Serum Calcium Levels and Long-Term Mortality in Patients with Acute Stroke

Abstract

Background: Calcium concentrations in serum are maintained within an exquisitely narrow range. Our aim was to examine the association between serum calcium and albumin-adjusted calcium (calcium_adj) levels and stroke outcome in a cohort of unselected patients with acute stroke. Methods: Consecutive patients hospitalized due to acute stroke (ischemic or intracerebral hemorrhage) throughout a large medical center were systematically assessed and followed for 1 year. Baseline total calcium and calcium_adj levels were collapsed into groups of low (<8.6 mg/dl), normal (8.7–9.9 mg/dl) and high (>10 mg/dl) levels and linear and quadratic relations with outcome were examined. Result: Among 784 patients (mean age 70.7 ± 12.5 years, 42.5% females), the mean ± SD total calcium level was 9.3 ± 0.6 mg/dl. For total calcium, the adjusted hazard ratio (HR) for all-cause death over 1 year was 1.83 [95% confidence interval (CI) 1.22–2.75] among patients with low versus normal levels. For calcium_adj, the adjusted HR for all-cause death among women was over 3-fold higher among patients with high calcium_adj levels versus those with normal levels (3.31; 95% CI 1.70–6.46), while no such associations were observed among men. In models developed to estimate the linear and quadratic relations, each unit increment in total calcium squared was associated with an increased adjusted HR of all-cause death over 1 year (p = 0.02) confirming nonlinear associations, and each unit increment in calcium_adj squared was associated with an increased adjusted HR of all-cause death over 1 year among women (p < 0.001) but not among men (p = 0.70). Conclusions: Serum calcium concentrations are a marker of mortality in acute stroke patients, but the associations are not linear, increasing at both extremes of calcium levels. Our findings suggest that long-term survival is optimal in a distinct range of serum calcium levels.

Low Serum Calcium Levels Contribute to Larger Hematoma Volume in Acute Intracerebral Hemorrhage

“…[4][5][6] In another study involving a majority of patients with ischemic stroke and few patients with ICH, low serum Ca levels were also associated with poor outcome. 7 In addition, ionized Ca is an essential cofactor for the coagulation cascade and associated with conversion of prothrombin to thrombin. Association of Ca levels with changes in clotting time and bleeding tendency was shown in the rodent models.…”

Prognostic Significance of Serum Calcium Level in a Sample of Egyptian Patients With Intracerebral Hemorrhage.

“…In line with the current study, Appel and colleagues 9 had studied 784 consecutive patients with acute strokes including both ischemic and hemorrhagic types. They demonstrated an association between the baseline serum Ca level and stroke severity and outcome.…”

“…Previous researchers [6][7][8] had reported an association between serum Ca level and ischemic strokes as it was observed that a high serum Ca level was associated with a small infract size and less severe ischemic stroke 7 . In addition, Appel et al, 9 observed that ischemic stroke patients with high ca level had a favorable outcome in comparison to those with low Ca level. Moreover, others demonstrated in a previous study that individuals with high dietary Ca intake had a reduced stroke risk 10 .…”

The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

“…An increase in the calcium level is reported to be an important indicator for oxidative stress-associated diseases. Patients with high serum calcium have been found to be more likely to suffer from a poor short-term prognosis and higher risk of long-term mortality after ischemic stroke [80]. Results from in vitro experiments indicated that inhibition of the activity of the MCU by the MCU inhibitor RU360 or siRNA or miRNA against Mcu rendered the cells resistant to oxidative stress.…”

“…Glutamate-induced excitotoxicity and mitochondrial calcium overload have been proven to be the main pathogenic factors in stroke patients and stroke model animals [133,134,135]. High levels of glutamate and calcium in plasma generally indicate a poor prognosis for acute ischemic stroke patients [80,136]. Strategies targeting glutamate and calcium channels have been carried out for decades.…”