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.

The association between hyperhomocysteinemia and the prevalence of bilateral carotid atherosclerotic plaques in a middle-aged population.

OBJECTIVE: We conducted a cross-sectional study to investigate the impact of hyperhomocysteinemia (HHcy) on the prevalence of CASP among middle-aged individuals, aiming to provide insights for CASP prevention. METHODS: 1105 subjects were categorized into HHcy group or normal tHcy group based on their plasma total homocysteine (tHcy). All participants underwent carotid artery ultrasonography to assess the presence of unilateral and bilateral CASP. Comparative analyses of demographic and clinical data were conducted between the two groups. Logistic regression and prespecified subgroup analyses were performed to determine whether HHcy independently contributed to bilateral CASP. RESULTS: 132 individuals exhibited bilateral CASP. The prevalence of bilateral CASP was significantly higher in the HHcy group compared to the normal tHcy group (21.55 % vs. 10.82 %, p = 0.003). Univariate logistic analysis showed a significant association between HHcy and the prevalence of bilateral CASP (OR = 2.056, 95 %CI 1.089-3.881, p = 0.026). In all four models of multivariate logistic analysis, HHcy consistently emerged as an independent risk factor for bilateral CASP, with odd ratios of 1.958, 2.047, 2.023, and 2.186. This association remained significant across all five subgroups stratified by age, sex, hypertension, diabetes, and BMI. CONCLUSION: Our studies demonstrated HHcy was an independent risk factor for the prevalence of bilateral CASP in the middle-aged population. Theses results emphasized the importance of addressing HHcy in preventive strategies aimed at mitigating the burden of CASP among middle-aged individuals.

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.

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.

Prevalence and clinical correlates of hyperhomocysteinemia in Chinese urban population with hypertension.

Context: The coexistence of hypertension and elevated homocysteine (Hcy) levels has a mutually reinforcing impact on the susceptibility to cardio-cerebrovascular disease. Objective: The aim was to assess the prevalence, clinical correlation, and demographic characteristics of hyperhomocysteinemia (HHcy) within the Chinese urban population with hypertension. Methods: A cohort of 473 individuals with hypertension were selected from four communities in Shenzhen, China. Demographic attributes, clinical profiles, and lifestyle behaviors were gathered and compared between individuals with and without HHcy. A logistic regression model was employed to examine potential factors associated with the prevalence of HHcy. Correlation between Hcy levels and clinical characteristics was assessed through multiple linear regression analysis. Results: The prevalence of HHcy in the population with hypertension was 31.3%. In comparison to individuals without HHcy, those with HHcy exhibited a higher proportion of males, a higher prevalence of smoking and alcohol consumption, and a higher proportion of cases with the homozygous (TT) genotype at the MTHFR C677T polymorphism. Moreover, individuals with HHcy had lower levels of folic acid (FA), and lower fruit and vitamin B12 intake. Furthermore, the risk factors for HHcy were male (B = 1.430, OR = 4.179) and MTHFR (TT) (B = 1.086, OR = 2.961). In addition, the multiple linear regression analysis revealed a significant association between Hcy levels and gender (B = -2.784, P = 0.004), MTHFR genotypes (B = 1.410, P = 0.005), and FA levels (B = -0.136, P = 0.030). Conclusion: The high prevalence of HHcy among hypertensive patients in this Chinese urban population underscores the necessity for interventions targeting modifiable risk factors such as dietary choices and lifestyle practices.

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.

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.

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.

Development and Validation of a Novel Model for Predicting Coronary Heart Disease in Snoring Hypertensive Patients with Hyperhomocysteinemia.

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.

Diminished ovarian reserve is associated with metabolic disturbances and hyperhomocysteinemia in women with infertility.

BACKGROUND: To distinguish the metabolic profile between women with diminished ovarian reserve (DOR) and those with normal ovarian reserve (NOR). METHODS: In this retrospective study, we enrolled 524 women under the age of 40 who were experiencing infertility: 261 in the DOR group and 263 in the NOR group. Physical characteristics and metabolic parameters were compared between these two groups. RESULTS: Women with DOR exhibited a higher propensity for elevated parameters including body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), as well as heightened serum levels of homocysteine (Hcy), triglycerides (TG), low-density lipoprotein (LDL), and triglyceride-glucose (TyG) index, while concurrently experiencing reduced serum levels of high-density lipoprotein (HDL) (P < 0.05). Furthermore, the incidence rates of TG ≥ 1.7 mmol/L, hyperhomocysteinemia (HHcy), BMI ≥ 25 kg/m2, SBP/DBP ≥ 130/85 mmHg, and metabolic syndrome (MS) were significantly elevated within the DOR group as compared to the NOR group (P < 0.05). CONCLUSION: The prevalence of metabolic disturbances and HHcy were notably elevated in women with infertility and DOR compared to those with NOR.

