| 1. |
- Almquist, Martin, et al.
(författare)
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Reproductive history, lifestyle factors and season as determinants for serum calcium concentrations in women.
- 2008
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68, s. 777-785
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Serum calcium concentrations have been associated with the risk of malignant disease, especially breast cancer. Thus, determinants of serum calcium concentrations, with special regard to risk factors of breast cancer, are of great interest. Material and methods. Previous studies have either been small or they have not focused on reproductive factors. The present study examined serum calcium concentrations in relation to reproductive history, selected lifestyle factors and screening season in a large population-based cohort study comprising 8,114 women. ANOVA followed by the Bonferroni t-test were used for comparison of means, and logistic regression and multiple regression analysis were used to test associations. Results. Serum calcium concentrations were lower in hormone replacement therapy users versus non-users (2.321 mmol/L versus 2.364; p<0.001) and in users of oral contraceptives versus non-users (2.304 versus 2.348; p<0.001). They were higher in peri-/postmenopausal versus premenopausal women (2.357 versus 2.319; p<0.001). Overweight and obese women had higher mean calcium concentrations (2.350 and 2.355) than women with body mass index between 20 and 25 (2.342; p<0.001). Serum calcium concentrations were higher in spring and autumn than in winter (2.352 and 2.353 versus 2.343; p = 0.002). Both younger (40-45 years) (2.334; p = 0.001) and older age groups (>55 years) (2.363; p<0.001) had higher mean calcium concentrations compared to those of women aged 45-50 years (2.320), even when adjusting for menopausal status, suggesting that age has an independent influence on calcium concentrations. Conclusions. It is concluded that reproductive factors such as menopausal status, use of oral contraceptives or hormone-replacement therapy, and age, BMI and season are associated with serum calcium concentrations.
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| 2. |
- Almquist, Martin, et al.
(författare)
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Serum calcium and breast cancer risk: results from a prospective cohort study of 7,847 women.
- 2007
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Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 18, s. 595-602
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Tidskriftsartikel (refereegranskat)abstract
- Experimental and epidemiological studies suggest that calcium-regulating hormones-parathyroid hormone (PTH) and vitamin D-may be associated with breast cancer risk. No prospective cohort study has investigated the association between pre-diagnostic calcium levels and subsequent risk of breast cancer. We have examined this in a cohort of 7,847 women where serum calcium levels and established risk factors for breast cancer had been assessed at baseline. During a mean follow-up of 17.8 years, 437 incident breast cancer cases were diagnosed. Incidence of breast cancer was calculated in different quartiles of serum calcium levels and a Cox's proportional hazards analysis was used to obtain corresponding relative risks (RR), with a 95% confidence interval (CI), adjusted for potential confounders. In premenopausal women, serum calcium levels were inversely associated with breast cancer risk in a dose-response manner. The adjusted RR (95% CI) of breast cancer was in the 2nd calcium quartile 0.91 (0.65-1.30), in the 3rd quartile 0.89 (0.60-1.31), and in the 4th quartile 0.56 (0.32-0.98), as compared to the 1st calcium quartile. In postmenopausal overweight women (BMI > 25), breast cancer risk was higher in calcium quartiles 2-4 as compared to the 1st quartile. Our findings may have implications for primary prevention of breast cancer and for the management of asymptomatic primary hyperparathyroidism.
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| 3. |
- Almquist, Martin, et al.
(författare)
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Serum calcium and tumour aggressiveness in breast cancer: a prospective study of 7847 women.
- 2009
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Ingår i: European Journal of Cancer Prevention. - 1473-5709. ; 18, s. 354-360
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Tidskriftsartikel (refereegranskat)abstract
- Experimental, epidemiological and clinical studies suggest that calcium and/or its regulating hormones affect breast cancer risk. There has been no prospective cohort study investigating serum calcium levels and breast cancer aggressiveness, as determined by tumour histology and stage. Dichotomized prediagnostic serum calcium levels were investigated in relation to breast cancer aggressiveness as determined by grade (mitotic frequency, tubule formation, nuclear atypia) and stage (tumour size and axillary lymph node status). Cox's proportional hazards analysis and heterogeneity analysis were used to investigate the associations between low/high calcium and grade/stage in a prospective cohort study of 7847 women, out of whom 462 women were diagnosed with incident breast cancer during a mean follow-up of 17.2 years. All analyses were stratified for body mass index and menopausal status. Prediagnostic serum calcium levels in premenopausal women were positively associated with increased tumour aggressiveness as determined by a higher risk of nodal metastasis; relative risk (RR) for calcium above median as compared with calcium below median was 1.88 with a 95% confidence interval (CI) of 1.04-3.38. In overweight women, prediagnostic serum calcium levels were also associated with tumour aggressiveness, as determined by both a higher risk of nodal metastasis [RR (95% CI) 1.69 (0.95-3.02)] and severe nuclear atypia [RR (95% CI) 2.06 (1.10-3.86)]. Results also indicate that, in overweight women, calcium is positively associated with worse grade as determined by tubule formation and mitotic frequency. In conclusion, prediagnostic serum calcium levels are positively associated with increased tumour aggressiveness in premenopausal and/or overweight women.
