Elevated Total Homocysteine Levels Research Articles

The Epidemiology of Deficiency of Vitamin B12 in Preschool Children in Turkey.

Background: Vitamin B12 is a water-soluble vitamin with important cellular functions; it is an essential vitamin. The aim of this study is to determine the B12 levels of children in the period from the 6th month when they start taking additional foods to the age of seven (preschool children) and the risk factors affecting them. Methods: One hundred pediatric patients aged 6-72 months who were diagnosed with vitamin B12 deficiency and their parents who agreed to attend Istanbul Atlas University, Medical Faculty, "Medicine Hospital" Pediatric Clinic between September 2022 and June 2023 were prospectively included in this study. Results: B12 deficiency was significantly higher in the 6-11 (25%)-month group than in the 12-23 (5.8%)- and 24-47 (2.8%)-month groups. Homocysteine levels were highest in those with insufficient B12 levels compared to the other groups. There was no statistically significant difference in weekly dairy and meat consumption levels between age groups. B12 levels were lower in the 6-11-month group than in the other groups. Homocysteine levels were highest in those with insufficient B12 levels (<200 pg/mL (148 pmol/L)). Folic acid levels were lower in the 24-47-month and 48-72-month groups than in the 6-11-month and 12-23-month groups. Conclusions: The results obtained in this study showed that low vitamin B12 and increased homocysteine levels seem to be important risk factors in preschool children, especially from the 6th month when they start consuming additional foods. The diagnosis of B12 deficiency can be confirmed by elevated serum total homocysteine levels, which are evidence of functional cobalamin deficiency.

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

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). 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. 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). Elevated levels of serum homocysteine can be an important modifiable risk factor in stroke patients with CKD, but not in those without CKD.

Characteristics and prognostic analysis of simultaneous bilateral sudden sensorineural hearing loss.

To evaluate the clinical characteristics of simultaneous bilateral sudden sensorineural hearing loss (Si-BSSNHL) as well as its prognostic factors. Patients with Si-BSSNHL who were admitted to the Department of Otology Medicine between December 2018 and December 2021 were enrolled in the case group. Propensity score matching (PSM) for sex and age was used to select the control group, which included people who had unilateral sudden sensorineural hearing loss (USSNHL) during the same time period. Hearing recovery, audiological examinations, vestibular function assessments, laboratory tests, and demographic and clinical manifestations were analyzed for intergroup comparisons. Binary logistic regressions were used for both univariate and multivariate analyses of Si-BSSNHL prognostic factors. Before PSM, the Si-BSSNHL and USSNHL groups differed significantly (p < 0.05) in terms of time from onset to treatment, initial pure-tone average (PTA), final PTA, hearing gain, audiogram curve type, proportion of tinnitus, high-density lipoprotein level, homocysteine level, and effective rate. After PSM, significant differences were also observed in time from onset to treatment, initial PTA, final PTA, hearing gain, total and indirect bilirubin levels, homocysteine level, and effective rate between the two groups (p < 0.05). There was a significant difference in the classification of therapeutic effects between the two groups (p < 0.001). For prognostic analysis, the audiogram curve type was significantly different between the effective group and the ineffective groups of Si-BSSNHL (p = 0.01), in which the sloping type was an independent risk factor for the prognosis of the right ear in Si-SSNHL (95% confidence interval, 0.006-0.549, p = 0.013). Patients with Si-BSSNHL had mild deafness, elevated total and indirect bilirubin and homocysteine levels, and poorer prognosis than those with USSNHL. Audiogram curve type was linked to the therapeutic effect of Si-BSSNHL, and the sloping type was an independent risk factor for a poor prognosis in the right ear of Si-SSNHL.

Elevated levels of total homocysteine after ischemic stroke: a potential marker for in-hospital outcomes

