ObjectiveTransthyretin amyloid cardiomyopathy (ATTR-CM) is a rare, progressive and fatal condition caused by deposition of transthyretin amyloid fibrils in the heart. This study aims to identify all patients diagnosed with ATTR-CM in Sweden, estimate the prevalence of ATTR-CM, describe patient characteristics and mortality, assess the importance of early symptoms (red flags) for identification of ATTR-CM, and compare with patients with heart failure (HF).MethodsThis retrospective study combined multiple national health registers covering all specialist visits and prescriptions for the entire population of Sweden. Between January 2008 and December 2018, patients with ATTR-CM were identified retrospectively based on a combination of diagnosis codes and compared with matched, all-cause non-ATTR HF patients.ResultsOverall, a total of 994 patients diagnosed with ATTR-CM were identified, with an average age at diagnosis of 73 years, and 30% of whom were female. The prevalence of diagnosed ATTR-CM cases in 2018 was 5.0 per 100 000. The median survival from diagnosis was 37.6 months (CI 33.8 to 43.8), with a lower median survival in women (27.9 months, CI 23.3 to 33.8) compared with men (43.5 months, CI 37.6 to 49.6). Patients with ATTR-CM demonstrated reduced survival compared with patients with HF (p<0.001). Compared with patients with HF, clinical identification of carpal tunnel syndrome, spinal stenosis, and atrioventricular and left bundle branch block can facilitate earlier diagnosis of ATTR-CM.ConclusionsThis study provides the first nationwide estimates of ATTR-CM prevalence and risk factors. The results reinforce the severity of the disease and the importance of earlier diagnosis, especially for female patients, in order to allow effective treatment and prevention of disease progression.

We studied effectiveness of osteoporosis treatment in women older than 80 years, who often are not included in clinical trials. Treatments were as effective on bone density and fractures as in younger women. Introduction To study real-world effectiveness of osteoporosis treatment on BMD and fractures in the oldest old women (≥ 80 years) compared with women (60-79 years) in the clinical setting using Swedish health register data. Methods National registers and data from DXA machines were used to study effectiveness of all available osteoporosis treatments in women 60-79 and ≥ 80 years using three approaches: (1) Total Hip BMD change up to 8 years after treatment start; (2) fracture incidence where patients served as their own controls, comparing the first 3 months after treatment start with the subsequent 12 months; and (3) comparison of fracture incidence post-fracture in women ≥ 80 years treated with osteoporosis treatment or calcium/vitamin D. Results Analysis 1: Total Hip BMD increased by up to 6.7% and 7.7% in women 60-79 and ≥ 80 years old, respectively. The mean increase in BMD was 1.1%-units per year in both age groups. Analysis 2: Relative to the 3-month baseline, fracture incidence decreased during the subsequent 12 months of treatment. Incidence rate ratios were estimated at 0.65, 0.74, 0.29, and 0.81 for any, hip, vertebral, and non-hip-non-vertebral fracture, respectively. Analysis 3: A 24-month incidence of any fracture in women ≥ 80 years given post-fracture osteoporosis treatment was lower (HR = 0.78) than in women given calcium/vitamin D, but treatment allocation was not random, with lower mortality (HR = 0.51) in patients receiving OP treatment. Conclusions Osteoporosis medication in women > 80 years in clinical practice likely works, and the magnitude of effect is similar to what was estimated in younger women. The choice between osteoporosis treatment and calcium/vitamin D after fracture in women ≥ 80 years is not random but appears associated with the patient's health status and presence of vertebral fractures, rather than the known risk profile of sustaining a fracture at a high age.

Background Secondary hyperparathyroidism (SHPT) is a common and major complication in chronic kidney disease (CKD), reflecting the increase of parathyroid hormone (PTH) in response to reduced Vitamin D signaling and hypocalcemia. This meta-analysis evaluated the impact of nutritional vitamin D (NVD) (cholecalciferol or ergocalciferol) on SHPT-related biomarkers. Methods A systematic literature search was performed in PubMed to identify relevant randomized control trials (RCTs) to be included in the meta-analysis. Fixed and random effects models were used to pool study level results. Effects were studied within NVD study arms and relative to control groups (placebo/no treatment); the former in order to identify the effect of actively altering biomarkers levels. Results Reductions in PTH from supplementation with NVD were small when observed within the NVD study arms (pooled reduction: 10.5 pg/ml) and larger when compared to placebo/no treatment (pooled reduction: 49.7 pg/ml). NVD supplementation increased levels of vitamin D (25(OH)D) in both analyses (increase within NVD study arm: 20.6 ng/ml, increase versus placebo/no treatment: 26.9 ng/ml). While small and statistically non-significant changes in phosphate and fibroblast growth factor 23 (FGF23) were observed, NVD supplementation caused calcium levels to increase when compared versus placebo/no treatment (increase: 0.23 mg/dl). Conclusions Our results suggest that supplementation with NVD can be used to increase 25(OH)D to a certain extent, while the potential of NVD to actively reduce PTH in ND-CKD patients with SHPT is limited.

