Role of lipoprotein (a) and LPA KIV2 repeat polymorphism in bicuspid aortic valve stenosis and calcification: a proof of concept study

Intern Emerg Med. 2019 Jan;14(1):45-50. doi: 10.1007/s11739-018-1925-8. Epub 2018 Aug 11.

Abstract

Hemodynamic valvular impairment is a frequent determinant of the natural history of bicuspid aortic valve (BAV). The role of elevated Lp(a) levels and LPA Kringle IV type 2 (KIV-2) size polymorphism in influencing aortic valve calcification and stenosis development in patients with tricuspid aortic valve was recognized. In this study, we investigate the association between Lp(a) and LPA KIV-2 repeat number, and the presence of calcification and stenosis in BAV patients. Sixty-nine patients [79.7% males; median age 45(30-53) yrs], consecutively referred to Center for Cardiovascular Diagnosis or Referral Center for Marfan syndrome or related disorders, AOU Careggi, from June to November 2014, were investigated. For each patient, clinical (ECG and echocardiography) and laboratory [Lp(a) (Immunoturbidimetric assay) and LPA KIV-2 repeat number (real-time PCR)] evaluation were performed. Patients were compared with 69 control subjects. No significant association between Lp(a) circulating levels and LPA KIV-2 repeat number and BAV was evidenced. Among BAV patients, significantly higher Lp(a) levels according to calcification degree were found [no calcifications:78(42-159) mg/L, mild/moderate: 134(69-189) mg/L; severe: 560(286-1511) mg/L, p = 0.008]. Conversely, lower LPA KIV-2 repeat numbers in subjects with more severe calcification degree were observed. Furthermore, higher Lp(a) levels in patients with aortic stenosis [214(67-501) mg/L vs 104(56-169) mg/L, p = 0.043] were also found. In conclusion, present data suggest the potential role for Lp(a) as a possible risk marker useful to stratify, among BAV patients, those with a higher chance to develop valvular calcifications and aortic stenosis.

Keywords: Bicuspid aortic valve; Calcification; Kringle IV type 2; Lipoprotein (a); Stenosis.

MeSH terms

  • Adult
  • Aortic Valve / abnormalities*
  • Aortic Valve / diagnostic imaging
  • Aortic Valve / pathology*
  • Aortic Valve Stenosis / blood
  • Aortic Valve Stenosis / diagnostic imaging
  • Aortic Valve Stenosis / genetics*
  • Bicuspid Aortic Valve Disease
  • Biomarkers / blood
  • Calcinosis / blood
  • Calcinosis / diagnostic imaging
  • Calcinosis / genetics*
  • Case-Control Studies
  • Echocardiography
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Heart Valve Diseases / blood
  • Heart Valve Diseases / diagnostic imaging
  • Heart Valve Diseases / genetics*
  • Humans
  • Kringles / genetics*
  • Lipoprotein(a) / blood*
  • Lipoprotein(a) / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Proof of Concept Study
  • Real-Time Polymerase Chain Reaction
  • Risk Factors

Substances

  • Biomarkers
  • Lipoprotein(a)

Supplementary concepts

  • Aortic Valve, Calcification of