ABSTRACT Objectives Our goal was to determine the risk conferred by elevated total homocysteine (tHcy) levels on recurrent stroke and cardiovascular disease (CVD) events after an ischemic stroke (IS), using data from the Chinese Stroke Center Alliance (CSCA). Methods The study consisted of 746,854 total participants with IS. Subjects were split into groups as well as quartiles according to tHcy level. Groups included a hyperhomocysteinemia (HHcy) group with tHcy ≥15 μmol/l and a normohomocysteinemia group (nHcy) with tHcy <15 μmol/l. The determined groups and quartiles underwent multiple logistic regression models with nHcy or quartile 1 as reference groups, respectively. The information from these analyses was adjusted for potential covariates and used to investigate the association between blood tHcy and in-hospital outcomes. Information collected at discharge included in-hospital stroke recurrence and CVD events. Results The mean [SD] age of participants was 66.2 [12.0] and 37.4% (n = 279,571) were female. The median hospital duration was 11.0 days (interquartile range, 8.0–14.0 days) and 343,346 (46.0%) patients were identified as HHcy cases (tHcy ≥15 μmol/). According to the tHcy quartile, the cumulative rates of stroke recurrence (from lowest quartile to highest) were 5.2%, 5.6%, 6.1%, and 6.6% (P < 0.0001). Similarly, those of CVD events were 5.8%, 6.1%, 6.7%, and 7.2% (P < 0.0001). Compared with the nHcy group, the HHcy group was associated with increased risks of in-hospital stroke recurrence (21912 [6.4%] vs. 22048 [5.5%], with the adjusted odds ratio (OR) 1.08, 95% CI: 1.05 to 1.10) as well as CVD events (24001 [7.0%] vs. 24236 [6.0%], with the adjusted OR: 1.08, 95% CI: 1.06 to 1.10) among patients with IS in the fully adjusted model. Conclusion HHcy was associated with increased in-hospital stroke recurrence and CVD events among patients with IS. In low-folate regions, tHcy levels may potentially predict in-hospital outcomes after IS.

Hyperhomocysteinemia in Patients with Newly Diagnosed Primary Hypertension in Can Tho City, Vietnam.

Elevated levels of blood total homocysteine is one of the cardiovascular risk factors in hypertensive patients. Determine the prevalence of hyperhomocysteinemia and its associated factors in newly diagnosed primary hypertension patients. A cross-sectional descriptive study on 105 patients with newly diagnosed primary hypertension at Can Tho University of Medicine and Pharmacy Hospital from May 2017 to May 2018. Total homocysteine levels and related factors were collected at the study time. The mean plasma total homocysteine level was 16.24 ± 4.49 µmol/L. There were 78 patients with elevated plasma total homocysteine levels ≥15 µmol/L, accounting for 74.3% of all patients. Being elderly, gender, hypertension stage, and diabetes were factors associated with hyperhomocysteinemia (p &lt; 0.05). Total homocysteine levels were positively correlated with SBP, DBP, and age with r(SBP) = 0.696, r(DBP) = 0.585, and r(age) = 0.286. Research on the subpopulation of Vietnamese people shows that hyperhomocysteinemia is common in patients with newly diagnosed primary hypertension, and high blood total homocysteine levels are often related to age, sex, hypertension stage, and diabetes.

Gender difference in association between H-type hypertension and subcortical ischemic vascular disease.

BackgroundSubcortical ischemic vascular disease (SIVD) is a leading cause of vascular dementia. The present study tries to explore not only the gender-specific association between H-type hypertension and SIVD but also the indirect effects of H-type hypertension on cognition through the ischemic brain injury caused by SIVD.Materials and methodsA total of 601 SIVD patients were included, comprising 322 males and 279 females. H-type hypertension was defined as hypertension accompanied with elevated serum total homocysteine (tHcy) level. The imaging manifestations of ischemic brain injury caused by SIVD were also evaluated, including white matter lesions (WML), lacunar infarction (LI) and brain atrophy (BA). Gender-specific subgroup analyses in association between H-type hypertension and SIVD were conducted, followed by a structural equation model based evaluation of the gender-specific mediating effects of SIVD on the relationship between H-type hypertension and cognition.ResultsFor males, there was no noticeable difference in WML, LI and BA scores among control group, isolated hypertension group, isolated high tHcy group, and H-type hypertension group in most brain regions, but significant difference was found in all brain regions for females. Multiple regression analyses showed that H-type hypertension was significantly associated with WML, LI and BA for females, but not for males. For males, H-type hypertension mainly affected cognition through direct effect, while the H-type hypertension effect was mediated by ischemic brain injury caused by SIVD for females.ConclusionH-type hypertension was more closely related to SIVD for females than males, suggesting a gender-specific difference in association patterns between H-type hypertension and cognition.