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| 4. |
- Almquist, Martin, et al.
(författare)
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Serum levels of vitamin D, PTH, calcium and breast cancer risk - a prospective nested case-control study.
- 2010
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 127:9, s. 2159-2168
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies indicate that calcium and its regulating hormones, i.e. parathyroid hormone (PTH) and vitamin D, might affect breast cancer risk. Evidence also suggests that this relationship could be influenced by menopausal status and BMI. We examined breast cancer risk related to pre-diagnostic serum levels of vitamin D (25OHD(2) and 25OHD(3)), PTH and calcium using a nested case-control design within the Malmö Diet and Cancer Study. There were 764 incident breast cancer cases, and 764 controls were selected by incidence density matching, using age as the underlying time scale, matching on calendar time at inclusion, menopausal status and age at inclusion. Using logistic regression analysis, odds ratios (OR) with 95% confidence intervals were calculated for breast cancer risk in different quartiles of the analysed factors. All analyses were adjusted for risk factors for breast cancer, and for levels of albumin, creatinine and phosphate. Analyses were repeated stratified for BMI and menopausal status, and for low vs. high levels of 25OHD(3), PTH and calcium. There was a weak, non-significant inverse association between breast cancer risk and 25OHD(3), and the OR for the 2(nd), 3(rd) and 4(th) quartiles, as compared to the first, were 0.84(0.60-1.15), 0.84(0.60-1.17), and 0.93(0.66-1.33). Serum calcium was positively associated with breast cancer in pre-menopausal women (OR for the 4(th) quartile = 3.10:1.33-7.22 and p for quartile trend=0.04), and in women with BMI>25 (OR for the 4(th) quartile=1.94:1.12-3.37 and p for trend<0.01). There was no association between baseline serum PTH and breast cancer risk. (c) 2010 UICC.
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| 5. |
- Almqvist, Erik, et al.
(författare)
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Cardiac dysfunction in mild primary hyperparathyroidism assessed by radio-nuclide angiography and echocardiography before and after parathyroidectomy
- 2002
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Ingår i: Surgery. - : Elsevier BV. - 1532-7361 .- 0039-6060. ; 132:6, s. 1126-1132
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Tidskriftsartikel (refereegranskat)abstract
- Background.. Primary hyperparathyroidism (PHPT) is associated with increased cardiovascular morbidity for reasons that are incompletely understood. The present study was undertaken to evaluate the effects of parathyroidectomy on cardiac function especially in patients with mild PHPT Methods. Fifty patients with mild PHPT (serum calcium, 2.55 to 2.95 mmol/L) were randomized to parathyroidectomy either directly (group A) or after 1 year of observation (group B). Equilibrium radionuclide angiography (ERNA) at rest and at exercise was performed in addition to echocardiography on all patients at inclusion in the study and 1 and 2 years later. Results. Left ventricular mass index was larger (P <.05) in group B compared with group A after 2 years and showed significant correlation to the serum concentration of parathyroid hormone (but not Serum calcium) after 1 year. ERNA showed transient subclinical changes in both systolic and diastolic function Parameters after parathyroidectomy (decrease of left ventricular ejection fraction and peak fill-ingrate, with return to preoperative Levels within 1 year). Conclusions. Combined evaluation by ERNA and echocardiography has shown previously unknown aspects of parathyroid/myocardial interaction, which is consistent with an inotropic influence exerted by parathyroid hormone, and is in favor of early surgical treatment for PHPT irrespective of serum calcium levels.
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| 6. |
- Almqvist, Erik, et al.
