Possible explanations for the common clinical familial hypercholesterolemia phenotypes in the Faroe Islands.

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 FH. Clinical FH cases had a lower intake of saturated fatty acids (SFAs) measured by a high fat-score and a lower content of SFAs in adipose tissue compared with controls. CONCLUSION: The high prevalence of FH in the Faroe Islands may be due to polygenic causes of hypercholesterolemia and to a lesser extent other genetic factors and elevated plasma lipoprotein(a) levels.

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.