Berit Storgaard Hedegaard

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. We aimed to investigate the positive predictive value of FH cases registered in the DNPR and DFH. We retrospectively retrieved a nationwide random sample of 800 patients with an FH diagnosis registered in the DNPR between 1^st of January 2020 and 1^st 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. 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). 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.

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.

Background 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). We investigated plasma lipoprotein(a) in subjects referred to Danish lipid clinics and evaluated the impact of plasma lipoprotein(a) for a diagnosis of FH. Methods Individuals referred to 15 Danish lipid clinics suspected of FH according to nationwide referral criteria were recruited between September 1st 2020 and November 30th 2021. All individuals were classified according to the Dutch Lipid 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 1,166 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) ≥50 mg/dL (105 nmol/L), while 2% had levels ≥180 mg/dL (389 nmol/L). We found that 27% (55/206) of those fulfilling a clinical diagnosis of FH was partly due to high lipoprotein(a). Conclusions Elevated lipoprotein(a) was common in individuals referred to Danish lipid clinics and one quarter of individuals who fulfilled a clinical diagnosis of FH were 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.