Evaluation of coronary calcium score in patients with normocalcemic primary hyperparathyroidism.
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ABSTRACT:
SUBMITTER: Mesquita PN
PROVIDER: S-EPMC5488767 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:ContextPatients with persistent primary hyperparathyroidism (PHPT) after parathyroidectomy or with contraindications to parathyroidectomy often require chronic treatment for hypercalcemia.ObjectiveThe objective of the study was to assess the ability of the calcimimetic, cinacalcet, to reduce serum calcium in patients with intractable PHPT.DesignThis was an open-label, single-arm study comprising a titration phase of variable duration (2-16 wk) and a maintenance phase of up to 136 wk.SettingThe study was conducted at 23 centers in Europe, the United States, and Canada.PatientsThe study included 17 patients with intractable PHPT and serum calcium greater than 12.5 mg/dl (3.1 mmol/liter).InterventionDuring the titration phase, cinacalcet dosages were titrated every 2 wk (30 mg twice daily to 90 mg four times daily) for 16 wk until serum calcium was 10 mg/dl or less (2.5 mmol/liter). If serum calcium increased during the maintenance phase, additional increases in the cinacalcet dose were permitted.Main outcome measureThe primary end point was the proportion of patients experiencing a reduction in serum calcium of 1 mg/dl or greater (0.25 mmol/liter) at the end of the titration phase.ResultsMean +/- sd baseline serum calcium was 12.7 +/- 0.8 mg/dl (3.2 +/- 0.2 mmol/liter). At the end of titration, a 1 mg/dl or greater reduction in serum calcium was achieved in 15 patients (88%). Fifteen patients (88%) experienced treatment-related adverse events, none of which were serious. The most common adverse events were nausea, vomiting, and paresthesias.ConclusionsIn patients with intractable PHPT, cinacalcet reduces serum calcium, is generally well tolerated, and has the potential to fulfill an unmet medical need.
| S-EPMC3214593 | biostudies-literature
Project description:To investigate genes modulated in the parathyroid glands by calcium, expression levels of mRNA for all genes expressed in parathyroid tissue explants (PTEs) obtained from patients with primary hyperparathyroidism (I-HPT) were analyzed by oligo-DNA microarray. PTEs obtained from 4 patients with I-HPT were precultured in normocalcemic medium (Ca++ 1.0-1.1 mM) for 7 days and then cultured in hypocalcemic medium (Ca++ 0.60 mM) or hypercalcemic (Ca++ 1.60 mM) medium for an additional 7 days. As expected, expression levels of mRNA for PTH and chromogranin A were decreased to less than 50% in hypercalcemic medium. Furthermore, oligo-DNA microarray analyses followed by GeneSpring GX analyses revealed that 7 genes were up-regulated by more than 2-fold and more than 30 genes were down-regulated by more than 1/2 in PTEs obtained from patients with I-HPT. Interestingly, 9 of these genes (up-regulated genes: chemokine ligand 8[CCL8], multiple C2 domain and transmembrane region protein 1 [MCTP1]; down-regulated genes: matrix metallopeptidase-9 [MMP9], B-box and SPRY domain-containing protein [BSPRY], nitric oxide synthase 2A [NOS2A], parathyroid hormone [PTH], cartilage acidic protein 1 [CRTAC1], chromogranin A [CHGA], and fibrin 1 [FBLN1]) were involved in calcium metabolism or calcium-signaling pathways in the parathyroid tissue. Unexpectedly, however, the expression level of mRNA for alpha-klotho was variable, and it was not constantly decreased in hypercalcemic medium under the present experimental conditions. Although it was not possible to use normal parathyroid tissue, this is the first reported study to have investigated the expression levels of mRNA for all genes in human parathyroid adenomas that are modulated by high calcium concentration in organ culture.
