Calcium can be measured as ionised (Ca-ionised) or albumin-adjusted total calcium (Ca-albumin). Current clinical guidelines predominantly utilise Ca-albumin, despite Ca-ionised being the gold standard. Discrepancies can occur between these measurement modalities and can lead to clinical dilemmas. It remains unclear how large these discrepancies are in older patients. This study investigated the discrepancies between Ca-ionised and Ca-albumin in geriatric patients.
This is an observational study of all geriatric patients (n = 876) in the Jeroen Bosch Hospital (January 2018 and January 2021) in whom both Ca-ionised and Ca-albumin were measured. Misclassification of calcaemic state (i.e. low, normal or high) was calculated (percentages), the measure of agreement was described using Cohen\'s Kappa and for the continuous data Pearson\'s correlation coefficient was used. Relevant categories of age and renal function were considered for effect modification effects and studied by interaction terms in a regression model.
In one-third of the measurements, there was a misclassification. Ca-albumin measurements failed to identify 28% of hypocalcaemia. In 3.5%, hypercalcemia based on Ca-albumin was not confirmed by Ca-ionised. The correlation coefficient between Ca-ionised and Ca-albumin was 0.743 (P = 0.01) and measure of agreement by Kappa was 0.213 (P < 0.001). In the oldest old (≥ 85 years) and patients with eGFR <30 ml/min/1.73 m2 ,the agreement by Kappa was lower, with values of 0.192 and 0.104, respectively.
There is a discrepancy between Ca-albumin and Ca-ionised in one-third of the geriatric patients, leading to clinical dilemmas. In the oldest old and patients with renal dysfunction, this problem is most pronounced.

Famine exposure and higher serum calcium levels are related with increased risk of many disorders, including Alzheimer\'s disease, atherosclerosis, diabetes, and osteoporosis. Whether famine exposure has any effect on serum calcium level is unclear. Besides, the normal reference range of serum calcium is variable among different populations. Our aims are 1) determining the reference interval of calcium in Chinese adults; 2) exploring its relationship with famine exposure.
Data in this study was from a cross-sectional study of the epidemiologic investigation carried out during March-August 2010 in Jiading district, Shanghai, China. Nine thousand and two hundred eleven participants with estimated glomerular filtration rate (eGFR) ≥60ml/min/1.73m2 were involved to calculate reference interval of total calcium from 10569 participants aged 40 years or older. The analysis of famine exposure was conducted in 9315 participants with complete serum biochemical data and birth year information.
After rejecting outliers, the 95% reference interval of total serum calcium was 2.122~2.518 mmol/L. The equation of albumin-adjusted calcium was: Total calcium + 0.019* (49-Albumin), with a 95% reference interval of 2.151~2.500 mmol/L. Compared to the age-balanced control group, there was an increased risk of being at the upper quartile of total serum calcium (OR=1.350, 95%CI=1.199-1.521) and albumin-adjusted calcium (OR=1.381, 95%CI=1.234-1.544) in subjects experienced famine exposure in childhood. Females were more vulnerable to this impact (OR= 1.621, 95%CI= 1.396-1.883 for total serum calcium; OR=1.722, 95%CI= 1.497-1.980 for albumin-adjusted calcium).
Famine exposure is an important environmental factor associated with the changes in circulating calcium concentrations, the newly established serum calcium normal range and albumin-adjusted calcium equation, together with the history of childhood famine exposure, might be useful in identifying subjects with abnormal calcium homeostasis and related diseases, especially in females.

Low circulating total calcium or albumin-adjusted calcium has been associated with higher mortality, especially in hospital settings; however, these measures tend to misclassify patients with derangements in calcium homeostasis.
As the association of the biologically active ionized calcium with mortality is poorly elucidated, we tested the hypothesis that low plasma ionized calcium is associated with higher risk of all-cause and cause-specific mortality in the general population.
We included 106 768 individuals from the Copenhagen General Population Study. Information on all-cause and cause-specific mortality was from registries and risks were calculated using Cox regression and competing-risks regression by the STATA command stcompet.
During a median follow-up period of 9.2 years, 11 269 individuals died. Each 0.1 mmol/L lower plasma ionized calcium below the median of 1.21 mmol/L was associated with a multivariable adjusted hazard ratio of 1.23 (95% CI, 1.10-1.38) for all-cause mortality. Corresponding hazard ratios for cancer and other mortality were 1.29 (1.06-1.57) and 1.24 (1.01-1.53), respectively. In contrast, for cardiovascular mortality, only high plasma ionized calcium was associated with mortality with a hazard ratio of 1.17 (1.02-1.35) per 0.1 mmol/L higher plasma ionized calcium above the median. We found no interactions between plasma ionized calcium and preexisting cardiovascular or renal disease on all-cause mortality.
In the general population, low plasma ionized calcium was associated with increased all-cause, cancer, and other mortality, while high levels were associated with increased cardiovascular mortality.

