Inflammatory Marker CAR Linked to All-cause Mortality in Parkinson’s

Highest CAR patients three times more likely to die from any cause than lowest CAR patients

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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The C-reactive protein-to-albumin ratio (CAR), a measure of inflammation in the body that can be read from a routine blood test, may be linked to all-cause mortality in people with Parkinson’s disease, according to study of people in Japan.

Data showed patients with the highest CAR were up to three times more likely to die from any cause than those with the lowest CAR.

These findings suggest “CAR may be a reliable prognostic biomarker for PD [Parkinson’s disease] patients,” the researchers wrote, adding that the relationship between CAR and all-cause mortality may be “worthy of further study.”

The study, “Association between C-reactive protein-albumin ratio and overall survival in Parkinson’s disease using publicly available data: A retrospective cohort study,” was published in Heliyon.

Parkinson’s is a disease of the nervous system that primarily affects a person’s ability to move. Its main symptoms include tremor, stiff muscles, and difficulty keeping coordination and balance. People with Parkinson’s can also experience a range of motor and nonmotor symptoms.

Growing evidence suggests inflammation may play a role in how Parkinson’s develops and worsens over time. Studies have shown that people with Parkinson’s have increased levels of inflammatory markers in the brain, blood, and other body fluids.

While the link between inflammation and Parkinson’s is becoming clearer, more research is needed to understand how inflammatory markers can be best used to understand the disease.

A team of researchers in China focused on the C-reactive protein-to-albumin ratio. While both proteins are made by the liver, C-reactive protein (CRP) is released into the bloodstream in response to inflammation, while albumin enters the bloodstream in part to prevent fluid from leaking out of blood vessels into other tissues. It’s also involved in transporting vitamins, enzymes, and hormones throughout the bloodstream and can be a marker of the body’s nutritional status.

CAR “is considered a better marker of inflammation than CRP,” the researchers wrote, with a higher ratio indicating more inflammation. A high CAR has been previously associated with poor overall survival in other diseases.

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Higher CAR and all-cause mortality

The researchers retrospectively analyzed clinical and laboratory data from 235 people in Japan (135 women, 100 men) who had Parkinson’s for a median of seven years and who were followed for up to 10 years between 2004 and 2014. At enrollment, their mean age was 62.2 and none showed signs of infections. Nearly two-thirds (63%) were in stages 1–3 of the modified Hoehn–Yahr (mH-Y) scale, indicating mild to moderate symptoms. The remaining patients (37%) were in stages 4–5, meaning they had severe disability due to Parkinson’s.

Less than half (42.6%) showed cognitive impairment, as assessed with the Mini-Mental State Examination (MMSE). Most (83%) were not on non-steroidal anti-inflammatory drugs (NSAIDs).

A total of 45 patients (19.1%) died during follow-up.

Older age, longer disease duration, and more advanced mH-Y stage were independently associated with higher all-cause mortality in Parkinson’s patients, statistical analyses showed.

“This result is consistent with previous reports, as it has been confirmed that age, PD duration, and mH-Y are associated with PD progression,” the researchers wrote.

Higher CAR was also found to be an independent risk factor for all-cause mortality. After adjusting for potential influencing factors, including age, sex, disease duration, NSAID use, mH-Y stage, and MMSE score, higher CAR was linked to a 54% higher risk of death from any cause.

The researchers next divided CAR into three levels, or tertiles. