressure.

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.

Voluntary Exercise Attenuates Hyperhomocysteinemia, But Does not Protect Against Hyperhomocysteinemia-Induced Testicular and Epididymal Disturbances.

The hyperhomocysteinemia (HHcy) is toxic to the cells and associated with several diseases. Clinical studies have shown changes in plasma concentrations of Hcy after physical exercise. This study aimed to assess the effect of HHcy on testis, epididymis and sperm quality and to investigate whether voluntary exercise training protects this system against damage caused by HHcy in Swiss mice. In this study, 48 mice were randomly distributed in the control, HHcy, physical exercise, and HHcy combined with physical exercise groups. HHcy was induced by daily administration of dl-homocysteine thiolactone via gavage throughout the experimental period. Physical exercise was performed through voluntary running on the exercise wheels. The plasma concentrations of homocysteine (Hcy) and testosterone were determined. The testes and epididymis were used to assess the sperm count, histopathology, lipoperoxidation, cytokine levels, testicular cholesterol, myeloperoxidase, and catalase activity. Spermatozoa were analyzed for morphology, acrosome integrity, mitochondrial activity, and motility. In the testes, HHcy increased the number of abnormal seminiferous tubules, reduced the tubular diameter and the height of the germinal epithelium. In the epididymis, there was tissue remodeling in the head region. Ultimately, voluntary physical exercise training reduced plasma Hcy concentration but did not attenuate HHcy-induced testicular and epididymal disturbances.

Association of air pollution and homocysteine with global DNA methylation: A population-based study from North India.

BACKGROUND: Anthropogenic air pollution has been implicated in aberrant changes of DNA methylation and homocysteine increase (>15µM/L). Folate (<3 ng/mL) and vitamin B12 (<220 pg/mL) deficiencies also reduce global DNA methylation via homocysteine increase. Although B-vitamin supplements can attenuate epigenetic effects of air pollution but such understanding in population-specific studies are lacking. Hence, the present study aims to understand the role of air pollution, homocysteine, and nutritional deficiencies on methylation. METHODS: We examined cross-sectionally, homocysteine, folate, vitamin B12 (chemiluminescence) and global DNA methylation (colorimetric ELISA Assay) among 274 and 270 individuals from low- and high- polluted areas, respectively, from a single Mendelian population. Global DNA methylation results were obtained on 254 and 258 samples from low- and high- polluted areas, respectively. RESULTS: Significant decline in median global DNA methylation was seen as a result of air pollution [high-0.84 (0.37-1.97) vs. low-0.96 (0.45-2.75), p = 0.01]. High homocysteine in combination with air pollution significantly reduced global DNA methylation [high-0.71 (0.34-1.90) vs. low-0.93 (0.45-3.00), p = 0.003]. Folate deficient individuals in high polluted areas [high-0.70 (0.37-1.29) vs. low-1.21 (0.45-3.65)] showed significantly reduced global methylation levels (p = 0.007). In low polluted areas, despite folate deficiency, if normal vitamin B12 levels were maintained, global DNA methylation levels improved significantly [2.03 (0.60-5.24), p = 0.007]. Conversely, in high polluted areas despite vitamin B12 deficiency, if normal folate status was maintained, global DNA methylation status improved significantly [0.91 (0.36-1.63)] compared to vitamin B12 normal individuals [0.54 (0.26-1.13), p = 0.04]. CONCLUSIONS: High homocysteine may aggravate the effects of air pollution on DNA methylation. Vitamin B12 in low-polluted and folate in high-polluted areas may be strong determinants for changes in DNA methylation levels. The effect of air pollution on methylation levels may be reduced through inclusion of dietary or supplemented B-vitamins. This may serve as public level approach in natural settings to prevent metabolic adversities at community level.

Homocysteine Solution-Induced Response in Aerosol Jet Printed OECTs by Means of Gold and Platinum Gate Electrodes.

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.

Combined effect of hyperhomocysteinemia and smoking on the severity of coronary artery disease in young adults ≤ 35 years of age: a hospital-based observational study.

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 (ß 0.302; 95% CI 0.141-0.462; P < 0.001) and pack-years of smoking (ß 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 (ß 17.892; 95% CI 11.314-24.469; P < 0.001), compared with HHcy (ß 7.471; 95% CI 0.009-14.934; P = 0.048) or current smoking (ß 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.