Association between anemia and stroke with its subtypes in adults: Insights from NHANES 2005-2016 and Mendelian randomization analyses.

Previous studies have suggested that exposure to air pollutants may be associated with specific blood indicators or anemia in certain populations. However, there is insufficient epidemiological data and prospective evidence to evaluate the relationship between environmental air pollution and specific types of anemia. We conducted a large-scale prospective cohort study based on the UK Biobank. Annual average concentrations of NO2, PM2.5, PM2.5-10, and PM10 were obtained from the ESCAPE study using the Land Use Regression (LUR) model. The association between atmospheric pollutants and different types of anemia was investigated using the Cox proportional hazards model. Furthermore, restricted cubic splines were used to explore exposure-response relationships for positive associations, followed by stratification and effect modification analyses by gender and age. After adjusting for demographic characteristics, 3-4 of the four types of air pollution were significantly associated with an increased risk of iron deficiency, vitamin B12 deficiency and folate deficiency anemia, while there was no significant association with other defined types of anemia. After full adjustment, we estimated that the hazard ratios (HRs) of iron deficiency anemia associated with each 10 μg/m3 increase in NO2, PM2.5, and PM10 were 1.04 (95%CI: 1.02, 1.07), 2.00 (95%CI: 1.71, 2.33), and 1.10 (95%CI: 1.02, 1.20) respectively. The HRs of folate deficiency anemia with each 10 μg/m3 increase in NO2, PM2.5, PM2.5-10, and PM10 were 1.25 (95%CI: 1.12, 1.40), 4.61 (95%CI: 2.03, 10.47), 2.81 (95%CI: 1.11, 7.08), and 1.99 (95%CI: 1.25, 3.15) respectively. For vitamin B12 deficiency anemia, no significant association with atmospheric pollution was found. Additionally, we estimated almost linear exposure-response curves between air pollution and anemia, and interaction analyses suggested that gender and age did not modify the association between air pollution and anemia. Our research provided reliable evidence for the association between long-term exposure to PM10, PM2.5, PM2.5-10, NO2, and several types of anemia. NO2, PM2.5, and PM10 significantly increased the risk of iron deficiency anemia and folate deficiency anemia. Additionally, we found that the smaller the PM diameter, the higher the risk, and folate deficiency anemia was more susceptible to air pollution than iron deficiency anemia. No association was observed between the four types of air pollution and hemolytic anemia, aplastic anemia, and other types of anemia. Although the mechanisms are not well understood, we emphasize the need to limit the levels of PM and NO2 in the environment to reduce the potential impact of air pollution on folate and iron deficiency anemia.

This study focuses on the potential role of vitamin D in the diagnosis and treatment of iron deficiency anemia (IDA), and evaluates causation using Mendelian randomization (MR). This cross-sectional study collected clinical information from 3728 respondents in the National Health and Nutrition Examination Survey (NHANES) cycles of 2005-2010 and 2015-2018. To determine the link between serum vitamin D levels and the risk of IDA, we established a robust nomogram. Calibration and net clinical benefits were examined through calibration curves and decision curve analysis (DCA). Restricted cubic spline (RCS) models were utilized to explore the relationship between the two. In addition, the data of single nucleotide polymorphism (SNP) related to vitamin D and IDA were obtained from open biological databases. The main analytical method for the MR analysis was the inverse variance weighted (IVW) method. A series of sensitivity analyses were conducted to evaluate pleiotropy. Our cross-sectional study showed that, after extensive adjustments, serum vitamin D levels remained an independent risk factor for predicting the development of IDA. The risk of developing IDA was significantly lower for participants in the highest quartile subgroup with vitamin D levels ≥ 78.1 nmol/L compared to those in the lowest quartile with vitamin D levels ≤ 42.8 nmol/L (p < 0.001). In terms of gender, serum vitamin D primarily exhibited a protective effect against IDA in females (OR:0.98, 95% CI: 0.98-0.99, p < 0.001). A non-linear relationship between the two was found (p < 0.001 for non-linear relationship). Meanwhile, using the IVW method in MR analysis, we identified a bidirectional causal relationship. The results of our cross-sectional analysis demonstrated a negative correlation between serum vitamin D levels and IDA. Additionally, genetic evidence from the MR analysis supported an association between serum vitamin D levels and IDA.