This study focused on the metabolic condition of women who had difficulty getting pregnant and had a decreased ovarian reserve. The findings indicated that these women had a higher likelihood of glucose and lipid metabolic disorders and elevated serum homocysteine levels compared to those with a normal ovarian reserve. These metabolic issues and elevated serum homocysteine levels were associated with an increased risk of cardiovascular disease.

Homocysteine as a predictor and prognostic marker of atherosclerotic cardiovascular disease: a systematic review and meta-analysis.

OBJECTIVE: Hyperhomocysteinemia is a well-known marker that is associated with an increased risk of atherosclerosis due to its toxic effect on endothelial cells. This, in turn, leads to cardiovascular injury and increases morbidity. Different studies have shown alterations in the levels of homocysteine with respect to multiple disease states. Whether this non-traditional marker is associated with cardiovascular injury or not is subject to conflicting results. The purpose of this systematic review is to evaluate the role of homocysteine in the formation of atherosclerotic cardiovascular disease in young adults and children. MATERIALS AND METHODS: This systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA). A search was done using specific keywords, including "homocysteine", "coronary artery disease", and "atherosclerosis", amongst several others, from the databases of PubMed, COCHRANE, and EBSCO. The data items included the diseased sample population along with the intervention used, or investigations carried out and the findings of the studies. Finally, 35 eligible studies were included. RESULTS: Young patients with atherosclerotic cardiovascular disease were more likely to have elevated levels of homocysteine compared to elderly patients. Elevated levels of homocysteine have been observed with several genetic, nutritional deficiencies, and autoimmune states such as rheumatoid arthritis. On the other hand, decreased levels of homocysteine have been observed after certain intervention treatments, such as oral contraceptive pills, L-thyroxine, and even the adoption of certain diets. In the majority of studies, whenever homocysteine levels were higher than normal, this was reflected by an increased carotid intima-media thickness. CONCLUSIONS: Homocysteine has a high correlation with atherosclerotic cardiovascular disease in young and overweight patients. In addition, the relationship of homocysteine with smoking, genetic polymorphism, specific hormonal and renal disorders, nutritional deficiencies (vitamin B12 and folic acid), and the use of specific medicines are among the other recurring findings. Given that many of these studies focus only on women, the relationship between homocysteine and atherosclerotic cardiovascular diseases in males is still unclear. Whether males are more prone to hyperhomocysteinemia needs to be assessed. Still, precise processes underlying variations in homocysteine in relation to all influencing factors are unclear and need further studies.

Association of hyperhomocysteinemia and chronic kidney disease in the general population: a systematic review and meta-analysis.

BACKGROUND: Increasing evidence shows that an elevated homocysteine(Hcy) level is associated with an increased risk of chronic kidney disease (CKD). This study systematically evaluated the correlation between homocysteine level and the incidence of CKD reported in cohort and cross-sectional studies. METHODS: We searched electronic databases and reference lists for relevant articles. 4 cohort studies and 7 cross-sectional studies including 79,416 patients were analyzed in a meta-analysis. Hyperhomocysteinemia was defined as a Hcy level > 15 µmol/L, which was the criterium used in previous studies. Meta-analyses were conducted of literature searches from online databases such as PubMed, Embase, Cochrane and Scopus. Computed pooled adjusted odds ratios with corresponding 95% confidence intervals (95% CI) were used to estimate the risk of new-onset CKD according to Hcy levels in the general population. RESULTS: People with high Hcy levels were more likely to suffer from CKD than people with normal Hcy levels (pooled OR, 2.09; 95% CI, 1.72-2.55). This positive relationship persisted across different study types such as cohort studies (summary OR, 2.2; 95% CI, 1.55-3.13) and cross-sectional studies (summary OR, 2.07; 95% CI, 1.63-2.63). CONCLUSIONS: People with hyperhomocysteinemia have a higher incidence of CKD, Hyperhomocysteinemia may also be an independent risk factor for CKD in the general population.

Platelet counts affect the association between hyperhomocysteinemia and pregnancy complications.

