Corrigendum: Integrated Genetics and Micronutrient Data to Inform the Causal Association Between Serum Calcium Levels and Ischemic Stroke

There has been an increased interest for observational studies or randomized controlled trials exploring the impact of calcium intake on cardiovascular diseases (CVD) including coronary artery disease (CAD) and ischemic stroke (IS). However, a direct relationship between total calcium intake and CVD has not been well established and remains controversial. Mendelian randomization (MR) studies have been performed to evaluate the causal association between serum calcium levels and CAD risk and found that increased serum calcium levels could increase the risk of CAD. However, MR analysis found no significant association between genetically higher serum calcium levels and IS as well as its subtypes. Hence, three MR studies reported inconsistent effects of serum calcium levels on CAD and IS. Here, we performed an updated MR study to investigate the association of serum calcium levels with the risk of IS using large-scale genome-wide association study (GWAS) datasets. We selected 14 independent genetic variants as the potential instrumental variables from a large-scale serum calcium GWAS dataset and extracted summary statistics corresponding to the 14 serum calcium genetic variants from the MEGASTROKE Consortium IS GWAS dataset. Interestingly, we found a significant association between serum calcium levels and IS risk using the robust inverse-variance weighted (IVW) and penalized robust IVW methods, with β = 0.243 and P = 0.002. Importantly, the MR results from the robust MR-Egger and penalized robust MR-Egger methods further supported the causal association between serum calcium levels and IS risk, with β = 0.256 and P = 0.005. Meanwhile, the estimates from other MR methods are also consistent with the above findings.

Download Full-text

Calcium Intake and Serum Calcium Level in Relation to the Risk of Ischemic Stroke: Findings from the REGARDS Study

Journal of Stroke ◽

10.5853/jos.2019.00542 ◽

2019 ◽

Vol 21 (3) ◽

pp. 312-323 ◽

Cited By ~ 1

Author(s):

Daniel T. Dibaba ◽

Pengcheng Xun ◽

Alyce D. Fly ◽

Aurelian Bidulescu ◽

Cari L. Tsinovoi ◽

...

Keyword(s):

Ischemic Stroke ◽

Serum Calcium ◽

Calcium Intake ◽

Calcium Level ◽

Serum Calcium Level ◽

Regards Study

Download Full-text

Correlation of serum calcium levels with infarct size and severity of stroke using NIHSS score in patients with acute ischemic stroke

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20195613 ◽

2019 ◽

Vol 8 (1) ◽

pp. 55

Author(s):

Prabhakar K. ◽

Pujitha S. N. ◽

Phaneesh Bharadwaj B. S.

Keyword(s):

Ischemic Stroke ◽

Infarct Size ◽

Acute Ischemic Stroke ◽

Serum Calcium ◽

Negative Correlation ◽

Tertiary Care ◽

Elevated Serum ◽

Significant Negative Correlation ◽

Total Calcium ◽

Nihss Score

Background: Normal cerebral membrane integration is important to maintain the cellular calcium homeostasis. Recent studies have suggested that elevated serum calcium levels at presentation correlates well with the infarct size and severity of stroke.Methods: A total of 73 patients with acute ischemic stroke satisfying inclusion and exclusion criteria were included in the study from November 1st 2017 to April 30th 2019 at a tertiary care centre in Kolar, Karnataka. Serum calcium (total, ionized and albumin corrected calcium) levels were measured at the time of presentation and compared with the infarct size and severity of stroke using NIHSS score (National Institute of Health Stroke Scale).Results: The levels of total calcium, albumin-corrected calcium, and ionized calcium were 9.13±0.89 mg/dL (range: 8.24-10.02), 9.56±0.82 mg/dL (range: 8.74-10.38), and 4.79±0.47 mg/dL (range: 4.3-5.2), respectively. Mean stroke size as measured on the CT scan was 47.38±17.7 cm (range: 21-88). Analysis revealed significant negative correlation between calcium levels (total, corrected, and ionized) and infarct size and severity of stroke.Conclusions: In this study, it was found that there was a statistically significant negative correlation between total, ionized and corrected calcium with the infarct size in patients with ischemic stroke and also the total calcium at presentation and severity of stroke calculated using NIHSS score.

