From the Guidelines
Lipoprotein(a) (Lp(a)) is a genetic risk factor for cardiovascular disease (CVD) and calcific aortic valve disease (CAVD), with elevated levels affecting 20-30% of the global population 1.
Definition and Composition
Lp(a) is a specialized type of lipoprotein particle in the blood that combines a low-density lipoprotein (LDL) particle with a protein called apolipoprotein(a) 1. It's primarily produced by the liver and circulates in the bloodstream.
Risk Factors and Association with CVD
Elevated levels of Lp(a) are considered an independent risk factor for CVD, including heart attacks and strokes, regardless of other cholesterol levels 1. This risk occurs because Lp(a) can contribute to atherosclerosis (plaque buildup in arteries) and blood clot formation.
Determinants of Lp(a) Levels
Lp(a) levels are largely determined by genetics rather than lifestyle factors, with approximately 20-30% of people having elevated levels 1.
Management and Treatment
Unlike other lipoproteins, Lp(a) levels don't respond well to traditional cholesterol-lowering medications or lifestyle changes 1. Currently, there are no approved medications specifically targeting Lp(a), though some treatments like PCSK9 inhibitors and niacin may modestly reduce levels 1. For those with high Lp(a), doctors typically focus on aggressively managing other cardiovascular risk factors like LDL cholesterol, blood pressure, and diabetes 1.
Ongoing Research and Development
Specialized treatments targeting Lp(a) are in clinical development but not yet widely available 1.
From the Research
Definition and Composition of Lipoprotein(a)
- Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL) cholesterol-like particle bound to apolipoprotein(a) 2
- It is composed of two major protein components: apoB100 and apolipoprotein(a) 3
- Lp(a) is a genetically determined, causal, and prevalent risk factor for atherosclerotic cardiovascular disease 3
Role of Lipoprotein(a) in Cardiovascular Disease
- High levels of Lp(a) are an independent and causal risk factor for atherosclerotic cardiovascular diseases through mechanisms associated with increased atherogenesis, inflammation, and thrombosis 3
- Lp(a) remains a risk factor for cardiovascular disease development even in the setting of effective reduction of plasma low-density lipoprotein cholesterol and apoB100 3
- Elevated Lp(a) levels are associated with a residual cardiovascular risk despite traditional risk factor optimization, including LDL cholesterol reduction 2
Prevalence and Measurement of Lipoprotein(a)
- An estimated 20% to 25% of the global population have Lp(a) levels of 50 mg/dL or higher, a level noted by the European Atherosclerosis Society to confer increased cardiovascular risk 2
- Plasma Lp(a) levels present a skewed distribution towards higher values and vary widely between individuals and according to ethnic background due to genetic variants in the LPA gene 4
- Guidelines have begun to advocate measurement of Lp(a) to identify patients with very high levels that have a family history of premature CVD or elevated Lp(a) 4
Treatment Options for Lipoprotein(a)
- Current treatment options for elevated Lp(a) include lipoprotein apheresis, proprotein convertase subtilisin/kexin type 9 inhibitors, and emerging nucleic acid-based therapies such as antisense oligonucleotides 2, 4, 5
- Statins have neutral or detrimental effects on Lp(a), while PCSK9 inhibitors significantly reduce its level by up to 30% 4, 5
- Specific lowering of Lp(a) with antisense oligonucleotides shows good safety and strong efficacy with up to 90% reductions 4