Screening program for familial dyslipidemias in patients with ischemic heart disease. cost-effectiveness of genetic testing

Abstract Introduction and purpose Familial hypercholesterolemia (FH) is a serious and highly prevalent condition in the general population, with an estimated 1 in 300 individuals affected. The prevalence may be significantly higher in populations who have experienced a coronary event. There are other familial dyslipidemias, such as Lipoprotein A (Lp(a)) hyperlipoproteinemia and polygenic hypercholesterolemia (PH), both with unknown prevalence, which are associated with cardiovascular disease (CVD). Active screening for these conditions is essential in patients with CVD, especially when the onset is early or when extremely elevated low-density lipoprotein cholesterol (LDL-C) levels are present. Methods This is a descriptive study in which active screening for FH and other genetic factors associated with an increased risk of cardiovascular disease (CVD) is performed. We analyzed 352 consecutive patients with ischemic heart disease referred to a Cardiac Prevention and Rehabilitation Unit between January 1, 2022, and April 1, 2023. All patients underwent the Dutch FH score assessment, and those with a score of at least 3 points or low-density lipoprotein cholesterol (LDL-C) levels above 150 mg/dl were tested for hypercholesterolemia using a genetic test, totaling 53 genetic tests performed. Results The prevalence of mutations associated with Lp(a) was 35.8%, with the most representative being the heterozygous mutation in the rs10455872 gene, found in 57.9% of cases, followed by the heterozygous mutation in the rs3798220 gene, observed in 31.6%, and lastly, 10.5% of patients had both copies in a heterozygous state. Regarding genetic variants associated with reduced efficacy or increased toxicity of certain statins, these were present in 45.3% of patients. Regarding polygenic hypercholesterolemia (PH), 36% of patients had an LDL-C score greater than 1.09. As for genetic coronary risk, 38.5% of patients had a Cardio inCode Score above 1.3. Regarding the diagnosis of FH, clinical diagnosis using the Dutch Score, which is considered definitive if ≥ 8, was present in 13% of patients; the genetic test was positive in 3.8% of patients, with uncertain significance mutations found in 9.6%. In 82.4% of all genetic tests, a mutation was detected. Conclusions Active screening for familial dyslipidemias, both through clinical criteria and genetic studies, is highly effective in patients with ischemic heart disease. The genetic test provides an additional, previously unknown risk factor in the majority of patients.Baseline characteristics Mutations