Aims Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive condition caused by deposition of transthyretin amyloid fibrils in the heart and is associated with poor quality of life and a shortened lifespan. This study aimed to describe the prevalence, clinical characteristics, and mortality of patients with ATTR-CM, using multiple national health registers in Denmark, Finland, Norway, and Sweden. Methods and resultsTransthyretin amyloid cardiomyopathy patients were identified during 2008-2018 using a combination of diagnosis codes for amyloidosis and heart disease and were matched to patients with non-ATTR heart failure (HF). An identical study design was used in each country to facilitate comparison and aggregation of results. A total of 1930 ATTR-CM patients were identified from national health registers in the four countries. In 2018, prevalence of ATTR-CM per 100 000 inhabitants ranged from 1.4 in Denmark to 5.0 in Sweden; a steep increase over time was observed in Sweden and Norway. Median survival from diagnosis was 30 months for ATTR-CM patients and 67 months for matched HF patients. Survival was significantly lower for female than for male ATTR-CM patients (median survival: 22 and 36 months), while no significant difference was observed in the HF cohort. Conclusions This study provides the first nationwide estimates of the prevalence, clinical characteristics, and mortality of patients with ATTR-CM, using identical study design across several countries. Findings corroborate previous case series showing high mortality in ATTR-CM, two-fold higher than for other HF patients and higher in women than men, highlighting the need for more precise and early diagnosis to reduce the disease burden.

Background and Aims Chronic kidney disease (CKD) is commonly associated with mineral and bone disorder (CKD-MBD). Secondary hyperparathyroidism (SHPT) is a critical component of CKD-MBD characterized by excessive PTH secretion and parathyroid hyperplasia. SHPT develops in CKD because of disturbances in CKD-MBD parameters such as increases in serum phosphate and fibroblast growth factor 23, and reductions in 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and serum calcium. Low vitamin D levels play a critical role in the development and progression of SHPT. Nutritional vitamin D (NVD) supplements are being frequently used to address SHPT, especially in early CKD. The objective of this meta-analysis (MA) was to evaluate the effectiveness of the NVDs cholecalciferol and ergocalciferol in reducing PTH and increasing 25(OH)D in patients with non-dialysis CKD (ND-CKD). Method A systematic literature search was performed in PubMed to identify relevant randomized control trials (RCTs) to be included in the MA. All analyses were performed using both random and fixed effects models with inverted-variance weighting. Comparisons were made between the effects of NVDs relative to placebo-treated or untreated patients and between the baseline and end-of-study values of the patients treated with the NVDs, i.e. the effects in treated patients only. Results A total of 14 RCTs comprising 974 patients were included in the analyses. Overall reductions in PTH were small when compared to baseline (reduction of 10.95 pg/ml, 95 % confidence interval (CI): -15.99 to -5.91 pg/ml), while reductions in PTH were approximately three times larger when compared to placebo-treated or untreated patient groups (reduction of 34.35 pg/ml, 95 % CI:-47.47 to -21.24 pg/ml). This indicated a limited potential to actively lower PTH with NVDs as the relative effect on PTH when compared to placebo-treated or untreated patient groups was driven to a large degree by increases in PTH in the comparator arms. Treatment with NVDs tended to increase levels of 25(OH)D both when compared to placebo-treated or untreated patients (increase of 26.54 ng/ml, 95 % CI: 24.62 to 28.46 ng/ml) and when only the changes in treated patients were considered (increase of 21.49 ng/ml, 95 % CI: 20.54 to 22.44 ng/ml). However, large variations in effect sizes on levels of 25(OH)D were observed, making judgements about the size of any true treatment effect difficult. Average levels of 25(OH)D in treated patients at the end of the study period were &gt;30 ng/ml in all but two RCTs and &gt;50 ng/ml in only five of the included RCTs. No clear relationship was observed between study length (range: 4 to 144 weeks) or doses administered (range: 14 000 to 75 000 UI weekly average) and effects on 25(OH)D or PTH. Conclusion Our results suggest that treatment with NVDs is not efficacious to reliably and consistently lower PTH in ND-CKD patients with SHPT. Although treatment with NVDs can potentially be used to correct vitamin D insufficiency, our results suggest that the potential of NVD treatment to raise 25(OH)D levels to &gt;50 ng/ml, a level needed to reduce PTH, is limited.