(författare)
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Early parathyroidectomy increases bone mineral density in patients with mild primary hyperparathyroidism: A prospective and randomized study
- 2004
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Ingår i: Surgery. - : Elsevier BV. - 1532-7361 .- 0039-6060. ; 136:6, s. 1281-1287
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Tidskriftsartikel (refereegranskat)abstract
- Background. There is an ongoing controversy regarding how to take care of patients with mild primary hyperparathyroidism (PHPT) and how to grade their disease activity in terms of bone parameters. This prospective and randomized study was undertaken to evaluate skeletal effects of delayed surgical treatment in such patients. Methods. Fifty patients with mild PHPT (serum calcium, 2.55 to 2.95 mmol/L, 10.2 to 11.8 mg/dL) were randomized to parathyroidectomy either at diagnosis or 1 year later. Hip and spine bone mineral density (BMD, determined by dual energy x-ray absorptiometry), bone alkaline phosphatase in serum, osteocalcin and P-CrossLaps in plasma, and calcium in urine were measured in all patients at inclusion in the study and 1 and 2 years later. Results. The skeletal effects of mild PHPT varied with anatomy and time of exposure. Parathyroidectomy decreased all biochemical bone markers (P <.0001) and increased lumbar spine BAW (P <.05) equally in both groups, even in patients without overt osteoporosis, whereas hip BAM was increased (P <.05) in the early intervention group only. Conclusion. Prolonged exposure to mild and seemingly stable PHPT is a risk factor for hip fractures, which adds to other reasons for surgical treatment of this condition without delay regardless of serum calcium levels.
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| 7. |
- Almqvist, Erik G., et al.
(författare)
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Factors influencing insulin sensitivity in patients with mild primary hyperparathyroidism before and after parathyroidectomy
- 2012
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 72:2, s. 92-99
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Primary hyperparathyroidism (PHPT) is associated with cardiovascular disease. The aims of this study were to investigate lipid and glucose metabolism in mild PHPT, and to identify whether insulin sensitivity correlates with circulating levels of adiponectin, SHBG, and osteocalcin before and after parathyroidectomy (PTX). Materials and methods. Forty-five patients with PHPT were examined before and 1 year after PTX. Circulating levels of triglycerides, total cholesterol, HDL-cholesterol, insulin, glucose, adiponectin, SHBG, osteocalcin, and erythropoietin were measured. Results. At baseline, the mean serum levels of total cholesterol, LDL-cholesterol and triglycerides were above the upper reference limit or in the upper normal range, and insulin sensitivity was reduced as assessed using the HOMA index. One year after parathyroidectomy, serum lipids as well as HOMA index and erythropoietin were unchanged while adiponectin had increased (p < 0.05), and SHBG and osteocalcin had decreased (p < 0.05 and p < 0.0001, respectively). HOMA index correlated negatively with circulating levels of adiponectin, SHBG and osteocalcin. In multiple regression analysis SHBG was the most important predictor of insulin sensitivity, both pre- and postoperatively. Conclusion. Untreated mild PHPT is associated with a moderate derangement of lipid and glucose metabolism. As previously shown in population-based cohorts, insulin sensitivity is positively associated with circulating concentrations of adiponectin, SHBG and osteocalcin. One year after PTX, the mean level of adiponectin was increased, but the levels of SHBG and osteocalcin had decreased and the levels of serum lipids and the insulin sensitivity remained unchanged as compared with baseline.
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| 8. |
- Almqvist, Erik G., et al.
(författare)
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Increased markers of inflammation and endothelial dysfunction in patients with mild primary hyperparathyroidism
- 2011
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 71:2, s. 139-144
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The association between primary hyperparathyroidism (PHPT) and cardiovascular disease is incompletely understood. The aims of this study were to evaluate how cardiac function and markers of inflammation and endothelial dysfunction correlate in patients with mild PHPT, and how these markers are influenced by surgical cure of the parathyroid disease (PTX). Material and methods: Forty-five patients with PHPT were examined before and 1 year after PTX. Serum/plasma concentrations of calcium, PTH, highly sensitive C-reactive protein (CRP), interleukin-6 (IL-6), vascular adhesion molecule-1 (VCAM1), E-selectin, and NT-proBNP were measured as well as erythrocyte sedimentation rate (ESR) and creatinine clearance. Cardiac function was evaluated by equilibrium radionuclide angiography. Results: The baseline serum level of IL-6 correlated negatively with baseline parameters of cardiac function (exercise capacity, p < 0.001, left ventricular ejection fraction at exercise, p < 0.01). The mean serum concentrations of IL-6 and CRP and the ESR had increased 1 year after PTX (p < 0.001, p < 0.01, and p < 0.001, respectively) in parallel with a decrease in cardiac function and an increase in circulating NT-proBNP. The mean serum level of VCAM1 was above the upper normal range at baseline and had not changed significantly 1 year after PTX. Conclusion: Patients with mild PHPT and normal renal function displayed signs of subclinical inflammation and endothelial dysfunction. One year after PTX, the inflammatory markers were increased in parallel with a subclinical decrease in cardiac function. Further studies are warranted to clarify the natural course and clinical implications of these changes.
