European Heart Journal 2010; 31: 2844-2853. Lipoprotein(a) consists of an LDL-like particle to which...

European Heart Journal 2010; 31: 2844-2853

Lipoprotein(a) consists of an LDL-like particle to which apolipoprotein(a) is covalently linked.

Nordestgaard B G et al. Eur Heart J 2010;31:2844-2853

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2010. For permissions please email: [email protected]

Lipoprotein(a)

apolipo-protein(a)

LDL-like particle

Koschinsky et al. Cur Opin Lipidol 2004;15:167-174

KIV-2 copy number variant:2 to >40 repeats

Typical distributions of lipoprotein(a) levels in the general population.



0 50 100 150 200Lp(a), mg/dL

0 50 100 150 200Lp(a), mg/dL

F

ract

ion

of P

opul

atio

n

Men Women

20% 20%

Copenhagen General Population Study

Low number of Kringle IV-2

repeats

High number of Kringle IV-2

repeats

Nordestgaard 2010

Risk ratios of coronary heart disease, ischaemic stroke and non-vascular death by quantiles of usual lipoprotein(a) levels.



Emerging Risk Factor Collaboration. JAMA 2009; 302: 412-23

Risk ratios for various vascular and non-vascular endpoints per 3.5-fold (i.e. 1 SD) higher than usual lipoprotein(a) levels adjusted for cardiovascular risk factors.



Risk of myocardial infarction by levels of lipoprotein(a) in the general population.



Figure II-3 Figure II-3

Kamstrup et al. JAMA 2009; 301: 2331-9

Copenhagen City Heart Study

Mean lipoprotein(a) levels in the Copenhagen City Heart Study as a function of quartiles of apolipoprotein(a) KIV-2 repeats.



Risk of myocardial infarction by quartiles of apolipoprotein(a) KIV-2 repeats in the Copenhagen City Heart Study (CCHS), the Copenhagen General Population Study (CGPS),

and the Copenhagen Ischemic Heart Disease Study (CIHDS).



Lipoprotein(a) KIV-2 quartile(mg/dL)

Multifactorially adjusted hazard ratio(95% confidence interval)

Trend: p<0.001 Trend: p<0.001

1st

2nd

3rd

4th

50 40 30 20 10 1.0 1.5 2.0

Figure. Levels of lipoprotein(a) and risk of myocardial infarction by KIV-2 genotype.

Trend p<0.001

50 40 30 20 10

1st

2nd

3rd

4th

1.0 1.5 2.0

Lipoprotein(a)(mg/dL)

KIV-2quartile

Hazard ratio(95% CI)

Trend p<0.001

Risk of Myocardial Infarction

Trend p<0.001

Kamstrup et al. JAMA 2009; 301: 2331-9

Clarke et al. New Engl J Med 2009; 361: 2518-28

Evidence for lipoproteins causing atherothrombotic disease?

LDL Lp(a)Epidemiology Direct association Direct association

Genetics FH Kringle IV-2

Animal models Watanabe Transgenic

Mechanism Aterosclerosis Aterosclerosis Thrombosis

Intervention Statins Niacin/apheresis

Interpretation Causal Probably causal

Nordestgaard et al. EAS Consensus Panel. Eur Heart J 2010;31:2844-2853

Whom to screen for Lp(a)

• Premature CVD

• Familial hypercholesterolemia

• Family history premature CVD or Lp(a)• Recurrent CVD despite statins

• ≥3% 10-year risk of fatal CVD

• ≥10% 10-year risk of fatal/nonfatal CHD


Desirable levels in the fasting or nonfasting state

Patients with CVD and/or diabetes

Other patients and individuals

Highest level of evidence for treatment

LDL chole-sterol

<2 mmol/L (<77 mg/dL)

<3 mmol/L (<116 mg/dL)

Ia: meta-analysis of randomised, controlled trials of statin treatment

Lp(a) <80th percentile (<~50 mg/dL)

<80th percentile (<~50 mg/dL)

Ia: meta-analysis of randomised, controlled trials of niacin treatment


0 50 100 150 200Lp(a), mg/dL

0 50 100 150 200Lp(a), mg/dL

F

ract

ion

of P

opul

atio

n

Men Women

20% 20%

Copenhagen General Population Study

Nordestgaard 2010

Desirable levels

CHD Stroke Early death0%

-10%

-20%

-30%Bruckert et al. Atherosclerosis 2010; 210 353-

361 & Coronary Drug Project. JACC 1986;8:1245-55

Niacin 1-3 g/day in randomised, controlled trials

Jaeger et al. Nat Clin Prac Cardiovasc 2009; 6: 229-39

High risk patients with Lp(a) >95th percentile

Apheresis added to optimal lipid lowering by drugs reduced Lp(a) 73%

p<0.0001

Pre Post Pre Post

Treatment of Lp(a)• Lifestyle changes minimal effect• Statins to lower LDL-C• Niacin 1-3 g/day lowers

–Lp(a) 30-40%–LDL-C–Triglycerides–and raises HDL-C

• Possibly apheresis


DisclosuresThis work including Consensus Panel meetings were supported by unrestricted educational grants to the European Atherosclerosis Society from Merck, Kowa, Roche, and AstraZeneca. These companies were not present at the Consensus Panel meetings, had no role in the design or content of the Consensus Statement, and had no right to approve or disapprove of the final document. Funding to pay the Open Access publication charges for this article was provided by funding from the European Atherosclerosis Society.


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