Background and aims Dietary guidelines recommend replacing saturated fatty acids with poly- or monounsaturated fatty acids (MUFA) to lower the risk of cardiovascular disease. The biological effects of MUFAs may differ between individual MUFAs, while their role in development of peripheral artery disease (PAD) remains unknown. We investigated associations between the content of MUFAs in adipose tissue and the risk of incident PAD. Methods We conducted a case-cohort study within the Danish Diet, Cancer and Health cohort (n = 57,053). Gluteal adipose tissue biopsies were obtained from all participants, in a random sample of 5000 participants, and in all PAD cases, and analysed for MUFA content by gas chromatography. Hazard ratios (HR) for PAD were estimated using weighted Cox proportional hazard regression. Results During a median follow-up of 20.6 years, 1,850 PAD cases were identified among 54,057 eligible participants. Comparing the highest quintile with the lowest, adipose tissue content of total MUFAs (HR: 1.40; 95% CI: 1.13-1.75), and the individual MUFAs 16:1ω7 (HR: 1.69; 95% CI: 1.36-2.10), and 18:1ω7 (HR: 2.48; 95% CI: 1.95-3.16) were associated with a higher risk of PAD, while no clear association was found for 20;1w9, 14:1ω5, 20:1ω11 and 18:1ω9. Conclusion Adipose tissue content of total MUFAs and of 18:1ω7 and 16:1ω7 were associated with a higher risk of PAD, while findings were less clear for other MUFAs. Our findings show that not all MUFAs are equal and that future studies also should focus on individual MUFAs and their origin.

Introduction:The Danish Familial Hypercholesterolemia (FH) Registry (DFH) was established in 2020 to monitor the detection rate of FH and quality of care provided among patients with FH. DFH is nationwide, and together with the Danish National Patient Registry (DNPR) includes more than 10,000 registered cases of FH. However, the validity of FH diagnoses in the DNPR and DFH is unknown. Purpose:We aimed to investigate the positive predictive value of FH cases registered in the DNPR and DFH. Methods:We retrospectively retrieved a nationwide random sample of 800 patients with an FH diagnosis registered in the DNPR between 1st of January 2020 and 1st of May 2023. Subsequently, we retrieved information on cases also registered in the DFH, and validated all registered cases based on medical records. Individuals with a Dutch Lipid Clinical Network-score ≥ 6 were considered valid FH cases. Positive predictive values with 95% confidence intervals were used to assess the validity of the registered diagnoses. Results:We found a positive predictive value of 63.8% (95% CI: 60.7; 67.0) for an FH diagnosis recorded in the DNPR (510/800), and 88.1% (95% CI: 82.2; 92.3%) for those diagnosed with genetic FH (141/160). A primary diagnosis of FH registered by cardiological departments had a positive predictive value of 71.0% (95% CI: 67.2; 74.6%) (417/587), and 88.3% (95% CI: 82.6; 92.8%) for genetic FH (113/128), respectively. The positive predictive value of FH cases registered in the DFH was 83.0% (95% CI: 78.9; 86.5) (318/383). Conclusion:The validity of FH cases in the DFH was high, while the validity of an FH diagnosis in the DNPR was relatively low. However, restricting the analysis to a primary diagnosis obtained from cardiological departments may be used to improve the validity of FH diagnoses in the DNPR.

