Reporting chronic kidney disease in Greenland.

Background: Chronic kidney disease (CKD) is a major health burden affecting more than 10% of the global population. It is a multifactorial disease with many risk factors attributed lifestyle diseases. The prevalence of CKD in Greenland is unknown; however, the prevalence of risk factors contributing to CKD is increasing.Objectives: To estimate the prevalence of CKD in Greenland.Methods: The study was a cross-sectional register-study including all Greenlandic residents aged ≥20 years with serum creatinine analysis within the last 2 years. We identified those with CKD based on eGFR and UACR and those registered with a CKD diagnosis code. Two limitations of the study are possible lack of data completeness and the reliance of a single time point to report CKD.Results: A total of 2,157 patients were identified with CKD with an age-standardised prevalence of 3.01%. Only 75 patients were registered with a diagnosis code for CKD. Approximately 80% of patients were classified with CKD stages 1-2.Conclusion: This is the first study reporting CKD in Greenland. We found a lower prevalence of CKD than reported by other studies, and a low number of patients correctly diagnosed with CKD. We call for increased awareness and diagnosis coding of CKD in Greenland.

Depression prevalence using the HADS-D compared to SCID major depression classification: An individual participant data meta-analysis.

OBJECTIVES: Validated diagnostic interviews are required to classify depression status and estimate prevalence of disorder, but screening tools are often used instead. We used individual participant data meta-analysis to compare prevalence based on standard Hospital Anxiety and Depression Scale - depression subscale (HADS-D) cutoffs of ≥8 and ≥11 versus Structured Clinical Interview for DSM (SCID) major depression and determined if an alternative HADS-D cutoff could more accurately estimate prevalence. METHODS: We searched Medline, Medline In-Process & Other Non-Indexed Citations via Ovid, PsycINFO, and Web of Science (inception-July 11, 2016) for studies comparing HADS-D scores to SCID major depression status. Pooled prevalence and pooled differences in prevalence for HADS-D cutoffs versus SCID major depression were estimated. RESULTS: 6005 participants (689 SCID major depression cases) from 41 primary studies were included. Pooled prevalence was 24.5% (95% Confidence Interval (CI): 20.5%, 29.0%) for HADS-D ≥8, 10.7% (95% CI: 8.3%, 13.8%) for HADS-D ≥11, and 11.6% (95% CI: 9.2%, 14.6%) for SCID major depression. HADS-D ≥11 was closest to SCID major depression prevalence, but the 95% prediction interval for the difference that could be expected for HADS-D ≥11 versus SCID in a new study was -21.1% to 19.5%. CONCLUSIONS: HADS-D ≥8 substantially overestimates depression prevalence. Of all possible cutoff thresholds, HADS-D ≥11 was closest to the SCID, but there was substantial heterogeneity in the difference between HADS-D ≥11 and SCID-based estimates. HADS-D should not be used as a substitute for a validated diagnostic interview.

Vitamin D and cognitive function: A Mendelian randomisation study.

The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, p curvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.

Vitamin D and cognitive function: The Tromsø Study.

BACKGROUND AND PURPOSE: There are indications that vitamin D may be important for more than skeletal health, including cognitive function. METHODS: The study was performed in Tromsø, Northern Norway (The Tromsø Study). In a cross-sectional study serum 25-hydroxyvitamin D (25(OH)D) was measured and cognitive function (word recall, digit-symbol coding, finger tapping, Mini Mental State Examination) tested in 4624 subjects; in a prospective study serum 25(OH)D was measured in samples from 1994 and compared to cognitive function tested in 3436 subjects in 2001 and 2044 subjects in 2007; and in a Mendelian randomization study single nucleotide polymorphisms (SNPs) related to vitamin D were evaluated versus cognitive function in 5980 subjects. RESULTS: In the cross-sectional study all tests were positively associated with serum 25(OH)D levels with ~5% better performance in subjects in the highest versus lowest serum 25(OH)D quartile. This relation was only seen in subjects older than 65 years. After full adjustment for season, age, gender, body mass index, blood pressure, physical activity and education, the relation was only significant for finger tapping. In the prospective study, serum 25(OH)D from 1994 similarly predicted cognitive function 7-13 years later. In the Mendelian randomization study, only one SNP in the VDR gene (Apal, rs7975232) was significantly associated with cognition (word recall and digit-symbol coding). CONCLUSIONS: There is an association between serum 25(OH)D and cognition, but randomized controlled trials are needed to establish causality.

