Effect Of Serum Calcium Levels Research Articles

The effect of serum calcium level on the success of diltiazem treatment: A retrospective cohort study

IntroductionDiltiazem is an antiarrhythmic drug widely used in the treatment of atrial fibrillation (AFib) with rapid ventricular response (RVR). It reveals its effect by blocking L-type calcium channels. Thus, it inhibits the extracellular calcium influx into the cytosol. The relationship between serum calcium level and the efficacy of intravenous (IV) diltiazem used in the treatment of AFib with RVR has not been investigated in vivo. The aim of this study is to investigate the mentioned relationship. MethodsThis study was planned as a single-center retrospective study. The data of 349 patients who presented to the emergency department with AFib with RVR and treated with diltiazem were retrospectively analyzed. A patient was considered to have responded to diltiazem treatment if the existing heart rhythm returned to sinus rhythm, or the heart rate decreased below 100 beats/min, or the heart rate decreased >20% provided that it was below 120 beats/min. The ionized calcium levels were recorded. The relationship between serum calcium level and the success of diltiazem treatment was examined. ResultsFifty five percent of the patients were female. The median age was 75 years. The rate of response to diltiazem treatment was 67.3%. The median of ionized calcium levels in the group which responded to diltiazem treatment (n = 235) was 1.14 mmol/L (IQR: 0.12), and the group which did not respond to diltiazem treatment (n = 114) was 1.11 mmol/L (IQR: 0.12) (p = 0.322). The patients were divided into three groups as low, normal, and high calcium levels according to the calcium reference levels determined by the hospital laboratory. The rate of response to diltiazem treatment was 61.4% in patients with low ionized calcium levels, 76.1% in patients with normal ionized calcium levels, and 40.0% in patients with high ionized calcium levels. The rate of response to diltiazem treatment was higher in patients with normal ionized calcium levels compared to patients with low or high ionized calcium levels (p = 0.004, p = 0.003). ConclusionThe success rate of diltiazem used in the treatment of AFib with RVR was highest in physiological calcium levels. The current study may provide the clinician with awareness about the consideration of serum ionized calcium levels when choosing drugs in patients with AFib with RVR.

Health Effects of Calcium: Evidence From Mendelian Randomization Studies.

ABSTRACTCalcium is widely used in conjunction with vitamin D to prevent osteoporosis. The use of calcium supplementation is also promoted for its potential benefits in lowering the risk for metabolic syndromes and cancers. However, the causal link between calcium and various health outcomes remains unclear. This review focuses on the evidence from 24 Mendelian randomization (MR) studies that were designed to minimize bias from confounding and reverse causation. These MR studies evaluated the effect of lifelong genetically higher serum calcium levels on various health outcomes. Overall, available MR studies found no conclusive effects of serum calcium levels on bone mineral density and fracture, ischemic stroke and heart failure, cancers, type 2 diabetes, Parkinson disease, or offspring birth weight. However, a higher serum calcium concentration was reported to have estimated causal effects on increased risks for coronary artery disease (especially myocardial infarction), migraine, renal colic, allergy/adverse effect of penicillin, and reduced risks for osteoarthrosis and osteoarthritis. In conclusion, supplementation of calcium in individuals from the general population is not predicted to influence the risk of most investigated diseases to date. Moreover, long‐term high serum calcium concentrations may result in adverse health outcomes. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Exploring Preoperative Hypocalcemia as a Biomarker for Post Left Ventricular Assist Device Survival and Adverse Events

<h3>Purpose</h3> Abnormal calcium handling in cardiomyocytes plays a cardinal role in the initiation and progression of heart failure. However, the effect of serum calcium levels has not been studied in chronic heart failure patients undergoing left ventricular assist device (LVAD) placement. We investigate the impact of preoperative hypocalcemia on adverse events and all-cause mortality in this population over a 24-month period post durable LVAD implantation. <h3>Methods</h3> At a single center, 177 patients received LVAD therapy between June 2011 and October 2018. Patients were classified into either hypocalcemia [(serum calcium < 8.7 mg/dL) n=40] or normocalcemia [(8.7- 10.2 mg/dL) n=108] based on preoperative levels. 29 patients were excluded due to missing data. Unadjusted and adjusted cox models were used to examine for association between hypocalcemia and 2-year all-cause mortality. Survival was compared using Kaplan-Meir plot and log-rank statistics. <h3>Results</h3> The majority of patients in both groups were undergoing LVAD placement for destination therapy (77 vs. 73%, p=0.009) and had a similar history of chronic kidney disease across groups (21 vs. 28%, p=0.36). However, there was a significantly greater number of Caucasian patients in the hypocalcemia group (85 vs. 63%, =0.004). 24-month survival was equal across groups (Log-Rank p=0.13). Likewise on Cox-modelling, there was no difference in survival seen on either the unadjusted [HR= 1.42 (0.89 - 2.27) (p=0.14)] or adjusted survival [1.39 (0.86 - 2.24) (p=0.18)] when adjusted for age, gender, INTERMACS category, and eGFR. Perioperative renal failure and need for hemodialysis were similar between groups. However, the hypocalcemia group required prolonged intubation (46 vs 28%, p=0.03), tracheostomy (28 vs 11%, p=0.001) and increased right ventricular assist device use (23 vs 8%, p=0.02). <h3>Conclusion</h3> Despite no significant impact on survival at 24-months, hypocalcemia may be a poor prognostic marker for some adverse events.