Background and aims Dietary and lifestyle counseling represent the cornerstone of treatment of hypertriglyceridemia, but limited knowledge exists on the dietary habits among patients with severe and extremely elevated plasma triglycerides. In this study we describe dietary habits in patients with moderate, severe or extreme hypertriglyceridemia referred to a lipid clinic. Furthermore, we present changes in plasma triglycerides levels achieved one year after dietary and lifestyle counseling and lipid-lowering medications in patients with hypertriglyceridemia. Methods This study utilized a retrospective cross-sectional and follow-up design, where data were collected from patients referred to the lipid clinic in the Northern Denmark region between September 1st 2016 and August 31st 2020. Information on diet was collected from a validated dietary questionnaire, while information on clinical characteristics was retrieved from medical records. We used logistic regression to investigate associations between dietary scores and severe to extreme hypertriglyceridemia, while a paired t-test was used to examine changes in plasma triglycerides one year after the initial assessment. Results We identified a total of 634 patients with plasma triglycerides above 1.7 mmol/L including 83.9% with moderate hyperglyceridemia, 12.1% with severe hypertriglyceridemia, and 3.9% with extreme hypertriglyceridemia. Higher dietary scores reflecting adherence to a healthy diet were associated with a modest lower occurrence of severe to extreme hypertriglyceridemia, but the associations were not statistically significant. However, we found that patients with extreme hypertriglyceridemia had average statistically significantly lower plasma triglycerides of 6 mmol/L one year after the initial assessment, while no major differences were found among subjects with modest and severe hypertriglyceridemia. Conclusion We found that higher dietary scores reflecting adherence to a healthy diet was associated with a statistically non-significant lower risk of severe-to-extreme HTG. Furthermore, in patients with extreme HTG we observed significant reduction in triglycerides one year after dietary counseling.

BACKGROUND:n-6 (ω-6) Polyunsaturated fatty acids may exert divergent biological effects, but limited knowledge exists about their associations with mortality. OBJECTIVES:To investigate the associations between adipose tissue content of individual n-6 polyunsaturated fatty acids - a long-term marker of endogenous exposure to these fatty acids - and all-cause mortality. METHODS:We used a prospective cohort study design. We followed a random sample of 4663 participants from the Danish diet, cancer, and health cohort, which was established between 1993 and 1997. Information on all-cause mortality was retrieved from the nationwide Danish civil registration system. An adipose tissue biopsy was collected from the buttock at recruitment and analyzed for fatty acid composition using gas chromatography. Hazard ratios were obtained using Cox proportional hazard regression. RESULTS:During a median of 21 y of follow-up, 1160 participants died. The median adipose tissue contents of linoleic acid and arachidonic acid were 10.60% and 0.36%, respectively. In multivariable continuous analyses, we observed a statistically significant inverse association between adipose tissue content of linoleic acid and all-cause mortality (P < 0.001). In contrast, a statistically nonsignificant positive association was found in continuous analyses of adipose tissue content of arachidonic acid and all-cause mortality (P = 0.078). Comparing the highest with the lowest quartile, the hazard ratio for mortality was 0.76 (95% confidence interval [CI]: 0.64, 0.90) for linoleic acid and 1.28 (95% CI: 1.07, 1.53) for arachidonic acid in adipose tissue, respectively. CONCLUSIONS:Adipose tissue content of linoleic acid was inversely associated with all-cause mortality, whereas adipose tissue content of arachidonic acid was associated with a higher all-cause mortality.

Unhealthy dietary patterns are a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD). International guidelines recommend reducing saturated fatty acid intake while increasing polyunsaturated and monounsaturated fatty acids (MUFAs) to mitigate cardiovascular risk. However, evidence regarding MUFAs and risk of ASCVD remains conflicting, with recent studies raising concern about a potential higher risk associated with MUFA intake. The aim of this narrative review is to provide an overview of current knowledge and gaps in the literature regarding MUFAs and the risk of ASCVD with a focus on intake, individual types, and content in adipose tissue as a biomarker of endogenous exposure. Main findings reveal that most studies have inappropriately combined all MUFAs together, despite individual MUFA types having different biological effects and showing varying correlations between dietary intake and adipose tissue content. Adipose tissue composition may serve as a biomarker of long-term MUFA exposure, reflecting cumulative intake over one to two years while minimizing biases inherent in dietary assessments. However, tissue levels reflect both dietary intake and endogenous synthesis, complicating interpretation. Importantly, the source of MUFAs appears critical, with plant-derived MUFAs potentially offering advantages over animal-derived sources. In conclusion, we suggest that future research should focus on individual MUFA types rather than treating them as a homogeneous group, investigate their specific dietary sources and associations with ASCVD risk, and use adipose tissue biomarkers to improve exposure assessment and clarify causal relationships while considering overall dietary patterns.

