Total Plasma Homocysteine and Depressive Symptoms in Older Hispanics

Background: Very few studies have investigated the association between total plasma homocysteine (tHcy) and depressive symptoms in older Hispanics. Objective: To test the hypothesis that high tHcy associate with depressive symptoms in older Hispanics. Methods: A total of 1,418 participants .55 years old from the Maracaibo Aging Study (MAS) underwent standardized neurological, neuropsychiatric, and cardiovascular assessments. The Neuropsychiatric Inventory Depression Subscale (NPId) was used to assess the burden of depressive symptoms. The tHcy levels and other biochemical parameters in blood samples were measured. Multivariable logistic regression models were applied. Results: Participants with depressive symptoms had higher levels of tHcy than those without (15.1 versus 13.9 µmol/L; p = 0.009). Elevated tHcy levels were associated with depressive symptoms after adjusting for age, sex, education, smoking, diabetes, hypertension, alcohol intake, stroke, and dementia (OR = 1.62; 95% CI, 1.10–2.21). Conclusion: Elevated levels of tHcy level were associated with depressive symptoms in older Hispanics living under the nutritional and environmental conditions of a developing country.

Homocysteine Associated With Low Cognitive Function Independent of Asymptomatic Intracranial and Carotid Arteries Stenoses in Chinese Elderly Patients: An Outpatient-Based Cross-Sectional Study

Introduction: A high homocysteine (Hcy) concentration is correlated with cognitive impairment; however, the exact underlying mechanism is still not fully elucidated. The present study aimed to investigate whether asymptomatic intracranial and carotid arteries stenoses are involved in Hcy-related low cognitive function. Methods: This was a cross-sectional study in outpatient clinics. Residents aged ≥60 years, who came to the Stroke and Rehabilitation Clinic of Shandong Provincial Third Hospital in Jinan, Shandong Province from December 2019 to May 2020 to seek consultation due to abnormal transcranial Doppler reports (eg., increased cerebral blood flow velocity) were eligible. Information including demographics, medical history, lifestyle habits were collected. Fasting blood was used to detect total serum homocysteine level (tHcy). Cerebrovascular magnetic resonance angiography and neck vascular ultrasound examination were used to confirm the diagnosis of intracranial and carotid artery stenoses. The Mini-Mental State Examination was used to assess the cognitive function of each participant. Logistic regression was used to evaluate the relationship between tHcy levels and cognitive function. Results: This study included 236 participants (mean age: 64.0 (SD, 7.5) years, female: 58.1%). Multivariable analyses adjusted for several potential confounders, including creatinine and cardiovascular risk factors, showed that tHcy was associated with carotid artery stenosis (CAS). After adjusting for CAS, ICAS and several potential confounders, the association between tHcy level and low cognitive function remained significant (odds ratio: 1.09, 95% confidence interval: (1.03, 1.16), P = 0.032) . Conclusion: Increased serum tHcy level was associated with low cognitive function independent of asymptomatic intracranial and carotid arteries stenoses.

Elevated total homocysteine predicts in-hospital pneumonia and poor functional outcomes in acute ischemic stroke

Background : 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. Methods: 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. Results: The risk of in-hospital pneumonia was significantly higher in patients with highest tHcy level (Q4) compared to those with 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; P-trend =0.044) in comparison to Q1 after adjustment for potential covariates including pneumonia. Conclusion: Having a high admission tHcy level was independently associated with in-hospital pneumonia, in-hospital mortality and poor outcome upon discharge in AIS patients.

The correlation between plasma total homocysteine level and gestational diabetes mellitus in a Chinese Han population

To assess the correlation between plasma total homocysteine (tHcy) level and gestational diabetes mellitus (GDM) in a Chinese Han population. This case–control study included 350 GDM patients and 346 gestational week-matched normal glucose tolerance (NGT) pregnant women. Plasma tHcy and insulin levels were analyzed by HPLC and ELISA respectively. Logistic regression analysis was used to investigate the correlation between plasma tHcy level and risk of GDM. Women with GDM had a higher plasma tHcy level than NGT women (6.61 ± 1.32 vs. 6.17 ± 1.29 μmol/L, P = 0.001)). The GDM risk was 1.79 (OR = 1.79, 95% CI 1.18–2.72, P = 0.006) times higher in women whose plasma tHcy level was ≥ 7.29 μmol/L compared to women with plasma tHcy level < 5.75 μmol/L. Stratified analysis showed the GDM risk were much higher when HOMA-IR index ≥ 2 (OR = 5.42, 95% CI 2.51–11.74, P < 0.001), age ≥ 30 years (OR = 5.14, 95% CI 2.78–9.52, P < 0.001), or women with a family history of type 2 diabetes mellitus (T2DM) (OR = 4.13, 95% CI 1.78–9.56, P = 0.001). In the Chinese Han population, an elevated plasma tHcy level may increase the overall risk of GDM especially in women with a high HOMA-IR index, increasing age or with family history of T2DM.