2009-10-23 | GSE18689 | GEO
Project description:A subset of PHPT patients exhibit a more severe disease phenotype characterized by bone loss, fractures, recurrent nephrolithiasis, and other dysfunctions, but the underlying reasons for this disparity in clinical presentation remain unknown.We sought to identify new mechanistic indices that could inform more personalized management of PHPT.Pre-, peri-, and postoperative data and demographic, clinical, and pathological information from patients undergoing parathyroidectomy for PHPT were collected. Univariate and partial Spearman correlation was used to estimate the association of parathyroid tumor calcium sensing capacity with select variables.An unselected series of 237 patients aged >18years and undergoing parathyroidectomy for PHPT were enrolled.Calcium sensing capacity, expressed as the concentration required for half-maximal biochemical response (EC50), was evaluated in parathyroid tumors from an unselected series of 74 patients and assessed for association with clinical parameters. The hypothesis was that greater disease severity would be associated with attenuated calcium sensitivity and biochemically autonomous parathyroid tumor behavior.Parathyroid tumors segregated into two distinct groups of calcium responsiveness (EC50<3.0 and ?3.0mM). The low EC50 group (n=27) demonstrated a mean calcium EC50 value of 2.49mM [95% confidence interval (CI): 2.43-2.54mM], consistent with reference normal activity. In contrast, the high EC50 group (n=47) displayed attenuated calcium sensitivity with a mean EC50 value of 3.48mM [95% CI: 3.41-3.55mM]. Retrospective analysis of the clinical registry data suggested that high calcium EC50 patients presented with a more significant preoperative bone mineral density (BMD) deficit with a t-score of -2.7, (95% CI: -3.4 to -1.9) versus 0.9, (95% CI: -2.1 to -0.4) in low EC50 patients (p<0.001). After adjusting for gender, age, BMI, 25 OH vitamin D level and preoperative iPTH, lowest t-score and calcium EC50 were inversely correlated, with a partial Spearman correlation coefficient of -0.35 (p=0.02).Impaired calcium sensing in parathyroid tumors is selectively observed in a subset of patients with more severe bone mineral density deficit. Assessment of parathyroid tumor biochemical behavior may be a useful predictor of disease severity as measured by bone mineral density in patients with PHPT.
| S-EPMC5561769 | biostudies-literature
Project description:BackgroundFamilial hypercholesterolemia (FH) is a monogenic disease characterized by a high concentration of low-density lipoprotein cholesterol. This population is considered to be at high cardiovascular risk; however, disease evolution remains heterogeneous among individuals. The coronary artery calcium (CAC) score is currently the best predictor of incidental major cardiovascular events in primary prevention in the general population. Few studies have described the CAC score in FH populations.MethodsThe objective of our study was to determine the predictors of the CAC score in FH patients. We retrospectively studied FH patients followed at the Montreal Clinical Research Institute (IRCM) Lipid Clinic who had a cardiac scan for CAC score, using the Agatston method, between 2013 and 2019.ResultsFinal analysis included 62 FH patients. Mean age was 48 ± 14 years old, and 48% were men. Overall, 25 patients had a CAC score of 0 (40%), and 37 patients had a nonzero CAC score (60%). Sex, age, Montreal-FH-SCORE (MFHS), waist circumference, and statin exposure in years were significant predictors (P ≤ 0,05) of a nonzero CAC score in a univariate model. MFHS was the only factor that remained significant in a multivariate model (odds ratio 1.34, 95% confidence interval 1.11-1.61, P = 0.002).ConclusionsIn conclusion, we found that MFHS, which includes traditional cardiovascular risk factors, was a predictor of a nonzero CAC score in FH patients. This finding suggests that MFHS may play a role in determining the cardiovascular risk and therefore the intensity of treatment in FH patients.
| S-EPMC7801205 | biostudies-literature
Project description:BACKGROUND Clinical cases of nonmedullary thyroid carcinoma (NMTC) in combination with primary hyperparathyroidism (PHPT) have been reported occasionally. However, the clinical characteristics and risk factors of concomitant NMTC in PHPT patients remain unclear. This study aimed to assess the association between PHPT and NMTC, and evaluate the clinical characteristics and risk factors of NMTC in Chinese patients with PHPT. MATERIAL AND METHODS This was a retrospective cohort analysis. We reviewed the medical records of 155 patients who underwent surgery for PHPT in two large medical centers in China between 2009 and 2014. The clinical manifestations, biochemical abnormalities, and histological characteristics of PHPT patients were analyzed. RESULTS Of the 155 patients with PHPT, 58 patients (37.4%) had thyroid nodules and 12 patients (7.7%) were ill with concomitant NMTC. PHPT patients with NMTC demonstrated significantly lower preoperative serum calcium levels compared to PHPT patients with benign thyroid nodules (p<0.05). A significantly negative association between preoperative serum calcium levels and the presence of NMTC was found in PHPT patients (p<0.05). Furthermore, ROC analysis revealed that albumin-corrected serum calcium levels <2.67 mmol/L had good capacity to differentiate the PHPT patients with NMTC from those with benign thyroid nodules. CONCLUSIONS Compared with the reported much lower prevalence of thyroid carcinoma in the general population, our results suggest that PHPT might be a risk factor for the malignancy of thyroid nodules; a lower level of serum calcium may predict the existence of NMTC in PHPT patients with thyroid nodules.
