By Christopher Piercecchi, MD | The Men’s Clinic for Wellness & Vitality | Tucson, Arizona
Most men are familiar with cholesterol. They know about LDL, often called “bad cholesterol,” and HDL, commonly referred to as “good cholesterol.” Many have their cholesterol checked every year and assume that if the numbers are acceptable, their cardiovascular risk is reasonably well understood.
Unfortunately, that is not always the case. There is another important cardiovascular risk factor that is not included in a standard cholesterol panel, is largely determined by genetics, and can remain completely unrecognized for decades. It is called lipoprotein(a), abbreviated Lp(a).
Approximately one in five people has an elevated Lp(a) concentration. Unlike many conventional cardiovascular risk factors, Lp(a) is largely unaffected by exercise, dietary changes, or weight loss. A man can be lean, physically active, metabolically healthy, and have relatively normal cholesterol levels while carrying a substantial inherited predisposition to cardiovascular disease.
This does not mean that everyone with elevated Lp(a) will develop heart disease. It means that a potentially important part of their cardiovascular risk may be missing from the evaluation.
What Exactly Is Lipoprotein(a)?
Lipoprotein(a) is a cholesterol-carrying particle that resembles LDL. Both contain apolipoprotein B-100, or ApoB, but Lp(a) has an additional protein attached to it called apolipoprotein(a). That structural difference is important because Lp(a) has biological properties that distinguish it from ordinary LDL particles.
Like LDL, Lp(a) can contribute to the development of atherosclerosis, the progressive accumulation of plaque within arterial walls. It also carries oxidized phospholipids and participates in inflammatory processes associated with vascular injury. Large observational studies, genetic investigations, and Mendelian randomization analyses have established elevated Lp(a) as a causal risk factor for atherosclerotic cardiovascular disease, rather than simply a marker associated with it.[1,2]
Elevated Lp(a) is also associated with calcific aortic valve disease and aortic stenosis, another potentially serious cardiovascular condition that becomes more prevalent with age.
What makes Lp(a) particularly interesting is that its concentration is determined predominantly by inherited variations in the LPA gene. Levels are generally established early in life and remain relatively stable throughout adulthood. Consequently, a person may be exposed to elevated Lp(a) for decades before developing any recognizable cardiovascular disease.
This is precisely why identifying it early can be valuable.
How Much Risk Does Elevated Lp(a) Actually Carry?
Lp(a) is not an all-or-nothing risk factor. Cardiovascular risk generally increases as its concentration rises, and the significance of any particular measurement depends on the individual’s overall cardiovascular risk profile.
The 2026 American College of Cardiology and American Heart Association dyslipidemia guideline identifies an Lp(a) concentration of 125 nmol/L or greater as a cardiovascular risk-enhancing factor. At this level, the associated relative risk of atherosclerotic cardiovascular disease is approximately 40% higher. At concentrations of 250 nmol/L or greater, the estimated relative risk is approximately doubled.[1]
Some laboratories report Lp(a) in milligrams per deciliter (mg/dL) rather than nanomoles per liter (nmol/L). The commonly referenced guideline thresholds are 50 mg/dL and 100 mg/dL, respectively. However, these units measure different properties, and results should not be converted using a fixed mathematical factor because Lp(a) particle size varies between individuals.
It is also important to distinguish relative risk from absolute risk. A doubling of cardiovascular risk does not mean that someone has a 100% probability of developing disease. A younger individual with otherwise excellent cardiovascular health may have a relatively low absolute risk despite elevated Lp(a). However, that same inherited risk becomes increasingly consequential as other cardiovascular risk factors accumulate with age.
The larger issue is cumulative exposure. A man with genetically elevated Lp(a) may experience decades of increased atherogenic exposure before conventional risk assessments identify him as someone requiring more aggressive prevention.
Why Isn’t Lp(a) Included in Routine Cholesterol Testing?
Historically, Lp(a) testing has not been a routine component of cardiovascular screening. Standard lipid panels measure total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides, but they do not provide a separate Lp(a) concentration.
This creates an important limitation. A man may have an LDL cholesterol level that appears acceptable while carrying an inherited cardiovascular risk factor that remains undetected.
Fortunately, recommendations have evolved. The 2026 ACC/AHA dyslipidemia guideline recommends measuring Lp(a) at least once in adulthood, regardless of whether someone has a known family history of cardiovascular disease.[1] This is consistent with earlier recommendations from the European Atherosclerosis Society and the National Lipid Association.[2,3]
Because Lp(a) levels are predominantly genetically determined and relatively stable, repeated measurements are generally unnecessary. One appropriately performed test is usually sufficient to establish the presence and magnitude of this risk factor.
When elevated Lp(a) is identified, testing first-degree relatives may also be appropriate. Parents, siblings, and children can share the inherited predisposition, and identifying elevated levels earlier in life may allow preventive strategies to begin before significant disease develops.
Can You Lower Lp(a)?
This is where the discussion becomes particularly important.
Unlike LDL cholesterol, Lp(a) generally does not respond meaningfully to conventional lifestyle interventions. Losing weight, exercising regularly, improving nutritional habits, and reducing saturated fat intake can produce meaningful improvements in many cardiovascular risk factors, but they typically have little effect on genetically elevated Lp(a).
That does not make lifestyle interventions unnecessary. Quite the opposite. A person with elevated Lp(a) has an additional reason to optimize every cardiovascular risk factor that can be modified.
