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    Statins and Cataract Risk

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    Danish researchers have found that a genetic proxy that mimics statin treatment is associated with an increased risk of cataract development and the need for cataract surgery.1

    The findings lend support to previ­ous studies linking statins to lens opac­ities. But while none of those earlier studies conclusively demonstrated an association between statins and the risk of cataract development, this study is different, said Jonas Ghouse, MD, PhD, at Copenhagen University Hospital in Denmark. “Using genetics, we were able to show that proxies for lifelong statin treatment may increase the risk of len­ticular opacities.”

    Study design. The researchers con­sidered whether the presence of delete­rious mutations in the HMGCR gene, which encodes HMG-CoA reductase, are associated with the risk of cataract and/or cataract surgery. (HMG-CoA reductase is a crucial enzyme in the cholesterol pathway and thus is the target of statins.)

    To test their hypothesis, they analyzed UK Biobank genetic sequencing data of more than 402,000 unrelated European individuals between 40 and 69 years of age. The Biobank data allowed them to create a genetic score weighted by each variant’s ability to lower low-density lipoprotein (LDL) cholesterol. Variants with larger effects were given larger weights.

    Association

    ASSOCIATION. Both common and rare variants of the HMGCR gene were linked to cataract development.

    Link emerges. The researchers found a strong association between the HMGCR score and LDL levels. Specifically, a 38.7 mg/dL reduction in LDL score was associated with higher risk for both cataract (odds ratio [OR], 1.14) and cataract surgery (OR, 1.25).

    To investigate whether the reported association was specific to the HMG-CoA pathway, the researchers looked at cataract risk associations between other genetic variants with known cholesterol-lowering effects. In particu­lar, they considered genetically proxied inhibition of PCSK9 and NPC1L1 on circulating LDL levels and cataract. They found no association.

    “What was important to investigate was whether it was the inhibition of the gene, rather than a global lower­ing of the cholesterol, that caused the reported association,” Dr. Ghouse said. “These results indicated that it was the inhibition of HMGCR, and not general LDL-lowering, that was associated with cataract risk.”

    Clinical implications. Dr. Ghouse stressed that the reported gene associ­ation mimics long-term statin treat­ment, as occurs in patients with familial hypercholesterolemia. Thus, they may not translate to the initiation of statins later in life. For now, the findings should not deter treatment, but they should be disclosed to patients, he rec­ommended.

    —Miriam Karmel

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    1 Ghouse J et al. J Am Heart Assoc. 2022;11(12):3025361.

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    Relevant financial disclosures: Dr. Ghouse—None.

    For full disclosures and the disclosure key, see below.

    Full Financial Disclosures

    Dr. Ghouse: None.

    Dr Hufnagel: None.

    Dr. Rush: None.

    Dr. Williams: NIHR: S.

    Disclosure Category

    Code

    Description

    Consultant/Advisor C Consultant fee, paid advisory boards, or fees for attending a meeting.
    Employee E Hired to work for compensation or received a W2 from a company.
    Employee, executive role EE Hired to work in an executive role for compensation or received a W2 from a company.
    Owner of company EO Ownership or controlling interest in a company, other than stock.
    Independent contractor I Contracted work, including contracted research.
    Lecture fees/Speakers bureau L Lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company.
    Patents/Royalty P Beneficiary of patents and/or royalties for intellectual property.
    Equity/Stock/Stock options holder, private corporation PS Equity ownership, stock and/or stock options in privately owned firms, excluding mutual funds.
    Grant support S Grant support or other financial support from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and\or pharmaceutical companies. Research funding should be disclosed by the principal or named investigator even if your institution receives the grant and manages the funds.
    Stock options, public or private corporation SO Stock options in a public or private company.
    Equity/Stock holder, public corporation US Equity ownership or stock in publicly traded firms, excluding mutual funds (listed on the stock exchange).

     

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