| S-EPMC5126969 | biostudies-other
Project description:ObjectiveSeveral studies indicate that patients with primary hyperparathyroidism (PHPT) undergoing parathyroid surgery have improvement in mood and neuropsychological functioning. The current analysis aims to examine the relationship between biochemical and clinical variables and the improvement in depression scores and in specific symptoms, after parathyroidectomy.DesignA prospective observational case-control study at a referral centre.PatientsPatients with PHPT undergoing parathyroidectomy (n = 88) or thyroid surgery (n = 85).MeasurementsThe Patient Health Questionnaire-9 (PHQ-9) was utilized to obtain depression scores at enrolment and 12 months after surgery. The changes in PHQ-9 were analysed and correlated with baseline clinical and biochemical parameters.ResultsAt enrolment, there was no difference between the groups in the number with a depression diagnosis (PHPT 34.1%, thyroid surgery, 35.5%, P = 0.86). However, baseline PHQ-9 scores were significantly higher in PHPT (median 7.5, range 0-27) than thyroid surgery patients (median 3.0, range 0-18, P < 0.0001). Following surgery, all PHQ-9 scores, total and symptom group (cognitive, somatic) improved and were no longer different between PHPT (total PHQ-9 median 2, range 0-16) and thyroid (median 1, range 0-14, P = 0.31) groups. Baseline parathyroid hormone level, but not calcium, had a weak relationship with change in PHQ-9 score after parathyroid surgery (P = 0.003). Baseline PHQ-9 score was correlated with change in PHQ-9 score at 12 months after parathyroid surgery (P < 0.001).ConclusionsDepression scores improve in both somatic and cognitive domains after parathyroidectomy for PHPT and baseline severity of depression predicts the response.
| S-EPMC9362855 | biostudies-literature
Project description:BackgroundCoronary artery calcium score (CACS) is an established marker of coronary artery disease (CAD) and has been extensively used to stratify risk in asymptomatic individuals. However, the value of CACS in predicting plaque morphology in patients with advanced CAD is less established. The present analysis aims to assess the association between CACS and plaque characteristics detected by near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) imaging in patients with obstructive CAD.MethodsSeventy patients with obstructive CAD underwent coronary computed tomography angiography (CTA) and 3-vessel NIRS-IVUS imaging were included in the present analysis. The CTA data were used to measure the CACS in the entire coronary tree and the segments assessed by NIRS-IVUS, and these estimations were associated with the NIRS-IVUS measurements at a patient and segment level.ResultsIn total, 65 patients (188 segments) completed the study protocol and were included in the analysis. A weak correlation was noted between the CACS, percent atheroma volume (r = 0.271, P = .002), and the calcific burden measured by NIRS-IVUS (r = 0.648, P < .001) at patient-level analysis. Conversely, there was no association between the CACS and the lipid content, or the incidence of high-risk plaques detected by NIRS. Linear regression analysis at the segment level demonstrated an association between the CACS and the total atheroma volume (coefficient, 0.087; 95% CI, 0.024-0.149; P = .008) and the calcific burden (coefficient, 0.117; 95% CI, 0.048-0.186; P = .001), but there was no association between the lipid content or the incidence of high-risk lesions.ConclusionsIn patients with obstructive CAD, the CACS is not associated with the lipid content or plaque phenotypes. These findings indicate that the CACS may have a limited value for screening or stratifying cardiovascular risk in symptomatic patients with a high probability of CAD.