At present, there is no medication approved specifically to reduce cardiovascular events through targeted Lp(a) lowering. Statins do not meaningfully reduce Lp(a), and concentrations may increase modestly in some individuals. Nevertheless, statins remain extremely valuable because reducing LDL cholesterol and atherogenic lipoprotein exposure lowers cardiovascular event risk. Similarly, PCSK9 inhibitors substantially reduce LDL cholesterol and can modestly lower Lp(a), although their established clinical benefit should not be attributed solely to the reduction in Lp(a).
Niacin can lower Lp(a) concentrations, but it has not demonstrated sufficient cardiovascular outcome benefit to justify its use specifically for this purpose. Supplements and other commonly marketed cholesterol remedies have likewise failed to establish a reliable role in treating elevated Lp(a).
The distinction is straightforward: lowering a laboratory value is not necessarily the same as lowering the risk of a heart attack or stroke.
That distinction has become especially relevant following a recent clinical trial.
What Did the Recent Lp(a)HORIZON Trial Show?
For several years, researchers have been developing medications designed specifically to suppress the production of Lp(a). One of the most closely watched was pelacarsen, an investigational antisense medication intended to reduce Lp(a) production in the liver.
The phase III Lp(a)HORIZON trial enrolled more than 8,300 patients with established cardiovascular disease and elevated Lp(a). Its purpose was to determine whether substantially reducing Lp(a), in addition to established cardiovascular treatments, would decrease major cardiovascular events.
In September 2026, the manufacturer announced that although pelacarsen successfully reduced Lp(a) concentrations, the trial did not achieve its primary endpoint of reducing cardiovascular events in the overall study population.[4]
The complete peer-reviewed results were not yet available at the time of this article, so the findings require careful interpretation. The negative result does not erase the extensive genetic and epidemiologic evidence linking elevated Lp(a) to cardiovascular disease. Nor does it establish that all future Lp(a)-lowering therapies will be ineffective.
It does, however, reinforce an essential principle of evidence-based medicine. Demonstrating that a medication changes a biological marker does not establish that it improves meaningful clinical outcomes.
Other Lp(a)-targeted therapies remain under investigation, and their cardiovascular outcome trials will help clarify whether different approaches to lowering Lp(a) can produce clinical benefit.
Until convincing outcome evidence becomes available, the most defensible strategy remains aggressive management of cardiovascular risk factors for which effective treatments already exist.
What Should You Do If Your Lp(a) Is Elevated?
An elevated Lp(a) result should not automatically trigger another medication or an expensive testing protocol. It should prompt a more careful assessment of the individual’s overall cardiovascular risk.
At The Men’s Clinic for Wellness & Vitality, cardiovascular prevention involves evaluating the interaction between inherited predisposition, atherogenic lipoprotein exposure, blood pressure, metabolic health, lifestyle, and evidence of existing cardiovascular disease.
For men with elevated Lp(a), particular attention should be directed toward achieving appropriate LDL cholesterol and ApoB levels, maintaining excellent blood pressure control, avoiding tobacco exposure, and identifying other modifiable risks. In selected individuals, coronary artery calcium scoring or other cardiovascular imaging may provide additional information about whether atherosclerosis is already present and how intensively treatment should be pursued.
A calcium score of zero can be reassuring regarding near-term risk, but it does not eliminate inherited cardiovascular risk or exclude all noncalcified coronary plaque. Imaging findings must therefore be interpreted in the context of the entire clinical picture.
The goal is not necessarily to normalize the Lp(a) concentration itself. The goal is to reduce the patient’s probability of developing cardiovascular disease despite an inherited risk factor that may not currently be directly treatable.
The Bottom Line
Lipoprotein(a) is one of the more important inherited cardiovascular risk factors that conventional cholesterol testing can overlook. It is common, largely genetically determined, and associated with increased risk of atherosclerotic cardiovascular disease and calcific aortic valve disease.
Although we do not yet have an approved medication proven to reduce cardiovascular events specifically by targeting Lp(a), identifying an elevated concentration has immediate clinical value. It allows physicians to recognize inherited risk, refine cardiovascular assessment, and determine whether earlier or more intensive preventive treatment is appropriate.
For many men, the most important step is simply knowing their number. A single blood test can identify a cardiovascular risk factor they may have carried throughout their lives without ever realizing it.
And when that risk is identified early enough, there is an opportunity to address the factors we can control before cardiovascular disease becomes clinically apparent.
At The Men’s Clinic for Wellness & Vitality, this is a fundamental part of our approach to preventive medicine: identifying meaningful risk early, interpreting it appropriately, and using established medical evidence to guide interventions that improve long-term health.
References
- Blumenthal RS, et al. 2026 ACC/AHA Multisociety Guideline on the Management of Dyslipidemia. Circulation. 2026. doi:10.1161/CIR.
0000000000001423. - Kronenberg F, Mora S, Stroes ESG, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. European Heart Journal. 2022.
- Koschinsky ML, Bajaj A, Boffa MB, et al. A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice. Journal of Clinical Lipidology. 2024;18–e319. doi:10.1016/j.jacl.2024.03.
001. - National Lipid Association. Top Line Results from the Phase 3 Lp(a)HORIZON Trial. September 14, 2026. Preliminary trial announcement; complete peer-reviewed results pending.