Lipoprotein a

• OMIM: 152200
• UniProt: P08519

• OMIM: 107730
• UniProt: P04114

Lipoprotein (a ), short- Lp (a), a lipoprotein, the protein portion of apolipoprotein (a) and apolipoprotein B -100 is made. It is part of the blood fats and possesses in its structure is very similar to LDL cholesterol. For cardiovascular complications such as heart attack or stroke, it is to be regarded as an additional independent risk factor, particularly when high levels are present in the blood. Mutations in the APOB gene can cause defective apoB -100 and this can often lead to hereditary hypolipoproteinemia ( FHBL ) and on hereditary ligand defect in apoB -100 ( FDB). In combination with other defects can cause hypocholesterolemia.

Characteristics

Lipoprotein ( a) was first described in 1963 by the Norwegian physician Berg and his staff as lipoprotein associated antigen. It lies with its molecular mass very close to the LDL - cholesterol. The lipoprotein (a) after a part of its structure such as the LDL - cholesterol to low density lipoproteins (LDL), and has adjacent to the block of ApoB -100, which is also present in LDL - cholesterol, in addition, the glycoprotein Apo (a). Apo ( a) has a similarity to plasminogen, which the lipoprotein (a ) may promote atherosclerosis in addition to its potency thromboses and embolisms.

Analogous to plasminogen, it may couple to its binding sites and so prevent its thrombolytic activity. Lipoprotein (a ) represents a link between blood lipids and coagulation molecules in the blood dar. There is very little secure knowledge about its normal functions in the body. It has effects on wound healing and blood clotting such as vitamin C and could therefore represent a protective mechanism against physiological consequences of vitamin C deficiency. These relationships are in accordance with the scientific literature but not yet fully proven.

The plasma levels of lipoprotein (a) are predominantly genetically determined and therefore very stable. The lipoprotein (a) determination is not suitable as a screening parameter but should be targeted. Do any of the following findings for a patient with vascular disease to and is the LDL cholesterol left untreated or treated within the normal range, a lipoprotein (a) determination is recommended:

• ≥ 2 cardiovascular events in the past 2 years.
• Clinically and / or documented by imaging methods is a progressive or recurrent cardiovascular disease despite effective treatment of other existing cardiovascular risk factors.
• Cardiovascular complications before age 50 despite treatment of existing cardiovascular risk factors.
• Family history for cardiovascular complications.

Lp (a ) increasing

Lipoprotein (a ) plasma levels from 30 mg / dl are associated with an increased cardiovascular risk and are considered increased. The lipoprotein (a) -mediated risk for vascular disease (coronary heart disease, myocardial infarction, stroke, and arterial occlusive disease) is enhanced by the interaction with other existing risk factors. Lipoprotein (a ) but can also be the primary determinant risk factor in patients with early or occurring particularly rapidly progressive vascular disease. Lipoprotein (a ) accumulates in areas with existing vessel damage in the inner vessel wall of the artery. Most extensive the importance of lipoprotein (a) is occupied for coronary heart disease in large epidemiological studies.

In the Copenhagen City Heart Study 2008 has been demonstrated that elevated lipoprotein ( a) levels have a predictive value for the occurrence of heart attacks in the general population. Above the 90th percentile of lipoprotein (a) was a 3 - to 4 - fold higher risk for the occurrence of myocardial infarction. Male individuals with high lipoprotein (a ) and other cardiovascular risk factors reported a 10 -year risk of 35 % to .. For females older than 65 years was found, however, in a study that Lp ( a) is not an independent cardiovascular risk factor.

Treatment of Lp (a ) increasing

The plasma levels of lipoprotein (a) are genetically determined, regardless of the levels of other blood fats and neither by diet nor to influence lifestyle changes clinically relevant. Under therapy with nicotinic acid preparations can an approximately 25% reduction can be achieved, which is insufficient with progressive vascular disease. The problem with the flush side effects limit the long-term therapy in combination with the recently approved ProstaglandinD2 - antagonists ( inhibitor flush symptoms ). The apheresis is currently the only possibility of a lowering of the effective targeted lipoprotein (a) levels. The use of apheresis for the treatment of patients with isolated Lp (a ) increase and therapeutically uncontrollable progressive coronary artery disease has been pursued since the early 1990s in Germany as a therapeutic trial. Pioneering work in the university hospitals in Berlin and Munich. The clinical successes were impressive, the number of patients was very small.

Lipid apheresis

The term lipid apheresis outpatient guided extracorporeal blood purification procedures are summarized, which can eliminate using various physicochemical separation principles ( filtration, precipitation or adsorption of plasma or whole blood) blood lipids, especially LDL- cholesterol and lipoprotein ( a).

