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Classification of anemias and most common causes. The reticulocyte index (% reticulocytes × patient’s hematocrit/45%) × (1/shift correction factor) classifies anemia as hypoproliferative or hyperproliferative. Hypoproliferative anemias can be further categorized as microcytic, normocytic or macrocytic, and the most common causes are different in each category. MCV, red cell volume
Source publication
Purpose of the Review
Anemia has been called the fifth cardiovascular risk factor. It is one of the most prevalent pathologies worldwide. In this article, we aimed to perform a narrative review of the main cerebrovascular complications of anemia and its influence on stroke prognosis.
Recent Findings
Both hypoproliferative anemia (thalassemia, iron...
Citations
... Anemia ranks as the fifth cardiovascular risk factor following smoking, diabetes, hypertension, and dyslipidemia [39]. The following may be the underlying mechanisms [40]: (1) reduction in tissue oxygen intake; (2) increased instability of the plaque; and (3) decreased nitric oxide secretion. ...
Background
Ischemic cardio-cerebrovascular disease is the leading cause of mortality worldwide. However, studies focusing on elderly and very elderly patients are scarce. Hence, our study aimed to characterize and investigate the long-term prognostic implications of ischemic cardio-cerebrovascular diseases in elderly Chinese patients.
Methods
This retrospective cohort study included 1026 patients aged ≥ 65 years who were categorized into the mono ischemic cardio-cerebrovascular disease (MICCD) (either coronary artery disease or ischemic stroke/transient ischemic attack) (n = 912) and the comorbidity of ischemic cardio-cerebrovascular disease (CICCD) (diagnosed with both coronary artery disease and ischemic stroke/transient ischemic attack at admission) (n = 114). The primary outcome was all-cause death. The mortality risk was evaluated using the Cox proportional hazards risk model with multiple adjustments by conventional and propensity-score-based approaches.
Results
Of the 2494 consecutive elderly patients admitted to the hospital, 1026 (median age 83 years [interquartile range]: 76.5–86.4; 94.4% men) met the inclusion criteria. Patients with CICCD consisted mostly of very elderly (79.2% vs. 66.1%, P < 0.001) individuals with a higher burden of comorbidities. Over a median follow-up of 10.4 years, 398 (38.8%) all-cause deaths were identified. Compared with the MICCD group, the CICCD group exhibited a higher adjusted hazard ratio (HR) (95% confidential interval, CI) of 1.71 (1.32–2.39) for long-term mortality after adjusting for potential confounders. The sensitivity analysis results remained robust. After inverse probability of treatment weighting (IPTW) modeling, the CICCD group displayed an even worse mortality risk (IPTW-adjusted HR: 2.07; 95% CI 1.47–2.90). In addition, anemia (adjusted HR: 1.48; 95% CI 1.16–1.89) and malnutrition (adjusted HR: 1.43; 95% CI 1.15–1.78) are also independent risk factors for all-cause mortality among elderly and very elderly patients.
Conclusions
Our results thus suggest that elderly patients with ischemic cardio-cerebrovascular disease and anemia or malnutrition may have higher mortality, which may be predicted upon admission. These findings, however, warrant further investigation.
Graphical Abstract
... The youth population can experience both hypoproliferative anemia and hyperproliferative anemia, which are linked to cerebrovascular diseases. These diseases range from transient ischemic attacks to ischemic stroke and hemorrhagic stroke (26). In adults, low hemoglobin levels have been associated with an increased risk of stroke in both men and women, irrespective of their gender. ...
Background
The relationship between hemoglobin concentration and stroke has garnered significant interest in the research community. However, findings from published observational epidemiological studies on this relationship have been inconclusive. By using publicly available genome-wide association study (GWAS) aggregated statistics, a two-sample Mendelian randomization analysis is conducted to explore the causal relationship between hemoglobin concentration and stroke.
Methods
Summary statistics data from UK Biobank for hemoglobin concentration and from the FinnGen R9 and MEGASTROKE consortium for stroke are used. A series of quality control steps are taken to select eligible instrumental SNPs closely related to exposure. In order to make the conclusion more robust and reliable, several robust analysis methods are employed including inverse variance weighted, weighted median, MR-Egger regression, which are based on different assumptions of two-sample MR Analysis. Meanwhile, sensitivity analyses such as pleiotropy test and MR-Egg regression, are performed to mitigate horizontal pleiotropy and heterogeneity.