Association of Vitamin B&lt;sub&gt;12&lt;/sub&gt; Status with Biochemical Parameters among the Adult Population (30 - 50 Years) of Vallabh Vidyanagar, Anand, Gujarat

Vitamin B12 deficiency is known to be very common amongst the vegan population and can cause hyperhomocysteinemia due to various hematologic and neuropsychiatric disorders. Vitamin B12 deficiency is a global epidemic caused by malabsorption and inadequate consumption. Vitamin B12 deficiency has the greatest impact on the blood and nervous system. Elevated Methylmalonic Acid (MMA) and/or total homocysteine levels are sensitive indications of vitamin B12 deficiency and have been linked to clinical problems. Hematological parameters like erythrocyte count, hemoglobin concentration or hematocrit, Mean Cell Volume (MCV), blood values such as plasma B12 and the metabolite MMA are only a few examples. A total of 398 subjects, aged 30-50 years were selected from Vallabh Vidyanagar, Anand, Gujarat. Fourty two percent of the subjects were suffering from vitamin B12 deficiency. The subjects were screened for their vitamin B12 status and several biochemical parameters like homocysteine, iron, hemoglobin, total RBC, PCV, MCV, MCH, MCHC and RDW. Total RBC, MCV, MCH, MCHC levels, and homocysteine concentration of the subjects were found to be significantly (P ? 0.05) associated with the vitamin B12 status of the subjects. A positive and significant (P ? 0.05) relationship was observed between serum vitamin B12 and iron levels (r = 0.127, P ? 0.05) of the subjects. In conclusion, vitamin B12 status was significantly associated with total RBC, MCV, MCH, MCHC levels and homocysteine concentration

Endothelial Dysfunction and Hyperhomocysteinemia-Linked Cerebral Small Vessel Disease: Underlying Mechanisms and Treatment Timing.

Cerebral small vessel disease (cSVD)—a common cause of stroke and vascular dementia—is a group of clinical syndromes that affects the brain's small vessels, including arterioles, capillaries, and venules. Its pathogenesis is not fully understood, and effective treatments are limited. Increasing evidence indicates that an elevated total serum homocysteine level is directly and indirectly associated with cSVD, and endothelial dysfunction plays an active role in this association. Hyperhomocysteinemia affects endothelial function through oxidative stress, inflammatory pathways, and epigenetic alterations at an early stage, even before the onset of small vessel injuries and the disease. Therefore, hyperhomocysteinemia is potentially an important therapeutic target for cSVD. However, decreasing the homocysteine level is not sufficiently effective, possibly due to delayed treatment, which underlying reason remains unclear. In this review, we examined endothelial dysfunction to understand the close relationship between hyperhomocysteinemia and cSVD and identify the optimal timing for the therapy.

Long-term functional correction of cystathionine β-synthase deficiency in mice by adeno-associated viral gene therapy.

Cystathionine β-synthase (CBS) deficiency is a recessive inborn error of sulfur metabolism characterized by elevated blood levels of total homocysteine (tHcy). Patients diagnosed with CBS deficiency are currently treated by a combination of vitamin supplementation and restriction of foods containing the homocysteine precursor methionine, but the effectiveness of this therapy is limited due to poor compliance. A mouse model for CBS deficiency (Tg-I278T Cbs-/- ) was used to evaluate a potential gene therapy approach to treat CBS deficiency utilizing an AAVrh.10-based vector containing the human CBS cDNA downstream of the constitutive, strong CAG promoter (AAVrh.10hCBS). Mice were administered a single dose of virus and followed for up to 1 year. The data demonstrated a dose-dependent increase in liver CBS activity and a dose-dependent decrease in serum tHcy. Liver CBS enzyme activity at 1 year was similar to Cbs+/- control mice. Mice given the highest dose (5.6 × 1011 genomes/mouse) had mean serum tHcy decrease of 97% 1 week after injection and an 81% reduction 1 year after injection. Treated mice had either full- or substantial correction of alopecia, bone loss, and fat mass phenotypes associated with Cbs deficiency in mice. Our findings show that AAVrh.10-based gene therapy is highly effective in treating CBS deficiency in mice and supports additional pre-clinical testing for eventual use human trials.

Независимые факторы сердечно-сосудистого риска: гипергомоцистеинемия и жесткость сосудов у больных с артериальной гипертензией