BACKGROUND: The joint effect of platelet and other modifiers on the risk of pregnancy complications is unknown. This study investigated whether platelet count (PC) and total homocysteine (tHcy) level have a synergistic effect on the incidence of pregnancy complications in a Chinese population. METHODS: Total 11,553 consecutive pregnant women who received whole blood cell and biochemical tests at the time of admission for labor in Changzhou Maternal and Child Health Care Hospital were analyzed. The primary outcome was the prevalence of pregnancy complications: gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP), pre-eclampsia (PE), and pregnancy induced hypertension (PIH). RESULTS: The prevalence of GDM, ICP, PE, and PIH was 8.4%, 6.2%, 3.4%, and 2.1%, respectively. The highest rate of ICP (28.6%) was observed in women with high tHcy (> 15 µmol/L) and low PC (quartile 1); and the lowest rate of GDM (0.6%) was found in women with high tHcy and high PC (quartiles 2 to 4). In low PC group, the prevalence of ICP in women with high tHcy was significantly higher than that in women with low tHcy (≤ 15 µmol/L) (28.6% vs. 8.4%), representing an absolute risk increment of 20.2% and a relative risk increment of 3.3-fold (OR: 3.34; 95% CI: 1.55, 7.17; P = 0.002), whereas no joint effect was observed among high PC group. CONCLUSIONS: Among Chinese pregnant women, one subgroup (high tHcy and low PC) has the highest risk of ICP and another (high tHcy and high PC) has the lowest risk of GDM; tHcy and platelet could be used as indicators to identify the women with high risk of ICP or low risk of GDM.

Dapagliflozin's effect on serum homocysteine in patients with hypertension complicated with insulin resistance.

Most patients with hypertension are complicated with insulin resistance (IR), which is one of the risk factors of hypertension and can increase the level of serum homocysteine (Hcy) by affecting Hcy's metabolic enzyme and insulin level. Investigations in recent years have shown that Hcy is an independent risk factor for cardiovascular diseases. At present, folic acid is the prominent medicine used to reduce Hcy, but its effection for Hcy has an obvious individual difference, which is closely related to individual genes. Moreover, folic acid is chiefly used in patients with Hcy ≥15 µmol/L, but Hcy ≥10 µmol/L has had an adverse effect on the cardiovascular system. Randomized clinical trials have shown that dapagliflozin can improve IR. Therefore, whether it can reduce Hcy has become a new direction. This study was a retrospective case-control study. Patients with high serum Hcy and hypertension complicated with IR were divided into two groups: the dapagliflozin group (n = 166) and the control group (n = 198). Before and after 12 weeks of treatment, the changes in serum Hcy and IR index were measured and compared. We found that dapagliflozin could reduce the serum Hcy level of patients with hypertension and IR to a certain extent. Dapagliflozin could be a viable option for hypertension complicated with IR and hyperhomocysteinemia. However, these findings need to be further confirmed in future randomized clinical trials with a large number of samples.

Association between body fat composition and hyperhomocysteinemia in the analysis of the baseline data of the Northwest China Natural Population Cohort: Ningxia Project (CNC-NX).

The authors conducted an observational study to explore the association between body fat composition and the risk of hyperhomocysteinemia (HHcy) and their combined effect on the risk of developing cardiovascular disease (CVD). Adults aged 18-74 years from the Northwest China Natural Population Cohort: Ningxia Project (CNC-NX) were recruited in this study. Association between body fat composition and HHcy was evaluated by logistic regression model. Restricted cubic spline was used to find nonlinear association. The impact of the interaction between HHcy and body fat composition on CVD was evaluated using the addition interaction model and mediation effect model. In total, 16 419 participants were included in this research. Body fat percentage, visceral fat level, and abdominal fat thickness were positively associated with overall HHcy (p for trend < .001). Adjusted odds ratios (ORs) in quarter 4 were 1.181 (95% CI: 1.062, 1.313), 1.202 (95% CI: 1.085, 1.332), and 1.168 (95% CI: 1.055, 1.293) for body fat percentage, visceral fat level, and abdominal fat thickness, respectively, compared with those in quarter 1. Subgroup analysis indicated age, estimated glomerular filtration rate (eGFR), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and CVD were the interaction factors of body fat percentage, visceral fat level, abdominal fat thickness with HHcy (all p for interaction < .05). ORs of CVD were higher in participants with HHcy and high body fat. Body fat composition was positively associated with HHcy, indicating that reducing body, abdominal, and visceral fat content may lower the risk of HHcy and CVD.

The association of hyperhomocysteinemia with acute post-operative complications following coronary artery bypass grafting.

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.

The relationship between hyperhomocysteinemia and total coronary artery occlusion: a cross-sectional study from Southwest China.

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.

Low estimated glomerular filtration rate explains the association between hyperhomocysteinemia and in-hospital mortality among patients with ischemic stroke/transient ischemic attack or intracerebral hemorrhage: Results from the Chinese Stroke Center Alliance.

