Genetic Study Shows Cholesterol-Lowering Statins May Increase the Risk of Cataracts

More than 40 million Americans take statins, a medicine that lowers LDL ("bad cholesterol"). They are, in fact, the most often prescribed medication class in the United States. Atorvastatin, lovastatin, pravastatin, fluvastatin, rosuvastatin, simvastatin, and pitavastatin are some of the most prevalent statins, with brand names including Lipitor, Crestor, Lescol XL, Altoprev, Livalo, Pravachol, Ezallor, Zocor, and Zypitamag.

Although it is successful in lowering cholesterol and lowering the risk of a heart attack or stroke, there are some possible negative effects. Some of them are harmful, such as memory loss, disorientation, kidney damage, and liver damage, although these are uncommon. A greater risk of cataracts is another negative effect.

Cataracts are hazy areas in the eye that cause visual loss. These usually appear gradually over time, affecting one or both eyes and causing hazy vision. The majority of the time, they can be addressed with vision-restoring surgery.

Research Highlights:

  • Researchers used data from the UK Biobank's large-scale genotyping and exome sequencing to learn more about the long-term impact of statin usage on cataract risk.
  • The study discovered that common genetic variations that mirror the effects of LDL-cholesterol-lowering statins are linked to an increased incidence of cataracts and cataract surgery in over 402,000 adults who were not taking statins.
  • They also discovered that uncommon genetic abnormalities, which mimicked statin use, raised the chance of cataracts by roughly five times in 169,172 persons.

According to new study published today (June 15, 2022) in the Journal of the American Heart Association, persons who have genetic variants related with decreasing LDL-cholesterol comparable to statin drugs appear to have an increased chance of getting cataracts and undergoing cataract surgery (JAHA). The American Heart Association's JAHA is an open access, peer-reviewed publication.

There is some indication that statin drugs may raise the risk of cataracts, according to previous study. In this study, researchers looked at whether some genes that behave similarly to statins may raise the risk of cataracts on their own.

Statins work by blocking an enzyme called HMG-CoA-reductase, which lowers LDL cholesterol levels (HMGCR). Variants in the HMGCR gene area of the human genome alter how people metabolize cholesterol, according to previous study.

Statins work by blocking an enzyme called HMG-CoA-reductase, which lowers LDL cholesterol levels (HMGCR). Variants in the HMGCR gene area of the human genome alter how people metabolize cholesterol, according to previous study.

”We were able to establish a link between genetic variants that mimic inhibition of HMGCR and the development of cataracts,” said lead study author Jonas Ghouse, M.D., Ph.D., a fellow in the cardiac genetics group at the University of Copenhagen's Laboratory for Molecular Cardiology in the department of biomedical sciences. “We were not able to find any association between newer non-statin, lipid-lowering medications and cataract risk, so this effect is likely specific to statins. However, it’s important to stress that the benefits of statins for lowering levels of low-density lipoproteins in people who have high blood cholesterol levels completely outweighs the small risk of cataracts, and cataract surgery is effective and safe.”

Researchers studied genetic data for more than 402,000 people using the UK Biobank, a massive database of UK residents that follows significant health and medical disorders of almost half a million adults. The researchers concentrated on five previously discovered genetic variations that reduce LDL cholesterol levels. They then generated genetic scores based on the influence of each mutation on LDL cholesterol that had previously been found. The researchers looked through genetic coding data to see if anyone had a predicted loss-of-function mutation in the HMGCR gene.

“When we carry a loss-of-function mutation, the gene is less likely to work,” Ghouse explained. “If that gene doesn’t work, the body can’t produce that protein. Simply put, the loss-of-function mutation in the HMGCR gene equals taking a statin medication.”

The study found:

  • The HMGCR genetic risk score indicated patients with a greater risk of cataracts and cataract surgery, according to the study. The genetic score was linked to a 14 percent increased incidence of cataracts and a 25% increased risk of cataract surgery for every 38.7 mg/dL reduction in LDL cholesterol.
  • 32 (0.02%) of the 169,172 people who had HMGCR sequencing data had one of 17 uncommon HMGCR predicted loss-of-function mutations. Carriers of these uncommon mutations were more than four-and-a-half times as likely to acquire cataracts and more than five times as likely to need cataract surgery as non-carriers. 
Ghouse was taken aback by the extent of the connection. “The main difference between the two analyses is that loss-of-function mutations are really more detrimental than common variants, meaning they mimic change that is often induced by medications,” he explained. “We believe that the true effect lies closer to the loss-of-function mutation association than the common variant association. When taking statins, you have an almost-complete inhibition of that protein, and when you have a loss-of-function mutation you also have a significantly reduced ability to produce that protein.”

One major limitation of the study, according to the authors, is that while carrying these genetic variants carries a lifelong risk of developing cataracts, that risk should not be evaluated the same way for people who start taking statins later in life, given the potential benefits of statins in lowering blood cholesterol levels. To corroborate these findings, further clinical studies examining this connection are needed.

“Our associations reflect lifelong treatment, whereas statin treatment typically occurs later in life,” Ghouse stated. “However, there is a specific group of patients who are diagnosed with high cholesterol in childhood and start statin treatment at a young age, so they could be identified and followed up more closely for cataracts.”