Routine biomarker results from hospital laboratory information systems, covering hospitals and general practitioners, in Denmark are available to researchers through access to the regional Clinical Laboratory Information System Research Database at Aarhus University and the nationwide Register of Laboratory Results for Research. This review describes these two data sources. The laboratory databases have different geographical and temporal coverage. They both include individual-level biomarker results that are electronically transferred from laboratory information systems. The biomarker results can be linked to all other Danish registries at the individual level, using the unique identifier, the CPR number. The databases include variables such as the CPR number, date and time (hour and minute) of sampling, NPU code, and name of the biomarker, identification code for the laboratory and the requisitioner, the test result with the corresponding unit, and the lower and upper reference limits. Access to the two databases differs since they are hosted by two different institutions. Data cannot be transferred outside Denmark, and direct access is provided only to Danish institutions. It is concluded that access to data on routine biomarkers expands the detailed biological and clinical information available on patients in the Danish healthcare system. The full potential is enabled through linkage to other Danish healthcare registries.

BackgroundMeasurement of serum cobalamin levels is routinely used to diagnose cobalamin deficiency. Surprisingly, approximately 15% of patients have high cobalamin levels and no consensus exists regarding the clinical implications.MethodsHospital-treated patients above 18 years of age referred for serum cobalamin measurement were included in groups of patients [percentage cobalamin supplemented] with low (<200 pmol/L, n = 200 [6%]), normal (200–600, n = 202 [6%]) high (601–1000, n = 217 [27%]) and very high (>1000, n = 199 [53%]) cobalamin levels. Total and cobalamin-saturated (holo) transcobalamin, total haptocorrin, soluble TC receptor, sCD320, and methylmalonic acid were analyzed. Data on diagnoses and medical prescriptions was obtained through medical files and the Aarhus University Prescription Database.ResultsAmong patients not cobalamin supplemented median total haptocorrin and holo transcobalamin levels were markedly higher in the groups with high/very high cobalamin levels compared to groups with low/normal cobalamin levels. Median total transcobalamin and sCD320 levels were similar across the groups. A number of diagnoses were significantly associated to very high Cbl levels (odds ratio (95% confidence interval)): alcoholism (5.74 (2.76–11.96)), liver disease (8.53 (3.59–20.23)), and cancer (5.48 (2.85–10.55)). Elevated haptocorrin levels were seen in patients with alcoholism, cancer, liver-, renal-, autoimmune-, and bronchopulmonary disease. No clinical associations to sCD320 and total and holo transcobalamin levels were found.ConclusionIn non-supplemented patients, high cobalamin levels were associated to high haptocorrin levels, and several diagnoses, including alcoholism, liver disease and cancer. Our study emphasizes that clinicians should take high serum cobalamin levels into consideration in the diagnostic process.

BackgroundA substantial proportion of patients referred for plasma vitamin B12 (cobalamin [Cbl]) measurement present with high Cbl levels, which have been reported in patients with different cancer types. However, the cancer risk among patients with newly diagnosed high Cbl levels has not been adequately examined.MethodsWe conducted this cohort study using population-based Danish medical registries. Patients referred for Cbl measurement with levels greater than the lower reference limit (≥200 pmol/L) were identified from the population of Northern Denmark during the period of 1998 to 2009 using a database of laboratory test results covering the entire population. Data on cancer incidence (follow-up 1998–2010), Cbl treatment, and prior diagnoses were obtained from medical registries. Patients receiving Cbl treatment were excluded. Cancer risks were calculated as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs), stratified by plasma Cbl levels. All statistical tests were two-sided.ResultsWe identified 333 667 persons without prevalent cancer and not receiving Cbl treatment. Six percent had Cbl levels greater than the upper reference limit (≥601 pmol/L). Cancer risk increased with higher Cbl levels and was highest during the first year of follow-up (Cbl 601–800 pmol/L: SIR = 3.44, 95% CI = 3.14 to 3.76; Cbl >800 pmol/L: SIR = 6.27, 95% CI = 5.70 to 6.88; both P < .001). The risks were particularly elevated for hematological and smoking- and alcohol-related cancers for persons with high Cbl levels.ConclusionsHigh Cbl levels were associated with the risk of subsequently diagnosed cancer, mostly within the first year of follow-up. This may have clinical implications for the interpretation of high Cbl levels.

