Polyunsaturated Fatty Acids and Risk of Ischemic Stroke

Ischemic stroke is a major cause of death and morbidity worldwide. It has been suggested that polyunsaturated fatty acids (PUFAs) may be associated with a lower risk ischemic stroke, but this has been far less studied than their role for coronary heart disease. In this paper, we summarize the main findings from previous follow-up studies investigating associations between intake or biomarkers of the major PUFAs including alpha-linolenic acid (ALA), marine n-3 PUFAs and linoleic acid (LA) and the development of ischemic stroke. Several follow-up studies have suggested that marine n-3 PUFAs may be associated with a lower risk of ischemic stroke although results have not been consistent and limited knowledge exist on the individual marine n-3 PUFAs and ischemic stroke and its subtypes. The role of ALA is less clear, but most studies have not supported that ALA is appreciably associated with ischemic stroke risk. Some studies have supported that LA might be associated with a lower risk of total ischemic stroke, while limited evidence exist on PUFAs and ischemic stroke subtypes. The associations may depend on the macronutrients that PUFAs replace and this substitution aspect together with focus on dietary patterns represent interesting areas for future research

Lipids, lipoproteins and prevalence of familial hypercholesterolemia in the Faroe Islands – Results from a nationwide laboratory database

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is one of the most common hereditary disorders. The population of the Faroe Islands was established by few founders, and genetic drift may have influenced lipid levels. The aim of this study was to describe the lipid distribution by providing age and sex-specific lipid values and to investigate the prevalence of FH in the Faroe Islands. METHODS: We used an electronic nationwide laboratory database that included lipid measurements obtained in the Faroe Islands between January 2006 and September 2020. Percentiles of lipid levels were calculated using quantile regression. The prevalence of FH was estimated according to the Make Early Diagnosis Prevent Early Death (MEDPED) diagnostic criteria and according to the LDL-C cut-off levels included in the Dutch Lipid Clinic Network (DLCN) criteria using generalized linear models with robust variance. RESULTS: According to the MEDPED age-specific cut-offs for LDL-C, a total of 216 subjects met the criteria for definite FH among 30,711 individuals corresponding to a prevalence of 0.70% (1:142). According to the LDL-C cut-offs included in the DLCN criteria, a total of 3,823 (1:8) subjects could be classified as having possible FH, and 10 (1:3,071) subjects could be classified as probable FH corresponding to a prevalence of 12.4% and 0.03%, respectively. Also, we found significant differences in lipid levels according to sex and age groups. CONCLUSION: The Faroe Islands might represent a founder population with a prevalence of possible FH as high as 1 in 8. Further investigation of genetic and clinical characteristics of FH in the Faroe Islands is needed

Intake of marine n-3 polyunsaturated fatty acids and the risk of rheumatoid arthritis:Protocol for a cohort study using data from the Danish Diet, Cancer and Health cohort and Danish health registers

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory joint disease with multifactorial aetiology. Smoking is a well-established lifestyle risk factor, but diet may also have an impact on the risk of RA. Intake of the major marine n-3 polyunsaturated fatty acids in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been hypothesised to lower the risk of RA due to their anti-inflammatory effects, although based on limited knowledge. Therefore, we aim to investigate the associations between dietary intake of EPA and DHA and the risk of incident RA. METHODS AND ANALYSIS: A cohort study. The follow-up design will be based on data from the Danish Diet, Cancer and Health cohort, which was established between 1993 and 1997. The participants will be followed through record linkage using nationwide registers including the Danish Civil Registration System, the Danish National Patient Registry and the Danish National Prescription Registry using the unique Civil Personal Registration number. Time-to-event analyses will be conducted with RA as the outcome of interest. The participants will be followed from inclusion until date of RA diagnosis, death, emigration or end of follow-up. HRs with 95% CIs obtained using Cox proportional hazard regression models, with age as underlying time scale and adjustment for established and potential risk factors, will be used as measures of association. ETHICS AND DISSEMINATION: The study has been approved by the Data Protection Committee of Northern Jutland, Denmark (2019-87) and the North Denmark Region Committee on Health Research Ethics (N-20190031). Study results will be disseminated through peer-reviewed journals and presentations at international conferences

