Caution Advised on Novel Cholesterol Medications Due to Potential Lung Function Impairment, Indicates Comprehensive Global Research

A groundbreaking study recently conducted has scrutinized genetic data from 340,000 participants in the UK Biobank and suggests that a novel category of cholesterol-lowering drugs known as PCSK9 inhibitors may have the adverse effect of compromising lung function. While the majority of cholesterol medications have been effective in reducing the risks associated with cardiovascular diseases without major side effects, the study also identified a relationship between statin use and increased body mass index (BMI), elevated levels of body fat, and diminished testosterone levels. Interestingly, the research also found a rise in the volume of the hippocampus region in the brain, which could potentially mitigate the risks of dementia and depression.

Statins do reduce dementia risks, but new pharmaceuticals may be detrimental to pulmonary function.

This recent research, led by the University of South Australia, is one of the most expansive global investigations into the ramifications of cholesterol-reducing medications. It is the first study globally that has juxtaposed low-density lipoprotein cholesterol (LDL-C) medications against a wide array of clinical and MRI biomarkers related to both heart and brain.

Analyzing genetic data from 340,000 UK Biobank contributors, the study probed into the merits and demerits of LDL-C medications. These results have been formally documented in the British Journal of Clinical Pharmacology.

In the overwhelming majority of instances, medications designated for the reduction of high cholesterol levels effectively fulfill their promise by markedly reducing the risks of cardiovascular diseases, hypertension, diabetes, and age-associated ailments. Other than instances of diarrhea in some patients, no significant adverse health conditions have been noted.

However, the researchers emphasize that PCSK9 inhibitors, a class of lipid-lowering medications designed to eliminate cholesterol from cells, may compromise lung functionality. Subsequent research is warranted to examine their long-term side effects.

Genetic markers indicative of another class of cholesterol-lowering drugs, statins, were associated with elevated BMI, higher body fat, and reduced levels of testosterone. Statins remain the most frequently prescribed form of cholesterol-lowering medication.

A serendipitous benefit associated with the consumption of statins was noted in the research: an enlargement of the hippocampus area of the brain was observed in some individuals, possibly decreasing the risk of both dementia and depression.

Kitty Pham, a Ph.D. student at the University of South Australia and the study’s lead author, underscores the necessity for more nuanced understanding of the long-term effects of various pharmaceuticals.

“Our research unveils relationships with pulmonary function and cerebral size, potentially affecting the future prescription or reevaluation of these medications,” says Pham. “These insights facilitate our understanding of individual responses to distinct pharmaceuticals and help evaluate the feasibility of novel therapeutic avenues.”

In contrast to statins, which inhibit cholesterol production, PCSK9 inhibitors actively destroy cholesterol within cells. Less is known about the long-term safety of these relatively new drugs.

The chief investigator, Professor Elina Hypponen, who is also the Centre Director of the Australian Centre for Precision Health at the University of South Australia, notes that genetic data was employed to contrast the outcomes of various LDL-C lowering medications that function differently.

“Executing such comparisons in a conventional clinical trial with a large sample size would usually be impractical, but genetic analyses like the one we have conducted offer valuable insights into drug safety by revealing associations with diseases and biomarkers,” states Professor Hypponen.

Reference: “Genetically instrumented LDL-cholesterol lowering and multiple disease outcomes: A Mendelian randomization phenome-wide association study in the UK Biobank” by Kitty Pham, Anwar Mulugeta, Amanda Lumsden and Elina Hypponen, published on 19 May 2023 in the British Journal of Clinical Pharmacology. DOI: 10.1111/bcp.15793

Frequently Asked Questions (FAQs) about PCSK9 inhibitors

More about PCSK9 inhibitors

• British Journal of Clinical Pharmacology
• University of South Australia Research
• UK Biobank Study Overview
• Cholesterol Medications: What You Need to Know
• About PCSK9 Inhibitors
• Statins and Their Side Effects
• Understanding MRI Biomarkers
• Australian Centre for Precision Health at UniSA
• Mendelian Randomization Studies