Study Objectives: To clarify the effects of sleep duration on stroke and stroke subtypes, we adopted a Mendelian randomization (MR) approach to evaluate their causal relationship.Methods: A genome-wide association study including 446,118 participants from UK biobank was used to identify instruments for short sleep, long sleep and sleep duration. Summary-level data for all stroke, ischemic stroke, intracerebral hemorrhage, and their subtypes were obtained from meta-analyses conducted by the MEGASTROKE consortium. MR analyses were performed using the inverse-variance-weighted method, weighted median estimator, MR pleiotropy residual sum and outlier (MR-PRESSO) test, and MR-Egger regression. Sensitivity analyses were further performed using leave-one-out analysis, MR-PRESSO global test and Cochran's Q test to verify the robustness of our findings.Results: By two-sample MR, we didn't find causal associations between sleep duration and risk of stroke. However, in the subgroup analysis, we found weak evidence for short sleep in increasing risk of cardio-embolic stroke (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.11–1.60; P = 0.02) and long sleep in increasing risk of large artery stroke [OR, 1.41; 95% CI, 1.02–1.95; P = 0.04]. But the associations were not significant after Bonferroni correction for multiple comparisons.Conclusions: Our study suggests that sleep duration is not causally associated with risk of stroke and its subtypes.

BackgroundAppendicular lean mass (ALM) is a good predictive biomarker for sarcopenia. And previous studies have reported the association between ALM and stroke or Alzheimer’s disease (AD), however, the causal relationship is still unclear, The purpose of this study was to evaluate whether genetically predicted ALM is causally associated with the risk of stroke and AD by performing Mendelian randomization (MR) analyses.MethodsA two-sample MR study was designed. Genetic variants associated with the ALM were obtained from a large genome-wide association study (GWAS) and utilized as instrumental variables (IVs). Summary-level data for stroke and AD were generated from the corresponding GWASs. We used random-effect inverse-variance weighted (IVW) as the main method for estimating causal effects, complemented by several sensitivity analyses, including the weighted median, MR-Egger, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. Multivariable analysis was further conducted to adjust for confounding factors, including body mass index (BMI), type 2 diabetes mellitus (T2DM), low density lipoprotein-C (LDL-C), and atrial fibrillation (AF).ResultsThe present MR study indicated significant inverse associations of genetically predicted ALM with any ischemic stroke ([AIS], odds ratio [OR], 0.93; 95% confidence interval [CI], 0.89–0.97; P = 0.002) and AD (OR, 090; 95% CI 0.85–0.96; P = 0.001). Regarding the subtypes of AIS, genetically predicted ALM was related to the risk of large artery stroke ([LAS], OR, 0.86; 95% CI 0.77–0.95; P = 0.005) and small vessel stroke ([SVS], OR, 0.80; 95% CI 0.73–0.89; P < 0.001). Regarding multivariable MR analysis, ALM retained the stable effect on AIS when adjusting for BMI, LDL-C, and AF, while a suggestive association was observed after adjusting for T2DM. And the estimated effect of ALM on LAS was significant after adjustment for BMI and AF, while a suggestive association was found after adjusting for T2DM and LDL-C. Besides, the estimated effects of ALM were still significant on SVS and AD after adjustment for BMI, T2DM, LDL-C, and AF.ConclusionsThe two-sample MR analysis indicated that genetically predicted ALM was negatively related to AIS and AD. And the subgroup analysis of AIS revealed a negative causal effect of genetically predicted ALM on LAS or SVS. Future studies are required to further investigate the underlying mechanisms.

Anemia during the Pregnancy: The Management and Outcomes Depending on the Etiology

Circulating lipoprotein(a) levels and health outcomes: Phenome-wide Mendelian randomization and disease-trajectory analyses

Diabetes is a prevalent global metabolic and endocrine disorder that is associated with a high incidence of complications and organ system dysfunction. Bone marrow (BM) as a previously neglected site of diabetic end-organ damage, characterized by microangiopathy, neuropathy, fat deposition, and inflammation. As a result, diabetes may lead to negative consequences for physiologic hematopoiesis, which may increase the risk of aplastic anemia (AA). Summary genetic data for diabetes mellitus (DM) were sourced from FinnGen; while the data for AA and immune cell traits were obtained from the IEU Open GWAS database. We performed a two-sample univariable Mendelian randomization (MR) analysis to investigate the causal effects of DM on AA. Simultaneously, multivariable MR was utilized to further estimate the direct effect of subgroup (distinct types) of diabetes on AA. Then, a two-step mediation MR analysis was conducted to examine 731 immune cell traits that may mediate these effects. Several methods were used to evaluate the robustness of the results, including sensitivity analyses with Cochran Q statistic, MR-Egger and MR-PRESSO, which also help mitigate potential bias from horizontal pleiotropy. The two-sample univariate MR analysis demonstrated DM was significantly and positively linked to the incidence of AA (IVW, OR = 1.12; 95% CI: 1.05-1.95; P = 5.11e-04), which was comparable to the direct effect estimated for type 2 diabetes on AA risk in multivariable MR (multivariable IVW, OR = 1.18; 95% CI: 1.03-1.35; P = 1.96e-02). In two-step mediation MR, we explored 54 immune cell traits associated with DM, among these, only the Resting CD4 + regulatory T cell absolute count emerged as a potential mediator influencing the risk of AA, accounting for 10.64% of the effect. We found robust genetic evidence for a causal association between DM and AA risk, and rest CD4+ Treg absolute count, might mediate this effect. However, the potential implications of our findings for AA prevention require validation through well-powered randomized clinical trials.

