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. 2018 Mar;41(3):385-391.
doi: 10.1002/clc.22881. Epub 2018 Mar 25.

Genetic diagnosis of familial hypercholesterolemia is associated with a premature and high coronary heart disease risk

Florent Séguro  1   2 , Jean-Pierre Rabès  3   4 , Dorota Taraszkiewicz  2 , Jean-Bernard Ruidavets  1 , Vanina Bongard  1 , Jean Ferrières  1   2
Affiliations

Genetic diagnosis of familial hypercholesterolemia is associated with a premature and high coronary heart disease risk

Florent Séguro et al. Clin Cardiol. 2018 Mar.

Abstract

Background: Familial hypercholesterolemia (FH) is a common autosomal dominant disease associated with premature coronary heart disease (CHD). Studies tend to show that patients with FH associated with an identified mutation (mutation+ FH) are at higher risk than patients without an identified mutation (mutation- FH). We compared the clinical and biological profile and the risk of CHD in patients with mutation+ FH and mutation- FH.

Hypothesis: In addition to LDL-C, a pathogenic mutation predicts premature CHD in FH.

Methods: We successively included all patients with suspected FH (LDL-C > 190 mg/dL if age > 18 years; LDL-C > 160 mg/dL if age < 18 years) and compared patients with a pathogenic mutation with those without an identified pathogenic mutation.

Results: We studied 179 patients with mutation+ FH and 147 with mutation- FH. The mean age was 44 (± 18) years. The lipid profile was more atherogenic in those with mutation+ FH, who had higher LDL-C (254 ± 69 mg/dL vs 218 ± 35 mg/dL; P < 0.01) and lower HDL-C (53 ± 14 mg/dL vs 58 ± 17 mg/dL; P < 0.01). Despite the more atherogenic nonlipid cardiovascular profile of patients with mutation- FH, the age of CHD onset was earlier in patients with mutation+ FH (48 vs 56 years; P = 0.026). After multiple adjustment, the presence of a positive mutation was significantly associated with premature CHD (OR: 3.0, 95% CI: 1.38-6.55, P < 0.01).

Conclusions: Patients with mutation+ FH have a more atherogenic lipid profile and a 3-fold higher risk of premature CHD, as well as earlier onset of CHD, than patients with mutation- FH.

Keywords: Dutch Lipid Clinic Network; Familial Hypercholesterolemia; Mutations; Premature Coronary Heart Disease.

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Conflict of interest statement

Jean Ferrières has received grants and lecture fees from Amgen, Merck, and Sanofi. The authors declare no other potential conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart of patient inclusion. Abbreviations: APOB, gene encoding apolipoprotein B; LDL‐C, low‐density lipoprotein cholesterol; LDLR, gene encoding the LDL receptor; PCSK9, proprotein convertase subtilisin/kexin‐type 9
See this image and copyright information in PMC

References

    1. Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34:3478a–3490a. - PMC - PubMed
    1. Ferrières J, Lambert J, Lussier‐Cacan S, et al. Coronary artery disease in heterozygous familial hypercholesterolemia patients with the same LDL receptor gene mutation. Circulation. 1995;92:290–295. - PubMed
    1. Benn M, Watts GF, Tybjaerg‐Hansen A, et al. Familial hypercholesterolemia in the Danish general population: prevalence, coronary artery disease, and cholesterol‐lowering medication [published correction appears in J Clin Endocrinol Metab. 2014;99:4758–4759]. J Clin Endocrinol Metab. 2012;97:3956–3964. - PubMed
    1. Catapano AL, Lautsch D, Tokgözoglu L, et al. Prevalence of potential familial hypercholesteremia (FH) in 54 811 statin‐treated patients in clinical practice. Atherosclerosis. 2016;252:1–8. - PubMed
    1. Benn M, Watts GF, Tybjaerg‐Hansen A, et al. Mutations causative of familial hypercholesterolaemia: screening of 98 098 individuals from the Copenhagen General Population Study estimated a prevalence of 1 in 217. Eur Heart J. 2016;37:1384–1394. - PubMed

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