Familial hypercholesterolaemia:a study protocol for identification and investigation of potential causes and markers of subclinical coronary artery disease in the Faroe Islands

INTRODUCTION: Familial hypercholesterolaemia (FH) is the most common monogenic autosomal dominant genetic disorder and is associated with a high risk of premature atherosclerotic cardiovascular disease. The prevalence of FH has been reported to be particularly high in certain founder populations. The population of the Faroe Islands is a founder population, but the prevalence of FH has never been investigated here. We aim to assess the prevalence of FH and to describe the genetic and clinical characteristics and potential causes of FH in the Faroe Islands. Furthermore, we aim to investigate whether indicators of subclinical coronary artery disease are associated with FH. METHODS AND ANALYSIS: The prevalence of FH will be estimated based on an electronic nationwide laboratory database that includes all measurements of plasma lipid levels in the Faroe Islands since 2006. Subsequently, we will identify and invite subjects aged between 18 and 75 years registered with a plasma low-density lipoprotein cholesterol above 6.7 mmol/L for diagnostic evaluation. Eligible FH cases will be matched to controls on age and sex. We aim to include 120 FH cases and 120 controls. Detailed information will be collected using questionnaires and interviews, and a physical examination will be undertaken. An adipose tissue biopsy and blood samples for genetic testing, detailed lipid analyses and samples for storage in a biobank for future research will be collected. Furthermore, FH cases and controls will be invited to have a transthoracic echocardiography and a cardiac CT performed. ETHICS AND DISSEMINATION: The project has been approved by the Ethical Committee and the Data Protection Agency of the Faroe Islands. The project is expected to provide important information, which will be published in international peer-reviewed journals

Subclinical atherosclerosis determined by coronary artery calcium deposition in patients with clinical familial hypercholesterolemia

BACKGROUND AND AIMS: Limited knowledge exists regarding the association between coronary artery calcium (CAC) deposition in patients with clinical familial hypercholesterolemia (FH) and FH subtypes such as polygenic causes. We studied CAC score in patients with clinical FH and subtypes including polygenic causes of FH compared to healthy controls. METHODS: In a case-control study, we identified potential clinical FH cases registered with an LDL-C >6.7 mmol/l within a nationwide clinical laboratory database on the Faroe Islands and invited them for diagnostic evaluation according to clinical FH scoring systems. Controls were identified in the background population. All subjects were aged 18–75 years and without a history of cardiovascular disease. FH mutation testing and genotypes of twelve LDL-C associated single nucleotide polymorphisms were determined using conventional methods in selected individuals. CAC scores were assessed by cardiac CT. Odds ratios obtained using multivariate logistic regression were used as measures of association. RESULTS: A total of 120 clinical FH patients and 117 age- and sex-matched controls were recruited. We found a very low frequency of monogenic FH (3%), but a high level of polygenic FH (60%) in those genetically tested (54%). There was a statistically significant association between the CAC score and a diagnosis of clinical FH with the highest observed odds ratio of 5.59 (95% CI 1.65; 18.94, p = 0.006) in those with a CAC score ≥300 compared to those with a CAC of zero. In supplemental analyses, there was a strong association between CAC scores and clinical FH of a polygenic cause. CONCLUSION: We found a statistically significant association between CAC levels and clinical FH with the highest observed risk estimates among clinical FH cases of a presumed polygenic cause

Novel variation and <i>de novo </i>mutation rates in population-wide <i>de novo</i> assembled Danish trios

Building a population-specific catalogue of single nucleotide variants (SNVs), indels and structural variants (SVs) with frequencies, termed a national pan-genome, is critical for further advancing clinical and public health genetics in large cohorts. Here we report a Danish pan-genome obtained from sequencing 10 trios to high depth (50 × ). We report 536k novel SNVs and 283k novel short indels from mapping approaches and develop a population-wide de novo assembly approach to identify 132k novel indels larger than 10 nucleotides with low false discovery rates. We identify a higher proportion of indels and SVs than previous efforts showing the merits of high coverage and de novo assembly approaches. In addition, we use trio information to identify de novo mutations and use a probabilistic method to provide direct estimates of 1.27e−8 and 1.5e−9 per nucleotide per generation for SNVs and indels, respectively