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.

Influence of hypocalcemia on the prognosis of septic patients

To investigate the effect of serum calcium level on the prognosis of patients with sepsis. Clinical data of 119 patients with sepsis admitted to intensive care medicine (ICU) of the First Affiliated Hospital of the University of Science and Technology of China from January 2017 to October 2018 were retrospectively analyzed. Gender, age, and C-reactive protein (CRP), procalcitonin (PCT), serum calcium levels, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure score (SOFA) within 24 hours of diagnosis, and 28-day mortality were collected. The patients were divided into the normal serum calcium group (serum calcium 2.00-2.67 mmol/L) and the hypocalcemia group (serum calcium < 2.00 mmol/L) according to their serum calcium level. The patients were divided into survival group and death group according to 28-day prognosis. Pearson correlation test was used to analyze the correlation between serum calcium level and clinical indicators. Receiver operator characteristic (ROC) curve was used to analyze the predictive value of serum calcium level on prognosis. A total of 119 patients with sepsis were included, including 50 patients with normal serum calcium, with serum calcium level of (2.14±0.10) mmol/L; and 69 patients of hypocalcemia, and the incidence of hypocalcemia was 57.98%, with serum calcium level of (1.81±0.14) mmol/L. In the hypocalcemia group, except that the APACHE II score was significantly higher than that of the normal serum calcium group (25.59±5.52 vs. 22.28±4.89, P < 0.01), there was no significant difference in gender, age, CRP, PCT and SOFA score between the two groups. The 28-day mortality rate of the hypocalcemia group was significantly higher than that of the normal serum calcium group [78.26% (54/69) vs. 48.00% (24/50), χ2 = 10.45, P < 0.01]. The level of serum calcium in the death group was significantly lower than that in the survival group (mmol/L: 1.90±0.20 vs. 2.04±0.19), while the APACHE II score was significantly higher than the survival group (25.78±5.25 vs. 21.20±4.68), with statistically significant differences (both P < 0.01). There was a negative correlation between serum calcium level and PCT, APACHE II scores in patients with sepsis (r1 = -2.10, P1 = 0.04; r2 = -3.91, P2 < 0.01), but no correlation with CRP and SOFA score (r1 = 0.75, P1 = 0.46; r2 = -1.21, P2 = 0.23). The ROC curve analysis showed that the area under the ROC curve (AUC) for predicting the prognosis of sepsis patients with serum calcium level was 0.70 [95% confidence interval (95%CI) = 0.602-0.798], and the best cut-off value was 1.92 mmol/L, with the sensitivity was 52.56%, and the specificity was 82.93%. The prognosis of sepsis patients with hypocalcemia is poor. Serum calcium level can be used as a predictor of prognosis in patients with sepsis.

Lower Serum Calcium as a Potentially Associated Factor for Conversion of Mild Cognitive Impairment to Early Alzheimer's Disease in the Japanese Alzheimer's Disease Neuroimaging Initiative.

Effect of serum calcium level to the incidence of mild cognitive impairment (MCI) conversion to early Alzheimer's disease (AD) remains uncertain. To investigate association between baseline serum calcium and the MCI conversion in the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) study cohort. In this sub-analysis of J-ADNI study, we reviewed data from MCI participants at baseline regarding their conversion to early AD during the 3 years of observation period and assessed the associated factors including serum calcium level. In addition, we compared our results from the J-ADNI study with the corresponding results from the North American (NA)-ADNI. Of 234 eligible MCI participants from the J-ADNI cohort, 121 (51.7%) converted to AD during the first 36 months of observation. Using univariate analysis, being female, having shorter years of education, and lower serum calcium level were correlated with increased risk of MCI-to-AD conversion exclusively in J-ADNI cohort. The lower corrected serum calcium level remained as one of conversion-associated factors in the J-ADNI cohort even after adjustment for multiple confounding variables, although this was not observed in the NA-ADNI cohort. Our findings suggest that lower serum calcium may be associated with an increased risk of MCI conversion to AD in Japanese cohorts. The reason for this correlation remains unclear and further external validation using other Asian cohorts is needed. It would be interesting for future AD studies to obtain serum calcium levels and other related factors, such as vitamin D levels, culture-specific dietary or medication information.

A study on effects of serum calcium levels in relation to ankle joint instability-A case control study

A study on effects of serum calcium levels in relation to ankle joint instability-A case control study

Using published data in Mendelian randomization: a blueprint for efficient identification of causal risk factors.