Download Full-text

Serum calcium and long-term outcome after ischemic stroke: Results from the China National stroke registry III

Atherosclerosis ◽

10.1016/j.atherosclerosis.2021.03.030 ◽

2021 ◽

Vol 325 ◽

pp. 24-29

Author(s):

Jun-Fang Zhang ◽

Xia Meng ◽

Jing Jing ◽

Yuesong Pan ◽

Yi-Long Wang ◽

...

Keyword(s):

Ischemic Stroke ◽

Serum Calcium ◽

Term Outcome ◽

Long Term Outcome ◽

Stroke Registry

Download Full-text

A cohort study of relationship between serum calcium levels and cerebral microbleeds (CMBs) in ischemic stroke patients with AF and/or RHD

Medicine ◽

10.1097/md.0000000000004033 ◽

2016 ◽

Vol 95 (26) ◽

pp. e4033 ◽

Cited By ~ 2

Author(s):

Junfeng Liu ◽

Deren Wang ◽

Yao Xiong ◽

Bian Liu ◽

Chenchen Wei ◽

...

Keyword(s):

Cohort Study ◽

Ischemic Stroke ◽

Serum Calcium ◽

Cerebral Microbleeds ◽

Stroke Patients

Download Full-text

Racial Differences in Association of Serum Calcium with Mortality and Incident Cardio- and Cerebrovascular Events

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2016-1802 ◽

2016 ◽

Vol 101 (12) ◽

pp. 4851-4859 ◽

Cited By ~ 6

Author(s):

Jun Ling Lu ◽

Miklos Z. Molnar ◽

Jennie Z. Ma ◽

Lekha K. George ◽

Keiichi Sumida ◽

...

Keyword(s):

Ischemic Stroke ◽

Serum Calcium ◽

Calcium Metabolism ◽

Health Care Facilities ◽

Major Incident ◽

Historical Cohort ◽

Stroke Incidence ◽

All Cause Mortality ◽

Interaction Term ◽

White Patients

Context: Abnormalities in calcium metabolism may potentially contribute to the development of vascular disease. Calcium metabolism may be different in African American (AA) vs white individuals, but the effect of race on the association of serum calcium with clinical outcomes remains unclear. Objective: This study sought to examine race-specific associations of serum calcium levels with mortality and with major incident cardiovascular events. Design and Setting: This was a historical cohort study in the U.S. Department of Veterans Affairs health care facilities. Participants: Participants included veterans (n = 1 967 622) with estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2. Main Outcome Measures: The association between serum calcium levels with all-cause mortality, incident coronary heart disease (CHD), and ischemic stroke incidence was examined in multivariable adjusted Cox proportional hazards models, including an interaction term for calcium and race. Results: The association of calcium with all-cause mortality was U-shaped in both AA and white patients, but race modified the association of calcium with all-cause mortality. Compared with white patients, AA patients experienced lower risk of mortality when calcium was ≥ 8.8 mg/dL, with a statistically significant interaction (P < .001). Conversely, AA vs white race was associated with higher mortality when calcium was < 8.8 mg/dL. Calcium showed no significant association with ischemic stroke or CHD in both races; and race did not modify these associations (P = .37 and 0.11, respectively for interaction term). Conclusions: Race modified the U-shaped association between calcium and all-cause mortality. Serum calcium is not associated with incident stroke or CHD in either AA or white patients. The race-specific difference in the association of calcium levels with mortality warrants further examination.

Download Full-text

SERUM CALCIUM LEVELS BUT NOT SERUM PHOSPHATE PREDICT ISCHEMIC STROKE IN THE COMMUNITY

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(11)60600-1 ◽

2011 ◽

Vol 57 (14) ◽

pp. E600

Author(s):

Emil Hagström ◽

Bernice Wiberg ◽

Lars Lind ◽

Johan Ärnlöv

Keyword(s):

Ischemic Stroke ◽

Serum Calcium ◽

Serum Phosphate

Download Full-text

Correlation of serum calcium levels with infarct size and severity of stroke using NIHSS score in patients with acute ischemic stroke

International Journal of Research in Medical Sciences ◽

10.18203//2320-6012.ijrms20195613 ◽

2019 ◽

Author(s):

Prabhakar K. ◽

Pujitha S. N. ◽

Phaneesh Bharadwaj B. S.

