Prevalence of familial hypercholesterolemia phenotype and ten-year risk of cardiovascular events in a working population in primary prevention: The ICARIA study

Atherosclerosis. 2021 Dec:338:39-45. doi: 10.1016/j.atherosclerosis.2021.11.007. Epub 2021 Nov 11.

Abstract

Background and aims: We aimed to assess the prevalence of familial hypercholesterolaemia (FH) and to determine the incidence of cardiovascular events during a 10-year follow up in individuals with FH, compared to unaffected individuals in a working, middle-aged/young population.

Methods and results: 576,724 active workers (36 ± 10 years-old, 70% men) without cardiovascular disease were given regular health check-ups and followed for a median of 8.5 years (i.e., 4,123,927 person-years). The FH phenotype was defined according to validated low-density lipoprotein-cholesterol thresholds, adjusted for age and sex. The primary outcome was a first cardiovascular event, whether fatal or non-fatal. We found that 707 workers (0.12% or 1 in 816 individuals) met the criteria for a heterozygous FH phenotype. During the follow-up, cardiovascular events occurred in 23 of 707 (3.25%) subjects with the FH phenotype and in 3297 of 576,017 (0.57%) subjects without the FH phenotype (p<0.001). The hazard ratio (HR, assessed with a Cox regression model) for the primary outcome was 5.7 (99% CI 3.33-9.78), before adjustments, and 4.7 (99% CI 2.62-8.58) after adjusting for sex, age, smoking, blood pressure, and diabetes. The HRs were significant for both men and women, but the magnitude of the effect was greater for men than for women.

Conclusions: Our findings confirmed the high incidence of cardiovascular disease in individuals with untreated FH. We showed that regular health check-ups in an active, and mostly young, working population could contribute to the early identification of FH. Therefore, this approach may provide an opportunity for early treatment.

Keywords: Cardiovascular diseases; Familial hypercholesterolemia; Follow-up studies; Prospective studies; Risk assessment; Risk factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cardiovascular Diseases* / diagnosis
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / prevention & control
  • Cholesterol, LDL
  • Female
  • Humans
  • Hyperlipoproteinemia Type II* / diagnosis
  • Hyperlipoproteinemia Type II* / epidemiology
  • Hyperlipoproteinemia Type II* / genetics
  • Male
  • Middle Aged
  • Phenotype
  • Prevalence
  • Risk Factors

Substances

  • Cholesterol, LDL