Elevated Lipoprotein(a) and Familial Hypercholesterolemia Tied to MI, ASCVD Risk

Equivalent levels of lipoprotein(a) to low-density lipoprotein (LDL) cholesterol in clinical familial hypercholesterolemia (FH) were 67-402mg/dL for myocardial infarction (MI) and 130-391mg/dL for atherosclerotic cardiovascular disease (ASCVD). In genetic FH, equivalent levels of lipoprotein(a) to LDL cholesterol were 180mg/dL for MI and 175mg/dL for ASCVD. These are the findings of a study published in the Journal of the American College of Cardiology.

For the study, researchers in Denmark sought to determine the level of plasma lipoprotein(a) that is equivalent to LDL cholesterol in FH clinically and genetically diagnosed on risk for MI and ASCVD.

The study included both prospectively and retrospectively collected data from the Copenhagen General Population Study (CGPS). The CGPS involved 69,644 invited individuals (100% White; 100% Danish descent) living in/near Copenhagen regarding lipoprotein(a) and FH. Participation rate was 43% with 42 years median follow-up. During follow-up, the researchers observed 4166 patients with MI and 11,464 patients with ASCVD.

They found the plasma lipoprotein level equivalent to LDL cholesterol in clinical FH was:

• 402mg/dL for probable+definite Dutch Lipid Clinic Network (DLCN),
• 256mg/dL for possible DLCN, 110mg/dL for Simon Broome, and
• 67mg/dL for MEDPED (make early diagnosis to prevent early death) for risk for MI.

For genetic FH they found this level to be 180mg/dL.

Regarding the risk for ASCVD, the researchers found the plasma lipoprotein level equivalent to LDL cholesterol in clinical FH was:

• 391mg/dL for probable+definite DLCN,
• 227mg/dL for possible DLCN, 150mg/dL for Simon Broome, and
• 130mg/dL for MEDPED. For genetic FH they found this level to be 175mg/dL.

The researchers noted individuals with elevated lipoprotein(a) plus either family history of premature MI or FH faced increased risk for MI and ASCVD vs individuals with only 1 of those genetic traits.

Individuals in the top 20% of lipoprotein(a) simultaneously with clinical FH vs the bottom 50% and without FH, the age- and sex-adjusted hazard ratios (HRs) for MI and ASCVD, respectively, were:

• MEDPED: 1.75 (95% CI, 1.03-2.96) and 1.34 (95% CI, 0.95-1.88)
• Simon Broome: 2.49 (95% CI, 2.01-3.10) and 1.87 (95% CI, 1.61-2.16)
• Possible DLCN: 4.91 (95% CI, 4.34-5.74) and 2.36 (95% CI, 2.11-2.63)
• Probable+definite DLCN: 14.0 (95% CI, 9.15-21.3) and 5.05 (95% CI, 3.41-7.48)
• Genetic FH: 5.01 (95% CI, 2.25-11.2) and 2.57 (95% CI, 1.28-5.14)

Study limitations include possible nonresponse bias, participants who were only White and of Danish descent, which limits generalizability, subtraction of 30% of total mass of lipoprotein(a) from LDL cholesterol baseline characteristics, and conversion of mg/dL values to nmol/L requiring a new conversion equation for each assay.

The researchers concluded their data suggest lipoprotein(a) levels greater than 70mg/dL may be equivalent to an FH diagnosis using genetic FH, Simon Broome, or MEDPED criteria.

Furthermore, they believe their findings “may be helpful for clinicians during individualized patient counselling, because explanation of the risk associated with elevated lipoprotein(a) on MI and ASCVD may be facilitated by comparison with the risk of having FH.”

They concluded: “[O]ngoing education of clinicians regarding diagnosis and risks associated with both FH and elevated lipoprotein(a) is needed.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.