Association between plasma total homocysteine level within normal range and bone mineral density in adults

Background Growing evidence indicates that homocysteine is a noteworthy marker for general health status. However, research regarding plasma total homocysteine (tHcy) levels and bone mineral density (BMD) is sparse and controversial. Hence, we aimed to investigate the association between plasma tHcy level within normal range and lumbar BMD in adults. Methods In this cross-sectional study, using the National Health and Nutrition Examination Survey database, data on 10748 adults aged between 30 and 85 years were analyzed. The weighted multiple logistic regression analyses were conducted to evaluate the association between plasma tHcy level and lumbar BMD. The fitted smoothing curves were performed to explore potential non-linear relationships. When non-linearity was detected, we further calculated the inflection point using a recursive algorithm and constructed a weighted two-piecewise linear regression model. Results After adjusting for all the covariates, the association between plasma tHcy and lumbar BMD was different in various age groups (adults aged 30–49 years: β = −0.0004, 95% CI −0.0025, 0.0018; adults aged 50–69 years: β = 0.0001, 95% CI −0.0025, 0.0026; adults aged 70–85 years: β = 0.0050, 95% CI 0.0008, 0.0092). In the subgroup analysis stratified by gender, this association also differed based on gender. There was a negative trend in females (aged 30–49 years: β = −0.0022, 95% CI −0.0054, 0.0011; aged 50–69 years: β = −0.0028, 95% CI −0.0062, 0.0007), and a positive trend in males (aged 30–49 years: β = 0.0018, 95% CI −0.0012, 0.0048; aged 50–69 years: β = 0.0027, 95% CI −0.0009, 0.0063) in both 30–49 years group and 50–69 years group. In the 70–85 years group, this association was significantly positive in males (β = 0.0136, 95% CI 0.0068, 0.0204), but was not significantly different in females (β = 0.0007, 95% CI −0.0046, 0.0060). Conclusion The correlation between plasma tHcy level within the normal range and lumbar BMD differs by age and gender.

Elevated total homocysteine predicts in-hospital pneumonia and poor functional outcomes in acute ischemic stroke

Background The impact of elevated total homocysteine (tHcy) on functional outcomes and pneumonia after acute ischemic stroke (AIS) is still not well understood. We investigated the association between tHcy levels upon hospital admission and in-hospital short-term outcomes in AIS patients. Methods 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 4 groups according to their level of admission tHcy: 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. Results During hospitalization, 332 patients (15.9%) had pneumonia, 57 patients (2.7%) died from all causes and 784 (37.6%) patients experienced poor outcome at discharge. The risk of in-hospital pneumonia was significantly higher in patients with highest tHcy level (Q4) compared to those with lowest (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(adjusted OR 3.35; 95% CI, 1.11–10.13; P -trend =0.015) and poor outcome upon discharge(adjusted OR 1.50; 95% CI, 1.06–2.12; P -trend =0.044) in comparison to Q1 after adjustment for potential covariates including pneumonia. Subgroup analyses further confirmed a significant association between higher tHcy levels and a high risk of short-term outcomes. Conclusions Having a high admission tHcy level was independently associated with in-hospital pneumonia, all cause in-hospital mortality and poor outcome upon discharge in AIS patients. Moreover, the association between higher tHcy and poor functional outcome was not modified by pneumonia.

MP6: HOMOCYSTEINE LEVEL IN PFO RELATED STROKE PATIENTS WITH RESPECT TO MEDICAL THERAPY VS PFO CLOSURE

Purpose of StudyHomocysteine is an independent risk factor of ischemic stroke by promoting vascular endothelial dysfunction and thrombotic process through oxidative stress. We previously found that PFO closure may reduce total homocysteine level (tHcy) in plasma. Here, we compare the effect of PFO closure and medical treatment in reducing mild homocysteinemia in PFO-related stroke patients.Methods Used28 PFO-related stroke patients with mildly elevated tHcy (>12 µmol/l) were prospectively recruited in accordance with IRB. 14 received PFO closure and 14 were treated by medical therapy (antiplatelet/anticoagulant) alone. None of the patients were on folate or vitamin B supplementation. Plasma was collected at baseline and 1 year follow-up after treatment. tHcy level was determined by selected reaction monitoring using mass spectrometry.Summary of ResultsCompared to medical therapy, PFO closure resulted in a lower tHcy level during follow-up (PFO closure: 11.13±3.94 µmol/L, medical therapy: 15.48±3.55 µmol/L, p=0.006), with no difference at baseline (PFO closure: 17.77±4.39 µmol/L, medical therapy: 16.47±7.50 µmol/L, p=0.575). Mild hyperhomocysteinemia patients post PFO closure had a significant reduction of tHcy by 37.34% (p=0.0005), with 71.43% of the patients (10 of 14) having tHcy levels back to normal (<12 µmol/l), while most of medically treated patients (13 of 14) stayed abnormal (p=0.4820) (χ2-test, adjusted p=0.002).ConclusionsWe found that compared with routine medical therapy, PFO closure reduced tHcy level in patients with mild hyperhomocysteinemia. Since PFO stroke patients tend to be younger, the life-time risk of even mildly elevated tHcy may be important for future thrombotic risk. Understanding the mechanism of PFO-related tHcy changes is important in optimizing medical treatment (e.g, folate replacement); studies are ongoing.Abstract MP6 Figure 1

