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Low serum calcium is associated with higher long-term mortality in myocardial infarction patients from a population-based registry.
Schmitz, T, Thilo, C, Linseisen, J, Heier, M, Peters, A, Kuch, B, Meisinger, C
Scientific reports. 2021;(1):2476
Abstract
Calcium plays an essential role in physiology of the cardiovascular system. Aberrations from normal serum calcium levels are known to be associated with several cardiovascular diseases. Its possible role as a predictor for long-term mortality after acute myocardial infarction (AMI) is still uncertain. In this study, a total of 3732 patients (aged 25-74 years) with incident AMI surviving at least 28 days after AMI was included. The median follow-up time was 6.0 years. Admission total serum calcium levels were divided into quartiles. The Kaplan-Meier-Curve suggested a division of the follow up time in two different time periods. So, Cox regression models were calculated to assess association between admission serum calcium levels and all-cause long-term mortality with two observation periods: 28-2500 days and > 2500 days. The final model was adjusted for various comorbidities, clinical characteristics, in-hospital treatment and medication. The third quartile (normal-high Calcium levels) served as the reference group. The fully adjusted Cox-regression model shows significantly higher mortality risk for low serum calcium (quartile 1) within the timeframe 28-2500 days after the event (OR 1.53 [1.19-1.98]). The other groups did not differ significantly from each other. In the later observation period (from 2500 days until death or censoring) no more significant differences were seen between the four calcium quartiles. In summary, low serum calcium is an independent predictor of adverse outcome in the first 2500 days (about 7 years) after AMI. On later points in time this effect attenuates, so that no more significant differences can be observed.
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Genetically Determined Serum Calcium Levels and Markers of Ventricular Repolarization: A Mendelian Randomization Study in the UK Biobank.
Young, WJ, Warren, HR, Mook-Kanamori, DO, Ramírez, J, van Duijvenboden, S, Orini, M, Tinker, A, van Heemst, D, Lambiase, PD, Jukema, JW, et al
Circulation. Genomic and precision medicine. 2021;(3):e003231
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BACKGROUND ECG markers of ventricular depolarization and repolarization are associated with an increased risk of arrhythmia and sudden cardiac death. Our prior work indicated lower serum calcium concentrations are associated with longer QT and JT intervals in the general population. Here, we investigate whether serum calcium is a causal risk factor for changes in ECG measures using Mendelian randomization (MR). METHODS Independent lead variants from a newly performed genome-wide association study for serum calcium in >300 000 European-ancestry participants from UK Biobank were used as instrumental variables. Two-sample MR analyses were performed to approximate the causal effect of serum calcium on QT, JT, and QRS intervals using an inverse-weighted method in 76 226 participants not contributing to the serum calcium genome-wide association study. Sensitivity analyses including MR-Egger, weighted-median estimator, and MR pleiotropy residual sum and outlier were performed to test for the presence of horizontal pleiotropy. RESULTS Two hundred five independent lead calcium-associated variants were used as instrumental variables for MR. A decrease of 0.1 mmol/L serum calcium was associated with longer QT (3.01 ms [95% CI, 2.03 to 3.99]) and JT (2.89 ms [1.91 to 3.87]) intervals. A weak association was observed for QRS duration (secondary analyses only). Results were concordant in all sensitivity analyses. CONCLUSIONS These analyses support a causal effect of serum calcium levels on ventricular repolarization, in a middle-aged population of European-ancestry where serum calcium concentrations are likely stable and chronic. Modulation of calcium concentration may, therefore, directly influence cardiovascular disease risk.
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Ionized calcium level at emergency department arrival is associated with return of spontaneous circulation in out-of-hospital cardiac arrest.
Kim, SJ, Kim, HS, Hwang, SO, Jung, WJ, Roh, YI, Cha, KC, Shin, SD, Song, KJ, ,
PloS one. 2020;(10):e0240420
Abstract
BACKGROUND Calcium level is associated with sudden cardiac death based on several cohort studies. However, there is limited evidence on the association between ionized calcium, active form of calcium, and resuscitation outcome. This study aimed to evaluate the potential role of ionized calcium in predicting resuscitation outcome in patients with out-of-hospital cardiac arrest. METHODS We analyzed the Korean Cardiac Arrest Research Consortium data (KoCARC) registry, a web-based multicenter registry that included 65 participating hospitals throughout the Republic of Korea. The patients with out-of-hospital cardiac arrest over 19 years old and acquired laboratory data including calcium, ionized calcium, potassium, phosphorus, creatinine, albumin at emergency department (ED) arrival were included. The primary outcome was successful rate of return of spontaneous circulation (ROSC) and the secondary outcomes were survival hospital discharge and favorable neurological outcome (cerebral performance category 1 or 2) at hospital discharge. RESULTS Eight-hundred and eighty-three patients were enrolled in the final analysis and 448 cases (54%) had ROSC. In multivariable logistic regression analysis, ionized calcium level was associated with ROSC (odds ratio, 1.77; 95% CI1.28-2.45; p = 0.001) even though calcium level was not associated with ROSC (odds ratio, 0.87; 95% CI 0.70-1.08; p = 0.199). However, ionized calcium level was not associated with survival discharge (odds ratio, 0.99; 95% CI 0.72-1.36; p = 0.948) or favorable neurologic outcome (odds ratio, 0.45; 95% CI 0.03-6.55, p = 0.560). CONCLUSION A high ionized calcium level measured during cardiopulmonary resuscitation was associated with an increased likelihood of ROSC.