Актуальность. Определение факторов риска и проведение предварительной оценки общего сердечно-сосудистого риска (ССР) у пациентов с артериальной гипертензией (АГ) — самая важная задача в клинической практике. У большинства пациентов, помимо повышенного артериального давления (АД), отмечаются и другие факторы ССР, усиливающие друг друга, что приводит к увеличению общего ССР. Одним из факторов ССР является жесткость артерий. Определение жесткости артерий проводят с помощью метода определения скорости распространения пульсовой волны (СРПВ). Вторым независимым фактором риска развития сердечно-сосудистых заболеваний является повышенный уровень гомоцистеина (ГЦ) в крови. Цель: оценить связь гипергомоцистеинемии (ГГц) с жесткостью сосудов у пациентов с АГ. Материалы и методы. Наше исследование было выполнено в рамках исследования ХИПСТЕР в Украине. В исследование было включено 40 пациентов с I и II степенью АГ (средний уровень офисного систолического (САД)/диастолического АД — 155,88/92,60 ± 1,63/1,43 мм рт.ст.), частота сердечных сокращений — 71,40 ± 1,29 уд/мин. Средний возраст больных составил 55,85 ± 2,09 года (26–74). Пациентов с уровнем ГЦ ≥ 10 мкмоль/л определяли как пациентов с ГГц (Н-тип АГ). Жесткость сосудов определяли по СРПВ. Результаты. Нами выявлено, что в начале исследования 75% (30 пациентов с мягкой и умеренной АГ) имели Н-тип АГ с повышенным уровнем ГЦ. Пациенты с Н-типом АГ (ГГц) и АГ без ГГц не отличались по возрасту, длительности АГ. При этом пациенты с Н-типом АГ имели большие массу тела, индекс массы тела (ИМТ). Офисное САД у пациентов с Н-типом АГ в начале и через 6 месяцев лечения было выше по сравнению с пациентами без ГГц (156,45 ±1,04 мм рт.ст. против 152,55 ± 1,41 мм рт.ст. в начале (р &lt; 0,05) и 130,65 ± 0,96 мм рт.ст. против 126,97±1,08мм рт.ст. через 6 месяцев (р &lt; 0,05)). ИМТ в начале исследования с Н-типом АГ — 30,72 ± 0,39 кг/м2 против 28,34 ± 0,69 кг/м2 без ГГц (р &lt; 0,05). Пациенты с Н-типом АГ хуже достигали целевых уровней АД на фоне лечения, и у них изначально были высокие показатели АД. Пациенты с Н-типом АГ по сравнению с пациентами без ГГц имели более выраженную степень инсулинорезистентности (по уровню индекса НОМА), меньшую скорость клубочковой фильтрации как в начале, так и в конце лечения. По данным суточного мониторирования АД до начала лечения пациенты с Н-типом АГ по сравнению с пациентами с АГ без ГГц имели достоверно более высокий уровень САД. После регрессионного анализа уровень гомоцистеина ассоциировался со СРПВ по артериям эластичного типа (СРПВэл) независимо от степени снижения АД (СРПВэл (6 месяцев), м/с, β = 0,307, Р = 0,001). Выводы. Мужской пол, индекс массы тела, скорость клубочковой фильтрации, уровень глюкозы крови, уровень офисного и центрального артериального давления ассоциировались с повышением уровня гомоцистеина крови у пациентов с артериальной гипертензией.

Estimation of stroke severity with National Institutes of Health Stroke Scale grading and retinal features: A cross-sectional study.

To estimate National Institutes of Health Stroke Scale (NIHSS) grading of stroke patients with retinal characteristics.A cross-sectional study was conducted in Shenzhen Traditional Chinese Medicine Hospital. Baseline information and retinal photos were collected within 2 weeks of admission. An NIHSS score was measured for each patient by trained doctors. Patients were classified into 0 to 4 score group and 5 to 42 score group for analysis. Three multivariate logistic models, with traditional clinical characteristics alone, with retinal characteristics alone, and with both, were built.For clinical characteristics, hypertension duration is statistically significantly associated with higher NIHSS score (P = .014). Elevated total homocysteine levels had an OR of 0.456 (P = .029). For retinal characteristics, the fractal dimension of the arteriolar network had an OR of 0.245 (P < .001) for the left eyes, and an OR of 0.417 (P = .009) for right eyes. The bifurcation coefficient of the arteriole of the left eyes had an OR of 2.931 (95% CI 1.573–5.46, P = .001), the nipping of the right eyes had an OR of 0.092 (P = .003) showed statistical significance in the model.The area under receiver-operating characteristic curve increased from 0.673, based on the model with clinical characteristics alone, to 0.896 for the model with retinal characteristics alone and increased to 0.931 for the model with both clinical and retinal characteristics combined.Retinal characteristics provided more information than clinical characteristics in estimating NIHSS grading and can provide us with an objective method for stroke severity estimation.

