Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden but Not With Venous Thromboembolism

Study Questions:

What effect does LPA gene variation have on atherosclerosis and thrombosis?

Methods:

Two LPA variants were combined and examined as LPA scores for the association with ischemic stroke (n = 9,396); peripheral arterial disease (n = 5,215); abdominal aortic aneurysm (n = 4,572); venous thromboembolism (n = 4,607); intracranial aneurysm (n = 1,328); coronary artery disease (CAD) (n = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588).

Results:

LPA score was associated with ischemic large artery stroke (odds ratio [OR], 1.27; p = 6.7 x 10–4), peripheral artery disease (OR, 1.47; p = 2.9 x 10–14), and abdominal aortic aneurysm (OR, 1.23; p = 6.0 x 10–5), but not with cardioembolic stroke (OR, 1.03; p = 0.69) or stroke related to small-vessel disease (OR, 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 x 10–12). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR, 1.26; p = 0.0010) and had earlier onset of CAD (–1.58 years/allele; p = 8.2 x 10–8) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR, 0.97; p = 0.63) or intracranial aneurysm (OR, 0.85; p = 0.15).

Conclusions:

The authors concluded that LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes.

Perspective:

Previous studies have demonstrated associations between LPA levels and atherothrombosis. The extent to which LPA affects thrombosis versus the underlying atherosclerosis is unclear. This genetic-based study examined the effect of two LPA single nucleotide polymorphisms, that have previously been shown to affect circulating LPA levels, on multiple vascular endpoints. This study confirms previous studies that these variants are associated with atherosclerosis, while the effect on a thrombotic process is less clear. However, it remains possible that other LPA variants associated with variable kringle repeats may affect thrombosis. Novel lipid-lowering therapies that also reduce LPA, such as PCSK-9 inhibitors, may provide exceptional reduction in vascular risk.

Clinical Topics: Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Advanced Lipid Testing, Lipid Metabolism, Interventions and Coronary Artery Disease, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Echocardiography/Ultrasound, Nuclear Imaging

Keywords: Risk, Coronary Artery Disease, Stroke, Atherosclerosis, Lipoprotein(a), Carotid Intima-Media Thickness, Apoprotein(a), Venous Thromboembolism, Peripheral Arterial Disease, Peripheral Vascular Diseases, Polymorphism, Genetic, Biological Markers, Coronary Angiography, Thrombosis, Phenotype, Intracranial Aneurysm


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