554 hyperlipoprotein(a) and premature coronary artery disease: a call for action

Abstract Background and Aims elevated Lipoprotein (a) levels are well recognized as a genetic risk factor for atherothrombotic events. Recently, new therapeutic approaches – such as small interfering RNA (siRNA) and antisense oligonucleotides (ASOs) – have been developed and are under evaluation in phase 3 trials. Evidences from literature suggest the need for screening Lp(a) in premature coronary artery disease. Aim of our study was to evaluate, in a real world scenario: 1) the percentage of premature CAD in whom clinicians choose to screen Lp(a); 2) the prevalence of hyperLp(a) in premature CAD. Methods we retrospectively evaluated data of patients admitted for acute coronary syndrome at Department of Cardiology of Careggi University Hospital, Florence, between 1st January 2018 and 31th July 2022. Inclusion criteria were: age < 50 years for men and < 55 years for women; confirmed diagnosis of acute coronary syndrome with obstructive coronary artery disease at hospital discharge. Results we selected 226 patients (50 F and 176 M; total median age 46 years, F median age 49 years, M median age 45 years). LDL median values at admission were 117.12 mg/dl). Nine out of 226 pts (3.9%) had LDL levels higher than 190 mg/dl, suggesting the possible diagnosis of Heterozygous Familial Hypercholesterolemia (with respect to the expected prevalence in the general population: 1/250 (0.004%). No patient had hepatic or thyroid disease. Sixty-eight out of 226 pts (30%) had triglycerides levels higher than 150 mg/dl; 41/226 (18.1%) with levels higher than 200 mg/dl. As regards Lp(a) levels, a dosage was performed in 93/226 patients (41.2%). We found that lipoprotein dosage was required more frequently in the 2020, 2021 and 2022 years (respectively in the 61%, 49% and 70% of patients) than in the 2018 and 2019 years (respectively in the 27% and 23% of patients) (Figure 1). Among patients in whom lipoprotein was dosed, elevated Lp(a) levels (> 300 mg/L) were documented in 45/93 (48.4%). 15/93 (16.1%) patients had extreme elevated Lp(a) levels (> 700 mg/L) (Figure 2). In two patients we documented both extreme Lp(a) levels and LDL levels higher than 190 mg/dl; in the other patients, elevated Lp(a) levels were the only lipid parameter out of range, and the only risk factor for premature CAD. By comparing these patients with an historical cohort of patients with ACS and age >50 and 55 yrs in men and women respectively, we found at a multivariate analysis adjusted for classical risk factors that both elevated Lp(a) levels (OR:2.1 (95% CI 1.3–4.2), p<0.005) and extreme elevated Lp(a) levels were significantly associated with the risk of premature CAD (OR: 1.8 (95% CI 1.4–3.9); p<0.05). Conclusions these results demonstrated that: 1) it is urgent, from a clinical point of view, to apply screening protocols in premature CAD including Lp(a) dosage; 2) elevated Lp(a) levels, and in particular extreme elevated Lp(a) levels, have an elevated prevalence in a population of premature CAD and are significantly and independently associated with the disease.