Association between H-type arterial hypertension and vascular stiffness (a pilot study)

Increased arterial stiffness is an important determinant of cardiovascular risk. Elevated total homocysteine (HC) levels appeared to be an independent risk factor for cardiovascular disease (CVD). To date, clinical studies on the relationship between HC and pulse wave velocity (PWV) assessment have shown conflicting results. Aim. To estimate the prevalence of hyperhomocystinemia (HHc) among patients with mild to moderate arterial hypertension and the effect of HHc on the vascular wall stiffness. Materials and methods. Our study was carried out as a part of the HYPSTER study in Ukraine. The study included 40 patients with I and II degree of arterial hypertension (AH) (average office systolic blood pressure (SBP)/diastolic (DBP) – 155.88/92.60 ± 1.63/1.43 mm Hg), heart rate – 71.40 ± 1.29 beats/min. The average age of the patients was 55.85 ± 2.09 (26–74) years. Patients with HC levels ≥10 μmol/l were defined as patients with H-type AH (HHc). Arterial stiffness was determined by PWV. Results. We found that at the beginning of the study, 75 % (30 patients with mild and moderate hypertension) had H-type hypertension with an increased level of HC. Patients with H-type AH and AH patients without HHc did not differ in age and AH duration. At the same time, patients with H-type AH had higher body weights and BMI. Office SBP in patients with H-type hypertension was higher compared to patients without HHc (156.45 ± 1.04 mm Hg vs. 152.55 ± 1.41 mm Hg at the beginning (P &lt; 0.05) and 130.65 ± 0.96 mm Hg vs. 126.97 ± 1.08 mm Hg after 6 months (P &lt; 0.05)) of treatment, respectively. BMI in H-type AH was 30.72 ± 0,39 kg/m2 vs. 28.34 ± 0.69 kg/m2 without HHc (P &lt; 0.05) at the beginning of the study. It was difficult to achieve target levels of BP in the patients with H-type hypertension during the treatment and they had high initial blood pressure values. In contrast to the patients without HHc, H-type AH patients had a more pronounced degree of insulin resistance (according to the HOMA index), lower GFR both at the beginning and at the end of the treatment. According to ambulatory BP monitoring, H-type AH patients presented with a significantly higher SBP level before starting the treatment compared to those with AH without HHc. The regression analysis revealed an association between HC and PWVel, regardless of the degree of BP reduction (PWVel (6 months), m/s, β = 0.307, P = 0.001). Conclusions. Hyperhomocystinemia was observed in 75 % of patients with arterial hypertension. Homocysteine levels were associated with vascular stiffness, regardless of the reduction in blood pressure level.

Elevated Total Homocysteine Predicts In-Hospital Pneumonia and Poor Functional Outcomes in Acute Ischemic Stroke.

We investigated the association between elevated total homocysteine (tHcy) levels upon hospital admission and short-term in-hospital outcomes, including pneumonia in acute ischemic stroke (AIS) patients. A total of 2,084 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in the present study. We divided patients into four groups according to their level of admission tHcy: quartile (Q1) (<9.70 umol/L), Q2 (9.70-12.3 umol/L), Q3 (12.3-16.9 umol/L), and Q4 (≥16.9 umol/L). Logistic regression models were used to estimate the effect of tHcy on the short-term outcomes, including in-hospital pneumonia, all-cause in-hospital mortality, and poor outcome upon discharge (modified Rankin Scale score ≥3) in AIS patients. The risk of in-hospital pneumonia was significantly higher in patients with the highest tHcy level (Q4) compared to those with the lowest tHcy level (Q1) (adjusted odds ratio [OR] 1.55; 95% confidence interval [CI], 1.03-2.33; P-trend =0.019). The highest tHcy level (Q4) was associated with a 3.35-fold and 1.50-fold increase in the risk of in-hospital mortality (OR 3.35; 95% CI, 1.11-10.13; P-trend =0.015) and poor outcome upon discharge (OR 1.50; 95% CI, 1.06-2.12; Ptrend =0.044) in comparison to Q1 after adjustment for potential covariates including pneumonia. Having a high admission tHcy level was independently associated with in-hospital pneumonia, in-hospital mortality, and poor outcome upon discharge in AIS patients.

Correlation between plasma homocysteine and first myocardial infarction in young patients: Case-control study in Constanta County, Romania.

