Impact of genetic defects on coronary atherosclerosis in patients suspected of having familial hypercholesterolaemia

Abstract

Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, the presence of a genetically ascertained FH is associated with a higher prevalence of coronary artery calcifications and a positive exercise stress test. These results suggest that despite a similar phenotype, patients carrying mutations suggestive of FH may have a greater cardiovascular risk than patients without these mutations.

Management of familial hypercholesterolemia in children and young adults: Consensus paper developed by a panel of lipidologists, cardiologists, paediatricians, nutritionists, gastroenterologists, general practitioners and a patient organization

“…Thirdly, HeFH may be clearly defined by genetic testing in both the parent and the child. Finally the hypercholesterolemia associated with HeFH is clearly considered as a high risk condition for cardiovascular disease (CVD), even higher than the risk of non-FH-hypercholesterolemia at similar LDL-C levels [16].…”

Exercise testing in asymptomatic patients with heterozygous familial hypercholesterolaemia

“…It has been proposed that heterozygotic individuals with FH should undergo myocardial ischaemia evaluation with thallium-201 scintigraphy early in life [9]. We preferred to use treadmill ET, because it has been reported to have an improved effectiveness in detecting myocardial ischaemia in asymptomatic patients in the presence of additional risk factors for CAD [6,10].…”

“…However, the sensitivity of ET for detecting myocardial ischaemia is expected to be, in accordance with Beyes' theory, increased in patients with a high pretest probability of being FH patients. In addition, patients with FH have been found to present a higher prevalence of electrocardiogram (ECG) abnormalities during ET than non-FH patients [6].…”

LDL-receptor mutations in Europe

“…In Belgium, the spectrum of LDLR mutations accounting for the FH phenotype is relatively heterogeneous: 45 mutations have been published so far [Descamps et al, 1997[Descamps et al, , 2003Van Gaal et al, 2001]. Among them, seven are nonsense mutations, 23 are missense mutations, six are splice defects, eight are frameshift mutations, and one is a large rearrangement.…”

“…When patients with LDLR gene mutations were compared to those without [Van Gaal et al, 2001], the first were found with severe hypercholesterolemia (i.e., increase of total cholesterol, LDL-cholesterol, and apoB, and lower HDL serum concentration), documenting the biochemical effect of mutations in this gene. In a recent study [Descamps et al, 2003] among patients with severe hypercholesterolemia and a family history of early cardiovascular disease, the presence of a genetically ascertained FH is associated with a higher prevalence of coronary artery calcifications and a positive exercise stress test. Thus, the authors suggest that, despite a similar phenotype, patients carrying mutations suggestive of FH may have a greater cardiovascular risk than patients without these mutations.…”