Abstract
In the last decades, high serum levels of lipoprotein(a) (Lp(a)) have been associated with increased cardiovascular disease (CVD) risk, in particular among individuals with smaller apolipoprotein(a) (apo(a)) isoforms than those with larger sizes. The aim of our analysis was to evaluate whether Lp(a) levels could predict early vascular aging, and whether smaller apo(a) isoforms had a predictive value for vascular aging different than larger apo(a) isoforms in a cohort of subjects free from CVD. We considered the data of a subset of Brisighella Heart Study (BHS) participants free from CVD (462 men and 516 women) who were clinically evaluated during the 2012 BHS population survey. Predictors of arterial stiffness, measured as carotid-femoral pulse wave velocity (cfPWV) were estimated by the application of a step-wise linear regression model. In our cohort, there were 511 subjects with small apo(a) size and 467 subjects with large apo(a) isoforms. Subjects with larger apo(a) isoform sizes had significantly lower serum levels of Lp(a). In the BHS subpopulation sample, cfPWV was predicted by age, systolic blood pressure (SBP), serum levels of high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and sex, higher HDL-C serum levels and female sex associated with lower values of cfPWV. In subjects with smaller apo(a) isoform sizes, predictors of cfPWV were age, SBP, sex and serum levels of HDL-C, being higher HDL-C serum levels and female sex associated to lower values of cfPWV. In subjects with larger apo(a) isoform sizes, cfPWV was predicted by age, SBP, serum levels of Lp(a) and sex, with female sex associated with lower values of cfPWV. In our subpopulation sample, Lp(a) did not predict cfPWV. However, in subjects with large apo(a) isoform sizes, Lp(a) was a significant predictor of arterial stiffness.
Highlights
Apo(a) consists of multiple copies of plasminogen-like kringle IV (KIV) domains and a single kringle V domain followed by an inactive serine protease domain [2]
Our analysis set out to evaluate whether smaller apo(a) isoforms had a predictive value for vascular aging different than larger apo(a) isoforms in a cohort of subjects free from cardiovascular disease (CVD)
We used the data of a subset of the Brisighella Heart Study (BHS)
Summary
Biomedicines 2022, 10, 656 molar ratio [1]. The primary structure of apo(a) has a strictly conserved 80-amino acids sequence—known as ‘kringle’—that is present in several human proteins involved in a number of vascular functions. Apo(a) consists of multiple copies of plasminogen-like kringle IV (KIV) domains and a single kringle V domain followed by an inactive serine protease domain [2]. KIV domain is subdivided and numbered from type 1–10. 3–10 (KIV3–10) are always present as a single copy, whereas KIV2 occurs in a variable number of identical repeats. Known alleles encode as few as 1 and as many as 34 KIV2 repeats, giving rise to apo(a) isoforms containing from 10 to 43 KIV-like domains [3]
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