Polyvascular subclinical atherosclerosis in familial hypercholesterolemia: The role of cholesterol burden and gender

https://doi.org/10.1016/j.numecd.2019.06.015Get rights and content

Highlights

  • •

    Multivascular atherosclerosis is found in asymptomatic HeFH patients.

  • •

    Men have a higher prevalence of coronary and femoral district involvement.

  • •

    Women have an increased prevalence of carotid and femoral atherosclerosis.

  • •

    Cholesterol burden is associated with coronary calcium score.

  • •

    Cholesterol burden is associated with carotid and femoral atherosclerotic burden.

Abstract

Background and aim

Heterozygous familial hypercholesterolemia (HeFH) is a genetic disease characterized by a heterogeneous phenotype. The assessment of cardiovascular (CV) risk is challenging for HeFH. Cholesterol burden (CB) allows to estimate the lifelong exposure to high levels of cholesterol. The aim of this study was to analyze the distribution of subclinical atherosclerosis and the relationship between atherosclerosis and the CB in a sample of HeFH patients, focusing on sex-related differences.

Methods and Results

154 asymptomatic HeFH subjects underwent coronary-artery-calcium score (CACs) and Doppler ultrasound of carotid and femoral arteries. Yearly lipid profiles and HeHF history were obtained from patients' files in order to calculate total CB. Atherosclerotic burden was defined by the presence of CACs > 0 or by the presence of carotid or femoral plaque. Study population was stratified according to gender. The prevalence of CAC, carotid and femoral atherosclerosis was of 62%, 55% and 56%, respectively. Coronary district was the least involved in women, who had a higher prevalence in carotid atherosclerosis. When two vascular districts were affected, women had an increased prevalence of femoral and carotid atherosclerosis whereas men had a higher prevalence of coronary and femoral atherosclerosis. CB correlated to the presence of atherosclerosis in any of the three vascular districts with a significant increasing trend depending on the number of affected areas.

Conclusions

A polyvascular atherosclerotic burden is found in asymptomatic HeFH patients. Gender differences in the territory distribution were observed. The early and lasting exposure to high cholesterol, as expressed by CB, is a major determinant of atherosclerotic burden.

Section snippets

Background

Familial hypercholesterolemia (FH, OMIM #143890) is an autosomal dominant genetic disease characterized by mutations in the genes codifying for the low-density lipoprotein receptor (LDLR), the apolipoprotein B (APOB), and the pro-protein convertase subtilisin/kexin 9 (PCSK9) even though other genes have recently been identified to be candidates for this inherited disease. The clinical phenotype of the heterozygous form (HeFH) is heterogeneous [1] and the prevalence may be as high as 1 in 200 to

Study population

Patients were recruited consecutively between May 2015 and May 2016 at the Cardiovascular Prevention Unit of the Pitié-Salpêtrière Hospital in Paris, France.

Inclusion criteria were: patients with genetically confirmed HeFH, aged between 20 and 70 years, in regular follow-up since the time of diagnosis, without symptoms or electrocardiographic signs of ischemia. The exclusion criteria were: denial of informed consent, contra-indication to computed tomography (CT), personal history of

Distribution of subclinical atherosclerosis

Table 1 shows the main characteristics of the whole sample (n = 154) and the population stratified according to gender. Men showed higher TC and HDL-C levels and were more treated with hypolipidemic treatment while Lp(a) was found to be higher in women. Cholesterol burden at diagnosis and total CB did not differ between men and women, who were also less treated with lipid-lowering drugs. Forty-two patients (27%) were smokers and 19 (14%) had arterial hypertension. The coronary calcium score was

Discussion

In this study, we explored subclinical atherosclerosis in three different vascular districts in a sample of patients with clinically and genetically determined familial hypercholesterolemia using non-invasive methods. The vast majority of patients (83%) had at least one territory involved. These results confirm the severity of atherosclerotic disease in asymptomatic HeFH patients. Independently from the number of vascular districts involved, the coronary district was the most affected in the

Conclusions

Heterozygous familial hypercholesterolemia is associated with early atherosclerotic disease in the absence of any clinical signs of coronary or peripheral vascular disease. Our study showed a simultaneous involvement of coronary, femoral and carotid vascular districts in one third of the study population, with the highest prevalence of coronary atherosclerotic burden.

This suggests that the coronary CT without contrast medium for the evaluation of coronary calcium in patients with familial

Acknowledgment

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

References (33)

  • G. Pasterkamp et al.

    Is plaque formation in the common carotid artery representative for plaque formation and luminal stenosis in other atherosclerotic peripheral arteries? A post mortem study

    Atherosclerosis

    (1998)
  • M. Laclaustra et al.

    Femoral and carotid subclinical atherosclerosis association with risk factors and coronary calcium: the AWHS study

    J Am Coll Cardiol

    (2016)
  • G.K. Hovingh et al.

    Diagnosis and treatment of familial hypercholesterolaemia

    Eur Heart J

    (2013)
  • M. Benn 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)
  • R.M. Conroy et al.

    Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project

    Eur Heart J

    (2003)
  • P.W. Wilson et al.

    Prediction of coronary heart disease using risk factor categories

    Circulation

    (1998)

    • Cited by (0)

    View full text
    © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.