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The effect of lanthanum carbonate on calciprotein particles in hemodialysis patients.
Nakamura, K, Nagata, Y, Hiroyoshi, T, Isoyama, N, Fujikawa, K, Miura, Y, Matsuyama, H, Kuro-O, M
Clinical and experimental nephrology. 2020;(4):323-329
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BACKGROUND Aggregation of solid-phase calcium-phosphate and fetuin-A form nanoparticles called calciprotein particles (CPP). Serum CPP levels are increased in CKD patients and correlated with vascular stiffness and calcification. In this study, we evaluated effects of lanthanum carbonate (LC) and calcium carbonate (CC) on serum CPP levels in hemodialysis (HD) patients. METHODS Twenty-four (24) HD patients (50% men, age; 68 ± 12 years, dialysis period; 6.2 ± 4.8 years, Kt/v; 1.74 ± 0.34) were treated with CC during 0-8 weeks and then switched to LC during 9-16 weeks. Blood samples were obtained at 0, 8, 16 weeks. Serum CPP levels (TCPP) were measured by the gel-filtration method. Low-density CPP (LCPP) levels were determined by centrifuging the serum samples at 16,000 g for 2 h and measuring CPP levels in the supernatant. The difference between TCPP and LCPP was defined as the high-density CPP (HCPP) level. We evaluated association of TCPP, LCPP, and HCPP with serum calcium (Ca), phosphorus (P), intact PTH, FGF23, Klotho, fetuin-A, aortic calcification index (ACI), LDL cholesterol, and hs-CRP. RESULTS TCPP and LCPP levels were significantly decreased after switching CC to LC, whereas Ca and P levels were not changed. HCPP levels were below the lower limit quantification in all patients. The changes in P, Ca × P, LDL cholesterol, but not ACI and the changes in hs-CRP, were correlated with the change in TCPP levels. CONCLUSION The TCPP levels were significantly decreased after switching CC to LC. Non-calcium-containing phosphate binders may be preferable for lowering CPP levels.
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Relationship between Serum Vitamin D and Calcium Levels and Vitamin D Receptor Gene Polymorphisms in Colorectal Cancer.
Al-Ghafari, AB, Balamash, KS, Al Doghaither, HA
BioMed research international. 2019;:8571541
Abstract
BACKGROUND Many epidemiological studies have shown that vitamin D deficiency is associated with various types of human cancers. The biological action of vitamin D and its metabolites is mediated by the transcription factor vitamin D receptor (VDR). The VDR gene is highly expressed in the colon and is involved in many biological functions. The aim of the current study was to assess the relationship between serum vitamin D metabolite and calcium levels with VDR polymorphisms in normal and colorectal cancer (CRC) patients. METHODS Fifty Saudi CRC patients and fifty controls were enrolled in the study. The levels of total vitamin D, 25(OH)D3, and calcium were measured in serum. RESULTS The homozygous genotype (aa) of the ApaI VDR polymorphism (rs7975232) was found to correlate with total serum vitamin D levels of CRC patients, while the heterozygous (Tt) TaqI VDR polymorphism (rs731236) was associated with serum calcium levels. In contrast, the BsmI and FokI VDR polymorphisms (rs1544410 and rs2228570, resp.) did not affect the serum levels of total vitamin D, 25-hydroxyvitamin D3, and calcium. CONCLUSION Appropriate vitamin D levels were shown to be important in preventing the onset of CRC.
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Do Symptoms and Serum Calcium Levels Affect the Results of Surgical Treatment of Primary Hyperparathyroidism?
