Peripheral arterial disease in heterozygous familial hypercholesterolemia

Atherosclerosis. 2015 Sep;242(1):174-8. doi: 10.1016/j.atherosclerosis.2015.07.022. Epub 2015 Jul 13.

Abstract

Background: Familial hypercholesterolemia is characterized by elevated plasma cholesterol and early coronary arterial disease onset. However, few studies investigated the association of heterozygous familial hypercholesterolemia with peripheral arterial disease.

Methods: In a cross sectional study 202 heterozygous familial hypercholesterolemia patients (91% confirmed by molecular diagnosis) were compared to 524 normolipidemic controls. Peripheral arterial disease was diagnosed by ankle-brachial index values ≤0.90.

Results: Compared with controls, familial hypercholesterolemia patients were older, more often female, with higher rates of hypertension, diabetes, previous coronary disease and higher total cholesterol levels. Smoking (previous and former) was more common among controls. The prevalence of peripheral arterial disease was 17.3 and 2.3% respectively in familial hypercholesterolemia and controls (p < 0.001). Results persisted after matching familial hypercholesterolemia and controls by a propensity score. Regression analyses demonstrated that age (odds ratio- OR = 1.03 95% CI 1.00-1.05, p = 0.033), previous cardiovascular disease (OR = 3.12 CI 95% 1.56-6.25, p = 0.001) and familial hypercholesterolemia diagnosis (OR = 5.55 CI 95% 2.69-11.44, p< 0.001) were independently associated with peripheral arterial disease. Among familial hypercholesterolemia patients, age (OR 1.05, 95% CI 1.02-1.09, p = 0.005), intermittent claudication (OR 6.32, 95% CI 2.60-15.33, p< 0.001) and smoking (OR 2.44, 95% CI 1.08-5.52, p = 0.032) were associated with peripheral arterial disease.

Conclusions: Peripheral arterial disease is more frequent in familial hypercholesterolemia than in normolipidemic subjects and it should routine screened in these individuals even if asymptomatic. However, its role as predictor of cardiovascular events needs to be ascertained prospectively.

Keywords: Atherosclerosis; Familial hypercholesterolemia; Peripheral artery disease.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Age Factors
  • Ankle Brachial Index
  • Brazil / epidemiology
  • Case-Control Studies
  • Chi-Square Distribution
  • Comorbidity
  • Cross-Sectional Studies
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Heterozygote*
  • Humans
  • Hyperlipoproteinemia Type II / diagnosis
  • Hyperlipoproteinemia Type II / epidemiology*
  • Hyperlipoproteinemia Type II / genetics*
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Peripheral Arterial Disease / diagnosis
  • Peripheral Arterial Disease / epidemiology*
  • Peripheral Arterial Disease / physiopathology
  • Prevalence
  • Propensity Score
  • Prospective Studies
  • Registries
  • Risk Assessment
  • Risk Factors
  • Smoking / adverse effects
  • Smoking / epidemiology

Substances

  • Genetic Markers