• Elevated Lp(a) Shows ‘Similar’ CV Risks to FH: Population Data

    The risk of myocardial infarction (MI) and atherosclerotic cardiovascular disease (ASCVD) associated with an elevated blood level of lipoprotein(a) [Lp(a)] is similar to that associated with familial hypercholesterolemia (FH), according to a new analysis of population data that provides equivalence measures for risk between raised Lp(a), FH, and raised low-density lipoprotein cholesterol (LDL-C).

    The study, published online Monday and in the Nov. 22 issue of Journal of the American College of Cardiology, noted that genetically elevated plasma Lp(a) and FH each result in premature ASCVD, but added that no direct comparison of these two genetic traits has been performed in the same population.

    “We need direct comparison in the same population of elevated plasma lipoprotein(a) and FH on risk of ASCVD, because the exact level of plasma lipoprotein(a) that is equivalent to LDL-C in FH on risk of ASCVD is unknown,” said the authors of the study, led by Berit Storgaard Hedegaard, RN, from the Regional Hospital Central Jutland, Aalborg University and Copenhagen University Hospital, all in Denmark.

    “In this study of 69,644 individuals from the Danish general population, Lp(a) levels equivalent to LDL-C in clinical and genetic FH were 67 to 402 mg/dL and 180 mg/dL for risk of MI and 130 to 391 mg/dL and 175 mg/dL for risk of ASCVD, respectively,” they said. “These findings are novel.”

    Our findings are also likely to inform subsequent guidelines if Lp(a) therapeutics prove of clinical value,” they said.

    Study setup

    Hedegaard and colleagues set out to determine the level of plasma Lp(a) that is equivalent to LDL-C in clinically and genetically diagnosed FH for the risk of MI and ASCVD using data from the Copenhagen General Population Study (CGPS) – an ongoing cohort study with participants recruited from 2003 to 2015 and followed up for a median of 42 years (range 0.16-42 years), with data collected prospectively and retrospectively through national Danish registries.

    “For the present study, we included all participants with an available lipoprotein(a) measurement, with most participants consecutively recruited, and supplemented with selected participants with MI and ASCVD,” they said, noting that these data included 69,644 individuals who were followed for a median of 42 years, during which time 4,166 individuals developed MI and 11,464, ASCVD.

    The team then estimated the magnitude of the change in plasma Lp(a) level that would demonstrate the same risk of association with myocardial infarction (MI) and ASCVD (MI, fatal coronary heart disease, and ischemic stroke) as that associated with a 38.7 mg/dL (1 mmol/L) change in LDL-C levels.

    Key findings

    For risk of MI, the plasma Lp(a) level equivalent to LDL cholesterol in FH was 67 mg/dL (142 nmol/L) for MEDPED (Make Early Diagnosis to Prevent Early Death); 110 mg/dL (236 nmol/L) for Simon Broome; 256 mg/dL (554 nmol/L) for possible DLCN (Dutch Lipid Clinic Network); and 402 mg/dL (873 nmol/L) for probable+/-definite DLCN; whereas it was 180 mg/dL (389 nmol/L) for genetic FH, said the team.

    Meanwhile, they noted that values for ASCVD were 130 mg/dL (280 nmol/L) for MEDPED, 150 mg/dL (323 nmol/L) for Simon Broome, 227 mg/dL (491 nmol/L) for possible DLCN, 391 mg/dL (849 nmol/L) for probable plus definite DLCN, and 175 mg/dL (378 nmol/L) for genetic FH.

    Furthermore, individuals with both elevated Lp(a) and either FH or a family history of MI had a higher risk of MI and ASCVD compared with individuals with only one of these genetic traits – with the highest hazard ratio [HR] being for Lp(a) upper 20% vs lower 50% of 14.0 (95% confidence interval [CI]: 9.15-21.3) for MI and 5.05 (95% CI: 3.41-7.48) for ASCVD.

    Hedegaard and colleagues concluded that Lp(a) levels equivalent to LDL-C in clinical and genetic FH were 67 to 402 mg/dL [for Lp(a)] and 180 mg/dL (for FH) for MI and 130 to 391 mg/dL [for Lp(a)] and 175 mg/dL (for FH) for ASCVD.

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

    “That said, FH continues to be underdiagnosed and poorly understood by most clinicians and patients. Thus, ongoing education of clinicians regarding diagnosis and risks associated with both FH and elevated Lp(a) is needed.”

    Answering unanswered questions

    Writing in an accompanying editorial comment, Pamela B. Morris, MD, from The Medical University of South Carolina; Jagat Narula, MD, PhD, from the Icahn School of Medicine at Mount Sinai, New York; and Sotirios Tsimikas, MD, from the University of California, San Diego, noted that although the existence of Lp(a) was identified nearly 60 years ago, incorporation of Lp(a) measurement into routine clinical practice has been “woefully slow.”

    “In recent years there has been dramatic progress in our understanding of Lp(a). However, a remaining important unanswered issue is how to put Lp(a) risk thresholds into clinical context relative to other cardiovascular risk factors, including elevation of low-density lipoprotein cholesterol (LDL-C) levels,” the editorialists said.

    “For the first time, the current study puts into clinical context Lp(a)-associated risk with that of clinically and genetically diagnosed FH and the well-established metric of every 1 mmol/L LDL-C being associated with a 20% relative risk of CVD event.”

    They added that the weight of evidence “strongly supports” that both genetic lipid disorders, elevated Lp(a) levels and FH, are causally associated with an increased risk of premature ASCVD and should be considered in risk assessment and management for ASCVD risk reduction.

    “In addition to performing a lipid panel periodically according to evidence-based guidelines, measurement of Lp(a) levels should also be performed at least once in an individual’s lifetime for ASCVD risk assessment,” the expert commentators suggested, adding that it is “vital” to continue to raise awareness among clinicians and patients of high-risk genetic lipid disorders.

    Sources:

    Hedegaard BS, Bork SC, Kaltoft M, et al. Equivalent Impact of Elevated Lipoprotein(a) and Familial Hypercholesterolemia in Patients With Atherosclerotic Cardiovascular Disease. J Am Coll Cardiol 2022;80:1998-2010.

    Morris PB, Narula J, Tsimikas S. Lipoprotein(a) and LDL-C: The Relevance of Equivalence. J Am Coll Cardiol 2022;80:2010-2012.

    Image Credit: luchschenF – stock.adobe.com

This site uses cookies. By continuing to browse the site you are agreeing to our use of cookies. Review our Privacy Policy for more details