OBJECTIVE:This study investigated the association between the plasma marine n-3 polyunsaturated fatty acids (n-3 PUFAs) eicosapentaenoic acid and docosahexaenoic acid and cardiovascular (CV) events and all-cause mortality in patients treated with hemodialysis. METHODS:Prospective multicenter cohort study with 5 years of follow-up. Primary outcome was CV events and secondary outcomes were all-cause mortality and each component of CV events. The sum of plasma eicosapentaenoic acid and docosahexaenoic acid was expressed as marine n-3 PUFAs in weight percentage (wt%). The population was divided into tertiles according to plasma n-3 PUFA levels: lower tertile <5.06 wt%, middle tertile 5.06-6.52 wt%, and upper tertile >6.52 wt%. RESULTS:In total, 336 patients were included. Median follow-up was 5.05 (5.02-5.07) years. Generally, the lower tertile was associated with a higher risk of CV events. Unadjusted, the middle tertile was associated with a 36% lower risk of CV events [hazard ratio (HR) 0.64 (95% confidence interval (CI) 0.43-0.96)], and the upper tertile was associated with a 34% lower risk of CV events [HR 0.66 (95% CI 0.44-0.98)]. After adjusting for confounders, the middle tertile was associated with a lower risk of CV events [HR 0.60 (95% CI 0.40-0.92)], peripheral arterial disease [HR 0.44 (95% CI 0.22-0.88)], and all-cause mortality [HR 0.61 (95% CI 0.42-0.86)]. A restricted cubic spline showed that the CV risk was higher in patients with levels below the median of 5.7 wt%, indicating a potential threshold effect. CONCLUSION:Low plasma marine n-3 PUFA levels were associated with a higher risk of CV events, peripheral arterial disease, and all-cause mortality in patients treated with hemodialysis.

BACKGROUND & AIMS:Diet and lifestyle are cornerstones in the prevention of atherosclerotic cardiovascular disease, especially in individuals with familial hypercholesterolaemia (FH). The aim of this cross-sectional study was to investigate dietary habits among adults admitted to lipid clinics on suspicion of FH. METHODS:From September 2020 through November 2021, all patients referred on suspicion of FH to all lipid clinics were invited to participate and 97.4 % (n = 1488) accepted. Information on dietary habits was collected using a validated food frequency questionnaire based on a score ranging from 0 to 100. RESULTS:A total of 1095 subjects were included of whom 5.7 % adhered to a heart-healthy diet. Overall, participants' diets were suboptimal and in particular the intake of fish, fruit, and vegetables was low with a median score of 52 points compared to the recommended heart-healthy 75 points. Women and individuals with a personal history of atherosclerotic cardiovascular disease showed marginally better adherence to a heart-healthy diet. Notably, intake of fish, fruit, vegetables, and whole-grains were insufficient in all groups. CONCLUSION:Most participants referred to lipid clinics on suspicion of FH did not adhere to a heart-healthy diet regardless of history of atherosclerotic cardiovascular disease. These findings reinforce the importance of providing and supporting dietary counselling among individuals with hypercholesterolaemia.

INTRODUCTION:A diet rich in marine n-3 polyunsaturated fatty acids (PUFAs) may lower the risk of coronary heart disease and ischemic stroke. However, the association between intake of marine n-3 PUFAs and risk of hemorrhagic stroke has only been sparsely explored. We aimed to investigate the associations between intake of the major marine n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and their sum, in relation to incident hemorrhagic stroke and its subtypes, intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). METHODS:We analyzed data from the Danish Diet, Cancer and Health Cohort, which was established between 1993 and 1997. Information on dietary intake of marine n-3 PUFAs was obtained through a validated food frequency questionnaire. Potential hemorrhagic stroke cases were identified by linkage to the Danish National Patient Register and subsequently validated. Hazard ratios obtained by Cox proportional hazard regression analyses were used as measures of association. RESULTS:A total of 394 subjects among 55,519 individuals developed hemorrhagic stroke during a median follow-up period of 13.5 years. In multivariable analyses including adjustment for established risk factors, we observed weak and statistically nonsignificant inverse associations between intake of EPA, DHA, and EPA + DHA and the rate of incident hemorrhagic stroke. In analyses of hemorrhagic stroke subtypes, we found indications of lower rates of ICH among participants in the highest quartile of EPA, DHA, and EPA + DHA compared with those in the lowest quartile and indications of lower rates of SAH in the highest quartile of EPA intake compared to the lowest quartile, but the findings were statistically nonsignificant. CONCLUSIONS:Inversely statistically nonsignificant associations were found between EPA, DHA, and EPA + DHA and hemorrhagic stroke.

