Greater preclinical atherosclerosis in treated monogenic familial hypercholesterolemia vs. polygenic hypercholesterolemia.
Atherosclerosis
; 263: 405-411, 2017 08.
Article
in En
| MEDLINE
| ID: mdl-28549500
ABSTRACT
BACKGROUND AND AIMS:
Familial hypercholesterolemia (FH) is a common inherited disorder of low density lipoprotein-cholesterol (LDL-C) metabolism. It is associated with higher risk of premature coronary heart disease. Around 60% of patients with a clinical diagnosis of FH do not have a detectable mutation in the genes causing FH and are most likely to have a polygenic cause for their raised LDL-C. We assessed the degree of preclinical atherosclerosis in treated patients with monogenic FH versus polygenic hypercholesterolemia.METHODS:
FH mutation testing and genotypes of six LDL-C-associated single nucleotide polymorphisms (SNPs) were determined using routine methods. Those with a detected mutation (monogenic) and mutation-negative patients with LDL-C SNP score in the top two quartiles (polygenic) were recruited. Carotid intima media thickness (IMT) was measured by B-mode ultrasound and the coronary artery calcium (CAC) score was performed in three lipid clinics in the UK and the Netherlands.RESULTS:
86 patients (56 monogenic FH, 30 polygenic) with carotid IMT measurement, and 166 patients (124 monogenic, 42 polygenic) with CAC score measurement were examined. After adjustment for age and gender, the mean of all the carotid IMT measurements and CAC scores were significantly greater in the monogenic than the polygenic patients [carotid IMT mean (95% CI) 0.74 mm (0.7-0.79) vs. 0.66 mm (0.61-0.72), p = 0.038 and CAC score mean (95%) 24.5 (14.4-41.8) vs. 2.65 (0.94-7.44), p = 0.0004].CONCLUSIONS:
In patients with a diagnosis of FH, those with a monogenic cause have a higher severity of carotid and coronary preclinical atherosclerosis than those with a polygenic aetiology.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Coronary Artery Disease
/
Carotid Artery Diseases
/
Multifactorial Inheritance
/
Polymorphism, Single Nucleotide
/
Hyperlipoproteinemia Type II
/
Mutation
Type of study:
Clinical_trials
/
Etiology_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
En
Journal:
Atherosclerosis
Year:
2017
Document type:
Article
Affiliation country:
Reino Unido