Dutch Lipid Clinic Criteria Research Articles

Abstract 19656: What is the Prevalence of Familial Hypercholesterolemia in the US?

Background: The prevalence of Familial Hypercholesterolemia (FH) ranges from 1 in 500, as commonly cited, to 1 in 200 in a population-based Danish study. The prevalence of FH in the US, particularly in those of non-European background, remains unknown. Methods: To estimate the US prevalence of FH in National Health and Nutrition Examination Survey (NHANES) 2001-2012 datasets (n = 59,423), we used the Dutch Lipid Clinic (DLC) criteria (Benn et al 2012), which classifies individuals as definite or probable FH based on personal history of premature coronary artery disease (CAD), family history in a first-degree relative of known premature CAD or vascular disease, LDL level, and genetic criteria. Genetic testing is not available in NHANES and therefore was not included. For persons reporting statin use, we multiplied by 1.43 to estimate untreated LDL levels. Results: The overall US prevalence of probable/definite FH in NHANES was 0.33% (95% CI 0.19-0.48) or 1 in 299 (1 in 210-519). The prevalence of FH was similar in males and females (0.34%; 1 in 293 vs. 0.33%; 1 in 305) and in blacks and whites (0.35%; 1 in 283 vs. 0.37%; 1 in 270), but lower in Mexican Americans (0.16%; 1 in 620) and other races (0.08%, 1 in 1235) and higher in other Hispanics (0.40%; 1 in 252). FH prevalence was lowest in 30-39 year olds (0.15%, Figure ), and highest in 50-59 year olds (0.60%), and higher with obesity (0.49%; 1 in 204) than non-obesity (0.26%; 1 in 387), likely reflecting the impact of increasing age and weight on LDL when using DLC criteria. Summary: Our analysis of NHANES data suggests a US prevalence of FH of 1 in 299, which is higher than the commonly cited estimate of 1 in 500 and is likely an underestimate due to the absence of genetic testing in NHANES. Higher prevalence with obesity and in middle-age highlights the influence of increasing age- and weight-related effects on LDL in FH prevalence estimates. Consideration should be given to incorporating genetic testing into future studies of US FH prevalence.

744 ASSOCIATION OF MACROPHAGE COLONY-STIMULATING FACTOR RECEPTOR POLYMORPHISM WITH STROKE IN CAUCASIAN POPULATION OF SIBERIA

diagnosed as FH patients, according to the Dutch Lipid Clinic Criteria for FH. Their lipid profile was assessed before any treatment was provided, we recorded their clinical signs (tendon xanthomas, xanthelasmas, corneal arcus) and we performed molecular analysis, by direct automated sequencing. We also recorded all major events and deaths from premature CVD of the parents, 1 and 2 degree relatives. Results: In 9 families (18 patients, 9 parents and 9 descendants) we found Africaner 2 (1285 G>A) while in 19 families (42 patients, 19 parents and 23 descendants) Genoa-Palermo (1646 G>A). FISHER’s exact test, showed that the rate of corneal arcus was greater among patients with Genoa-Palermo, compared to those with Africaner 2 (78% vs 23.5%, p < 0.001). We also found that all patients with Genoa-Palermo (100%), had 1 and 2 degree relatives who had developed premature CVD, while the respective rate for patients with Africaner 2 was 78%. FISHER’s exact test showed that this was statistically significant (p = 0.006). Conclusions: According to our findings, Genoa-Palermo seems to have a greater impact on the incidence of premature CVD, compared to Africaner 2.

Diagnosis and screening for familial hypercholesterolaemia: finding the patients, finding the genes

Familial hypercholesterolaemia (FH) is a genetic disorder in which the concentration of serum cholesterol is elevated from birth and leads to premature coronary heart disease. FH is commonly caused by a mutation in the LDL receptor, but mutations in other genes can lead to a phenotype similar to FH. FH exhibits marked phenotypic variability due to genetic, metabolic and environmental factors. The presence of tendon xanthomata is the characteristic clinical sign seen in many patients with FH, but they may also have other non-specific signs of lipid disorders such as corneal arcus and xanthelasmata. Premature vascular disease is apparent in many patients. The wide variety of mutations and phenotypic variability have made it difficult to establish definite diagnostic criteria, but three sets of clinical criteria commonly used are the Simon Broome criteria, the Dutch Lipid Clinic criteria and the American criteria. FH screening fits the Wilson and Jungner recommendations for validity of a screening programme. Screening could be carried out on a population basis, in a clinical setting or by application to relatives of probands. This latter approach, termed cascade testing, appears to be the more cost-effective compared with population screening and can be carried out using clinical criteria or genetic testing, or by a combination of both methods. Clinicians need to be made more aware of the clinical features of FH and how to diagnose it in order to increase the index of suspicion and instigate appropriate treatment early, with the aim of preventing premature coronary heart disease.