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| 9. |
- Almqvist, Erik, et al.
(författare)
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Increase of bioavailable testosterone is associated with gain in bone mineral density after cure of primary hyperparathyroidism in postmenopausal women
- 2006
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 64:1, s. 58-62
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Tidskriftsartikel (refereegranskat)abstract
- Objective The recovery of bone mineral density (BMD) after surgical cure of primary hyperparathyroidism (PHPT) seems to be multifactorial and not just dependent on declining PTH. The aim of the present study was to evaluate the role of sex steroids in this context. Design and patients Thirty-six postmenopausal women with PHPT were examined before and 1 year after curative parathyroidectomy. Their mean age at inclusion in the study was 71.7 +/- 1.1 years (range 54-83). BMD was measured in hip and lumbar spine using dual energy X-ray absorptiometry. No patient received any replacement therapy with sex hormones or treatment with corticosteroids, oestrogen receptor modulators or bisphosphonates. Measurements Serum concentrations of oestradiol, testosterone, androstenedione, dehydroepiandrosterone sulphate, SHBG, PTH and calcium. Results Postoperative increase of free (bioavailable) testosterone was positively correlated to the change of BMD in the hip (P < 0.01), whereas the change of PTH in serum correlated to the change of BMD in the lumbar spine (P < 0.05). Multiple regression analysis showed that bioavailable testosterone was the most important determinant of change in BMD in both spine and hip (femoral neck: P < 0.05; Ward's triangle: P < 0.001; trochanter: P < 0.01; lumbar spine: P < 0.05). The increase of bioavailable testosterone after curative parathyroidectomy was related to declining SHBG. Conclusions An increase of bioavailable testosterone following surgical cure of PHPT is related to improvement of hip and lumbar spine BMD in postmenopausal women. This previously unknown hormonal interaction may also be important to other aspects of hyperparathyroidism.
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| 10. |
- Almqvist, Erik, et al.
(författare)
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Increased plasma concentrations of N-terminal pro-B-type natriuretic peptide in patients with mild primary hyperparathyroidism.
- 2006
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Ingår i: Clinical endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 65:6, s. 760-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Primary hyperparathyroidism (PHPT) is associated with heart disease. The aims of the present study were to evaluate how cardiac function and secretion of N-terminal pro-B-type natriuretic peptide (NT-proBNP) correlate in patients with mild PHPT, and how the plasma level of NT-proBNP is influenced by cure of the parathyroid disease. DESIGN AND PATIENTS: Forty-two patients with PHPT without symptoms of heart disease were examined before and 1 year after curative parathyroidectomy. MEASUREMENTS: Plasma or serum concentrations of NT-proBNP, calcium, PTH, creatinine, oestradiol, testosterone and SHBG were measured. Cardiac function was evaluated by equilibrium radionuclide angiography (ERNA). RESULTS: At baseline, NT-proBNP levels correlated negatively with systolic function [left ventricular ejection fraction (LVEF), P < 0.001]. Twelve per cent of the patients had NT-proBNP levels above normal reference values preoperatively. One year postoperatively, the corresponding proportion was 21%. The mean plasma concentration of NT-proBNP increased after parathyroidectomy (P < 0.01) in parallel with a dip in diastolic function (peak filling rate, P < 0.05) and a falling trend in systolic function (LVEF, P = 0.08). The postoperative percentage changes in circulating NT-proBNP and total oestradiol correlated positively (P < 0.05). CONCLUSIONS: Patients with mild PHPT and normal renal function may have high levels of circulating NT-proBNP despite the absence of symptomatic heart disease. Cure of the parathyroid disease is followed by a further increase in NT-proBNP secretion in parallel with ERNA measures, indicating subclinical changes in heart function. These results are in line with data indicating an association between PHPT and increased risk of premature death.
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