Yu, Q, Liu, K, Ma, D, Xie, C, Wu, Y, Dai, W, Jiang, H
BioMed research international. 2019;:2150159
Abstract
INTRODUCTION The purpose of this study was to investigate the difference in surgical outcomes between symptomatic and asymptomatic patients with primary hyperparathyroidism (PHPT) and between patients with high serum calcium and those with normal blood calcium, as well as to explore the epidemiological trend of PHPT in northern China. METHODS Clinicopathologic data of 197 patients (50 men and 147 women) with PHPT who underwent surgery at the First Affiliated Hospital of Harbin Medical University from 2008 to 2017 were analyzed. Changes in clinicopathology were compared among different subgroups of patients. Patients were categorized into subgroups based on serum calcium levels, whether or not they presented with symptoms, and admission time. RESULTS Of the total patients, 82.23% had hypercalcemic primary hyperparathyroidism (HCPHPT), 17.77% had normocalcemic primary hyperparathyroidism (NCPHPT), 45.18% had symptomatic primary hyperparathyroidism (SPHPT), and 54.82% had asymptomatic primary hyperparathyroidism (ASPHPT). Seventy-seven cases of PHPT involved thyroid nodules, with 22 confirmed as papillary thyroid carcinoma, and 29 confirmed as nodular goiter. There was no significant difference in the success rate of surgery, postoperative recurrence rate, and the symptoms of temporary hypocalcemia between the HCPHPT and NCPHPT groups, and between the SPHPT and ASPHPT groups. The incidence of PHPT has increased threefold since 2013. CONCLUSIONS Symptoms and serum calcium levels did not affect the results of surgical treatment for PHPT. The incidence of PHPT in northern China is increasing. Moreover, PHPT manifestation has shifted from the symptomatic to the asymptomatic form. Thyroid surgery should be performed in PHPT patients with thyroid nodules.
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Curcumin induces endoplasmic reticulum stress-associated apoptosis in human papillary thyroid carcinoma BCPAP cells via disruption of intracellular calcium homeostasis.
Zhang, L, Cheng, X, Xu, S, Bao, J, Yu, H
Medicine. 2018;(24):e11095
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BACKGROUND Thyroid cancer is the most common endocrine tumor. Our previous studies have demonstrated that curcumin can induce apoptosis in human papillary thyroid carcinoma BCPAP cells. However, the underlined mechanism has not been clearly elucidated. Endoplasmic reticulum (ER) is a major organelle for synthesis, maturation, and folding proteins as well as a large store for Ca. Overcoming chronically activated ER stress by triggering pro-apoptotic pathways of the unfolded protein response (UPR) is a novel strategy for cancer therapeutics. Our study aimed to uncover the ER stress pathway involved in the apoptosis caused by curcumin. METHODS BCPAP cells were treated with different doses of curcumin (12.5-50 μM). Annexin V/PI double staining was used to determine cell apoptosis. Rhod-2/AM calcium fluorescence probe assay was performed to measure the calcium level of endoplasmic reticulum. Western blot was used to examine the expression of ER stress marker C/EBP homologous protein 10 (CHOP) and glucose-regulated protein 78 (GRP78). X-box binding protein1 (XBP-1) spliced form was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS Curcumin significantly inhibited anchorage-independent cell growth and induced apoptosis in BCPAP cells. Curcumin induced ER stress and UPR responses in a dose- and time-dependent manner, and the chemical chaperone 4-phenylbutyrate (4-PBA) partially reversed the antigrowth activity of curcumin. Moreover, curcumin significantly increased inositol-requiring enzyme 1α (IRE1α) phosphorylation and XBP-1 mRNA splicing to induce a subsets of ER chaperones. Increased cleavage of activating transcription factor 6 (ATF6), which enhances expression of its downstream target CHOP was also observed. Furthermore, curcumin induced intracellular Ca influx through inhibition of the sarco-endoplasmic reticulum ATPase 2A (SERCA2) pump. The increased cytosolic Ca then bound to calmodulin to activate calcium/calmodulin-dependent protein kinase II (CaMKII) signaling, leading to mitochondrial apoptosis pathway activation. Ca chelator BAPTA partially reversed curcumin-induced ER stress and growth suppression, confirming the possible involvement of calcium homeostasis disruption in this response. CONCLUSIONS Curcumin inhibits thyroid cancer cell growth, at least partially, through ER stress-associated apoptosis. Our observations provoked that ER stress activation may be a promising therapeutic target for thyroid cancer treatment.(Figure is included in full-text article.).
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The Effect of a Short-Term Exposure to Lead on the Levels of Essential Metal Ions, Selected Proteins Related to Them, and Oxidative Stress Parameters in Humans.
