What does an elevated Lipoprotein(a) (Lp(a)) level mean?

From the Guidelines

An elevated lipoprotein(a), or Lp(a), indicates an increased risk for cardiovascular disease, including heart attacks and strokes, with levels above 30-50 mg/dL or 75-125 nmol/L considered to be in the atherothrombotic range 1. This particle is similar to LDL cholesterol but contains an additional protein called apolipoprotein(a), making it particularly harmful to blood vessels. Lp(a) levels are primarily determined by genetics and remain relatively stable throughout life. Normal levels are generally below 30 mg/dL (or 75 nmol/L), with higher levels corresponding to greater cardiovascular risk. Some key points to consider include:

• Lp(a) is a highly prevalent, genetic risk factor for cardiovascular disease (CVD) and calcific aortic valve disease (CAVD) 1
• Elevated Lp(a) levels affect 20-30% of the global population, with possibly higher incidence in patients with established CVD and CAVD 1
• Convincing evidence has emerged from pathophysiological, epidemiologic, and genetic studies on the causality of Lp(a) in contributing to CVD and CAVD 1 Unfortunately, there are currently no medications specifically approved to lower Lp(a), though some treatments like PCSK9 inhibitors (evolocumab, alirocumab) and niacin may modestly reduce levels. If you have elevated Lp(a), the focus should be on aggressively managing other cardiovascular risk factors: maintaining optimal LDL cholesterol (often below 70 mg/dL), controlling blood pressure and diabetes if present, not smoking, exercising regularly, and following a heart-healthy diet 1. Your doctor might recommend more intensive statin therapy or additional cholesterol-lowering medications. Regular cardiovascular check-ups are important, and you should discuss with your doctor whether aspirin therapy might be appropriate for your specific situation. It is essential to note that the European Society of Cardiology (ESC) guidelines recommend measuring Lp(a) in patients at high risk of cardiovascular disease (CVD) and to target levels below 50 mg/dL 1.

From the Research

Elevated Lipoprotein(a) Levels

Elevated lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL) cholesterol-like particle bound to apolipoprotein(a) that acts through induction of vascular inflammation, atherogenesis, calcification, and thrombosis 2.

Association with Cardiovascular Disease

• Elevated Lp(a) levels are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis 2, 3, 4.
• Compelling evidence from pathophysiological, observational, and genetic studies suggests a potentially causal association between high Lp(a) levels and ASCVD 2.
• Lp(a) levels of 50 mg/dL or higher are noted to confer increased cardiovascular risk by the European Atherosclerosis Society 2.

Management and Treatment

• Reducing LDL-C to the lowest attainable value with a high-potency statin should be the primary focus of lipid-modifying therapies 4.
• If Lp(a) levels are 30 mg/dL or higher in patients with residual LDL-C elevations despite maximum-potency statins, the clinician may consider adding niacin (up to 2 g/d) 4.
• Emerging nucleic acid-based therapies, such as the antisense oligonucleotide pelacarsen and the small interfering RNA olpasiran, have potent Lp(a)-lowering effects and appear safe 2.
• PCSK9 inhibition with alirocumab increases the catabolism of Lp(a) particles in statin-treated patients with elevated Lp(a) 3.

Patient Experiences and Awareness

• People with elevated Lp(a) often experience it as an "invisible" disorder with very low awareness in the general population 5.
• Clinicians are often reluctant to measure Lp(a) levels as no effective treatment is available to people with elevated values 5.
• Lifestyle modifications and cholesterol-lowering medications are common interventions after confirmed elevated Lp(a) levels, but patients often perceive a healthy lifestyle as unsuccessful in managing overall CVD risk 5.