Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism
Key result
LPA variants linked to ~47% higher PAD risk, but not venous thromboembolism.
- OR 1.47
- P=2.9 × 10(-14)
Why the study?
It is unclear whether LPA variants rs10455872 and rs3798220 confer susceptibility to vascular diseases predominantly via atherosclerosis or thrombosis.
Are LPA genetic variants associated with atherosclerotic and thrombotic vascular diseases?
Comparison
LPA genetic variants rs10455872 and rs3798220 combined as LPA scores vs absence or lower LPA score
Design
Observational cohort study
Authors
Discussion
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Member takes
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
DVDeepak VooraInstructor of Medicine, Cardiology, Duke University
“The main conclusion to draw from this work is that Lp(a) is probably a strong causal factor in not only CAD, but also the development of atherosclerosis in other arterial trees. Although there is no evidence from this study that Lp(a) levels contribute to venous thrombosis, the investigators do not exclude a role for Lp(a) in arterial thrombosis.”
Implication
LPA genetic risk variants are strongly associated with systemic atherosclerotic burden across multiple vascular beds, but not with primarily thrombotic phenotypes like venous thromboembolism.
Key Points
- To determine whether genetic variants in the apolipoprotein(a) gene (LPA) influence vascular disease susceptibility primarily through atherosclerotic or thrombotic pathways.
- Constructed a combined LPA score from sequence variants rs10455872 and rs3798220 across multiple vascular disease cohorts.
- Evaluated associations with coronary artery disease (effective sample size [n(e)] = 12,716), ischemic stroke subtypes (n(e) = 9,396), peripheral arterial disease (n(e) = 5,215), venous thromboembolism (n(e) = 4,607), abdominal aortic aneurysm (n(e) = 4,572), intracranial aneurysm (n(e) = 1,328), and angiographic CAD severity (n = 5,588).
- LPA score was significantly associated with large artery atherosclerosis stroke (OR: 1.27; p = 6.7 × 10⁻⁴), peripheral artery disease (OR: 1.47; p = 2.9 × 10⁻¹⁴), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 × 10⁻⁵).
- LPA variants associated with obstructed coronary vessel count (p = 4.8 × 10⁻¹²), earlier CAD onset (-1.58 years/allele; p = 8.2 × 10⁻⁸), and non-coronary atherosclerotic manifestations (OR: 1.26; p = 0.0010).
- No association was observed with venous thromboembolism (OR: 0.97; p = 0.63), cardioembolic stroke (OR: 1.03; p = 0.69), small vessel disease stroke (OR: 1.06; p = 0.52), or intracranial aneurysm (OR: 0.85; p = 0.15).
Study Design
Type
Observational
Structured PICO
Are LPA genetic variants associated with atherosclerotic and thrombotic vascular diseases?
P
Population
Genetic association study examining the effects of LPA variants on various atherosclerotic and thrombotic vascular diseases across multiple large cohorts.
E
Exposure
LPA genetic variants rs10455872 and rs3798220 combined as LPA scores
C
Comparator
Absence of LPA risk variants or lower LPA score
O
Outcome
Association with ischemic stroke (and TOAST subtypes), peripheral arterial disease, abdominal aortic aneurysm, venous thromboembolism, intracranial aneurysm, CAD, carotid intima-media thickness, and angiographic CAD severityhard clinical
Main Result
Odds Ratio: 1.47
p-value: p=2.9 × 10(-14)
LPA genetic risk variants are strongly associated with systemic atherosclerotic burden across multiple vascular beds, but not with primarily thrombotic phenotypes like venous thromboembolism.
Cite This Study
Helgadóttir et al. (2012) conducted an observational in Systemic Atherosclerosis and Coronary Atherosclerotic Burden. LPA genetic sequence variants (rs10455872 and rs3798220) vs. Non-carriers or lower LPA score was evaluated on Peripheral artery disease (OR 1.47, p=2.9 × 10(-14)). LPA sequence variants were associated with peripheral artery disease (OR 1.47; p=2.9×10^-14) and other atherosclerotic burdens, but not with venous thromboembolism (OR 0.97; p=0.63).