A study of the psychometric properties of the Beck Depression Inventory-II, the Montgomery and Åsberg Depression Rating Scale, and the Hospital Anxiety and Depression Scale in a sample from a healthy population.

The objective of this study is to evaluate internal consistency and psychometric properties of the Hospital Anxiety and Depression Scale (HADS), the Beck Depression inventory-II (BDI-II) and the Montgomery and Åsberg Depression Rating Scale (MADRS) for screening for major depressive episode (MDE) in a selected sample from a healthy population. Participants answered the BDI-II and the HADS questionnaires and were interviewed with MADRS. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV Axis I Disorders-Clinician Version (SCID-CV) was used to diagnose MDE. Current MDE was diagnosed in 20 (6%) of the 357 participants. All three scales including the depression sub-scale for HADS had high area under the receiver operating characteristics curve (ROC) (AUC) (0.84-0.87), and internal consistency was also high for all scales (0.75-0.89). Optimal cut-off for MDE was ≥ 12 for BDI-II, MADRS ≥ 8, HADS total ≥ 9, and HADS-D ≥ 4, which all resulted in sensitivities = 85% and specificities > 78%. Diagnostic accuracy was low on all depression scales (Cohen's kappa = 0.20-0.40). Reports of the properties of depression scales in a healthy population are limited. We found BDI-II, HADS and MADRS to be acceptable as screening instruments for MDE in a selected sample from healthy population with recommend cut-offs as mentioned above.

The phosphodiesterase 8B gene rs4704397 is associated with thyroid function, risk of myocardial infarction, and body height: the Tromsø study.

OBJECTIVE: High serum thyrotropin (TSH) levels predict cardiovascular disease (CVD). Recently several single nucleotide polymorphisms (SNPs) associated with TSH levels have been identified, one of them being the rs4704397 SNP in the phosphodiesterase 8B (PDE8B) gene. If the relation between thyroid function and CVD is causal, one could also expect rs4704397 genotypes to predict CVD and possibly health in general. METHODS: DNA was prepared and genotyping performed for rs4704397 in subjects who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints myocardial infarction (MI), type 2 diabetes (T2DM), cancer, or death, as well as a randomly selected control group. Similarly, genotyping was performed in subjects who had participated in clinical trials where serum TSH, free T4 (fT4), and free T3 (fT3) were measured. RESULTS: From the Tromsø Study, 8938 subjects without thyroid disease or thyroid medication were successfully genotyped for rs4704397. Among these, 2098 were registered with MI, 1025 with T2DM, 2748 with cancer, and 3592 had died. The minor homozygote genotype (A:A) had a median serum TSH level that was 0.29 mIU/L higher than in the major homozygote genotype (G:G). The A:A genotype had a significantly increased risk of MI as compared to the G:G genotype (1.14 [1.00-1.29], hazard ratio [confidence interval], Cox regression with adjustment for age, sex, and body mass index). No significant associations were seen with the other endpoints or CVD risk factors. Furthermore, subjects with the G:G genotype were significantly taller than subjects with the A:A genotype (mean difference 1.5 cm). In 584 subjects with serum TSH, fT4, and fT3 measurements, the subjects with the A:A genotype had significantly higher serum TSH and nonsignificantly lower serum fT3 (mean difference 0.15 pmol/L) levels than subjects with the G:G genotype. CONCLUSION: rs4704397 is associated with thyroid function, risk of MI, and body height. However, confirmation in other cohorts is needed before firm conclusions can be drawn.

The serum 25-hydroxyvitamin D response to vitamin D supplementation is related to genetic factors, BMI, and baseline levels.

OBJECTIVE: The serum 25-hydroxyvitamin D (25(OH)D) level is not only dependent on vitamin D intake and production in the skin but also dependent on genetic factors. Thus, in large genome-wide association studies, it has been shown that single nucleotide polymorphisms (SNPs) in the vitamin D binding protein (DBP), as well as in enzymes related to activation or degradation of vitamin D and its metabolites, are as important for the serum 25(OH)D level as the effect of season. How these SNPs affect the serum 25(OH)D response to vitamin D supplementation is uncertain. DESIGN AND METHODS: Data were pooled from three randomized controlled trials where 40, 000 IU vitamin D/week was given for 6 months. Serum 25(OH)D was measured before and at the end of the intervention, and the subjects were genotyped for SNPs related to the serum 25(OH)D level. RESULTS: Baseline 25(OH)D levels were significantly related to SNPs in the DBP and CYP2R1 genes. Those with SNPs associated with the lowest baseline 25(OH)D levels also had the smallest increase (delta) after supplementation. Those with the lowest baseline serum 25(OH)D (without regard to genotypes) had the highest increase (delta) after supplementation. Subjects with high BMI had lowest baseline 25(OH)D levels and also the smallest increase (delta) after supplementation. CONCLUSIONS: The serum 25(OH)D response to supplementation depends on genes, baseline level, and BMI. However, whether this is clinically important or not depends on the therapeutic window of vitamin D, an issue that is still not settled.

