For Physicians
Lipoprotein(a) elevation (Lipoprotein (a) - Hyperlipoproteinemia), A Profound Causal and Independent Risk Factor for Cardiovascular Disease and Calcified Aortic Valve Stenosis (CAVC)
Christian G. Schrock, MD
Multiple genetic and epidemiological studies have clearly established that elevated Lipoprotein(a) [Lipoprotein(a)-hyperlipoproteinemia][Hyperlipoproteinemia(a)] is a causal and independent risk factor for cardiovascular (CVD) disease. 20% of the world’s population have elevated levels and 5% are in the top quartile with 10 fold increase in male of MI or MACE often at a young age. It is estimated to be responsible for 1/14 MI’s in the US and 1/7 Calified Aortic Value Stenosis (CAVS). Particularly in the United States this is little known; only 2% of physicians and caregivers are aware of the significance of elevated Lipoprotein(a). Lipoprotein(a) level determination is not a part of routine lipid screening and seldom tested even when family and/or patient circumstances suggests the possibility of an elevated Lipoprotein(a). Families with mutiple blood relatives affected is common because of autosomal dominant inheritance. This is the case despite the fact that testing of Lipoprotein(a) levels is now well standardized, readily available (Quest, ARUP, Mayo Reference Laboratory and via of many other laboratories) and inexpensive (cost is less than $25 at reference laboratories). In the United States it is rarely treated except with statins that are of questionable value and may be detrimental. A recent prospective, randomized, sham controlled cross- over study of patients with refractory angina due to elevated Lipoprotein (a) reached a p =<0.0001 significance favoring apheresis. This study and other studies have established apheresis as effective therapy in reducing Lipoprotein(a) levels and treatment of associated CVD. Presently there only 31 patients treated with apheresis for elevated Lipoprotein (a) in the entire United States compared to over 1500 in Germany alone.
CONCLUSION
In the United States Lipoprotein(a) elevation (Lipoprotein(a)-hyperlipoproteinemia) [Hyperliproteinemia (a)] is an unappreciated, seldom tested for, and very rarely effectively treated disease entity despite being a profound risk factor for CVD disease.
Schematic drawing of Lp(a) from: "Targeting Lipoprotein (a): an Evolving Therapeutic Landscape"
Current Lp(a) Treatment Options
Treatment Options for Patients with Elevated Lipoprotein(a)
PCSK9 Inhibitors
Can reduce levels of lipoprotein(a) which would eventually lead to heart attack.
Lp(a) Apheresis
Typical distributions of lipoprotein(a) levels in the general population
These graphs are based on non-fasting fresh serum samples from ∼3000 men and 3000 women from the Copenhagen General Population Study collected from 2003 through 2004.2 Green colour indicates levels below the 80th percentile, whereas red colour indicates levels above the 80th percentile.
Quantitative CMR perfusion pixel maps pre and post apheresis and pre and post sham
Quantitative CMR perfusion pixel maps pre and post apheresis and pre and post sham (A) and group data from myocardial perfusion at rest (left), perfusion with stress (middle) and the myocardial perfusion reserve (right) (B). (A) Quantitative CMR perfusion pixel maps pre- and postapheresis and pre- and post-sham. The colour scale shows perfusion from 0–4 mL/g/min as low (black-green), medium (mauve-pink) and high (orange-white), therefore brighter colours represent greater perfusion. In this single patient example, there is clear improvement in stress perfusion after apheresis compared with baseline, but no change is seen during sham treatment. (B) Group data are shown from myocardial perfusion at rest (left), perfusion with stress (middle) and the myocardial perfusion reserve (right). There are no changes in rest perfusion with apheresis or sham, but stress perfusion increases significantly with apheresis compared with sham. The myocardial perfusion reserve increases with apheresis because of the improved stress perfusion.
Link to original article
Clinical course of patients with progressive CVD associated with Lp(a)-HLP in the Pro(a)LiFe study
Clinical course of patients with progressive CVD associated with Lp(a)-HLP in the Pro(a)LiFe study. Mean annual rates of MACE (major adverse cardiac event, i. e. cardiovascular death, nonfatal myocardial infarction, coronary bypass surgery, percutaneous coronary intervention,or stent) in dark orange bars. Light orange bars depict MACE plus disease progression detected by imaging techniques accounted as equivalent event. Progression of CVD without clinical event was accounted as equivalent event with the following findings: incidence of new or additional CVD at a new vascular location or region, or deterioration of existing CVD, e. g. 2‑vessel CAD progressed to 3‑vessel CAD, new appearance of stenosis or plaques within an already affected vessel or vessel region, >20% deterioration of existing stenosis, appearance of in-stent stenosis, or stenosis in artery bypass. MACE, major adverse cardiac event; CVD, cardiovascular disease; LA, lipoprotein apheresis; Lp(a)-HLP, Lp(a)-hyperlipoproteinemia.
