From the Guidelines
Elevated apolipoprotein levels, particularly apolipoprotein(a) [Lp(a)], indicate an increased risk of cardiovascular disease and calcific aortic valve disease, with levels above 30-50 mg/dL or 75-125 nmol/L considered to be in the atherothrombotic range. According to the NHLBI working group recommendations 1, Lp(a) is a highly prevalent genetic risk factor for cardiovascular disease, affecting 20-30% of the global population. The evidence suggests that Lp(a) contributes to atherogenesis and thrombosis, and its levels are associated with an increased risk of coronary artery disease, myocardial infarction, and stroke 1.
Key Points to Consider
- Lp(a) levels are primarily determined by the LPA gene locus encoding apo(a), with some influence from the APOE locus and PCSK9 R46L loss of function mutations 1
- Elevated Lp(a) levels are associated with a higher risk of cardiovascular disease, even at low LDL-C levels, highlighting the importance of measuring Lp(a) in clinical practice 1
- Lifestyle modifications, such as a heart-healthy diet and regular exercise, may help lower Lp(a) levels, but medications such as statins, ezetimibe, PCSK9 inhibitors, or bile acid sequestrants may be necessary for individuals with high Lp(a) levels 1
Clinical Implications
- Regular monitoring of Lp(a) levels through lipid panel tests is important to assess treatment effectiveness and cardiovascular risk 1
- The mechanisms through which Lp(a) contributes to cardiovascular disease are not fully understood, but it is thought to involve its LDL-like component, pro-inflammatory effects, and anti-fibrinolytic/pro-thrombotic effects 1
- Further research is needed to fully understand the role of Lp(a) in cardiovascular disease and to develop effective treatments for elevated Lp(a) levels 1
From the Research
Apolipoprotein Elevated Explanation
- Apolipoprotein B (apoB) is a primary component of low-density lipoprotein (LDL) cholesterol and is considered a more accurate measure of cardiovascular risk than LDL-C or non-high-density lipoprotein cholesterol (non-HDL-C) 2.
- Elevated levels of lipoprotein(a) [Lp(a)] are causal for atherosclerotic cardiovascular disease (ASCVD) and are the most prevalent inherited dyslipidemia and strongest genetic ASCVD risk factor 3.
- The relationship between apoB and LDL-C or non-HDL-C targets can be altered by statin therapy, and reducing LDL-C to a pre-determined goal may still leave an excess of atherogenic lipoproteins, as reflected in apoB levels 4.
- Therapeutic lowering of apoB has been shown to reduce mortality and major adverse cardiovascular events, with a relative risk of 0.95 for all-cause mortality and 0.93 for cardiovascular mortality for every 10 mg/dL decrease in apoB 5.
- Candidates for Lp(a) screening include patients with a personal or family history of premature cardiovascular disease, familial hypercholesterolemia, recurrent cardiovascular events, or inadequate LDL-C responses to statins 6.
- Reducing LDL-C to the lowest attainable value with a high-potency statin should be the primary focus of lipid-modifying therapies, and if the Lp(a) level is 30 mg/dL or higher, the clinician may consider adding niacin or LDL apheresis 6.