Calcium And Stroke: What's The Connection?

Calcium is a major mediator in ischemic neuronal cell death. During an ischemic stroke, there is a rapid and massive influx of calcium into the cell, which activates membrane phospholipases and protein kinases. This influx of calcium also leads to the production of free fatty acids, including arachidonic acid, which is a potent prostaglandin inducer. The degradation of the membrane by phospholipases damages membrane integrity, further reducing the efficiency of calcium pumping and leading to further calcium overload.

Some studies have shown that elevated serum calcium levels at admission in patients with stroke have been associated with less severe clinical deficits and better outcomes. However, other studies have shown no significant association between serum calcium levels and ischemic stroke.

Serum calcium and long-term outcomes after ischemic stroke

Calcium is a major mediator in ischemic neuronal cell death. An elevated intracellular calcium level is a major initiator and activator of the ischemic cell death pathway. During ischemia, there is an interruption in the oxygen-dependent generation of high-energy compounds, leading to a disturbance in cellular calcium homeostasis. This results in a rapid and massive influx of calcium into the cell.

Several studies have found that elevated serum calcium levels at admission in patients with stroke are associated with less severe clinical deficits and better outcomes. However, the underlying biological mechanism responsible for this is not well established. Some experimental studies have shown that the influx of calcium ions into neuronal cells is a mechanism of ischemic cell death. Inhibition of the effectors of calcium toxicity, such as calmodulin, calcineurin, or neuronal nitric oxide synthase, protects neurons against the toxic effects of excitatory amino acids.

A study by Chung et al. found that higher albumin-corrected calcium levels were of prognostic significance in terms of early neurological outcome and long-term mortality after acute ischemic stroke. In this study, the second and third tertiles of serum calcium level and the third tertile of albumin-corrected calcium level were found to be independent risk factors for a poor discharge outcome. Furthermore, the relationship between albumin-corrected calcium level and mortality was also found to be significant when the albumin-corrected calcium level was analysed as a linear variable.

In a study by Ovbiagele et al., higher serum calcium levels were associated with smaller infarct volumes in acute ischemic stroke. Another study by Buck et al. also found a statistically significant correlation between serum calcium and infarct size in ischemic stroke.

In a large multicentre cohort study by Zhang et al., high calcium levels were associated with all-cause mortality. The study included 9375 stroke patients from the China National Stroke Registry III, and participants were divided into four groups according to albumin-corrected calcium quartiles. Compared with the lowest calcium quartile (≤2.16 mmol/L), the adjusted hazard ratio of the top quartile (≥2.31 mmol/L) was 1.56 for all-cause mortality.

In conclusion, high serum calcium levels at baseline are associated with all-cause mortality at 1 year after ischemic stroke, suggesting that serum calcium may be a potential prognostic biomarker and therapeutic target for ischemic stroke.

Serum calcium and first stroke: A community-based nested case-control study

Stroke is the second leading cause of death globally, and about 77% of strokes are first events. The study aimed to evaluate the association between serum albumin-corrected calcium and the risk of the first stroke in the Chinese community-dwelling population.

Methods

The study sample population was drawn from the "H-type Hypertension and Stroke Prevention and Control Project." A nested case-control study design was used, matching 1,255 first-stroke cases with 1,255 controls for age, sex, and village. Serum calcium was measured by inductively coupled plasma mass spectrometry, and associations with first stroke were assessed using conditional logistic regression.

Results

The mean serum albumin-corrected calcium was 8.9 ± 0.6 mg/dl. Compared to the middle tertile (8.7-9.1 mg/dl), the multivariate-adjusted odds ratios of first total stroke associated with the lowest and highest tertiles of serum albumin-corrected calcium were 1.37 and 1.30, respectively. Similar trends were observed for the first ischemic stroke. Restricted cubic spline analysis revealed a U-shaped association between serum albumin-corrected calcium and the risk of total and ischemic stroke. However, no significant association was found with the first hemorrhagic stroke. No significant effect modification was observed in the subgroup analysis.

