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High "population attributable fraction" for coronary heart disease mortality among relatives in monogenic familial

Melissa A Austin1, Ron L Zimmern, Steve E Humphries

  • 1Institute for Public Health Genetics and Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington 98195-7236, USA.

Genetics in Medicine : Official Journal of the American College of Medical Genetics
|August 13, 2002
PubMed

Insights

Screening first-degree relatives of familial hypercholesterolemia (FH) patients can prevent significant coronary heart disease (CHD) mortality. This family-based approach offers a higher potential for preventing fatal CHD compared to general population strategies.

Area of Science:

  • Cardiovascular Medicine
  • Genetics
  • Public Health

Background:

  • Monogenic familial hypercholesterolemia (FH) is a genetic disorder leading to high cholesterol levels.
  • Elevated cholesterol significantly increases the risk of coronary heart disease (CHD) mortality.
  • First-degree relatives of FH patients have a high probability of inheriting the condition.

Purpose of the Study:

  • To estimate the population attributable fraction (PAF) for CHD mortality in relatives of FH patients.
  • To compare this PAF with the PAF for hypercholesterolemia in the general population.

Main Methods:

  • Calculated PAF using the formula [f(R - 1)/[1 + f(R - 1)]], where f is risk factor frequency and R is relative risk.
  • Assumed 50% frequency (f) for FH relatives based on dominant inheritance.
  • Utilized Simon Broome Register data for relative risk (R) and Framingham risk equations for general population data.

Main Results:

  • Cholesterol reduction could potentially prevent 44% of male and 57% of female 5-year CHD mortality in FH relatives.
  • In the general population, hypercholesterolemia accounts for only 5% of male and 10% of female 5-year fatal CHD prevention.
  • PAF for CHD mortality is substantially higher in FH relatives compared to the general population.

Conclusions:

  • Family-based screening for FH and subsequent lipid-lowering treatment is highly effective.
  • This strategy significantly reduces CHD deaths among first-degree relatives of FH patients.
  • Targeted interventions in FH families offer a potent method for cardiovascular disease prevention.
Abstract

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