Daytime sleepiness and risk of stroke: A Mendelian randomization analysis

Recent Versus Conventional Iron Status Parameters for Diagnosis of Anemia in Juvenile Idiopathic Arthritis Patients

Stroke is a leading cause of mortality and disability worldwide. Identifying predictive biomarkers and modifiable risk factors is crucial for stroke prevention in the context of predictive, preventive, and personalized medicine (PPPM). We aimed to investigate the association of serum pyridoxal 5'-phosphate (PLP) levels with stroke prevalence in a nationally representative cohort and to assess the causal relationship using bidirectional Mendelian randomization (MR) analysis, with a focus on the implications for PPPM strategies in stroke management. We included 6839 participants aged ≥ 18years from the National Health and Nutrition Examination Survey (NHANES) 2005-2013. Serum PLP levels were measured by high-performance liquid chromatography. Stroke prevalence was ascertained by self-report. We used generalized linear models, Kaplan-Meier curves, restricted cubic splines, stratified analysis, receiver operating characteristic (ROC) curves, and bidirectional two-sample MR to examine the association of PLP levels with stroke prevalence and assess the causal relationship. In the fully adjusted model, participants with low serum PLP levels had significantly higher odds of stroke compared to those with high levels (odds ratio (OR) = 6.51e-01, 95% confidence interval (CI) 4.46e-01-9.50e-01, P = 2.74E-02). Kaplan-Meier curves showed significantly lower survival probability in the low PLP group (P < 0.05). The restricted cubic spline analysis revealed a non-linear association, with the highest stroke risk at lower PLP levels. The stratified analysis showed significant associations in several subgroups. The ROC analysis indicated good predictive performance of the fully adjusted model (area under the curve (AUC) > 0.7). The MR analysis supported a protective causal effect of PLP on stroke risk (OR = 0.7723581, 95% CI 0.6388086-0.9336201, P = 0.00345), while the reverse MR analysis did not suggest a causal effect of stroke on PLP levels. Low serum PLP levels are significantly associated with higher stroke prevalence in a nationally representative the United States (US) sample. Integration of observational and genetic evidence supports a protective causal role of PLP in stroke risk. Serum PLP may serve as a promising predictive biomarker for stroke risk assessment and a potential target for personalized nutritional interventions in stroke prevention, in line with PPPM strategies. Our findings highlight the importance of maintaining optimal vitamin B6 status for effective PPPM-guided stroke prevention and management. The online version contains supplementary material available at 10.1007/s13167-024-00392-2.

Background: Nutritional anemia or anemia due to dietary causes is the most common form, yet the easiest to manage compared to other forms of anemia. Some of the most common nutritional deficiencies are iron, cobalamin, folate, and also other elements like copper. Anemia due to diet is mostly asymptomatic in the initial phase until the stores are depleted, which can take a few months to several years, depending upon the cause. Methodology: We conducted this review using a comprehensive search of MEDLINE, PubMed, and EMBASE from January 1987 to March 2017. The following search terms were used: nutritional anemia, dietary anemia, iron deficiency anemia, cobalamin deficiency, folic acid deficiency anemia, dietary anemia treatment Aim of the work: In this study we aimed to understand about the different types of anemia caused as a result of dietary deficiency. We will also briefly study about their presentation, pathophysiology, and treatment. Conclusion: Various causes, presentations, and complications are associated with different types of nutritional anemia, but they still are the easiest to treat and manage. Most cases are due to an underlying occult disorder rather than simple dietary insufficiency, making diagnosis more difficult in some cases, and requiring thorough history and investigations integration to reach an accurate diagnosis and treat the underlying cause.

Is There an Increased Risk for Ischemic Stroke in Patients with Multiple Sclerosis, and If So, Should Preventive Treatment Be Considered?