Supplementation with High Doses of Vitamin D to Subjects without Vitamin D Deficiency May Have Negative Effects: Pooled Data from Four Intervention Trials in Tromsø.

Data were pooled from four randomized clinical trials with vitamin D performed in Tromsø with weight reduction, insulin sensitivity, bone density, and depression scores as endpoints. Serum lipids, glycated hemoglobin (HbA1c), and high sensitivity C-Reactive Protein, (HS-CRP) were measured at baseline and after 6-12 months of supplementation with vitamin D 20 000 IU-40 000 IU per week versus placebo. A total of 928 subjects who completed the interventions were included. At baseline the mean serum 25-hydroxyvitamin D (25(OH)D) level in those given vitamin D was 55.9 (20.9) nmol/L and the mean increase was 82.4 (40.1) nmol/L. Compared with the placebo group there was in the vitamin D group at the end of the studies a slight, but significant, increase in HbA1c of 0.04%, an increase in HS-CRP of 0.07 mg/L in those with serum 25(OH)D < 50 nmol/L, and in those with low baseline HDL-C and serum 25(OH)D < 50 nmol/L a slight decrease serum HDL-C of 0.08 mmol/L (P < 0.05). No serious side-effects were seen. In conclusion, in subjects without vitamin D deficiency, there is no improvement in serum lipids, HbA1c, or HS-CRP with high dose vitamin D supplementation. If anything, the effect is negative.

Association between headache and serum 25-hydroxyvitamin D: the Tromsø Study: Tromsø 6.

BACKGROUND: High prevalence of headache has been associated with high latitude, thus suggesting a relation with vitamin D. However, there are so far no reports on the association between serum 25-hydroxyvitamin D (25[OH]D) and headache. OBJECTIVE: To investigate the association between headache and serum 25(OH)D in a general population. METHODS: Cross-sectional study based on questionnaires from 11,614 persons who participated in the sixth survey of the Tromsø Study (Tromsø 6) carried out in 2007-2008. The data were stratified according to smoking status and analyzed with regard to migraine and non-migraine headache. Adjustments were done for age, body mass index (BMI), gender, season, chronic diseases, education, physical exercise, and alcohol consumption. RESULTS: Headache of non-migraine type was associated with low levels of serum 25(OH)D with an odds ratio (OR) of 1.20 (1.04-1.39) in the lowest quartile as compared to the highest serum 25(OH)D quartile. No significant association was found between migraine and serum 25(OH)D. CONCLUSION: Non-migraine headache was associated with low levels of serum 25(OH)D. Although adjustment were done for possible confounders, this finding may still reflect lifestyle rather than causality, and further studies are needed to investigate this. No association was found between serum 25(OH)D and migraine.

Effect of vitamin D supplement on depression scores in people with low levels of serum 25-hydroxyvitamin D: nested case-control study and randomised clinical trial.

AIMS: To compare depressive symptoms in participants with low and high serum 25-hydroxyvitamin D (25(OH)D) levels and to examine whether supplementation with vitamin D(3) would improve symptoms in those with low serum 25(OH)D levels. METHOD: Participants with low 25(OH)D levels were randomised to either placebo or 40 000 IU vitamin D(3) per week for 6 months. Individuals with high serum 25(OH)D levels were used as nested controls. Depressive symptoms were evaluated with the Beck Depression Inventory, Hospital Anxiety and Depression Scale, Seasonal Pattern Assessment Scale and Montgomery-Åsberg Depression Rating Scale. The study was registered at ClinicalTrials.gov (NCT00960232). RESULTS: Participants with low 25(OH)D levels (n = 230) at baseline were more depressed (P<0.05) than participants with high 25(OH)D levels (n = 114). In the intervention study no significant effect of high-dose vitamin D was found on depressive symptom scores when compared with placebo. CONCLUSIONS: Low levels of serum 25(OH)D are associated with depressive symptoms, but no effect was found with vitamin D supplementation.