Context Cholesterol carried in lipoprotein(a) adds to measured low-density lipoprotein cholesterol (LDL-C) and may therefore drive some diagnoses of clinical familial hypercholesterolemia (FH). Objective We investigated plasma lipoprotein(a) in individuals referred to Danish lipid clinics and evaluated the effect of plasma lipoprotein(a) on a diagnosis of FH. Methods Individuals referred to 15 Danish lipid clinics who were suspected of having FH according to nationwide referral criteria were recruited between September 1, 2020 and November 30, 2021. All individuals were classified according to the Dutch Lipid Clinical Network criteria for FH before and after LDL-C was adjusted for 30% cholesterol content in lipoprotein(a). We calculated the fraction of individuals fulfilling a clinical diagnosis of FH partly due to elevated lipoprotein(a). Results We included a total of 1166 individuals for analysis, of whom 206 fulfilled a clinical diagnosis of FH. Median lipoprotein(a) was 15 mg/dL (29 nmol/L) in those referred and 28% had lipoprotein(a) greater than or equal to 50 mg/dL (105 nmol/L), while 2% had levels greater than or equal to 180 mg/dL (389 nmol/L). We found that in 27% (55/206) of those fulfilling a clinical diagnosis of FH, this was partly due to high lipoprotein(a). Conclusion Elevated lipoprotein(a) was common in individuals referred to Danish lipid clinics and in one-quarter of individuals who fulfilled a clinical diagnosis of FH, this was partly due to elevated lipoprotein(a). These findings support the notion that the LPA gene should be considered an important causative gene in patients with clinical FH and further support the importance of measuring lipoprotein(a) when diagnosing FH as well as for stratification of cardiovascular risk.

BACKGROUND:Omega-3 fatty acids derived from seafood acids may influence cardiac arrhythmogenesis, whereas the role of the major plant-derived omega-3 fatty acid, alpha-linolenic acid (ALA), on atrial fibrillation (AF) is largely unknown. OBJECTIVES:We aimed to investigate the association between ALA intake and risk of incident AF overall and in subjects with a low intake of marine omega-3 fatty acids. METHODS:We followed a total of 54,260 middle-aged men and women enrolled into the Danish Diet, Cancer, and Health cohort for development of AF using nationwide registries. Intake of ALA was assessed using a validated food frequency questionnaire and modeled as a restricted cubic spline. Statistical analyses were conducted using Cox proportional hazards regression. RESULTS:We identified a total of 4902 incident AF events during a median of 16.9 y of follow-up. In multivariable analyses, we observed indications of a statistically nonsignificant inverse association between ALA intake and risk of AF up to an ALA intake of 2.5 g/d, whereas no appreciable association was found for higher intakes of ALA. A statistically significant dose-dependent negative association was found between ALA intake and risk of AF in individuals consuming < 250 mg marine omega-3 fatty acids daily, whereas no association was found in those with a higher intake of marine omega-3 fatty acids. CONCLUSIONS:Intake of ALA was associated with a lower risk of AF in individuals consuming a low intake of marine omega-3 fatty acids. This finding is novel and warrants further investigation.