Results
The two-sample Mendelian randomized study indicates a negative association between hemoglobin concentration and stroke, suggesting that hemoglobin concentration acts as a protective factor against stroke. From the FinnGen database, there is a negative association between hemoglobin concentration and stroke, with an odds ratio (OR) of 0.82 and a 95% confidence interval (CI) of 0.73–0.92, p = 0.0006. Similarly, the MEGASTROKE database findings reinforce this observation. The negative association between hemoglobin concentration and stroke (OR: 0.91, 95%CI: 0.83–1.00, p = 0.040), ischemic stroke (OR: 0.87, 95%CI: 0.79–0.96, p = 0.004), and cardiogenic stroke (OR: 0.82, 95% CI: 0.69–0.99, p = 0.039) further suggests that higher hemoglobin levels might confer a protective effect against these conditions.
Conclusion
Hemoglobin concentration serves as a protective factor against stroke, and managing abnormal hemoglobin levels can effectively reduce the incidence of stroke.
... The causes for high incidence and poorer outcomes of ischemic stroke in SCA patients are complex and multifaceted (13). The known causes include anemia, stress-induced erythrocyte sickling, faster thrombus formation, chronic vasculopathy, and sensitivity to transient hypoxia-ischemia (17,(26)(27)(28). While anemia is a common risk factor for cerebrovascular complications, the presence of inflammatory or proliferative-occlusive vasculopathy in SCA is unique among Post-stroke collateral circulation deficits in SS-chimera mice. ...
... Frontiers in Neurology 07 frontiersin.org hemoglobinopathy and contributes greatly to the high incidence of stroke in this population (28). Accordingly, transgenic sickle mice are more sensitive to hypoxia/ ischemia-induced thrombosis than mouse models of β-thalassemia, despite similar levels of anemia (17,29). ...
Patients with sickle cell anemia (SCA) have a high incidence of ischemic stroke, but are usually excluded from thrombolytic therapy due to concerns for cerebral hemorrhage. Maladaptation to cerebral ischemia may also contribute to the stroke propensity in SCA. Here we compared post-stroke cortical collateral circulation in transgenic sickle (SS) mice, bone marrow grafting-derived SS-chimera, and wildtype (AA) controls, because collateral circulation is a critical factor for cell survival within the ischemic penumbra. Further, it has been shown that SS mice develop poorer neo-collateral perfusion after limb ischemia. We used the middle cerebral artery (MCA)-targeted photothrombosis model in this study, since it is better tolerated by SS mice and creates a clear infarct core versus peri-infarct area. Compared to AA mice, SS mice showed enlarged infarction and lesser endothelial proliferation after photothrombosis. SS-chimera showed anemia, hypoxia-induced erythrocyte sickling, and attenuated recovery of blood flow in the ipsilateral cortex after photothrombosis. In AA chimera, cerebral blood flow in the border area between MCA and the anterior cerebral artery (ACA) and posterior cerebral artery (PCA) trees improved from 44% of contralateral level after stroke to 78% at 7 d recovery. In contrast, blood flow in the MCA-ACA and MCA-PCA border areas only increased from 35 to 43% at 7 d post-stroke in SS chimera. These findings suggest deficits of post-stroke collateral circulation in SCA. Better understanding of the underpinnings may suggest novel stroke therapies for SCA patients.
... The major anemia classes comprise hyperproliferative (RI ≥ 2.5) and hypoproliferative (RI < 2.5) anemia. Hypoproliferative anemias divide into microcytic (MCV < 80 femtoliters (fL)), normocytic (MCV 80-100 fL), and macrocytic (MCV > 100 fL) anemia types [5]. Anemia is not a disease, but a presentation of an underlying condition [6]. ...
