Extremely high lipoprotein (a) as a marker of early atherosclerosis: analysis of a large real-world cohort

Lipoprotein (a) (Lp(a)) is a genetically determined risk factor for atherosclerosis, with extremely high levels associated with very high cardiovascular risk. Despite this, in routine clinical practice these patients often remain insufficiently identified. Aim . To characterize the prevalence and severity of subclinical atherosclerosis in various vascular beds in patients with Lp(a) ≥ 180 mg/dL, including younger age groups. Materials and methods . We performed a retrospective analysis of a database comprising 101,078 outpatients, from which 1105 (1.09%) individuals with Lp(a) ≥ 180 mg/dL and available lipid profile data were selected; women accounted for 67.2%, and the mean age was 52.74 ± 14.59 years. The presence of atherosclerotic cardiovascular disease (ASCVD) was ascertained from medical records, and atherosclerosis was assessed by duplex ultrasound of the brachiocephalic arteries (BCA) and lower extremity arteries (LEA), as well as by the Agatston coronary artery calcium score (CACS). At least one vascular bed was evaluated in 69.8% of patients, and all three were evaluated in 6.2%. Results. Most patients showed elevated levels of total cholesterol and low-density lipoprotein cholesterol. From the age of 25–44 years onward, a substantial proportion of patients already showed atherosclerotic involvement of the BCA and LEA with stenosis ≥20% and pronounced coronary calcification (CACS > 100 units), with a shift toward more severe lesions in older age groups. In the subgroup that underwent imaging of all three vascular beds, 60.0% of patients aged 25–44 years had two or three beds that were affected; the proportion of patients with involvement of all three vascular beds increased to 40.0% in those aged 45–59 years, 76.9% in those aged 60–74 years, and reached 100% in patients aged ≥ 75 years (p < 0.001). The prevalence of clinically documented ASCVD increased from 10.3% in the 25–44 age group to 67.1% in patients aged ≥ 75 years. Even among patients without documented ASCVD, atherosclerotic involvement of the BCA, LEA and coronary calcification was detected in 85.9%, 82.6% and 37.1% of cases, respectively. Conclusion . Patients with Lp(a) ≥ 180 mg/dL are characterized by a high prevalence and early onset of subclinical, frequently multifocal atherosclerosis, with a pronounced age-related gradient of progression. These findings support the case for designating this cohort as a priority group for in-depth evaluation, risk re-stratification and more intensive preventive management.