Objectives To investigate the 5-year all-cause mortality in patients with RA compared with the general population. Methods This was a nationwide population-based matched cohort study. RA patients diagnosed between 1996 and the end of 2015 were identified using administrative heath registries and followed until the end of 2020 allowing 5 years of follow-up. Patients with incident RA were matched 1:5 on year of birth and sex with non-RA individuals from the Danish general population. Time-to-event analyses were performed using the pseudo-observation approach. Results Compared with matched controls in 1996-2000, the risk difference for RA patients ranged from 3.5% (95% CI 2.7%, 4.4%) in 1996-2000 to -1.6% (95% CI -2.3%, -1.0%) in 2011-15, and the relative risk from 1.3 (95% CI 1.2, 1.4) in 1996-2000 to 0.9 (95% CI 0.8, 0.9) in 2011-15. The age-adjusted 5-year cumulative incidence proportion of death for a 60-year-old RA patient decreased from 8.1% (95% CI 7.3%, 8.9%) when diagnosed in 1996-2000 to 2.9% (95% CI 2.3%, 3.5%) in 2011-15, and for matched controls from 4.6% (95% CI 4.2%, 4.9%) to 2.1% (95% CI 1.9%, 2.4%). Excess mortality persisted in women with RA throughout the study period, while the mortality risk for men with RA in 2011-15 was similar to their matched controls. Conclusions Enhanced improvement in mortality was found in RA patients compared with matched controls, but for sex-specific differences excess mortality was only persistent in women with RA.

Abstract Background and Aims Cardiovascular (CV) disease is the leading cause of death in patients with end-stage renal disease (ESRD) receiving hemodialysis (HD). The two major marine n-3 polyunsaturated fatty acids (n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may have cardioprotective effects. This study aimed to investigate the predictive value of plasma n-3 PUFAs on CV events and all-cause mortality in patients with ESRD receiving HD. Method A validated prospective multicenter cohort study of 336 patients with ESRD receiving HD with 5 years of follow-up was conducted. Blood samples were collected at baseline and analyzed for the plasma levels of EPA and DHA expressed as a weight percentage (wt%) of total plasma fatty acids. The primary outcome was CV events defined as acute myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, peripheral artery disease (PAD), or cardiovascular mortality. The secondary outcomes were all-cause mortality and each individual component of CV events. The sum of EPA and DHA (EPA+DHA) was used in all analyses and expressed as n-3 PUFAs in wt%. The population was divided into three groups according to n-3 PUFA tertiles. Kaplan-Meier curves and multivariable Cox regressions adjusted for relevant confounders were used to analyze the association between plasma n-3 PUFA levels and study outcomes. Results Median follow-up time was 5.05 years (IQR, 5.02-5.07). Mean age was 65 ± 15 years and plasma n-3 PUFA levels ranged from 2.1 to 16.8 wt%, with a median of 5.7 wt% (IQR, 4.72-6.96 wt%). During follow-up 60% of the cohort died, 17% died of CV disease, and 42% had a CV event. Figure 1 shows the unadjusted associations between the plasma n-3 PUFA tertiles and the risk of CV events. A n-3 PUFA level between 5.06-6.52 wt% was associated with a 36% lower risk of CV events [unadjusted HR 0.64 (95% CI 0.43-0.96)]. Additionally, a n-3 PUFA level above 6.52 wt% was associated with a 34% lower risk of CV events [unadjusted HR 0.66 (95% CI 0.44-0.98)], both in comparison to levels below 5.06 wt%. After adjusting for relevant confounders, as shown in Figure 2, n-3 PUFA levels between 5.06 to 6.52 wt% were associated with a significantly lower risk of CV events [adjusted HR 0.60 (95% CI 0.40-0.92)], PAD [adjusted HR 0.44 (95% CI 0.22-0.88)], and all-cause mortality [adjusted HR 0.61 (95% CI 0.42-0.86)], when compared to levels below 5.06 wt%. Conclusion In this study of patients with ESRD receiving HD, a low plasma level of n-3 PUFA was associated with a higher risk of CV events, peripheral artery disease, and all-cause mortality.