The study found a U-shaped association between serum calcium and first stroke, with both low and high serum calcium levels associated with an increased risk of the first stroke in the Chinese population. Serum calcium may be a potentially modifiable risk factor and a biomarker for monitoring and intervention.

Serum calcium and infarct size in acute ischemic stroke: Observations from Northeast India

Calcium is a well-known mediator of ischemic neuronal cell death. Recent studies have shown that patients with elevated serum calcium levels at the time of admission for a stroke tend to have less severe clinical deficits and better outcomes. The aim of this study is to determine the correlation between serum calcium (total, corrected, and ionized) and infarct size (IS) in patients with acute ischemic stroke.

Materials and Methods

Data was collected from 61 patients presenting with acute ischemic stroke over a one-year period at a tertiary care institute in Northeast India. Only patients aged 40 years or older who were diagnosed with acute ischemic cerebrovascular stroke through clinical examination and confirmed by a computed tomography (CT) scan were included in the study. Serum calcium levels (total, albumin corrected, and ionized) were categorised into quartiles, and these were used to calculate the correlation with IS. Pearson's correlation coefficient was used to compare calcium levels with IS.

Results

The study found that total calcium, albumin-corrected calcium, and ionized calcium had a statistically significant negative correlation with IS. Total and ionized calcium showed a significant negative correlation with IS across all four quartiles. Albumin-corrected calcium levels showed a significant negative correlation with IS only across the lowest and highest quartiles.

The findings suggest that serum calcium can be used as a prognostic indicator in ischemic stroke as its levels directly correlate with the IS.

Serum calcium and ischemic cell death

Serum calcium levels are associated with ischemic cell death, and can be used as a biomarker for short-term mortality in patients with ischemic stroke. Calcium is the most abundant mineral in the human body, and plays a role in signal transduction, maintenance of the stability of the cell membrane, the coagulation process, movement of the smooth muscle or skeletal muscle, and endocrine function.

Calcium influx into cells is a mechanism of ischemic cell death, and is triggered by the release of glutamate from neurons and glia, which activates the N-methyl-D-aspartate (NMDA) receptor. This causes a rapid translocation of Ca2+ from extracellular to intracellular spaces in cerebral tissues.

Calcium is one of the triggers involved in ischemic cell death, whatever the mechanism.

Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study

Calcium is a known mediator of ischemic neuronal cell death. Several studies have shown that elevated serum calcium levels in patients with stroke have been associated with less severe clinical deficits and better outcomes. However, the underlying biological mechanism is not well understood.

A study by Chung et al. found that higher albumin-corrected calcium levels were associated with a poorer short-term outcome and greater risk of long-term mortality after acute ischemic stroke. The study hypothesized that elevated levels of serum calcium may be associated with a poor outcome after stroke in terms of neurological severity at discharge and mortality. The study found that high levels of albumin-corrected calcium were associated with a poor discharge outcome and a higher incidence of mortality after acute ischemic stroke.

In contrast, a study by Borah et al. found that serum calcium levels had a negative correlation with infarct size in patients with ischemic stroke, and this correlation was statistically significant. The study suggested that ischemic stroke patients with larger infarct sizes tend to have lower levels of serum calcium, and those with smaller infarct sizes tend to have higher levels.

Another study by Ding et al. found a U-shaped association between serum calcium and first stroke; both low and high serum calcium levels were associated with an increased risk of the first stroke in the Chinese population. The study also found that low calcium levels could increase the calcium channels on vascular smooth muscle cells, leading to intracellular calcium overload, which is one of the most important links in the process of atherosclerotic plaque formation or thrombogenesis.

In summary, while the exact mechanisms are still being elucidated, these studies suggest that serum calcium levels may play a role in the prognosis and outcome of ischemic stroke, with both low and high levels potentially having adverse effects.

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