An elevated level of total plasma homocysteine has been associated with a higher risk of atherosclerosis and coronary heart disease. The aim of our research was to study the relation between homocysteine and myocardial infarction (MI) in young patients. We conducted a case-control study in Constanţa County, Romania including 61 patients, divided in two groups. The first group, the MI group, consisted of 28 patients, male (67.9%) and female (32.1%) aged less than 45 years who were consecutively admitted to the Intensive Coronary Care Unit of the Emergency County Hospital of Constanţa from September 1, 2017 to August 31, 2018 (12 months), with an established diagnosis of first acute MI. The second group, the control group, included 33 patients, male (75.8%) and female (24.2%) aged less than 45 years, with cardiovascular risk factors and/or stable angina pectoris that were consecutively addressed for ambulatory cardiac evaluation at the Outpatient Clinic of Emergency County Hospital of Constanţa during the same period. Fasting plasma homocysteine was determined in both groups, within 24 h after MI onset, respectively after first cardiac exam in the controls. High homocysteine was statistically confirmed to be a risk factor in the study group, especially in association with smoking, chronic kidney disease (CKD), and to a lesser extent with diabetes mellitus (DM) and hypertension. Data analysis was performed using IBM SPSS Statistics 23. The procedures used included descriptive statistics, parametric statistical tests (Independent sample t-test), non-parametric statistical tests [Chi-square test of the association, with the evaluation of odds ratio (OR)]; the significance level used in the analysis (P-value) was 0.05. After adjusting for variables, our study results pointed out a strong association between plasma homocysteine and first acute MI among young patients, emphasising plasma homocysteine as a possible risk factor for myocardial infarction.

Estimated prevalence of moderate to severely elevated total homocysteine levels in the United States: A missed opportunity for diagnosis of homocystinuria?

Classical homocystinuria (HCU) is a genetic disorder caused by mutations in the cystathionine beta synthase gene, which results in impaired metabolism of the sulfur-bearing amino acid homocysteine and its accumulation in blood and tissues. Classical HCU can be detected via newborn screening in the United States, but the test is widely acknowledged to miss many patients. While severely elevated homocysteine levels (>100 μmol /L) frequently lead to a classical HCU diagnosis, intermediate levels (>30 to 100 μmol /L), though linked to many of the known complications of HCU, are not always recognized as associated with HCU. We aimed to identify and describe potentially undiagnosed classical HCU patients using a nationally-representative database of administrative claims and laboratory results. We estimated the national prevalence of patients with homocysteine >30 μmol /L, and compared their demographic and clinical characteristics to those of patients with homocysteine levels ≤30 μmol/L. Among 57,580 patients with a homocysteine test result, 1.8% had a value >30 μmol /L. Patients with homocysteine >30 μmol /L were more frequently diagnosed with hypothyroidism (39.2% vs. 20.7%, p < .001) and renal disease (9.7% vs. 5.5%, p < .001), and were more likely to have a prescription for an anxiolytic/antidepressant (44.5% vs. 38.9%), opioid (58.4% vs. 53.1%), steroid (46.4% vs. 42.5%), or thyroid hormone (38.8% vs. 18.8%), compared to patients with homocysteine ≤30 μmol /L (all p < .05). Both groups were equally likely to have a diagnosis of homocystinuria or another disorder of sulfur-bearing amino acid metabolism (3.8% vs. 4.0%, p = .752). The age-adjusted national prevalence of homocysteine >30 μmol /L was estimated at 33,068 (95% CI: 1033 - 35,104). These findings suggest that thousands of people in the US may be living with intermediate to severely elevated homocysteine levels and may require further evaluation for the presence of classical HCU.

Is folate deficiency a common cause of distal symmetric polyneuropathy in Zambian clinics?

ObjectivesTo evaluate the odds of vitamin B12 and folate deficiencies among Zambian clinic attendees with distal symmetric polyneuropathy (DSP) and age, sex, and HIV matched controls. MethodsCases were adults from clinics in urban/peri-urban Zambia. Controls were enrolled among persons not seeking personal medical care, such as a caregiver or person collecting antiretrovirals without a medical complaint. Participants underwent structured interviews, physician examination, and assessments of complete blood count, renal and liver profiles, serum vitamin B12 and folate, erythrocyte folate, plasma total homocysteine and methylmalonic acid. HIV testing and CD4 counts were performed when appropriate. ResultsAmong 107 consenting matched case-control pairs, 65% were female, 52% HIV positive, with mean age of 47.6 (SD 13.5) years. Among HIV positive participants, mean CD4 count was 484 (SD 221) and 482 (SD 236) for cases and controls, respectively (p = .93). DSP symptoms and severity did not differ by HIV status (p's > 0.05). Height, history of tuberculosis treatment, alcohol use, education, asset index, dietary diversity, and nutritional supplement use did not differ between cases and controls (p's > 0.05). DSP cases had at least 3:1 odds of having low serum folate (p = .0001), severely low erythrocyte folate (p = .014), and elevated total homocysteine (p = .001) levels compared to controls. Markers of vitamin B12 deficiency were not associated with case status (p's > 0.05). ConclusionMarkers of folate deficiency are highly associated with DSP among Zambian clinic attendees. Future studies should consider a broader range of comorbid nutritional deficiencies, and strategies for interventions.

