To test, or not to test: that is the question for the future of lipoprotein(a)

ABSTRACT

Introduction: Lipoprotein(a) [Lp(a)] is a potent, highly heritable and common risk factor for atherosclerotic cardiovascular disease (ASCVD). Evidence for a causal association between elevated Lp(a) and ASCVD has been provided by large epidemiological investigations that have demonstrated a curvilinear association with increased risk, as well as from genetic examinations and cellular and transgenic animal studies. Although there are several therapies available for lowering Lp(a), none are selective for Lp(a) and there is no clinical trial data that has specifically shown that lowering Lp(a) reduces the risk of ASCVD. Hence, screening for elevated Lp(a) is not routinely incorporated into clinical practice.

Areas covered: This paper reviews the current evidence supporting the causal role of Lp(a) in the primary and secondary prevention of ASCVD, screening approaches for high Lp(a), current guidelines on testing Lp(a), and barriers to the routine screening of elevated Lp(a) in clinical practice.

Expert opinion: At present, there is a moderate level of evidence supporting the routine screening of elevated Lp(a). Current guidelines recommend testing for elevated Lp(a) in individuals at intermediate or high risk of ASCVD.

KEYWORDS:

• Lipoprotein(a)
• atherosclerotic cardiovascular disease
• screening
• guidelines
• therapies

Article highlights

• Elevated Lp(a) is a common and potentially causal risk factor for ASCVD; however, it is not routinely screened for in clinical practice.

• The inclusion of Lp(a) to standard risk algorithms may improve risk stratification in the setting of primary prevention; the evidence is less clear for secondary prevention.

• Current barriers to screening for elevated Lp(a) include the absence of a standardized assay for the measurement of Lp(a), the lack of available therapies for specifically lowering Lp(a) and an absence of clinical trial data that has tested the Lp(a) hypothesis.

• Clinical outcome trial data on selective Lp(a)-lowering therapies is awaited and will demonstrate whether a reduction in plasma Lp(a) translates to a reduction in ASCVD events.

The present guidelines recommend testing for elevated Lp(a) in individuals at intermediate or high risk of ASCVD, including those with a strong personal family history of ASCVD, recurrent events despite optimal lipid management, or FH. The value of universal screening for elevated Lp(a) is not currently noted.

Declaration of interest

G Watts has received research grants from Amgen, Sanofi, and Regeneron, and is on the advisory board for Amgen, Sanofi, Regeneron, and Gemphire. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the Raine Medical Research Foundation, Royal Perth Hospital Medical Research Foundation.