Low serum 25-hydroxyvitamin D levels are associated with depression in an adult Norwegian population.

Observational and intervention studies have suggested an association between low levels of 25-hydroxyvitamin D (25(OH)D) and depressive symptoms in several subgroups of disease and age. This study tests the hypothesis in a general population. Our data are based on 10,086 persons who participated in the sixth Tromsø study carried out in 2007-2008. Depressive symptoms were evaluated using the Hopkins Symptoms Check List 10 (SCL-10) based on answers from a questionnaire. Results were adjusted for known confounders such as age, gender, body-mass index, physical exercise, alcohol, education, marital status, kidney function and chronic disease. Results are presented for smokers (N=1966) and non-smokers (N=8120) separately as our immunoassay seems to overestimate 25(OH)D levels for smokers. Low serum 25(OH)D levels were found to be a significant predictor of depressive symptoms in both smokers and non-smokers. The association seemed to be stronger in women. The odds ratios for depression in the highest 25(OH)D quartile were 0.59 (0.39-0.89) in smokers and 0.74 (0.58-0.95) in non-smokers compared with the lowest quartile. However, no conclusions with regard to causality can be drawn due to the cross-sectional design of the study.

Frequent left ventricular hypertrophy independent of blood pressure in 1851 pre-western Inuit.

BACKGROUND: Elevated blood pressure is a risk factor for cardiovascular disease and may be detected by left ventricular hypertrophy (LVH) in electrocardiogram (ECG). Pre-western Inuit had frequent signs of LVH in ECG predominantly in the 3rd decade while a low occurrence of ischemic heart disease. METHODS: We evaluated the association between blood pressures and ECG signs of LVH, cardiac auscultation, and symptoms related to heart disease in the recently recovered data from the survey of 1851 Inuit conducted in 1962-1964 in East Greenland. RESULTS: The participation rate was 97%. Among the 812 Inuit aged 18 years or above blood pressure was unaltered until the age of 39 years (systolic, p=76; diastolic, p=0.36) and increased subsequently (both, p<0.001). Systolic blood pressure >140 mmHg was more frequent when aged >40 years (p<0.001) and diastolic blood pressure >90 mmHg was more common in men (p<0.001) and in men and women aged >40 years (p<0.001). ECG signs of LVH were more frequent in men (p<0.01) but the occurrence decreased from the age of 40 years (p<0.01), and were not influenced by systolic (p=0.97), diastolic (p=0.87) or pulse pressure (p=0.69). CONCLUSIONS: Blood pressure rose only after the age of 40 years in pre-western Inuit. Left ventricular hypertrophy peaked among 30-year olds and was independent of elevated blood pressure. It may be speculated that the common left ventricular hypertrophy was due to marked physical activity that contributed to the low occurrence of ischemic heart disease among pre-western Inuit.

Low occurrence of ischemic heart disease among Inuit around 1963 suggested from ECG among 1851 East Greenland Inuit.

BACKGROUND: The prevalence of coronary heart disease among Greenland Inuit today is similar to that of western populations. The cardiovascular risk profile among Inuit has changed over the past four decades with the introduction of a western life style. An unaltered prevalence of coronary heart disease has been proposed, but no pre-westernisation data exist. AIM: To describe pre-westernisation prevalence of coronary heart disease among East Greenland Inuit. DESIGN: A population study of 1851 Inuit living in East Greenland was conducted in 1962-1964. It included ECG, cardiac auscultation and recording of symptoms. ECGs were evaluated for ischemic signs, arrhythmia, hypertrophy, and conduction abnormalities. RESULTS: The participation rate was 97%. A12-lead ECG was performed in 181 adults, including 65% of men aged 40 years and above. Hypertrophy was seen in 15% and peaked in 30-39 year olds. Pathological conduction disturbances were seen in 4% and 1% had ischemic signs. The age-standardised prevalence of ischemic ECG findings was 5.5%. Abnormal ECG findings did not correlate with pathologic findings on cardiac auscultation or symptoms related to heart disease. CONCLUSIONS: Hypertrophy peaked among 30 years olds. Ischemic ECG findings were present in East Greenland Inuit before westernisation, the prevalence clearly lower than today.