Platelet Count Affects Efficacy of Folic Acid in Preventing First Stroke

BackgroundThe role of platelets and important effect modifiers on the risk of first stroke is unknown. ObjectivesThis study examined whether low platelet count (PLT) and elevated total homocysteine (tHcy) levels jointly increase the risk of first stroke, and, if so, whether folic acid treatment is particularly effective in stroke prevention in such a setting. MethodsA total of 10,789 Chinese hypertensive adults (mean age 59.5 years; 38% male, with no history of stroke and myocardial infarction) were analyzed from the China Stroke Primary Prevention Trial, where participants were randomly assigned to daily treatments of 10 mg enalapril and 0.8 mg folic acid (n = 5,408) or 10 mg enalapril alone (n = 5,381). The primary endpoint was first stroke. ResultsDuring 4.2 years of follow-up, a total of 371 first strokes occurred. In the enalapril-alone group, the lowest rate of first stroke (3.3%) was found in patients with high PLT (quartiles 2 to 4) and low tHcy (<15 μmol/l); and the highest rate (5.6%) was in patients with low PLT (quartile 1) and high tHcy (≥15 μmol/l) levels. Following folic acid treatment, the high-risk group had a 73% reduction in stroke (hazard ratio: 0.27; 95% confidence interval: 0.11 to 0.64; p = 0.003), whereas there was no significant effect among the low-risk group. ConclusionsAmong Chinese hypertensive adults, the subgroup with low PLT and high tHcy had the highest risk of first stroke, and this risk was reduced by 73% with folic acid treatment. If confirmed, PLT and tHcy could serve as biomarkers to identify high-risk individuals who would particularly benefit from folic acid treatment. (China Stroke Primary Prevention Trial [CSPPT]; NCT00794885)

Low risk of ischaemic stroke in hyperhomocysteinaemia

Whether elevated serum homocysteine concentrations (ie, hyperhomocysteinaemia) are a risk factor for ischaemic stroke and if normalising hyperhomocysteinaemia might reduce stroke risk are controversial issues. Hyperhomocysteinaemia can be primary (ie, hereditary) or secondary (ie, due to vitamin B12 deficiency, diabetes, etc). The effect of both primary and secondary hyperhomocysteinaemia on putative stroke risk is debated. One study 1 Wang W Gao C Yu C et al. No association between elevated total homocysteine levels and functional outcome in elderly patients with acute cerebral infarction. Front Aging Neurosci. 2017; 9: 70 Crossref PubMed Scopus (13) Google Scholar has shown that hyperhomocysteinaemia is an independent risk factor for ischaemic stroke, whereas other studies have reached different conclusions. 2 Pang H Han B Fu Q Zong Z Association of high homocysteine levels with the risk stratification in hypertensive patients at risk of stroke. Clin Ther. 2016; 38: 1184-1192 Summary Full Text Full Text PDF PubMed Scopus (20) Google Scholar , 3 Toole JF Malinow MR Chambless LE et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA. 2004; 291: 565-575 Crossref PubMed Scopus (1212) Google Scholar , 4 Bønaa KH Njølstad I Ueland PM et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006; 354: 1578-1588 Crossref PubMed Scopus (1264) Google Scholar , 5 Lonn E Yusuf S Arnold MJ et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006; 354: 1567-1577 Crossref PubMed Scopus (1527) Google Scholar In The Lancet Neurology, J David Spence and colleagues 6 Spence D Yi Q Hankey GJ B Vitamins in stroke prevention: time to reconsider. Lancet Neurology. 2017; 16: 750-760 Summary Full Text Full Text PDF PubMed Scopus (81) Google Scholar advocate the use of B vitamins (folic acid, vitamin B12, and vitamin B6) to normalise hyperhomocysteinaemia for the prevention of ischaemic stroke. Their Personal View raises concerns about arguments in favour of normalising hyperhomocysteinaemia. B vitamins in stroke prevention: time to reconsiderB vitamin therapy lowers plasma total homocysteine concentrations, and might be a beneficial intervention for stroke prevention; however, cyanocobalamin (a form of vitamin B12) can accelerate decline in renal function and increase the risk of cardiovascular events in patients with impaired renal function. Although early trials did not show benefit in reduction of stroke, these results might have been due to harm in participants with impaired renal function. In patients with diabetic nephropathy, cyanocobalamin is harmful, whereas B vitamins appear to reduce cardiovascular events in study participants with normal renal function. Full-Text PDF

No Association between Elevated Total Homocysteine Levels and Functional Outcome in Elderly Patients with Acute Cerebral Infarction.