Keyword(s):

Ischemic Stroke ◽

Infarct Size ◽

Acute Ischemic Stroke ◽

Serum Calcium ◽

Negative Correlation ◽

Tertiary Care ◽

Elevated Serum ◽

Significant Negative Correlation ◽

Total Calcium ◽

Nihss Score

Background: Normal cerebral membrane integration is important to maintain the cellular calcium homeostasis. Recent studies have suggested that elevated serum calcium levels at presentation correlates well with the infarct size and severity of stroke.Methods: A total of 73 patients with acute ischemic stroke satisfying inclusion and exclusion criteria were included in the study from November 1st 2017 to April 30th 2019 at a tertiary care centre in Kolar, Karnataka. Serum calcium (total, ionized and albumin corrected calcium) levels were measured at the time of presentation and compared with the infarct size and severity of stroke using NIHSS score (National Institute of Health Stroke Scale).Results: The levels of total calcium, albumin-corrected calcium, and ionized calcium were 9.13±0.89 mg/dL (range: 8.24-10.02), 9.56±0.82 mg/dL (range: 8.74-10.38), and 4.79±0.47 mg/dL (range: 4.3-5.2), respectively. Mean stroke size as measured on the CT scan was 47.38±17.7 cm (range: 21-88). Analysis revealed significant negative correlation between calcium levels (total, corrected, and ionized) and infarct size and severity of stroke.Conclusions: In this study, it was found that there was a statistically significant negative correlation between total, ionized and corrected calcium with the infarct size in patients with ischemic stroke and also the total calcium at presentation and severity of stroke calculated using NIHSS score.

Download Full-text

Serum Calcium is Related to the Degree of Artery Stenosis in Acute Ischemic Stroke

Cellular Physiology and Biochemistry ◽

10.1159/000489069 ◽

2018 ◽

Vol 46 (3) ◽

pp. 1189-1197

Author(s):

Jiayan Wu ◽

Junchao Xie ◽

Yanxin Zhao ◽

Li Gong ◽

Xueyuan Liu ◽

...

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Serum Calcium ◽

Density Lipoprotein ◽

Enrichment Analysis ◽

Artery Stenosis ◽

Gene Set Enrichment Analysis ◽

Signaling System

Background/Aims: Acute ischemic stroke is caused by stenosis of artery supplying to brain. We aimed to detect some metabolites in the serum that would be related to the degree of artery stenosis and to analyze potential mechanisms. Methods: Patients diagnosed with acute ischemic stroke were divided into two groups according to their degree of artery stenosis (which was determined by computed tomographic angiography): a mild group (stenosis ≤ 30%) and a severe group (stenosis > 30%). Serum from these patients was collected, and we focused on the differences in the concentrations of calcium, uric acid, low density lipoprotein and homocysteine. The dataset GSE11583 from the Gene Expression Omnibus database was analyzed to find the potential mechanism using bioinformatics methods. Results: Among the four metabolites, the only difference that reached significance between the two groups was in the concentration of calcium in serum (2.27±0.08 mmol/L vs 2.21±0.08 mmol/L). By comparing the gene expression levels between normal endothelial cells and adaptive remodeling endothelial cells in GSE11583, we identified 51 upregulated and 40 downregulated genes in adaptive remodeling endothelial cells. The gene set enrichment analysis revealed that upregulated genes were enriched in a phosphatidylinositol signaling system, which is closely involved in the calcium signaling pathway. Conclusion: Our results suggest that the concentration of serum calcium is higher in patients with more severe artery stenosis lesions and that the phosphatidylinositol signaling system is a key biological pathway involved in this process.

Download Full-text