With all currently in Germany in the routine work process, it is possible per therapy session the quality criterion of at least 60% reduction of LDL - cholesterol to realize in lipoprotein ( a) 70 % can be achieved. The treatment is carried out weekly to biweekly. The Lipid apheresis is in the treatment of severe, on medication regimens appealing hypercholesterolemia (increase in LDL cholesterol ) a safe and routinely conducted therapy in Germany.

Takeover by the health insurance

The Lipid apheresis is an essential part of the treatment of severe hypercholesterolemia levels, there are since 1991 in this regard refund policies in the field of public health insurance. In 1996, the consideration of the entire cardiovascular risk profile with explicit inclusion of lipoprotein (a) has been added. In the new version in 2003 Lipoprotein ( a) was denied a indikationsbegründende importance. Patients could be treated since then only after unsafe individual case decisions of the fund or to referral to the legal Klagewegs. After several years of public protests also affected and treating doctors revised the Federal Joint Committee, the committee for establishing the services provided by statutory health insurance, in 2008 his decision. The following indications for apheresis was admitted and explained:

• At the same time clinically and documented by imaging techniques, there is a progressive cardiovascular disease (coronary heart disease, peripheral vascular disease or cerebrovascular disease).
• With the use of established methods of treatment has not been able to stop the progression of the disease.
• Lipoprotein (a ) is greatly increased with > 60 mg / dl, LDL cholesterol is within the normal range.
• An expert Commission has made a careful individual assessment and issued based on an individual benefit-risk assessment a positive recommendation for the use of apheresis.
• Patients who are to receive an Lp ( a) apheresis should be asked whether they want to participate in clinical studies to evaluate the utility of Lp ( a) apheresis or not.

Overall, to be used as the " ultima ratio " for refractory course according JFC directives, the apheresis. In the foreground balancing the indication of the patient 's overall risk profile should be. These empirical and pragmatic regulation of indications is patient needs. The level of lipoprotein (a) level in the blood is not enough to provide the indication for apheresis. The progression of cardiovascular disease has been documented clinically or by imaging an essential condition. The Federal Joint Committee requested as part of its Decision the submission of further scientific findings on the effectiveness of lipid apheresis on lipoprotein (a) increase in parallel with the refund. A clinical trial is scheduled to begin in 2010.

Effectiveness of apheresis with isolated Lipoprotein (a ) elevation

The effectiveness of lipid apheresis on lipoprotein (a) increase was analyzed in a retrospective work-up in Germany on the basis of multi-year courses before and after the onset of chronic lipid apheresis. The primary study parameter was related to the annual rate of major cardiovascular events (myocardial infarction, coronary intervention, coronary artery bypass surgery, sudden cardiac death ). The mean concentration of lipoprotein (a) was 118 mg / dl before initiation of apheresis. The mean trough levels after the initiation of apheresis was 33 mg / dl corresponding to a 72 % reduction. The incidence of serious cardiovascular events was in the patients than average at about 1 / year and thereby rose in the period before Apheresebeginn with increasing disease duration exponentially. Comparing the classification according to the Framingham score, which defines the high risk of infarction as > 20 % in 10 years, it is clear that an extreme risk group was recorded. The mean rate of major cardiovascular events during the observation period under apheresis was only 0.14 / year according to a statistically significant 86 % reduction in event rate. What was remarkable was the rapid drop after the initiation of apheresis. All used apheresis procedures were equivalent in this respect. These results confirm the assumption that increased lipoprotein favor ( a) levels atherothrombotic complications and a progressive course of vascular disease, and the lowering of lipoprotein (a) levels by apheresis can prevent subsequent complications.

Lipoprotein (a ) may be the primary determinant risk factor in patients with early or occurring particularly progressive vascular disease. The results to date on the effectiveness of lipid apheresis confirm that elevated lipoprotein favor ( a) levels atherothrombotic complications and a progressive course of vascular disease, and the lowering of lipoprotein (a ) level may prevent subsequent complications. The Federal Joint Committee thus has the plausible use of apheresis in isolated lipoprotein (a) increase according to the best available evidence patient justice translated into a reimbursement scheme of the statutory health insurance. Lipoprotein (a ) should be included in the risk assessment of familial, premature onset of cardiovascular complications and rapidly progressive vascular disease. The genetically determined value needs to be determined only once principle. Due to the not yet generally standardized measurement methods, laboratories should be chosen with expertise in lipid metabolism diagnostics. The Lipid apheresis is for patients in which lipoprotein (a ) was identified as the dominant factor of the severe course of their vascular disease. Other scientific results are required to underpin the existing refund mechanism scientifically and to specify the indications.