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.

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.

Adipose Tissue Lipophilic Index and Risk of Ischemic Stroke-A Danish Case-Cohort Study.

Diet may influence the risk of ischemic stroke by several mechanisms. A potential and hitherto unknown mechanism may relate to an effect on the lipophilic index, which is a new and convenient indicator of membrane fluidity. This study investigated the association between the adipose tissue lipophilic index and ischemic stroke and its subtypes. A case-cohort study was conducted based on the Danish cohort study Diet, Cancer, and Health, which includes 57,053 subjects aged 50⁻64 years at enrolment. A subcohort (n = 3500) was randomly drawn from the whole cohort. All ischemic stroke cases were validated and categorized into subtypes. The lipophilic index was calculated based on fatty acid profiles in adipose tissue. Subjects were divided into quintiles and a weighted Cox proportional hazards regression model was used to calculate hazard ratios. After appropriate exclusions, a subcohort of 3194 subjects and 1752 cases of ischemic stroke were included. When comparing the fifth quintile of the lipophilic index with the first quintile, the hazard ratio for ischemic stroke was 0.92 (95% confidence interval 0.75, 1.13) and the trend across quintiles was not statistically significant (p = 0.1727). In conclusion, no association was found between the lipophilic index and ischemic stroke or its subtypes.

Plasma homocysteine, angiographically proven coronary artery disease, and wine consumption.

BACKGROUND: Plasma total homocysteine (p-tHcy) is considered to be an independent risk factor for atherosclerotic vascular disease. This cross-sectional study was undertaken to examine p-tHcy levels and their relationship to coronary artery disease (CAD) and alcohol intake. METHODS: We consecutively studied 291 patients referred for elective coronary angiography due to suspected CAD. The patients completed an alcohol questionnaire, and blood samples were drawn after an overnight fast for measurement of p-tHcy. RESULTS: Patients without CAD (n=85) had significantly lower p-tHcy (10.1+/-4.7 µmol/l) than patients with at least one significant coronary artery stenosis (n=206, p-tHcy: 11.9+/-6.4 µmol/l). Patients with a previous myocardial infarction (MI; n=74) also had a higher p-tHcy (12.3+/-4.0 µmol/l) than patients without MI (n=217; p-tHcy: 10.7+/-6.2 µmol/l). Patients with a daily intake of wine (n=30) had lower p-tHcy (9.4+/-2.8 µmol/l) than patients who did not drink wine (n=47; p-tHcy: 12.1+/-6.0 µmol/l; P<0.05), independent of age, prior MI, and degree of CAD. CONCLUSIONS: p-tHcy correlated positively with CAD. There was an inverse correlation between p-tHcy and wine consumption, suggesting a new potential mechanism by which wine consumption may lower the risk of CAD.