Circulating total calcium or albumin-adjusted calcium is a risk factor for cardiovascular disease. As the biologically active ionized calcium is a physiologically more relevant measure and its association with cardiovascular disease is poorly understood, we tested the hypothesis that high plasma ionized calcium is associated with higher risk of myocardial infarction and ischemic stroke in individuals in the general population.
We included 106 774 individuals from the Copenhagen General Population Study, and defined hypocalcemia and hypercalcemia by the lowest and highest 2.5 percentiles, respectively, using the central 95% reference interval. Information on myocardial infarction and ischemic stroke was from registries and risks calculated using Cox regression and Fine and Gray competing-risks regression.
During a median follow-up of 9.2 years, 4932 individuals received a diagnosis of either myocardial infarction or ischemic stroke. Hypercalcemia was associated with subdistribution hazard ratios of 1.67 (95%CI: 1.05-2.67) for myocardial infarction, 1.28 (0.81-2.02) for ischemic stroke, and of 1.54 (1.10-2.15) for the combined endpoint compared to individuals with plasma ionized calcium within the reference interval; hypocalcemia was not associated with cardiovascular disease. In models using plasma ionized calcium as a continuous variable, the associations were nonlinear; above the median, each 0.1 mmol/L higher plasma ionized calcium was associated with a hazard ratio of 1.31(1.02-1.68) for myocardial infarction, 1.21 (0.95-1.54) for ischemic stroke, and of 1.28 (1.08-1.53) for the combined endpoint.
High plasma ionized calcium is associated with higher risk of myocardial infarction and ischemic stroke compared to plasma ionized calcium within the reference interval.

Total calcium is a less accurate test in predicting ionized calcium (Ca2+) in patients suspected of calcium metabolic disease. Nevertheless, total calcium continues to be used as routine measurement instead of adjusted Ca2+ (at pH 7.4). In the current study we evaluate a new multichannel instrument, the ISE Module E1200 for adjusted Ca2+ (at pH 7.4), containing three different ion-selective electrode (ISE) units.
Serum from 1350 patients was compared to the ABL835 flex and KoneLab. Total calcium was also evaluated on the Dimension Vista 1500 system. Correlations between instruments were assessed by Deming regression and degree of agreement by Cohen\'s kappa (κ).
Analytical imprecisions for the three ISE units for adjusted Ca2+ (at pH 7.4) was between 0.36% and 2.52%, and for pH between 0.32% and 3.24%. Results were comparable for each ISE unit (r = 0.797-0.917; all P < 0.0001) and in high-throughput settings (r = 0.871; P < 0.0001). The degree of agreement between instruments was moderate to good (κ  =  0.52-0.77). In contrast, there was a very poor agreement (κ = -0.14) for total calcium with discrepancy in 53.4% of the samples.
The new ISE Module E1200 is comparable with the ABL835 flex and KoneLab 30i and therefore may be used for routine analysis of serum adjusted Ca2+ (at pH 7.4). The measured adjusted Ca2+ (at pH 7.4) was less comparable with very poor agreement to total calcium measured on the Dimension Vista 1500 system.

Background Total blood calcium (TCa) is routinely used to diagnose and manage mineral and bone metabolism disorders. Numerous laboratories adjust TCa by albumin, though literature suggests there are some limits to this approach. Here we report a large retrospective study on agreement rate between ionized calcium (iCa) measurement and TCa or albumin-adjusted calcium measurements. Methods We retrospectively selected 5055 samples with simultaneous measurements of iCa, TCa, albumin and pH. We subgrouped our patients according to their estimated glomerular filtration rate (eGFR), albumin levels and pH. We analyzed each patient\'s calcium state with iCa as reference to determine agreement rate with TCa and albumin-adjusted calcium using Payne, Clase, Jain and Ridefelt formulas. Results The Payne formula performed poorly in patients with abnormal albumin, eGFR or pH levels. In patients with low albumin levels or blood pH disorders, Payne-adjusted calcium may overestimate the calcium state in up to 80% of cases. Similarly, TCa has better agreement with iCa in the case of hypoalbuminemia, but performed similarly to the Payne formula in patients with physiological albumin levels. The global agreement rate for Clase, Jain and Ridefelt formulas suggests significant improvement compared to Payne calcium adjustment but no significant improvement compared to TCa. Conclusions Total and albumin-adjusted calcium measurement leads to a misclassification of calcium status. Moreover, accurate calcium state determination depends on blood pH levels, whose measurement requires the same pre-analytical restrictions as iCa measurement. We propose that iCa should instead become the reference method to determine the real calcium state.