Chairs: Y. Endo (Otsu, Japan), tba
|Actual situation of lipoprotein apheresis in patients with elevated lipoprotein(a)
1 University Hospital at the Technische Universität Dresden, Department of Internal Medicine III, Dresden, Germany
Abstract text :
In Germany, the number of patients with elevated Lipoprotein(a) (Lp(a)) levels who newly started lipoprotein apheresis (LA) was steadily increasing in the last years. The official as well as own data will be shown. But the definition of an isolated Lp(a) hyperlipidemia is still quite unclear with respect to LDL cholesterol (LDL-C) levels. Several patients have an elevation of both parameters despite being treated with lipid-lowering drugs. The Federal Joint Committee required that a progress of atherosclerosis has been documented as a part of the indication for LA. The definition of such a progress is still under discussion. The age of a given patient, the severity of the cardiovascular event and the family history should also be taken into consideration. Usually, all vascular territories should be investigated. Should a Cardio-CT be performed in these high-risk patients?
|Lipoprotein(a) – Marker and Target for Lipoprotein Apheresis
1 Apheresis Research Institute, , Cologne, Germany
Abstract text :
Lipoprotein(a) (Lp(a)) is composed of an LDL-like particle in which apoB is covalently bound to apolipoprotein(a) (apo[a]). Lp(a) is an independent cardiovascular (CV) risk factor playing a causal role for atherosclerotic cardiovascular disease (CVD) and calcific aortic valve stenosis. Recent studies have suggested that elevated Lp(a) remains a risk factor even in patients who achieve LDL-C <70mg/dl. Within populations, there is extensive apo(a) size heterogeneity, with >40 different isoforms. Within individuals, >80% carry 2 different-sized apo(a) isoforms. Data showed an inflection for risk of myocardial infarction at Lp(a) >30mg/dl. Genome-wide association studies and Mendelian randomization studies were also consistent with these estimates. Lp(a) levels are generally expressed as mg/dl of the mass of the entire particle, which includes the protein content of apoB-100 and apo(a), and their associated lipids (cholesterol, cholesteryl esters, phospholipids, and triglycerides), as well as carbohydrates attached to apo(a), or in nmol/l as a particle number of apo(a). Lp(a) mass assays have an inherent limitation due to the heterogeneity of Lp(a) particle sizes, making it difficult to standardize assays with appropriate calibrators. Unlike normally distributed LDL-C, Lp(a) levels are skewed leftward, and most individuals (~70%) have values in the normal range of <30 mg/dl.
Lipoprotein apheresis (LA) is a safe well tolerated outpatient treatment to lower LDL-C and Lp(a) by 60%-70%, and is the ultimate therapeutic option in patients with hyperlipoproteinemias (HLP) involving LDL particles. Major therapeutic effect of LA is preventing CV events. Lp(a)-HLP associated with progressive CVD despite effective treatment of all other CV risk factors in particular LDL-C has been approved as indication for LA in Germany since 2008.
The Pro(a)LiFe-study investigated with a prospective multicenter design the long-term preventive effect of LA on incidence rates of CV events over a period of 5 years in 170 consecutive patients with a mean Lp(a) concentration of 108mg/dl and progressive CVD after in median 2 CV events had occurred (Roeseler, 2016). 154 patients (90.6%) completed 5 years follow-up. Significant decline of the mean annual major adverse cardiac event (MACE) rate was observed comparing two years prior to LA to 5 years with regular LA (p<0.0001). Although in most patients small isoforms accounted for the high Lp(a) level, in 4.7% of patients large isoforms were solely responsible for the elevated Lp(a), but patients were clinically indistinguishable. Calculation of isoform specific concentrations allowed to confirm the equivalence of 60 mg/dl or 120 nmol/l as Lp(a) thresholds of the German LA guideline.
Ref.: Roeseler for the Pro(a)LiFe-study group. Arterioscler Thromb Vasc Biol 2016; 36: 2019-2027.
|Treating Lipoprotein(a)-hyperproteinemia and Progressive Cardiovascular Disease with Lipid-Apheresis in North America
1 University of Kansas Medical Center, Clinical Pharmacology, Kansas City, United States
Abstract text :
Background: Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor, found in more than 20% of the world"s population, but presently no appropriate pharmacotherapy exists for lowering Lp(a). In Germany, lipid-apheresis (LA) therapy, acutely lowers Lp(a) >60%, is approved for Lp(a)- hyperproteinemia and progressive cardiovascular disease (CVD) irrespective of LDL-C levels. In North America, LA treatment for Lp(a) is approved for patients if their LDL-C level is >160mg/dL.
Methods: Examine a single site"s experience using biweekly LA therapy for the reduction of cardiovascular events in CVD patients who received LA therapy for more than 6 months with an Lp(a) >50mg/dL and LDL-C <160mg/dL.
Results: A total of 15 CVD patients (9 male), ages 56±16 (range 13-82), qualified with a mean Lp(a) level of 123.28 mg/dL and LDL-C level of 100.14 mg/dL. The mean period of LA treatment was 3.54 years (range 8 months-7.5 years). Mean pre-apheresis cardiovascular events and interventions occurred 4.28 years (range 1-11.5 years) before initiation of LA therapy. Since beginning LA therapy only 2 patients experienced a cardiovascular event consisting of stent placement (6 months and 3 years post-LA) for angina symptoms.
Conclusion: Lp(a) is an independent CVD risk factor and LA is currently the only therapy available to successfully treat Lp(a). Until future treatments become available LA therapy should be considered for Lp(a)-hyperproteinemia patients with progressive CVD, on maximum lipid modifying pharmacotherapy, irrespective of their LDL-C levels.
Pre-LA is defined as the time period before LA therapy was initiated, post-LA is defined at the time period that patients received LA therapy.