Iron deficiency anemia (IDA) has reached epidemic proportions in developing countries and has become a major global public health problem, affecting mainly 0–5-year-old children and young women of childbearing age, especially during pregnancy. Iron deficiency can lead to life-threatening loss of red blood cells, muscle function, and energy production. Therefore, the pathogenic features associated with IDA are weakness and impaired growth, motor, and cognitive performance. IDA affects the well-being of the young generation and the economic advancement of developing countries, such as India. The imbalance between iron intake/absorption/storage and iron utilization/loss culminates into IDA. However, numerous strategic programs aimed to increase iron intake have shown that improvement of iron intake alone has not been sufficient to mitigate IDA. Emerging critical risk factors for IDA include a composition of cultural diets, infections, genetics, inflammatory conditions, metabolic diseases, dysbiosis, and socioeconomic parameters. In this review, we discuss numerous IDA mitigation programs in India and their limitations. The new multifactorial mechanism of IDA pathogenesis opens perspectives for the improvement of mitigation programs and relief of IDA in India and worldwide.
... Inherited hemoglobin disorders, including thalassemia and sickle cell disease (SCD), often cause anemia that is called the fifth cardiovascular risk factor owing to its high prevalence in patients with cardiovascular diseases (Kaiafa et al., 2015;Fonseca et al., 2021). In SCD, a single point-mutation in the β-globin gene produces abnormal polymer bundles of hemoglobin tetramer HbS (α 2 β 2 S ) and premature death of red blood cells (RBCs), leading to endothelial dysfunction and a propensity to vaso-occlusions that present as overt stroke or silent cerebral infarct (Sundd et al., 2019). ...
β-thalassemia is associated with multiple hematological and cerebrovascular symptoms linked to a hypercoagulable state that has not been fully replicated in animal models for the development of stroke treatments. Herein we compared the physiological properties and responses to transient cerebral hypoxia-ischemia (tHI) between six-month-old wildtype and heterozygous Th3/+ mice, a model of non-transfusion-dependent β-thalassemia intermedia (β-TI). We found that Th3/+ mice developed microcytic anemia, splenomegaly, higher platelet counts, and increased platelet-erythrocyte plus erythrocyte-leukocyte aggregates. Furthermore, Th3/+ mice showed diminished cerebrovascular reactivity (CVR) and cortical oxygen saturation under repetitive hypercapnic challenges. When subjected to a sub-threshold tHI insult, platelets and leukocytes in Th3/+ mice adhered to the cerebrovascular wall or formed aggregates, while their counterparts flew through smoothly in wildtype mice. Subsequently, Th3/+ mice showed increased fibrin deposition around cerebral blood vessels and larger infarction than wildtype mice, especially in female Th3/+ mice. Collectively these results showed that Th3/+ mice mimic key clinical features and a propensity to thromboembolism in β-TI patients. The hypercoagulable state in Th3/+ mice is likely caused by multiple hematological and CVR anomalies that are similar, but are not identical to those in the mouse model of sickle cell anemia. As such, we suggest that Th3/+ mice are a useful model to study the pathological mechanisms and prophylactic stroke treatments in thalassemia patients.
Background
To evaluate the retinal vascular caliber using fundus photography in patients with newly diagnosed iron deficiency anemia (IDA).
Methods
This study included 56 eyes of 28 female patients with IDA and the 56 eyes of 28 age- and sex-matched healthy participants. Retinal vascular calibers were measured using image analysis software from fundus photographs. The central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE) and arteriole-to-venule ratio (AVR) were compared between groups. Linear regression analysis was used to quantify the relative impact of hemoglobin level on CRAE, CRVE, and AVR.
Results
The CRAE was significantly narrower in patients with IDA. However, no such difference appeared between groups in CRVE. AVR was significantly lower among patients with IDA than in the control group. Linear regression analysis revealed that in patients with IDA, hemoglobin level was associated with CRAE and CRVE but not with AVR. Among non-anemic individuals, there was also no association between hemoglobin level and CRAE, CRVE, or AVR.
Conclusions
Our results showing that the CRAE is significantly narrower in patients with IDA than in healthy non-anemic individuals suggests that vascular caliber may reflect early microvascular alterations resulting from IDA. Added to that, hemoglobin level was associated with CRAE and CRVE in our linear regression analysis of patients with IDA. Certain changes in retinal vascular caliber are also clearly associated with high blood pressure, cardiovascular risk, and mortality. It may be critical to identify all alterations in retinal vascular caliber in order to prevent potential ocular and systemic disorders in patients with IDA.
