Neutrophil–Monocyte-to-Lymphocyte Ratio Predicts Long-Term Amputation Risk in Peripheral Artery Disease: A Multicenter Chinese Cohort Study with External Validation in the UK Biobank
This multicenter Chinese cohort study, externally validated in the UK Biobank, demonstrates that an elevated preoperative neutrophil–monocyte-to-lymphocyte ratio (NMLR) is an independent predictor of long-term amputation risk in patients with peripheral artery disease, offering valuable risk stratification beyond traditional anatomical classifications.
Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer
Peripheral artery disease is a condition where the arteries that carry blood to the legs become narrowed or blocked, often due to a buildup of fatty plaque. When blood flow is severely restricted, the tissues in the legs can begin to die, leading to pain, non-healing wounds, and in the most severe cases, the need to remove part or all of a limb. Doctors currently assess the risk of such outcomes by looking at the physical blockage in the arteries and the patient's symptoms, using a standard system that grades the severity of the disease. However, the body's internal environment plays a massive role in how these conditions progress. The immune system, which usually fights infection and heals wounds, can sometimes turn against the body, creating a state of chronic inflammation that accelerates tissue damage. Scientists have long known that certain blood cells act as messengers for this inflammation, but finding a single, simple way to measure the overall inflammatory pressure a patient is under has remained a challenge.
A team of researchers from hospitals in China, led by scientists at Beijing Hospital, set out to investigate a specific combination of blood cells that might serve as a better warning signal for limb loss. They focused on a calculation that mixes three types of white blood cells: neutrophils and monocytes, which are the body's first responders to inflammation and infection, and lymphocytes, which are the cells that help regulate the immune response and fight off viruses. When a person has high levels of the aggressive cells and low levels of the regulating cells, it suggests the body is in a state of high alert and stress. The researchers called this combination the neutrophil–monocyte-to-lymphocyte ratio. While similar measures have been used to predict heart attacks and stroke outcomes, no one had previously tested whether this specific ratio could predict the risk of amputation in patients with peripheral artery disease.
To find the answer, the researchers looked back at the medical records of 1,445 patients with peripheral artery disease who had been treated at four different hospitals in China between 2016 and 2025. They examined the blood tests taken just before these patients underwent surgery. The team tracked these patients for a median of about two years to see who would eventually require an amputation. They found a clear pattern: patients with the highest levels of this inflammatory ratio were significantly more likely to lose a limb than those with the lowest levels. Specifically, during the follow-up period, about 14 percent of the patients in the highest group required an amputation, compared to only about 3 percent of those in the lowest group. This difference was not a fluke; even after the researchers adjusted for other known risk factors like age, diabetes, smoking, and the severity of the artery blockage, the high ratio remained a strong, independent predictor of the outcome.
The study did not stop at the Chinese hospitals. To ensure the findings were not unique to one population or healthcare system, the researchers tested their results on a massive, independent group of patients from the United Kingdom known as the UK Biobank. This group included over 9,000 people with peripheral artery disease. The results were consistent: in this completely different population, patients with the highest inflammatory ratios still faced a significantly higher risk of amputation than those with the lowest ratios. This cross-continental agreement suggests that the link between this specific blood cell balance and limb loss is a fundamental biological truth, not just a local observation. The researchers also used advanced computer models to confirm that this ratio provided information that went beyond what doctors could see just by looking at the physical blockage in the arteries. It appears that the body's internal inflammatory state adds a layer of risk that standard imaging cannot always detect.
The implications of this discovery are practical and immediate. The test required to calculate this ratio is already part of a standard blood draw that almost every patient receives before surgery. It costs nothing extra and requires no special equipment. The researchers suggest that by simply adding this calculation to the existing risk assessments, doctors could identify patients who are at high risk of losing a limb even if their artery blockage does not look severe on an X-ray. This could allow medical teams to intervene earlier, perhaps with more aggressive anti-inflammatory treatments or closer monitoring, to save the limb. While the study was retrospective, meaning it looked at past data rather than following patients forward in a new trial, the consistency of the results across two large groups and multiple statistical methods makes the finding robust. The work points toward a future where a simple blood test could help doctors make more precise decisions about who needs the most urgent care to prevent the devastating loss of a leg.
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