Finding individual-level data for adequately-powered Mendelian randomization analyses may be problematic. As publicly-available summarized data on genetic associations with disease outcomes from large consortia are becoming more abundant, use of published data is an attractive analysis strategy for obtaining precise estimates of the causal effects of risk factors on outcomes. We detail the necessary steps for conducting Mendelian randomization investigations using published data, and present novel statistical methods for combining data on the associations of multiple (correlated or uncorrelated) genetic variants with the risk factor and outcome into a single causal effect estimate. A two-sample analysis strategy may be employed, in which evidence on the gene-risk factor and gene-outcome associations are taken from different data sources. These approaches allow the efficient identification of risk factors that are suitable targets for clinical intervention from published data, although the ability to assess the assumptions necessary for causal inference is diminished. Methods and guidance are illustrated using the example of the causal effect of serum calcium levels on fasting glucose concentrations. The estimated causal effect of a 1 standard deviation (0.13 mmol/L) increase in calcium levels on fasting glucose (mM) using a single lead variant from the CASR gene region is 0.044 (95 % credible interval −0.002, 0.100). In contrast, using our method to account for the correlation between variants, the corresponding estimate using 17 genetic variants is 0.022 (95 % credible interval 0.009, 0.035), a more clearly positive causal effect. Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-015-0011-z) contains supplementary material, which is available to authorized users.

APOE genotype modulates the effect of serum calcium levels on cognitive function in old age

The APOE genotype and serum calcium levels have both been associated with cognitive impairment. Animal studies have shown variation in apoE isoforms to play a critical role in intraneuronal calcium homeostasis, but the contribution of this interaction to cognitive function in man is unknown. Here, we studied whether the APOE genotype modulates the association between serum calcium levels and cognition. Within the Leiden 85-plus Study, a prospective population-based study of 599 subjects aged 85 years, we measured serum calcium levels and APOE genotype at baseline. During a 5-year follow-up period, cognitive function was annually assessed using the Mini-Mental State Examination (MMSE) and a standardized neuropsychological test battery. Both at baseline and during follow-up, high serum calcium levels were associated with worse cognitive function in epsilon3epsilon4 carriers and to a lesser extent in epsilon3epsilon3 carriers, but not in epsilon2epsilon3 carriers. The MMSE score during the entire follow-up period differed between those with high and low serum calcium levels, with 5.5 points in epsilon3epsilon4 carriers (p < 0.001), 1.6 points in epsilon3epsilon3 carriers (p = 0.010), and 0.1 point in epsilon2epsilon3 carriers (p = 0.935). Formal testing showed an interaction between APOE genotype and serum calcium levels in relation to global cognitive function (p = 0.003). In old age, APOE genotype modulates the association between serum calcium levels and cognitive function. High serum calcium levels associate with worse cognitive function, especially in APOE epsilon4 allele carriers, but not in carriers of the epsilon2 allele.

Calcium levels as a risk factor for delayed graft function.

Delayed graft function (DGF) occurs in up to 50% of renal transplants. Hypercalcemia and hyperparathyroidism are associated with impaired renal function. Little is known on the effects of serum calcium levels on DGF. This issue was addressed in the current study. Patients receiving a cadaveric renal transplant between 1986 and 1996 were studied. Data on calcium metabolism and histologic characteristics of nephrocalcinosis, acute tubular necrosis (ATN), and acute rejection in biopsies taken within the first week were related to the occurrence of DGF. The incidence of DGF in a cohort of 585 cadaveric transplants was 31%. DGF correlated independently with serum calcium levels (odds ratio [OR] 1.14 [95% confidence interval (CI) 1.04-1.26] per 0.1 mmol/L). The use of calcium channel blockers before transplantation protected against DGF (OR 0.5 [95% CI 0.29- 0.87]). In this selected group, we found an association with histologic signs of ATN and DGF. However, most of the biopsies also had features of acute rejection or nephrocalcinosis. Nephrocalcinosis was found in 12 of 71 biopsies and was not associated with serum calcium levels or the occurrence of DGF. In this study, serum calcium levels were independently associated with DGF. This could not be explained by the presence of microscopic nephrocalcinosis. Therefore, DGF is attributed to high intracellular calcium levels. Because calcium supplementation and vitamin D analogues are commonly used in dialysis practice, hypercalcemia influences long-term graft outcome by its effect on DGF. The pretransplant use of calcium channel blockers has a protective effect on the occurrence of DGF.

The effect of serum calcium levels on the rate of epidermal renewal in the rat

The growth and differentiation of epidermal cells in vitro show a marked dependence on the calcium concentration of the medium. In this study the effect of experimentally produced hyper- and hypocalcaemia on the rat epidermis in vivo has been investigated. Hypercalcaemia, induced by injections of calcium chloride, produced a decrease in epidermal labelling index and some epidermal thinning. On the other hand hypocalcaemia, induced by calcitonin, failed to lead to changes in these measurements. The diurnal variation in epidermal labelling index and serum calcium levels was also measured. Whilst the labelling index decreased considerably over the period 09.00 hours to 18.00 hours, no significant changes were observed in serum calcium. These results suggest that while, under certain circumstances in vivo, the epidermal cell shows the same sensitivity to calcium as it does in vitro, calcium is not a major regulator of epidermopoiesis.