LDL-cholesterol goal achievement, cardiovascular disease, and attributed risk of Lp(a) in a large cohort of predominantly genetically verified familial hypercholesterolemia

Martin P Bogsrud; Asgeir Græsdal; Dan Johansen; Gisle Langslet; Anders Hovland; Kjell-Erik Arnesen; Liv J Mundal; Kjetil Retterstøl; Cecilie Wium; Kirsten B Holven

doi:10.1016/j.jacl.2019.01.010

LDL-cholesterol goal achievement, cardiovascular disease, and attributed risk of Lp(a) in a large cohort of predominantly genetically verified familial hypercholesterolemia

J Clin Lipidol. 2019 Mar-Apr;13(2):279-286. doi: 10.1016/j.jacl.2019.01.010. Epub 2019 Jan 30.

Authors

Affiliations

¹ Norwegian National Advisory Unit on Familial Hypercholesterolemia, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway; The Lipid Clinic, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway; Unit for Cardiac and Cardiovascular Genetics, Department of Medical Genetics, Oslo University Hospital, Oslo, Norway. Electronic address: mabogs@ous-hf.no.
² Vestfold Medical Center, Sandefjord, Norway.
³ Norwegian National Advisory Unit on Familial Hypercholesterolemia, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway.
⁴ Norwegian National Advisory Unit on Familial Hypercholesterolemia, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway; The Lipid Clinic, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway.
⁵ Division of Internal Medicine, Nordland Hospital Bodø, Bodø, Norway; Department of Clinical Medicine, University of Tromsø, Tromsø, Norway.
⁶ The Lipid Clinic, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway.
⁷ The Lipid Clinic, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
⁸ Norwegian National Advisory Unit on Familial Hypercholesterolemia, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

PMID: 30910667
DOI: 10.1016/j.jacl.2019.01.010

Abstract

Background: Current treatment goals for familial hypercholesterolemia (FH) recommended by the European Atherosclerosis Society (EAS) are LDL-C ≤2.5 mmol/L (∼100 mg/dL) or ≤1.8 mmol/L (∼70 mg/dL) in very high-risk subjects.

Objective: The objective of the present study was to investigate characteristics and treatment status in subjects with genetically verified FH followed at specialized lipid clinics in Norway.

Methods: Data from treatment registries of 714 adult (>18 years) subjects with FH.

Results: Fifty-seven percent were female. Mean age (SD) at last visit was 44 (16.3) years, and the subjects had been followed at a lipid clinic for 11.1 (7.9) years. Two hundred forty-five (34%) were classified as very-high-risk, and 44% of these had established coronary heart disease. Very-high-risk FH subjects more often received maximal statin dose (54% vs 33%, P < .001), ezetimibe (76% vs 48%, P < .001) or resins (23% vs 9%, P < .001), and achieved LDL-C was lower (3.2 vs 3.5 mmol/L [124 vs 135 mg/dL], P = .003) than normal-risk FH. LDL-C treatment goal was achieved in 25% and 8% of subjects with normal-risk and very-high-risk FH, respectively. Lp(a) levels were available in 599 subjects, and they were divided into 2 groups: ≥90 mg/dL (n = 96) and <90 mg/dL (n = 503). Despite similar lipid levels, body mass index, smoking status, presence of diabetes, and blood pressure, prevalence of coronary heart disease was doubled in the high- compared to low-Lp(a) group (30% vs 14%, P < .001).

Conclusion: Very few FH subjects achieve their LDL-C treatment goal. New treatment modalities are needed. Independent of LDL-C and other risk factors, high Lp(a) seem to be an important additional risk factor in genetically verified FH.

Keywords: Familial hypercholesterolemia; LDL-cholesterol; Lipoprotein (a); Proprotein convertase subtilisin/kexin type 9 (PCSK9); Treatment goal achievement.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cardiovascular Diseases / complications*
Cholesterol, LDL / blood*
Female
Goals*
Humans
Hyperlipoproteinemia Type II / blood
Hyperlipoproteinemia Type II / complications
Hyperlipoproteinemia Type II / drug therapy*
Hyperlipoproteinemia Type II / genetics*
Lipoprotein(a) / blood*
Male
PCSK9 Inhibitors
Risk Factors
Serine Proteinase Inhibitors / pharmacology
Smoking
Young Adult

Substances

Cholesterol, LDL
Lipoprotein(a)
PCSK9 Inhibitors
Serine Proteinase Inhibitors