Lipoprotein(a): An FAQ on Awareness, Risk, and Screening Gaps

Lipoprotein(a) (Lp[a]) is a genetically determined, low-density lipoprotein (LDL)-like particle that an estimated 1 in 5 people carry at elevated levels, yet fewer than 2% of Americans have ever been tested for it.¹ That gap is starting to close as new outcomes data and a major 2026 guideline update push Lp(a) further into mainstream cardiovascular care.

Katherine Wilemon, founder and CEO of the Family Heart Foundation, has spent over a decade tracking US screening rates and pushing for broader testing. Her insights, paired with the latest clinical and coverage data, answer the questions patients and clinicians are asking most.

What Is Lp(a), and Why Is It Sometimes Called a "Triple Threat"?

Lp(a) contributes to atherosclerotic cardiovascular disease (ASCVD) through 3 distinct mechanisms: it promotes plaque buildup in arteries, behaves as a pro-inflammatory particle, and raises clotting risk. Unlike LDL cholesterol, Lp(a) levels are almost entirely set by genetics at birth and stay relatively stable throughout a person's life, which is why a single lifetime measurement is generally considered sufficient.²

How Many Individuals Have High Lp(a)?

Roughly 20% of the global population—about 1 in 5 people—carries a genetic predisposition to elevated Lp(a).³ Because Lp(a) levels are inherited in a co-dominant pattern, identifying elevated levels in one family member typically prompts cascade screening of parents, siblings, and children.⁴

The Family Heart Foundation has tracked US Lp(a) testing trends since 2012, and for much of that period, testing remained uncommon. Awareness began increasing around 2019, when the Lp(a)HORIZON (NCT04023552) outcomes trial began phase 3 enrollment and generated broader clinical interest, according to Wilemon.¹ Testing momentum slowed during the COVID-19 pandemic but has since increased, with Wilemon reporting that testing volume has approximately doubled every 2 years. Despite this progress, only about 1% of the US population has ever been screened.

Moreover, a Family Heart Foundation analysis of more than 273,000 US adults with established ASCVD, published in the European Heart Journal, found that recurrent cardiovascular event risk increased continuously as Lp(a) levels rose, with no clear plateau. Compared with the lowest Lp(a) category, adjusted HRs reached 1.15 at 80–179 nmol/L, 1.29 at 180–299 nmol/L, and 1.45 at 300 nmol/L or higher.

At the highest levels, this represented approximately a 45% higher relative risk of a recurrent cardiovascular event within 5 years. Wilemon noted that this type of timeframe can be easier for patients to understand than abstract lifetime-risk estimates.

Do Current Guidelines Actually Recommend Testing Everyone?

Yes. The 2026 ACC/AHA Guideline on the Management of Dyslipidemia recommends universal once-in-a-lifetime Lp(a) measurement in adults as a Class I recommendation—the strongest level a guideline issues. The guideline identifies elevated risk beginning at 125 nmol/L (approximately 50 mg/dL), with observational data suggesting cardiovascular risk may approximately double at levels above 250 nmol/L (100 mg/dL).^2,5

This marks the first time a US cholesterol guideline has recommended Lp(a) testing for all adults regardless of personal cardiovascular risk factors.

Will Insurance Cover the Test?

This is where guideline recommendations and coverage policy diverge. Lp(a) testing is not included in a standard lipid panel and must be ordered separately.² Many commercial plans cover testing, although patients may face cost-sharing because it is not generally classified as a preventive service.

Medicare coverage remains variable. Many Medicare Administrative Contractors continue to rely on Local Coverage Determinations developed before the current evidence base and before the 2026 guideline's universal screening recommendation. The gap between guideline recommendations and reimbursement policy is one reason advocacy groups continue to push payers to expand coverage.

What Can Someone With High Lp(a) Do Right Now, Given That No Lp(a)-Lowering Drug Is Approved Yet?

Wilemon recommends aggressively addressing all other modifiable cardiovascular risk factors, beginning with LDL cholesterol. The Family Heart Foundation analysis found that the excess recurrent-event risk associated with elevated Lp(a) appeared attenuated among patients receiving intensive LDL-lowering therapy, particularly PCSK9 inhibitors.¹ Because these findings come from observational data, they do not establish that LDL lowering eliminates Lp(a)-associated risk.

Beyond lipid management, clinicians should emphasize tobacco avoidance, regular physical activity, weight management, and appropriate cardiovascular follow-up. A high Lp(a) result can provide an opportunity for earlier risk reduction rather than a fatalistic diagnosis.

What's Coming Down the Treatment Pipeline?

Four Lp(a)-lowering therapies are currently in phase 3 development, and none has yet received FDA approval:

• Pelacarsen (Novartis/Ionis): This antisense oligonucleotide is administered monthly and is being evaluated in the Lp(a)HORIZON outcomes trial. Topline results have not yet been released, with companies previously guiding toward a mid-2026 readout window
• Olpasiran (Amgen): This quarterly small interfering RNA (siRNA) therapy is being studied in the approximately 7300-patient OCEAN(a)-Outcomes trial (NCT05581303), with results expected by the end of 2026
• Lepodisiran (Eli Lilly): This long-acting siRNA therapy is being evaluated in the phase 3 ACCLAIM-Lp(a) (NCT06292013) cardiovascular outcomes trial
• Muvalaplin (Eli Lilly): This oral small molecule disrupts apolipoprotein A particle assembly and is being studied in the MOVE-Lp(a) program (NCT07157774)

As awareness of Lp(a) grows, the focus for clinicians, patients, and health plans is shifting from recognition to action. Universal screening recommendations provide an opportunity to identify individuals with inherited cardiovascular risk earlier, while ongoing outcomes trials will determine whether directly lowering Lp(a) can translate into fewer cardiovascular events.

In the meantime, identifying elevated Lp(a) can help guide more intensive prevention strategies, close care gaps, and ensure that patients receive appropriate risk assessment long before cardiovascular disease develops or progresses.

References

1. MacDougall DE, Tybjærg-Hansen A, Knowles JW, et al. Lipoprotein(a) and recurrent atherosclerotic cardiovascular events: the US Family Heart Database. Eur Heart J. 2025;46(44):4762-4775. doi:10.1093/eurheartj/ehaf297
2. Blumenthal RS, Morris PB, Gaudino M, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of dyslipidemia: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2026;87(19):2624-2757. doi:10.1016/j.jacc.2025.11.016
3. Family Heart Foundation launches new initiative to increase understanding and screening for high lipoprotein(a), the most common genetic risk factor for premature cardiovascular disease. News release. Family Heart Foundation. November 4, 2025. Accessed August 10, 2026. https://www.businesswire.com/news/home/20251104552099/en/Family-Heart-Foundation-Launches-New-Initiative-to-Increase-Understanding-and-Screening-for-High-Lipoproteina-the-Most-Common-Genetic-Risk-Factor-for-Premature-Cardiovascular-Disease
4. Lipoprotein(a). American Heart Association. Accessed August 10, 2026. https://www.heart.org/en/health-topics/cholesterol/genetic-conditions/lipoprotein-a
5. ACC/AHA issue updated guideline for managing lipids, cholesterol. American College of Cardiology. March 13, 2026. Accessed August 10, 2026. https://www.acc.org/about-acc/press-releases/2026/03/13/18/01/accaha-issue-updated-guideline-for-managing-lipids-cholesterol