Background The study of cell-free DNA (cfDNA) has attracted great interest these years. Some research studies detected the origin of cfDNA and used it to monitor the treatment response and predict disease progression. Objective We aimed to detect the erythroid cfDNA as a valuable noninvasive marker for differentiation between many types of anemia. Patients and methods A total of 76 patients and 25 age-matched and sex-matched controls were enrolled in this study. Patients were divided into four groups depending on type of anemia: group I (n=20, patients with ß-thalassemia major), group II (n=20, patients with chronic kidney disease), group III [n=16, patients with aplastic anemia (AA)], and group IV (n=20, patients with iron-deficiency anemia). Group III was further subdivided into two subgroups: subgroup A (n=8 patients with AA responsive to treatment) and subgroup B (n=8 patients with AA not responding to treatment). Erythroid cfDNA (E%) was estimated using quantitative real-time PCR. Results There was a highly significant difference in the percentage of erythroid DNA (E%) when comparing each group with the control group; furthermore, E% was more sensitive than the reticulocyte count for discrimination between group II and the control group, and more specific for discrimination between groups III and IV and the control group. Conclusion The erythroid cfDNA is a sensitive noninvasive tool when compared with reticulocytic count for discrimination between different types of anemia.

BackgroundDiabetes mellitus is one of the most common diseases worldwide with significant morbidity and mortality. HbA1c remains one of the most important methods for diagnosis and monitoring of the disease. Since HbA1c is a reflection of the glucose attached to red blood cells, factors affecting hemoglobin and red blood cells’ half-life can influence HbA1c measurements.ObjectiveThis study aims to evaluate the effect of different types of anemia including iron deficiency anemia, sickle cell anemia, β -thalassemia trait, and megaloblastic anemia on HbA1c levels in a tertiary hospital over the past 6 years (2016–2022).MethodThis is a retrospective chart review study of 324 patients including those with one of the four types of anemia mentioned above and a control group. The control group were healthy adults with normal HbA1c and hemoglobin, who were not known to have diabetes or anemia. Patients with diabetes or prediabetes based on self-reporting or elevated fasting, random blood sugar, or 2 hours post-prandial blood glucose were excluded.ResultsThe mean HbA1c levels were significantly higher in sickle cell anemia at 5.83% (95% CI = 5.39–6.28) and in iron deficiency anemia at 5.75% (95% CI = 5.68–5.82) when compared to the control group at 5.32% (95% CI = 5.22–5.41). However, the mean HbA1c levels in megaloblastic anemia were 5.38% (95% CI = 5.26–5.5) and 5.45% (95% CI = 5.21–5.69) in beta thalassemia trait, which were not significantly different when compared to the control group. HbA1c significantly decreased from 5.75 to 5.44% after treatment in the iron-deficient group with a p-value of < 0.001. Moreover, lower hemoglobin and higher red cell distribution width correlated with higher HbA1c levels in patients with sickle cell anemia.ConclusionThis study found a significant increase in HbA1c levels in iron deficiency anemia and sickle cell disease in patients not known to have diabetes. However, there was no significant effect in those patients with β-thalassemia trait and megaloblastic anemia. Treatment of iron deficiency anemia significantly decreased the HbA1c level, bringing it back to normal.

Patients with colorectal cancer often have anemia and other symptoms after diagnosis, especially in patients with advanced colorectal cancer. This study explored the association between different types of preoperative anemia and tumor characteristics and inflammatory response in patients with colorectal cancer and to evaluate the prognosis of patients with different types of anemia before operation. The clinical data of 95 patients with colorectal cancer treated in the Fourth Hospital of Hebei Medical University from February 2016 to January 2018 were retrospectively analyzed. According to the hemoglobin concentration (Hb), mean corpuscular volume (MCV), mean hemoglobin content (MCH) and mean hemoglobin concentration (MCHC), the patients were divided into the non-anemia group, normal cell anemia group, and small cell anemia group. The three groups' general data, oncological characteristics, and mGPS scores were compared. The patients were followed up for five years, and the survival analysis was carried out. The cox proportional hazard regression model was used to analyze the prognostic factors of patients with colorectal cancer. The preoperative anemia rate of patients with colorectal cancer was 43.15% (41/95). There were significant differences in gender, weight loss, CA724, tumor location, tumor size, TNM stage, mGPS score, and positive expression rate of Ki-67 among different anemia groups. There was a significant difference in survival time among a non-anemia group, small cell anemia group, and normal cell anemia group (P<0.05). Multivariate analysis showed that tumor size, TNM stage, distant metastasis, mGPS score, Ki-67 positive expression rate, and anemia type were independent risk factors affecting the prognosis of colorectal cancer patients (P<0.05). The oncological characteristics of colorectal cancer patients with different types of preoperative anemia are different. Preoperative anemia and systemic inflammatory status are independent risk factors for the prognosis of colorectal cancer patients.