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Value of Measuring Lipoprotein(a) During Cascade Testing for Familial Hypercholesterolemia

Katrina L Ellis1, Leopoldo Pérez de Isla2, Rodrigo Alonso3

  • 1School of Medicine, Faculty of Medicine and Health Sciences, University of Western Australia, Perth, Australia; School of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Western Australia, Perth, Australia.

Journal of the American College of Cardiology
|March 9, 2019
PubMed

Insights

Cascade screening for familial hypercholesterolemia (FH) effectively identifies individuals with elevated lipoprotein(a) [Lp(a)], a risk factor for atherosclerotic cardiovascular disease (ASCVD). Combining FH and Lp(a) testing enhances ASCVD risk detection in relatives.

Area of Science:

  • Cardiovascular Genetics
  • Lipid Metabolism
  • Public Health Screening

Background:

  • Familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] are inherited conditions linked to premature atherosclerotic cardiovascular disease (ASCVD).
  • While FH cascade testing is recommended, similar guidelines for elevated Lp(a) are lacking.
  • This highlights a gap in screening strategies for these related genetic cardiovascular risk factors.

Purpose of the Study:

  • To evaluate the effectiveness of Lp(a) testing within an existing FH cascade screening program.
  • To determine if Lp(a) testing can identify individuals at higher ASCVD risk among FH relatives.
  • To assess the yield of detecting elevated Lp(a) in different FH proband subgroups.

Main Methods:

  • A cohort of 2,927 family members from 755 FH index cases (SAFEHEART study) underwent genetic FH and Lp(a) testing (≥50 mg/dl).
  • Prevalence and detection rates of elevated Lp(a) were compared between FH relatives of probands with and without high Lp(a).
  • A prospective analysis examined the association between elevated Lp(a) and ASCVD events over 5 years.

Main Results:

  • Systematic screening of FH probands with elevated Lp(a) yielded 1 new case of high Lp(a) per 2.4 individuals screened.
  • Opportunistic screening of FH probands without elevated Lp(a) identified 1 case per 5.8 individuals.
  • Both FH and elevated Lp(a) independently increased ASCVD event risk (HRs 2.47 and 3.17, respectively).
  • Individuals with both FH and elevated Lp(a) faced the highest risk (HR 4.40), independent of traditional risk factors.

Conclusions:

  • Integrating Lp(a) testing into FH cascade screening is effective for identifying at-risk relatives.
  • This combined approach enhances the detection of elevated Lp(a) and associated heightened ASCVD risk.
  • The strategy is particularly valuable when the FH proband also has elevated Lp(a).
Abstract

Keywords:
atherosclerotic cardiovascular diseasecascade screeningfamilial hypercholesterolemialipoprotein(a)

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