Background: An elevated plasma total homocysteine (tHcy) level is an independent risk factor for vascular events. The aim of the present study was to investigate the association between tHcy levels in the acute phase of cerebral infarction and functional outcome among elderly patients.Methods: Between October 2009 and December 2012, we recruited 594 elderly patients (age > 75) with first-onset acute cerebral infarction who were consecutively admitted to the Department of Neurology of Tianjin Huanhu Hospital, China. Levels of tHcy and other biochemical values were measured within 24 h after admission. tHcy values were classified according to quartiles (<9.94; 9.94 to <12.7; 12.7 to <16.8; and ≥16.8 μmol/L). We examined the relationship between tHcy levels at admission and modified Rankin Scale scores (mRS) using univariate and multivariate analyses. Patients were followed up at 3 months and 1 year after stroke.Results: Within 3 months after stroke, 64 patients died, 37 had recurrent ischemic stroke, and 22 were lost to follow-up; thus, 471 patients were reviewed and analyzed. By the time of the 1-year follow-up, an additional 48 patients had died, 44 had recurrent ischemic stroke, and 40 had been lost to follow-up; the remaining 339 patients were thus reviewed and analyzed. Elevated tHcy levels were not associated with functional outcome among elderly patients with acute cerebral infarction (p > 0.05). Only the National Institutes of Health Stroke Scale score was associated with a poor outcome after adjusting for confounders at 3 months and 1 year (adjusted odds ratio, 1.38; 95% CI, 1.28–1.49; p < 0.01; adjusted odds ratio, 1.34; 95% CI, 1.25–1.44; p < 0.01, respectively).Conclusion: Among elderly patients with acute cerebral infarction, elevated tHcy at admission was not a predictive factor of outcome at 3 months and 1 year after stroke onset.

Homocysteine and all-cause mortality in hypertensive adults without pre-existing cardiovascular conditions

Previous studies support an association between elevated total homocysteine (tHcy) levels and increased all-cause mortality. However, few prospective studies have examined this association in hypertensive patients, and/or tested any effect modification by the methylene tetrahydrofolate reductase (MTHFR) C677T genotype. This was a post hoc analysis of the China Stroke Primary Prevention Trial. Serum tHcy and folate were measured at baseline. Individual MTHFR C677T genotype (CC, CT, and TT) was determined. Evidence for death included death certificates or home visits. Cumulative hazards of all-cause mortality by tHcy quartiles were estimated using the Kaplan-Meier method, and group differences were compared by log-rank tests. Hazard ratios (HRs) and 95% confidence intervals were estimated by Cox proportional-hazard regression models, adjusting for age, sex, baseline folate, vitamin B12, blood pressure, body mass index, smoking and alcohol drinking status, study center, total cholesterol, triglycerides, high-density lipoprotein cholesterol, fasting glucose, creatinine, and treatment group. Potential effect modification by the MTHFR genotype on the relationship between tHcy and all-cause mortality was tested. The analyses included 20,424 hypertensive patients (41% males) without a history of myocardial infarction or stroke. Baseline mean age (SD) was 60 ± 7.5 years and mean (SD) serum tHcy was 14.5 ± 8.4 μmol/L. After a mean follow-up period of 4.5 years, there were 612 (3%) all-cause deaths. Kaplan-Meier survival curves revealed a graded relationship between tHcy quartiles and all-cause mortality. The HRs, using the lowest quartile as the reference, were 1.2, 1.2, and 1.5 in Q2, Q3, and Q4, respectively. A linear trend test, using natural log-transformed tHcy, resulted in an HR of 1.5 (95% confidence interval 1.2-1.9, P < .001) after adjustment for lifestyle and health-related variables. Whereas the MTHFR genotype alone had little effect on mortality, it significantly modified the tHcy-mortality association, which was much stronger in the CC/CT genotype than in the TT genotype (P for interaction < 0.05). Among Chinese hypertensive patients without cardiovascular comorbidities, elevated tHcy was a significant risk marker for death from all causes, and the association was subject to effect modification by MTHFR genotypes. If confirmed that tHcy and MTHFR genotypes may serve as useful biomarkers for mortality risk assessment and targeted intervention.