Phenotypic Characterization of Genetically Lowered Human Lipoprotein(a) Levels
Key result
Genetically lowered Lp(a) linked to ~29% lower CHD risk per standard deviation.
- OR 0.71
- 95% CI 0.69 to 0.73
- n=112,338
Why the study?
Does genetically lowered Lp(a) reduce the risk of coronary heart disease and other cardiovascular diseases?
Population
112,338 participants from the UK Biobank, plus summary association results from large-scale genome-wide…
Comparison
Genetically lowered Lp levels via LPA gene… vs Higher genetically determined Lp(a) levels
Design
Cohort
Authors
Discussion
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Implication
Genetically lowered Lp(a) is associated with a reduced risk of CHD, peripheral vascular disease, stroke, heart failure, and aortic stenosis, suggesting that pharmacological lowering of Lp(a) may have broad cardiovascular benefits.
Key Points
- To determine the full phenotypic spectrum of LPA gene variation and characterize the dose-response relationship between genetically predicted plasma lipoprotein(a) levels and coronary heart disease risk.
- Analyzed genetic variants at the LPA locus across three resources: individual-level records from 112,338 UK Biobank participants, summary-level genome-wide association study data, and LPA gene sequencing cohorts of coronary heart disease cases and controls.
- Each 1-SD genetically predicted decrease in Lp(a) was associated with reduced risk of coronary heart disease (OR: 0.71; 95% CI: 0.69 to 0.73), peripheral vascular disease (OR: 0.69; 95% CI: 0.59 to 0.80), stroke (OR: 0.87; 95% CI: 0.79 to 0.96), heart failure (OR: 0.83; 95% CI: 0.73 to 0.94), and aortic stenosis (OR: 0.63; 95% CI: 0.47 to 0.83).
- Gain-of-function LPA variants raised coronary heart disease risk while loss-of-function variants reduced risk, with no detectable associations observed across 31 non-cardiovascular phenotypes including type 2 diabetes and cancer.
Study Design
Type
Observational (n=112,338)
Multicenter
Yes
Structured PICO
Does genetically lowered Lp(a) reduce the risk of coronary heart disease and other cardiovascular diseases?
P
Population
112,338 participants from the UK Biobank and additional large-scale genetic datasets evaluated for the phenotypic impact of LPA gene variation on cardiovascular diseases.
E
Exposure
Genetically lowered Lp(a) levels via LPA gene variation (1 standard deviation decrease)
C
Comparator
Higher genetically determined Lp(a) levels
O
Outcome
Risk of coronary heart disease (CHD)hard clinical
Main Result
Odds Ratio: 0.71 (95% CI 0.69–0.73)
Genetically lowered Lp(a) is associated with a reduced risk of CHD, peripheral vascular disease, stroke, heart failure, and aortic stenosis, suggesting that pharmacological lowering of Lp(a) may have broad cardiovascular benefits.
Cite This Study
Emdin et al. (2016) conducted an observational in Coronary heart disease (n=112,338). Genetically lowered lipoprotein(a) levels vs. Unexposed/reference group was evaluated on Coronary heart disease (CHD) (OR 0.71, 95% CI 0.69 to 0.73). One standard deviation genetically lowered Lp(a) level was associated with a 29% lower risk of coronary heart disease (OR 0.71; 95% CI 0.69 to 0.73).