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Lowering Lp(a) may decrease risk for variety of atherosclerosis-related diseases
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Researchers found that genetically lowered lipoprotein(a) levels are associated with decreased risk for various atherosclerosis-related diseases, indicating that pharmacological lowering of plasma Lp(a) may lower risk for peripheral vascular disease, stroke, HF and aortic stenosis, as well as CHD.
Connor A. Emdin, DPhil, from the Broad Institute of MIT and Harvard, and colleagues investigated the full phenotypic effect of variation in the LPA gene.
They examined genetic variants of the LPA gene in three data sources. First, data from 112,338 participants in the U.K. Biobank were considered at an individual level. Second, the researchers looked at results from large-scale genome-wide association studies. Third, LPA gene sequencing results were examined for individuals with CHD and free of CHD.
At one standard-deviation genetically lowered Lp(a) level, the following associations were found: a 29% lower risk for CHD (OR = 0.71; 95% CI, 0.69-0.73), a 31% lower risk for peripheral vascular disease (OR = 0.69; 95% CI, 0.59-0.8), a 13% lower risk for stroke (OR = 0.87; 95% CI, 0.79-0.96), a 17% lower risk for HF (OR = 0.83; 95% CI, 0.73-0.94) and a 37% lower risk for aortic stenosis (OR = 0.63; 95% CI. 0.47-0.83), the researchers wrote.
“Variants that led to gain of LPA gene function increased the risk for CHD, whereas those that led to loss of gene function reduced the CHD risk,” Emdin and colleagues wrote.
Among 31 other disorders examined, including type 2 diabetes and cancer, no other associations were found.
“These results suggest that Lp(a) inhibition may be a viable therapeutic strategy to prevent a range of diseases beyond CHD,” Emdin and colleagues wrote.
In a related editorial, Anne Tybjærg-Hansen, MD, professor of clinical biochemistry at the University of Copenhagen, wrote that the study “helps to consolidate high Lp(a) levels as a potentially treatable [CV] risk factor. Emdin et al confirm previous results that genetically determined variation in Lp(a) levels in plasma are associated with CHD, aortic valve stenosis, [HF] and peripheral vascular disease, and they extend these findings to risk of stroke and possibly renal dysfunction. Because genetic lowering of Lp(a) may mimic the effects and side effects of lowering Lp(a) levels pharmacologically, the results suggest that pharmacological lowering of Lp(a) may reduce the risk of these diseases in a dose-dependent manner.” – by Suzanne Reist
Disclosure: Emdin is supported by the Rhodes Trust. Please see the full study for a list of the other researchers’ relevant financial disclosures. Tybjærg-Hansen reports no relevant financial disclosures.
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