It is well-established that more than 8% of patients examined for vitamin B12 deficiency unexpectedly have increased plasma levels of the vitamin, but so far there are no guidelines for the clinical interpretation of such findings. In this review, we summarise known associations between high plasma cobalamin and diseases. We report associations mainly with cancer, liver and kidney diseases, but also with a number of other diagnostic entities. The pathogenic background is poorly understood and is likely to be multi-factorial, involving increased concentrations of one or both of the circulating cobalamin binding proteins, transcobalamin and haptocorrin. Based on current knowledge, we suggest a strategy for the clinical interpretation of unexpected high plasma cobalamin. Since a number of the associated diseases are critical and life-threatening, the strategy promotes the concept of ' think the worst first ' . It is important to realise that high cobalamin levels can be an unspecific marker for cancer. If this can be ruled out, diseases of the liver and kidney should be considered.

Background: Elevated vitamin B12 levels (B12) are associated with increased short-term cancer risk. However, the implications for early cancer detection in primary care have not been assessed. Methods: Individuals with plasma B12 measurements were sampled from The Health Improvement Network primary care database, UK. Persons with low B12 levels were excluded together with persons with cancer or B12 treatment before date of B12 measurement. Incident cancer was the outcome of interest and was identified through Read codes. Individuals were disaggregated according to plasma B12 levels (unit: pmol/L): 150-600 (reference range values), 601-800, 801-1,000, and >1,000. Results: Among the 757,185 persons who met the inclusion criteria, we identified 33,367 incident cancers during 2,874,059 years of follow-up. We found a higher 1-year cancer risk among the 25,783 (3.4%) persons with elevated B12 levels compared with those with normal B12 levels. After multivariable adjustment for lifestyle factors and social deprivation, persons with B12 >1,000 pmol/L had a 1-year incidence rate ratio of 4.72 (95% confidence interval: 3.99-5.58). The association showed a nonlinear dose-response pattern, and it remained robust in stratified analyses, including when reducing the risk of confounding by indication in subanalyses. The risks were particularly elevated for liver cancer, pancreas cancer, and myeloid malignancies among persons with elevated B12 levels. Conclusions: Elevated plasma B12 levels were associated with a higher 1-year cancer risk than normal B12 levels among persons seen in UK primary care, suggesting that some cancers may affect B12 metabolism. Impact: Elevated B12 may mark occult cancer.

Cancer patients with elevated Cbl levels had higher mortality than those with normal Cbl levels. These findings may have clinical significance for assessing the prognosis of cancer patients.

An ELISA was established for measurement of soluble CD320 and it was shown that the protein is present in human serum. The serum concentrations of soluble CD320 correlated positively with serum cobalamin levels.

Background and Purpose Previous studies suggest an association between increased homocysteine (Hcy) and risk of ischemic stroke. Yet, it remains unknown whether a dose-response association exists between Hcy levels and risk of ischemic stroke. Methods Systematic literature searches were performed in PubMed, Embase, Scopus, and Web of Science. Inclusion criteria were studies investigating ischemic stroke risk in an adult population with measured Hcy levels. We computed odds ratios (ORs) for a 5 µmol/L increase in Hcy levels using a random effects meta-analysis. Results In total, 108 studies met the inclusion criteria of which 22 were rated as high-quality studies, and 20 studies included a dose-response analysis. Hcy levels were analyzed either as a continuous or categorical variable. The majority of the studies found an increased risk of ischemic stroke when comparing the highest-to-lowest Hcy strata. A graded association was observed over the Hcy strata, indicating a dose-response association, with the most apparent effect when Hcy levels exceeded approximately 15 µmol/L. No studies explored a potential nonlinear association between Hcy levels and ischemic stroke. Six studies were included in a meta-analysis, showing an OR of 1.43 (95% confidence interval [CI]: 1.28–1.61) per 5 µmol/L increase in Hcy levels. Conclusion This review and meta-analysis indicate a dose-response association between Hcy levels and ischemic stroke. An evident increase in effect measures was observed when Hcy levels exceeded 15 µmol/L, indicating a nonlinear association between ischemic stroke and Hcy levels. This nonlinear association warrants further study.This study is registered with clinical trial ( https://www.crd.york.ac.uk/prospero/ ; unique identifier: CRD42019130371).