CARDIOVASCULAR MEDICINE

Long term statin treatment reduces lipoprotein(a) concentrations in heterozygous familial hypercholesterolaemia

S van Wissen¹, T J Smilde², M D Trip¹, Th de Boo³, J J P Kastelein¹ and A F H Stalenhoef²

¹ Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands
² Department of Medicine, Division of General Internal Medicine, University Medical Centre Nijmegen, Nijmegen, Netherlands
³ Department of Epidemiology and Biostatistics, University Medical Centre Nijmegen

Correspondence to:
Correspondence to:
Dr S van Wissen, Academic Medical Centre, Department of Vascular Medicine, Room C2-431, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands;
s.vanwissen{at}amc.uva.nl

Background: Raised plasma lipoprotein(a) (Lp(a)) is associated with increased risk of cardiovascular disease. It is unknown whether increased Lp(a) is an additional risk factor for coronary artery disease in familial hypercholesterolaemia (FH) or whether statin treatment can reduce Lp(a) concentrations in the long term.

Objective: To investigate Lp(a) concentrations in relation to statin treatment and the progression of atherosclerosis in a large cohort of FH patients.

Design: A two year, randomised, double blind trial (the ASAP trial).

Patients: 325 heterozygous FH patients.

Intervention: Treatment with 80 mg atorvastatin or 40 mg simvastatin.

Main outcome measure: Change in Lp(a) concentrations and intima–media thickness of carotid artery segments at one year and two years.

Results: At baseline, median Lp(a) concentrations were 327 mg/l and 531 mg/l in the atorvastatin and simvastatin arms, respectively (p = 0.03). In the atorvastatin arm, Lp(a) concentrations decreased to 243 mg/l after one year (p < 0.001) and to 263 mg/l after two years (p < 0.001). In the simvastatin arm, Lp(a) concentrations decreased to 437 mg/l after one year (p < 0.001) and to 417 mg/l after two years (p < 0.001). The difference in Lp(a) reduction between the two treatment arms was significant after one year (p = 0.004), but not after two years (p = 0.086). Lp(a) concentrations at baseline were not related to cardiovascular events at baseline. There was no correlation between baseline Lp(a) concentrations and low density lipoprotein cholesterol concentrations or intima–media thickness at baseline. Change in Lp(a) concentrations was not correlated with change in intima–media thickness after one or two years.

Conclusions: Long term statin treatment significantly lowers Lp(a) in FH patients. However, this reduction was unrelated to changes in intima–media thickness and casts doubt on the importance of Lp(a) in the progression of atherosclerotic disease in these patients.

Keywords: familial hypercholesterolaemia; statins; lipoprotein(a); Lp(a); intima; media thickness

Abbreviations: ASAP, effects of atorvastatin versus simvastatin on atherosclerosis progression; ARIC, atherosclerosis risk in community; ELISA, enzyme linked immunosorbent assay; FH, familial hypercholesterolaemia; HDL-c, high density lipoprotein cholesterol; LAARS, LDL-apheresis atherosclerosis regression study; LDL-c, low density lipoprotein cholesterol; Lp(a), lipoprotein(a); TGFß, transforming growth factor ß

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