Format

Send to

Choose Destination
J Am Coll Cardiol. 2019 Dec 17;74(24):2982-2994. doi: 10.1016/j.jacc.2019.10.019. Epub 2019 Dec 9.

Lipoprotein(a) Concentration and Risks of Cardiovascular Disease and Diabetes.

Author information

1
deCODE genetics/Amgen, Reykjavik, Iceland; School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
2
deCODE genetics/Amgen, Reykjavik, Iceland; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland; Division of Cardiology and Cardiovascular Research Center, Internal Medicine Services, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland.
3
deCODE genetics/Amgen, Reykjavik, Iceland.
4
deCODE genetics/Amgen, Reykjavik, Iceland; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
5
Division of Nephrology, Internal Medicine Services, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland.
6
Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland; Division of Nephrology, Internal Medicine Services, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland.
7
deCODE genetics/Amgen, Reykjavik, Iceland; Department of Ophthalmology, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland.
8
deCODE genetics/Amgen, Reykjavik, Iceland; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland; Department of Immunology, Landspitali, The National University Hospital of Iceland.
9
Mjodd Laboratory, Reykjavik, Iceland.
10
Department of Clinical Biochemistry, Akureyri Hospital, Akureyri, Iceland.
11
Department of Clinical Biochemistry, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland.
12
Division of Cardiology and Cardiovascular Research Center, Internal Medicine Services, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland.
13
Laekning, Medical Clinics, Reykjavik, Iceland.
14
deCODE genetics/Amgen, Reykjavik, Iceland; School of Science and Engineering, Reykjavik University, Reykjavik, Iceland.
15
Division of Endocrinology and Metabolic Medicine, Internal Medicine Services, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland.
16
Department of Neurology, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland.
17
Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland; Division of Endocrinology and Metabolic Medicine, Internal Medicine Services, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland.
18
deCODE genetics/Amgen, Reykjavik, Iceland; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. Electronic address: kari.stefansson@decode.is.

Abstract

BACKGROUND:

Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular diseases that has no established therapy. The attribute of Lp(a) that affects cardiovascular risk is not established. Low levels of Lp(a) have been associated with type 2 diabetes (T2D).

OBJECTIVES:

This study investigated whether cardiovascular risk is conferred by Lp(a) molar concentration or apolipoprotein(a) [apo(a)] size, and whether the relationship between Lp(a) and T2D risk is causal.

METHODS:

This was a case-control study of 143,087 Icelanders with genetic information, including 17,715 with coronary artery disease (CAD) and 8,734 with T2D. This study used measured and genetically imputed Lp(a) molar concentration, kringle IV type 2 (KIV-2) repeats (which determine apo(a) size), and a splice variant in LPA associated with small apo(a) but low Lp(a) molar concentration to disentangle the relationship between Lp(a) and cardiovascular risk. Loss-of-function homozygotes and other subjects genetically predicted to have low Lp(a) levels were evaluated to assess the relationship between Lp(a) and T2D.

RESULTS:

Lp(a) molar concentration was associated dose-dependently with CAD risk, peripheral artery disease, aortic valve stenosis, heart failure, and lifespan. Lp(a) molar concentration fully explained the Lp(a) association with CAD, and there was no residual association with apo(a) size. Homozygous carriers of loss-of-function mutations had little or no Lp(a) and increased the risk of T2D.

CONCLUSIONS:

Molar concentration is the attribute of Lp(a) that affects risk of cardiovascular diseases. Low Lp(a) concentration (bottom 10%) increases T2D risk. Pharmacologic reduction of Lp(a) concentration in the 20% of individuals with the greatest concentration down to the population median is predicted to decrease CAD risk without increasing T2D risk.

KEYWORDS:

Lp(a); Mendelian randomization; coronary artery disease; genetics; type 2 diabetes

PMID:
31865966
DOI:
10.1016/j.jacc.2019.10.019
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center