Efficacy of Methylcobalamin to Normalise Elevated Homocysteine of Vitamin B12 Deficient Vegetarians: A Double Blind Placebo Control Study

Vegetarians are known to be deficient in vitamin B12, due to a lack of dietary animal products, which can elevate plasma total homocysteine (tHcy). Elevated total tHcy can render vegetarians susceptible to cardiovascular disease (CVD). There are a limited number of published studies in relation to the efficacy of methylcobalamin to normalise plasma tHcy of vitamin B12 deficient vegetarians. The primary objective of the present study was to explore the relationship between supplementary oral methylcobalamin and levels of tHcy of vitamin B12 deficient vegetarians; to reduce the risk of developing primary CVD. A randomised double blind placebo controlled pilot study was conducted to monitor and analyse baseline and post treatment levels of plasma tHcy, 49 volunteer vegetarians were recruited to participate in this study. Statistical analysis employing SPSS software indicated that methylcobalamin reduced mean baseline plasma tHcy of 15.5 µmolL-1 (n=39) to a mean plasma tHcy level of 8.4 µmolL-1 (P < 0.001). In a second group that contained details of ten withdrawn participants, which was conducted on an ‘Intention to Treat’ (ITT) basis, indicated that methylcobalamin was shown to be reduced from a mean baseline plasma tHcy of 14.7 µmolL-1(n=49) to a mean plasma tHcy level of 9.1 µmolL-1 (P < 0.001). The findings of the study have the potential to alert vegetarians of the possible risk of becoming vitamin B12 deficient, and to help avoid the risk of developing homocysteine related CVD. The quality data obtained in the study will allow an accurate sample size to be calculated for a future definite clinical study.

Plasma total homocysteine levels and other biochemical parameters in Algerian patients with deep vein thrombosis

We studied total plasma homocysteine levels (tHcy) in Algerian patients with a deep venous thrombosis (DVT). We measured tHcy levels in a total of 99 subjects enrolled in this study, including 40 patients with DVT and 59 healthy controls. The mean tHcy level in the patients was 12.62±8.7 μmol/L and that in the controls was 10.2± 2.1 μmol/L. In a univariate regression model, tHcy concentrations were inversely correlated with triglycerides (TG) (

HYPERHOMOCYSTEINEMIA AS A FACTOR OF FIBRINOLYSIS DISTURBANCES IN PATIENTS WITH ACTIVATED INTRAVASCULAR COAGULATION

Background. High blood concentration of D-dimer is a reliable marker of activation of intravascular coagulation, but does not provide unambiguous information about the functional potential of the ibrinolytic system.Objective. To determine the contribution of hyperhomocysteinemia (HHcy) in ibrinolysis disturbances in patients with activated intravascular coagulation. Design and methods. Plasma samples of 141 patients with activated intravascular coagulation of various etiologies [82 women (58,2 %) and 59 men (41,8 %), mean age 53,2 ± 7,8 years] with the level of D-dimer > 500 ng/ml were studied. The level of total Hcy (tHcy) was determined by high-performance liquid chromatography. In 57 samples ibrinolytic capacity was investigated by turbidimetric global coagulation and ibrinolysis test using as inducers thrombin and tissue plasminogen activator, respectively. 20 samples of donors matched for age and sex served as a comparison group. Results. In 52 patients (36,9 % of the total sample) tHcy level was greater than 12 µM, thus a modest HHcy was observed. In 29 patients (50,9 % of the patients tested for ibrinolysis capacity) the activation of intravascular coagulation was combined with hypoibrinolysis, and the frequency of HHcy in this group reached 58,6 %. A strong correlation between the time of ibrinolysis and tHcy concentration was found (Rs = 0,564, p = 0,0001).Conclusion. Thus, it appears that moderate HHcy is not only one of the risk factors for the activation of intravascular coagulation, but also causes inhibition of ibrinolysis in this pathology.