Dobrakowski, M, Boroń, M, Birkner, E, Kasperczyk, A, Chwalińska, E, Lisowska, G, Kasperczyk, S
Oxidative medicine and cellular longevity. 2017;:8763793
Abstract
The present study was designed to explore the possible influence of subacute exposure to lead on the levels of selected essential metals, selected proteins related to them, and oxidative stress parameters in occupationally exposed workers. The study population included 36 males occupationally exposed to lead for 36 to 44 days. Their blood lead level at the beginning of the study was 10.7 ± 7.67 μg/dl and increased to the level of 49.1 ± 14.1 μg/dl at the end of the study. The levels of calcium, magnesium, and zinc increased significantly after lead exposure compared to baseline by 3%, 3%, and 8%, respectively, while the level of copper decreased significantly by 7%. The malondialdehyde (MDA) level and the activities of catalase (CAT) and superoxide dismutase (SOD) did not change due to lead exposure. However, the level of lipid hydroperoxides (LPH) in serum increased significantly by 46%, while the level of erythrocyte lipofuscin (LPS) decreased by 13%. The serum levels of essential metals are modified by a short-term exposure to lead in occupationally exposed workers. A short-term exposure to lead induces oxidative stress associated with elevated levels of LPH but not MDA.
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Assessment of coronary artery calcium by chest CT compared with EKG-gated cardiac CT in the multicenter AIDS cohort study.
Chandra, D, Gupta, A, Leader, JK, Fitzpatrick, M, Kingsley, LA, Kleerup, E, Haberlen, SA, Budoff, MJ, Witt, M, Post, WS, et al
PloS one. 2017;(4):e0176557
Abstract
RATIONALE Individuals with HIV are at increased risk for coronary artery disease (CAD). Early detection of subclinical CAD by assessment of coronary artery calcium (CAC) may help risk stratify and prevent CAD events in these individuals. However, the current standard to quantify CAC i.e. Agatston scoring requires EKG-gated cardiac CT imaging. OBJECTIVE To determine if the assessment of CAC using non-EKG-gated chest CT and the Weston scoring system is a useful surrogate for Agatston scores in HIV-infected and HIV-uninfected individuals. METHODS AND MEASUREMENTS CAC was assessed by both the Weston and Agatston score in 108 men enrolled in the Multicenter AIDS Cohort Study. RESULTS Participants were 55.2 (IQR 50.4; 59.9) years old and 62 (57.4%) were seropositive for HIV. Inter-observer agreement (rs = 0.94, κ = 90.0%, p<0.001, n = 21) and intra-observer agreement (rs = 0.95, κ = 95.2%, p<0.001, n = 97) for category of Weston score were excellent. Weston scores were associated with similar CAD risk factors as Agatston scores (age, race, HDL cholesterol level, all p<0.05) in our cohort. There was excellent correlation (rs = 0.92, p<0.001) and agreement (κw = 0.77, p<0.001) between Weston and Agatston scores. CONCLUSIONS This study is the first to examine calcium scoring using chest CT in HIV-infected individuals and to independently validate the Weston score as a surrogate for the Agatston score. In clinical or research settings where EKG-gated cardiac CT is not feasible for the assessment of coronary calcium, Weston scoring by using chest CT should be considered.
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Fixed Full Arches Supported by Tapered Implants with Knife-Edge Thread Design and Nanostructured, Calcium-Incorporated Surface: A Short-Term Prospective Clinical Study.
Bechara, S, Lukosiunas, A, Dolcini, GA, Kubilius, R
BioMed research international. 2017;:4170537
Abstract
Purpose. To evaluate implant survival, peri-implant bone loss, and complications affecting fixed full-arch (FFA) restorations supported by implants with a knife-edge thread design and nanostructured, calcium-incorporated surface. Methods. Between January 2013 and December 2015, all patients referred for implant-supported FFA restorations were considered for enrollment in this study. All patients received implants with a knife-edge thread design and nanostructured calcium-incorporated surface (Anyridge®, Megagen, South Korea) were restored with FFA restorations and enrolled in a recall program. The final outcomes were implant survival, peri-implant bone loss, biologic/prosthetic complications, and "complication-free" survival of restorations. Results. Twenty-four patients were selected. Overall, 215 implants were inserted (130 maxilla, 85 mandible), 144 in extraction sockets and 71 in healed ridges. Thirty-six FFAs were delivered (21 maxilla, 15 mandible): 27 were immediately loaded and 9 were conventionally loaded. The follow-up ranged from 1 to 3 years. Two fixtures failed, yielding an implant survival rate of 95.9% (patient-based). A few complications were registered, for a "complication-free" survival of restorations of 88.9%. Conclusions. FFA restorations supported by implants with a knife-edge thread design and nanostructured, calcium-incorporated surface are successful in the short term, with high survival and low complication rates; long-term studies are needed to confirm these outcomes.