Abstract
Familial hypercholesterolemia (FH) is an underdiagnosed genetic inherited condition that may lead to premature coronary artery disease (CAD). FH has an estimated prevalence in the general population of about 1:313. However, its prevalence in patients with premature STEMI (ST-elevation myocardial infarction) has not been widely studied. This study aimed to evaluate the prevalence of FH in patients with premature STEMI. Cardiovascular risk factors, LDLc (low-density lipoprotein cholesterol) evolution, and differences between genders were also evaluated. Consecutive patients were referred for cardiac catheterization to our center due to STEMI suspicion in 2018. From the 80 patients with confirmed premature CAD (men < 55 and women < 60 years old with confirmed CAD), 56 (48 men and eight women) accepted to be NGS sequenced for the main FH genes. Clinical information and DLCN (Dutch Lipid Clinic Network) score were analyzed. Only one male patient had probable FH (6–7 points) and no one reached a clinically definite diagnosis. Genetic testing confirmed that the only patient with a DLCN score ≥6 has HF (1.8%). Smoking and high BMI the most frequent cardiovascular risk factors (>80%). Despite high doses of statins being expected to reduce LDLc levels at STEMI to current dyslipidemia guidelines LDL targets (<55 mg/dL), LDLc control levels were out of range. Although still 5.4 times higher than in general population, the prevalence of FH in premature CAD is still low (1.8%). To improve the genetic yield, genetic screening may be considered among patients with probable or definite FH according to clinical criteria. The classical cardiovascular risk factors prevalence far exceeds FH prevalence in patients with premature STEMI. LDLc control levels after STEMI were out range, despite intensive hypolipemiant treatment. These findings reinforce the need for more aggressive preventive strategies in the young and for intensive lipid-lowering therapy in secondary prevention.
Highlights
Coronary artery disease (CAD) is the most frequent cause of death worldwide, and one of the most frequent causes of premature death, with an increasing prevalence [1]
We systematically evaluated the prevalence of familial hypercholesterolemia (FH), evaluated by both clinical and genetic testing, in a cohort of patients with confirmed premature atherothrombotic CAD presenting with myocardial infarction (MI) with ST-elevation (STEMI)
We evaluated the 3 genes related to heterozygous FH (LDLR, apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9)), one gene related to autosomal recessive FH (LDLRAP1) and 2 other genes related to hyperlipidemia (APOE and LIPA)
Summary
Coronary artery disease (CAD) is the most frequent cause of death worldwide, and one of the most frequent causes of premature death, with an increasing prevalence [1]. Between the ages of 30 and 54, ischemic heart disease has an incidence of 1% per year in men and 0.4% in women [3] In this context, familial hypercholesterolemia (FH) is known to be a predisposing cause of premature CAD [4]. Familial hypercholesterolemia (FH) is known to be a predisposing cause of premature CAD [4] Patients with this genetic disorder have elevated low-density lipoprotein cholesterol (LDLc) levels from birth. Pathogenic variants in the genes encoding for the LDL receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9), are known to cause heterozygous FH, an autosomal dominant inherited condition [4,5]. Other interesting genes, not responsible for FH but associated with hyperlipidemia (such as APOE and LIPA), have been identified
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