Researchers at Washington University School of Medicine in St. Louis have made a groundbreaking discovery that could revolutionize the way peripheral artery disease (PAD) is diagnosed and treated. They have found that high levels of a specific protein called circulating fatty acid synthase (cFAS) in the blood accurately indicate the presence of a severe form of PAD, which narrows the arteries in the legs and increases the risk of heart attack and stroke. This finding could enable doctors to identify high-risk patients earlier and provide more aggressive treatment, potentially saving lives and improving quality of life.
Peripheral artery disease affects around 12 million people in the United States, with approximately 1 million suffering from chronic limb-threatening ischemia, a severe form of the condition. Patients with chronic limb-threatening ischemia often require vascular surgery to restore blood flow to the legs, and in severe cases, amputation may be necessary. Tragically, about half of these patients die within two years. Identifying patients at high risk of developing this severe form of the disease is crucial for effective intervention.
Dr. Mohamed A. Zayed, the senior author of the study and an associate professor of surgery and radiology, emphasized the devastating impact of limb loss on patients' quality of life. He stated, "We need to identify these patients sooner so we can help treat them aggressively much earlier in the disease course. Our data suggest that levels of cFAS in the blood could be an accurate predictor for which patients are at high risk of the severe forms of this condition."
The researchers collected blood samples from 87 patients with chronic limb-threatening ischemia before they underwent vascular surgery. They discovered that elevated levels of cFAS were independently associated with the disease. Additionally, the study revealed a strong correlation between the presence of Type 2 diabetes, smoking, and chronic limb-threatening ischemia. When considering all three factors together, the researchers achieved an 83% accuracy rate in predicting the presence of the disease.
Moreover, the study demonstrated that cFAS levels in the blood were linked to the fatty acid synthase content found in plaque samples from the femoral artery, the primary blood vessel supplying the legs. Intriguingly, the researchers also found that cFAS circulates through the bloodstream while bound to low-density lipoprotein (LDL), commonly known as "bad" cholesterol. This raises questions about the role of LDL and enzymes associated with it in conferring cardiovascular disease risk, particularly in the peripheral and coronary arteries.
Dr. Zayed noted that patients with high LDL but no arterial disease pose a challenge for physicians. He questioned whether these patients should be prescribed cholesterol-lowering medication and if they are still at high risk of cardiovascular disease. His suspicion is that the issue lies not only with LDL but with enzymes attached to LDL that contribute to cardiovascular disease development in peripheral, coronary, and carotid arteries, which supply blood to the brain.
The researchers determined that cFAS is less abundant than LDL in the bloodstream, suggesting that the crucial factor is not LDL alone but the quantity of LDL carrying cFAS. Previous work by Dr. Zayed and his team demonstrated elevated blood cFAS levels in patients with plaque buildup in the carotid arteries. This research also revealed that cFAS originates from the liver and is transported via LDL, ultimately contributing to plaque formation in vital arteries throughout the body. The team is now investigating cFAS as a potential target for new drug therapies aimed at reducing plaque buildup and treating or preventing cardiovascular disease.
Dr. Zayed discussed their ongoing efforts, stating, "There are drugs that inhibit fatty acid synthase, and we're working on evaluating new ones that are more targeted. None of them are ready for clinical trials in people for this
purpose yet, but we're using those drugs to test animal models of the disease to see if they actually decrease the buildup of plaque in the arteries." The ultimate goal is to develop precise vascular medicine that tailors therapy to high-risk patients, reducing their risk of severe complications from cardiovascular disease.
While further research and clinical trials are necessary, the discovery of cFAS as a reliable biomarker for severe PAD represents a significant advancement in cardiovascular medicine. By harnessing the potential of this blood test, doctors may soon be able to identify patients at high risk of developing severe complications and intervene earlier, potentially saving lives and improving patient outcomes.
Journal Information: Shirli Tay et al, Prevalence of elevated serum fatty acid synthase in chronic limb-threatening ischemia, Scientific Reports (2021). DOI: 10.1038/s41598-021-98479-7