Statin initiation in high risk patients not to be delayed due to cataract risk: JAHA
Denmark: A recent study, published in the Journal of the American Heart Association found that HMG-CoA reductase inhibition (the target of statins) is associated with a high risk of cataract development.
The authors, however, suggest that the beneficial effects of statins are unequivocal, "the reported link with lens opacities should not prevent statin initiation in high‐risk adults, but should be disclosed to the patient, particularly when indicated for primary prevention." Jonas Ghouse, University of Copenhagen, Denmark, and colleagues wrote in their study.
There have been increasing concerns regarding the potential cataractogenic effects of statin treatment. Dr. Ghouse and the team aimed to investigate whether common and rare genetic variants in HMGCR are associated with cataract risk, to gauge the likely long‐term effects of statin treatment on lenticular opacities.
For this purpose, the researchers used genotyping data and exome sequencing data of unrelated European individuals in the UK Biobank for testing the association between genetically proxied inhibition of HMGCR and cataract risk. First, they constructed an HMGCR genetic score consisting of 5 common variants weighted by their association with low‐density lipoprotein cholesterol. Second, they analyzed exome sequencing data to identify carriers of predicted loss‐of‐function mutations in HMGCR. Then, common and rare variants were tested for association with cataracts and cataract surgery.
Based on the study, the researchers reported the following findings:
- In an analysis of more than 402 000 individuals, a 38.7 mg/dL (1 mmol/L) reduction in low‐density lipoprotein C by the HMGCR genetic score was associated with a higher risk for cataracts (odds ratio, 1.14) and cataract surgery (odds ratio, 1.25).
- Among 169 172 individuals with HMGCR sequencing data, we identified 32 participants (0.02%), who carried a rare HMGCR predicted loss‐of‐function variant.
- Compared with noncarriers, heterozygous carriers of HMGCR predicted loss‐of‐function had a higher risk of developing cataracts (odds ratio, 4.54) and cataract surgery (odds ratio, 5.27).
- In exploratory analyses, we found no significant association between genetically proxied inhibition of PCSK9, NPC1L1, or circulating low‐density lipoprotein cholesterol levels and cataract risk.
"We found that genetically proxied inhibition of the HMGCR gene mimicking long‐term statin treatment was associated with a higher risk of cataracts," the researchers concluded. "Clinical trials with longer follow-ups are needed to confirm these findings."
"A closer clinical follow‐up may be warranted in younger patients with familial hypercholesterolemia, who are subject to almost life‐long statin therapy often initiated in childhood or early adolescence," the researchers wrote their study.
Reference:
The study titled, "Association of Common and Rare Genetic Variation in the 3‐Hydroxy‐3‐Methylglutaryl Coenzyme A Reductase Gene and Cataract Risk," was published in the Journal of the American Heart Association.