OBJECTIVES: To investigate the association between hyperhomocysteinemia (HHcy) and in-hospital mortality following ischemic stroke (IS), transient ischemic attack (TIA), or intracerebral hemorrhage (ICH). METHODS: Data on patients with ischemic cerebrovascular disease (IS/TIA) or ICH enrolled in the Chinese Stroke Center Alliance (CSCA) from 2015 to 2019 were extracted. Patient characteristics and in-hospital mortality were analyzed and multiple adjusted logistic regression analyses performed to investigate the association between blood tHcy (total homocysteine) and in-hospital mortality in patients with HHcy (tHcy ⩾ 15 µmol) and patients with normohomocysteinemia (nHcy) (tHcy < 15 µmol). RESULTS: A total of 823,622 participants were included. Mean (SD) age was 65.9 (12.1), and 62.5% (n = 514,888) were male. A total of 379,807 (46.0%) patients were identified as having HHcy, and 70,364 (8.5%) patients had an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. An eGFR < 60 mL/min/1.73 m2 was the strongest independent risk factor for HHcy in both patients with IS/TIA (adjusted odds ratio (aOR) 2.67, 95% confidence interval (CI): 2.49-2.86), and those with ICH (2.94, 2.46-3.50). On multivariable logistic regression, after adjusting for potential confounding factors, HHcy was associated with in-hospital mortality (aOR: 1.25, 95% CI: 1.13-1.37 for patients with IS/TIA; aOR: 1.40, 95% CI: 1.12-1.76 for patients with ICH). However, after additionally adjusting for eGFR, this association disappeared among patients with both IS/TIA (aOR: 1.09, 95% CI: 0.99-1.20) and those with ICH (aOR: 1.17, 9% CI: 0.96-1.43). CONCLUSION: HHcy was associated with in-hospital mortality among the patients with IS/TIA or ICH but this association disappeared after controlling for eGFR, suggesting HHcy was acting as a marker of poor renal function which itself was the predictor of poor outcome. Our results suggest the prevention and management of renal impairment may be an important measure in the reduction of mortality in patients with HHcy after IS/TIA or ICH.

The role of the deficiency of vitamin B12 and folic acid on homocysteinemia in children with Turner syndrome.

OBJECTIVES: Premature atherosclerosis and ischemic heart disease represent a major cause of comorbidities among children with Turner syndrome. The identification of non-traditional risk aspects is crucial for the early identification and management of such comorbidities through establishing effective preventive measures. The aim of the study is to explore the role of the deficiency of vitamin B12, folic acid and homocysteine in children with Turner syndrome. METHODS: The study included 78 children with Turner syndrome and 67 healthy age and sex matched children. Karyotype was implemented for all patients. The serum levels of vitamin B12, folic acid and serum homocysteine were assessed. The prevalence of the deficiency of vitamin B12 and folic acid was estimated to study its correlation to hyperhomocysteinemia in Turner syndrome children. RESULTS: The karyotype analysis showed 45,X (monosomy X) in the 78 patients. Vitamin B12 and folic acid were significantly decreased in children with Turner syndrome in 65-73% of the patients, respectively, while the serum level of homocysteine significantly increased to 48.7% compared to healthy controls. Homocysteine level negatively correlated with vitamin B12 and folic acid. The deficiency of vitamin B12 and folic acid increased the risk of hyperhomocysteinemia in children with Turner syndrome (OR 2.49 and 2.36, respectively). CONCLUSIONS: This report highlights that hyperhomocyste-inemia in children with Turner syndrome may be related to the deficiency vitamin B12 and folic acid.

Hyperhomocysteinemia Increases Vascular Risk in Stroke Patients with Chronic Kidney Disease.

AIMS: We aimed to assess the prognostic impact of hyperhomocysteinemia (HHcy) on the recurrent vascular event risk in stroke patients with or without chronic kidney disease (CKD). METHODS: In this prospective observational study, 621 patients (mean age, 69.5 years; male, 62.2%) with ischemic stroke or transient ischemic attack were consecutively enrolled within 1 week of onset and followed-up for 1 year. HHcy was defined as elevated levels of fasting total homocysteine ＞15 µmol/L. CKD was defined as an estimated glomerular filtration rate of ＜60 mL/min/1.73 m2 or a history of renal replacement therapy. The primary outcome was a composite of major adverse cardiovascular events (MACEs), including nonfatal stroke, nonfatal acute coronary syndrome, major peripheral artery disease, and vascular death. RESULTS: The prevalence of HHcy was 18.5%. Patients with HHcy were more likely to have intracranial (37.4% versus 24.8%; p=0.008) and extracranial (20.9% versus 13.0%; p=0.037) artery stenosis than were those without HHcy. At 1 year, patients with HHcy were at a greater risk of MACE than were those without HHcy (annual rate, 17.8% versus 10.4%; log-rank p=0.033). In the Cox proportional hazard regression models, HHcy was independently associated with an increased risk of MACE in patients with CKD (adjusted hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.02-4.20), whereas HHcy was not predictive of MACE in those without CKD (adjusted HR, 1.00; 95% CI, 0.30-3.32). CONCLUSIONS: Elevated levels of serum homocysteine can be an important modifiable risk factor in stroke patients with CKD, but not in those without CKD.