The challenge of familial hypercholesterolaemia
Familial hypercholesterolaemia (FH) is the most common inherited cause of premature cardiovascular disease and atherosclerosis. Between 14 and 34 million people suffer from FH worldwide. This genetic disorder is characterized by high to extremely high blood levels of low-density lipoprotein cholesterol (LDL-C or "bad cholesterol"). There are two genetically distinct forms of FH: homozygous (HoFH) and heterozygous (HeFH). Typically, LDL-C concentrations range from 310 to 580 mg/dL (8–15 mmol/L) in heterozygous cases and from 460 to 1,160 mg/dL (12–30 mmol/L) in homozygous cases.1
An effective reduction in LDL-C levels in homozygous patients is not possible through dietary measures or pharmacological treatment alone. Extracorporeal lipoprotein apheresis, when performed regularly in conjunction with dietary measures and drug treatment, is currently the state-of-the-art approach to effectively reducing LDL-C in these patients.
High levels of lipoprotein(a) [Lp(a)] also advance the development of atherosclerosis.
Lp(a) is structurally similar to LDL-C, with an additional apolipoprotein (apolipoprotein (a)) on the surface. The blood concentration is mainly genetically determined. The function and metabolism of Lp(a) are to date not fully understood.
However, there is a clear link between cardiovascular (CV) risk and Lp(a):
Lp(a) is a proven independent CV risk factor.2 Elevated Lp(a) levels cannot be efficiently managed through dietary measures or drug treatment.
Lipoprotein apheresis is the most effective method for removing Lp(a) in patients with Lp(a) levels of more than 60 mg/dL (120 mmol/L)3 and concomitant cardiovascular disease.
In lipoprotein apheresis, the removal of lipoproteins (e.g., low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a)) takes place in an extracorporeal circuit. The patient's blood is removed from a vein in their arm and passed to the apheresis device, which monitors the extracorporeal circulation. After the removal of LDL-C and Lp(a), the purified blood is returned via a vein in the other arm. Depending on the method used, lipoprotein apheresis takes 60 to 150 minutes on average.
Since the concentration of lipids starts to increase again after a certain time, lipoprotein apheresis must be repeated at regular intervals. Frequency of treatment ranges from once a fortnight to twice a week and depends on national treatment guidelines and the patient’s clinical condition. Target levels for patients with very high CV risk are less than 70 mg/dL (1.8 mmol/L) for LDL-C and less than 50 mg/dL for Lp(a), according to European (ESC/EAS) guidelines.4, 5
LDL/Lp(a) target levels according to EAS/ESC guidelines.4,5
Recommended target levels
Very high cardiovascular risk
High cardiovascular risk
Moderate cardiovascular risk
Low cardiovascular risk
BP = blood pressure; CKD = chronic kidney disease; DM = diabetes mellitus; GFR = glomerular filtration rate; SCORE = systemic coronary risk estimation
1 Nordestgaard BG et al.; European Heart Journal Dec. 2013; 34(45): 3478–90a
2 Nordestgaard BG, Langsted A.; Journal of Lipid Research Nov. 2016; 57(11): 1953–1975
3 Richtlinie Methoden vertragsärztliche Versorgung, 16 May 2015.
4 Catapano AL et al.; Atherosclerosis Journal. Oct. 2016; 253: 281–344.
5 Nordestgaard BG et al.; Lipoprotein(a): EAS Recommendations for Screening, Desirable Levels and Management, A Handbook for Clinicians, 2012.