| S-EPMC11307846 | biostudies-literature
Project description:Background: The association of known cardiovascular risk factors with poor prognosis of coronavirus disease 2019 (COVID-19) has been recently emphasized. Coronary artery calcium (CAC) score is considered a risk modifier in the primary prevention of cardiovascular disease. We hypothesized that the absence of CAC might have an additional predictive value for an improved cardiovascular outcome of hospitalized COVID-19 patients. Materials and methods: We prospectively included 310 consecutive hospitalized patients with COVID-19. Thirty patients with history of coronary artery disease were excluded. Chest computed tomography (CT) was performed in all patients. Demographics, medical history, clinical characteristics, laboratory findings, imaging data, in-hospital treatment, and outcomes were retrospectively analyzed. A composite endpoint of major adverse cardiovascular events (MACE) was defined. Results: Two hundred eighty patients (63.2 ± 16.7 years old, 57.5% male) were included in the analysis. 46.7% patients had a CAC score of 0. MACE rate was 21.8% (61 patients). The absence of CAC was inversely associated with MACE (OR 0.209, 95% CI 0.052-0.833, p = 0.027), with a negative predictive value of 84.5%. Conclusion: The absence of CAC had a high negative predictive value for MACE in patients hospitalized with COVID-19, even in the presence of cardiac risk factors. A semi-qualitative assessment of CAC is a simple, reproducible, and non-invasive measure that may be useful to identify COVID-19 patients at a low risk for developing cardiovascular complications.
| S-EPMC8301217 | biostudies-literature
Project description:Purpose: Many patients with ischemic stroke have concomitant coronary artery disease (CAD). However, it remains unclear which stroke patients should undergo evaluation for asymptomatic CAD, and which screening tools are appropriate. We investigated the role of coronary artery calcium (CAC) score as a screening tool for asymptomatic but severe CAD in acute stroke patients. We determined the selection criteria for CAC screening based on risk factors and cerebral atherosclerosis. Materials and Methods: The present study included consecutive patients with acute stroke who had undergone cerebral angiography and multi-detector computed tomography coronary angiography. Severe CAD was defined as left main artery disease or three-vessel disease. Enrolled patients were randomly assigned to two sets; a set for developing selection criteria and a set for validation. To develop selection criteria, we identified associated factors with severe CAD regarding clinical factors and cerebral atherosclerosis. CAD predictability of selection criteria with the CAC score was calculated. Results: Overall, 2,658 patients were included. Severe CAD was present in 360 patients (13.5%). CAC score was associated with CAD severity (P < 0.001). In the development set (N = 1,860), severe CAD was associated with age >65 years [odds ratio (95% confidence interval), 2.62 (1.93-3.55)], male sex (1.81 [1.33-2.46]), dyslipidemia (1.77 [1.25-2.61]), peripheral artery disease (2.64 [1.37-5.06]) and stenosis in the cervicocephalic branches, including the internal carotid (2.79 [2.06-3.78]) and vertebrobasilar arteries (2.08 [1.57-2.76]). We determined the combination of clinical and arterial factors as the selection criteria for CAC evaluation. The cut-off criterion was two or more elements of the selection criteria. The area under the curve (AUC) of the selection criteria was 0.701. The AUC significantly improved to 0.836 when the CAC score was added (P < 0.001). In the validation set (N = 798), the AUC of the selection criteria only was 0.661, and that of the CAC score was 0.833. The AUC of the selection criteria + CAC score significantly improved to 0.861(P < 0.001). Conclusion: The necessity for CAC evaluation could be determined based on the presence of risk factors and significant stenosis of the cervicocephalic arteries. CAC evaluation may be useful for screening for severe CAD in stroke patients.
| S-EPMC7134382 | biostudies-literature
Project description:BackgroundDysregulated lncRNA score and PVT1 expression may be involved in cancer. However, relationships of lncRNAs with hyperparathyroidism and parathyroid cancer (PC) diagnosis remain mysterious.MethodsUsing quantitative real-time polymerase chain reaction (RT-qPCR), expression profile of PVT1 was evaluated in 57 patients with primary hyperparathyroidism, including 11 with parathyroid cancer (PC) and 46 with parathyroid adenoma (PA).ResultsHigher levels of lncRNA score and PVT1 expression were associated with increased serum calcium level after water ingestion and PC risk (P < 0.05). Accordingly, lncRNA score and PVT1 expression were increased with varying degrees of hypercalcemia in PC. A higher level of lncRNA score (but not PVT1) was an independent risk factor of PC, with an AUC up to 0.872 (95% CI: 0.756-0.945, P < 0.001). Moreover, lncRNA score was more valuable (with AUC 0.974, sensitivity of 85.71% and specificity of 100%, respectively) than intact parathyroid hormone (iPTH) in predicting risk of PC among patients with hypercalcemia (especially based on greater AUC, P = 0.010).ConclusionIncreased lncRNA score is correlated with an elevated level of serum calcium, which may serve as a potential biomarker for PC diagnosis, especially with hypercalcemia.
| S-EPMC8082613 | biostudies-literature