ObjectiveTo investigate and compare trends in incidence rates (IRs) of seropositive and seronegative rheumatoid arthritis (RA) in Denmark using various data sources for serostatus definition.MethodThis nationwide population-based cohort study was based on data from Danish healthcare and clinical quality registries between 2000 and 2018. Information on anti-cyclic citrullinated peptide and immunoglobulin M rheumatoid factor was obtained, and definitions of seropositivity according to the number of applied data sources were prespecified. Annual age- and sex-standardized IRs were calculated as the number of incident seropositive and seronegative cases, divided by the number of person-years (PY) in the general population in that given year.ResultsAn increasing temporal trend in IR of seropositive RA and a decreasing trend in seronegative RA were observed. The IRs were higher for seropositive RA than for seronegative RA from 2009 onwards, with a widening of the IR gap between 2009 and 2016 regardless of the definition of seropositivity. When combining laboratory- and physician-reported autoantibody information and ICD-10 codes, the IR of seropositive RA in 2018 was approximately twice that of seronegative RA, at 19.0 and 9.0 per 100 000 PY, respectively. The level of antibody testing increased significantly during the study period.ConclusionsThe IR of seropositive RA increased over time, whereas the IR of seronegative RA decreased. Temporal IR changes may be caused by a real change in the RA serology subtypes, an increase in autoantibody testing and availability, changes in registration practice over time, or a combination of these factors.

Background Tissue levels of n-3 polyunsaturated fatty acids (PUFAs) have been inversely related with risk of myocardial infarction (MI). Whether ratios of n-3 to n-6 PUFAs, reflecting both dietary intake of n-3 PUFAs and competing n-6 PUFAs, are better predictors of future MI than n-3 PUFA fractions is unclear. We aimed at investigating whether such ratios in adipose tissue better predict MI than n-3 PUFA fractions.Methods Subcutaneous adipose tissue biopsies were obtained in a random sample (n = 3,500) of the Diet, Cancer and Health cohort (n = 57,053). Adipose tissue content of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), arachidonic acid (AA) and linoleic acid was determined using gas chromatography. Fractions of selected n-3 PUFAs and n-3/n-6 PUFA ratios were correlated to the 15-year occurrence of MI in a case-cohort design.Results A total of 2,406 participants experienced an MI during follow-up. Adipose tissue total marine n-3 PUFAs, EPA +DHA, EPA, EPA/AA, DHA/AA and (EPA + DPA + DHA)/AA were all inversely associated with risk of incident MI. Evaluating the predictive power (Harrel's C-index) of the selected metrics, fractions of marine n-3 PUFAs and ratios of EPA/AA, DHA/AA, (EPA + DHA)/AA and (EPA + DPA + DHA)/AA all refined risk prediction over age and sex alone. At multivariable analyses, however, the above ratios were the only metrics providing additional risk prediction. Differences in ratios were related to differences in food intake.Conclusions Both adipose tissue n-3 PUFAs fractions and ratios of n-3 PUFAs/AA were associated with a lower occurrence of MI, but ratios provided superior risk prediction. Dietary strategies affecting n-3/n-6 PUFA ratios should be further investigated for prediction of MI with dietary interventions at the population level and in intervention studies. (Am Heart J 2023;262:38-48.)

BACKGROUND & AIMS:Recent randomized clinical trials have raised concerns regarding potential off target adverse effects from supplementation of n-3 polyunsaturated fatty acids (PUFA) on atrial fibrillation (AF) risk. We aimed to assess risk and potential mediators of AF and 'micro-AF' from n-3 PUFA in post-myocardial infarction (MI) patients. METHODS:In the OMEMI trial, 70-82 y. o. patients with a recent MI were randomized to 1.8 g/day of eicosapentaenoic-/docosahexaenoic acid (EPA/DHA) or placebo (corn oil) for two years. New-onset AF and 'micro-AF' was recorded by clinical detection and by screening with Zenicor thumb-ECG (adjudicated by blinded investigators). Serum EPA and DHA were measured at baseline and study end. RESULTS:At baseline, 759 of 1014 (75%) patients had no AF history. These patients were aged 75 ± 4 years and 71% were male. During follow-up, 43 patients developed new-onset AF (39 clinically-detected and 4 by thumb-ECG screening). In addition, 27 patients had episodes of micro-AF, yielding a total of 70 patients with new-onset AF or 'micro-AF'. In the n-3 PUFA group 46 (11.9%) had AF/'micro-AF' (28 AF, 18 'micro-AF') and in the placebo group 24 (6.5%) had AF/micro-AF (15 AF, 9 micro-AF); HR 1.90 (95%CI 1.16-3.11), P = 0.011. Changes in serum EPA (but not DHA) mediated the effect from n-3 PUFA on AF risk, explaining 65% of the association. CONCLUSION:Supplementation of n-3 PUFA post MI increases the risk of 'micro-AF' and AF, and increases in EPA seems to be an important mediator of the treatment effect from n-3 PUFA on the risk of AF. STUDY REGISTRATION:OMEMI Study; ClinicalTrails.gov identifier: NCT0184194.

