A single nucleotide polymorphism (SNP) of the LPA-Aspirin genotype has been shown to predict increased CVD risk and event reduction during aspirin therapy* ^1-5. The LPA-Aspirin gene encodes the apo(a) component of Lp(a). The SNP associated with risk of CVD consists of an isoleucine residue (Ile4399) that can be replaced with a methionine residue (4399Met)**. The genotypes of LPA-Aspirin carriers have either one or two 4399Met alleles (e.g., Met/Met or Met/Ile), and the LPA-Aspirin noncarrier genotype lacks the 4399Met allele (e.g., Ile/Ile).

Risk Associated with the LPA-Aspirin Genotype:

• LPA-Aspirin 4399Met Carriers had Approximately Two-Fold Higher Risk of CVD Events than Noncarriers in Case-Control and Prospective Studies ^1-4 (Figure A)

Event Reduction from Aspirin in LPA-Aspirin Carriers ^1,5:

• In the Women’s Health Study (WHS), Aspirin Therapy Resulted in a Greater Reduction of CVD Events in LPA-Aspirin Carriers than in Noncarriers***¹ (Figure B)

• The authors of the LPA-Aspirin analysis in WHS reported that the Number-Needed-to-Treat (NNT) with aspirin to prevent 1 CVD event was 37 for LPA-Aspirin carriers and 625 for noncarriers
• In a population of men and women in the Atherosclerosis Risk in Communities (ARIC) study, the observations regarding LPA-Aspirin carriers were similar to those reported in WHS⁵

CVD Events Prevented vs Bleeding Events ^1,6:

• In WHS, the use of aspirin to prevent one CVD event resulted in about 15-fold more bleeds in noncarriers than in carriers

Based on this data, LPA-Aspirin genotyping may help clinicians assess the potential cardiovascular benefit of aspirin therapy as compared to the bleeding risk.

Due to the unique nature of genetic testing, physicians may suggest patients consider genetic counseling. Informed consent is recommended and required for patients according to state law. Consent forms are available from Berkeley HeartLab upon request.

*Studied populations predominantly consisted of Caucasian men and women 45-79 years of age.  LPA-Aspirin carrier frequency was approximately 4% in Caucasian populations.  Preliminary studies indicate LPA-Aspirin carrier frequencies of 16% in Chinese and Japanese populations⁶ 28% in Hispanics⁶, and 2% in African Americans⁵.  The CVD risk associated with the 4399Met polymorphism and aspirin benefit has thus far only been observed in a Caucasian population. 

**The 4399Met polymorphism (rs3798220) is also referred to as 1891Met in public genome databases.

***In WHS, aspirin therapy was studied with low dose (100 mg) aspirin taken orally on alternate days.  The data in WHS are limited to initially healthy Caucasian women, and the number of cardiovascular events among LPA-Aspirin carriers was modest. 

The LPA-Aspirin test was developed and its performance characteristics were determined by Berkeley HeartLab, Inc., a CLIA-certified and CAP-accredited laboratory. It has not been reviewed or approved by the FDA.

References:

1. Chasman DI, et al. Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy. Atherosclerosis, 2009; 203:371–6
2. Luke MM, et al. A polymorphism in the protease-like domain of apolipoprotein(a) is associated with severe coronary artery disease. Arterioscler Thromb Vasc Biol 2007; 27:2030-6
3. Shiffman D, et al. Analysis of 17,576 potentially functional SNPs in three case-control studies of myocardial infarction. PLoS ONE 2008; 3:e2895
4. Shiffman D, et al. Association of gene variants with incident myocardial infarction in the cardiovascular health study. Arterioscler Thromb Vasc Biol. 2008; 28:173-9
5. Shiffman D, et al. Coronary Heart Disease Risk, Aspirin Use, and Apolipoprotein(a) 4399Met allele in the Atherosclerosis Risk in Communities (ARIC) Study. Thromb Haemost. 2009;102:179-80
6. International HapMap Project
7. Ridker PM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005; 352:1293-1304

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