Perspective:

The study involves nearly half of the Icelanders who are genetically linked. Lp(a) levels are 80-90% genetically determined in an autosomal co-dominant inheritance pattern with full expression by 1-2 years of age and adult-like levels achieved by approximately 5 years. Outside of acute inflammatory states, the Lp(a) level remains stable through an individual’s lifetime. The link between Lp(a) levels and atherosclerotic CV disease (ASCVD), particularly familial premature including acute myocardial infarction; the degree of coronary stenosis, carotid stenosis, and ischemic strokes; aortic stenosis; and CV and all-cause mortality is unclear. Cholesterol content of particles contribute minimally to the low-density lipoprotein cholesterol level. More likely, it is the homology between apo(a) and plasminogen that may promote thrombosis by inhibiting fibrinolysis, as well as the explanation for increased risk for deep vein thrombosis/pulmonary embolism. Additionally, oxidized phospholipids co-localized with Lp(a) particles may promote endothelial dysfunction, inflammation, and calcification in the vasculature [see the ACC Expert Analysis: Lipoprotein(a) in Clinical Practice; July 2, 2019]. Indications for measurement include premature ASCVD and first-degree relatives with premature ASCVD as a risk enhancer in borderline risk persons and in severe hypercholesterolemia (HeFH) where it increases risk significantly. The ACC/AHA guideline recommends reporting Lp(a) levels as concentration (nmol/L). High levels per the guideline are ≥125 nmol/L (approximately ≥50 mg/dl), which approximates the 80th percentile in the Caucasian US populations.