Background and aims: It is unclear to what extent genetic testing improves the ability to diagnose familial hypercholesterolaemia (FH). We investigated the percentage with FH among individuals referred to Danish lipid clinics, and evaluated the impact of genetic testing for a diagnosis of FH.Methods: From September 2020 through November 2021, all patients referred for possible FH to one of the 15 Danish lipid clinics were invited for study participation and >97% (n = 1488) accepted. The Dutch Lipid Clinical Network criteria were used to diagnose clinical FH. The decision of genetic testing for FH was based on local practice.Results: A total of 1243 individuals were referred, of whom 25.9% were diagnosed with genetic and/or clinical FH. In individuals genetically tested (n = 705), 21.7% had probable or definite clinical FH before testing, a percentage that increased to 36.9% after genetic testing. In individuals with unlikely and possible FH before genetic testing, 24.4% and 19.0%, respectively, had a causative pathogenic variant.Conclusions: In a Danish nationwide study, genetic testing increased a diagnosis of FH from 22% to 37% in patients referred with hypercholesterolaemia suspected of having FH. Importantly, approximately 20% with unlikely or possible FH, who without genetic testing would not have been considered having FH (and family screening would not have been undertaken), had a pathogenic FH variant. We therefore recommend a more widespread use of genetic testing for evaluation of a possible FH diagnosis and potential cascade screening.

Background: The prevalence of clinical familial hypercholesterolemia (FH) is very high in the Faroe Islands, but the possible causes are unknown. Objectives: We aimed to describe potential genetic causes of FH in the Faroe Islands and to investigate whether levels of lipoprotein(a) and measures of dietary habits were associated with clinical FH in the Faroe Islands. Methods: In this case-control study, we identified potential clinical FH cases aged 18-75 years registered within a nationwide clinical laboratory database in the Faroe Islands and invited them for diagnostic evaluation according to clinical FH scoring systems. Controls were identified in the background population. Lipoprotein(a) was measured in plasma, while the fatty acid composition was determined in adipose tissue. The habitual diet of the participants was assessed using a food frequency questionnaire. Genetic testing for FH and polygenic variants was performed in a selection of clinical FH cases. Results: A total of 121 clinical FH cases and 123 age-and sex-matched controls were recruited. We found a very low frequency of monogenic FH (2.5%), but a high level of polygenic FH (63%) in those genetically tested (67%). High levels of plasma lipoprotein(a) were associated with high odds of clinical

Purpose The objective of this study was to investigate the association between intake of seafood and plant-derived n-3 polyunsaturated fatty acids (PUFA) and development of total atherosclerotic cardiovascular disease (ASCVD) and acute major ischemic events. Methods A total of 53,909 men and women were enrolled between 1993 and 1997 into the Danish Diet, Cancer and Health cohort and followed through nationwide Danish registries for development of total ASCVD defined as a first registration of myocardial infarction, peripheral artery disease, or ischemic stroke due to large artery atherosclerosis or small-vessel occlusion. At recruitment, the intake of the major marine n-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the plant-derived n-3 PUFA, alpha-linolenic acid (ALA), was assessed using a validated food frequency questionnaire. Statistical analyses were conducted using sex-stratified multivariable Cox proportional hazard regression models. Results During a median of 13.5 years of follow-up, 3958 participants developed ASCVD including 3270 patients with an acute major ischemic event. In multivariable analyses including adjustment for established risk factors, we found no associations for intake of ALA, but indications of inverse associations between intake of EPA, DHA and EPA + DHA and the rate of total ASCVD and acute major ischemic events. Conclusions A high intake of marine n-3 PUFA was associated with a lower risk of total ASCVD and acute major ischemic events, whereas no association could be demonstrated for the plant-derived ALA.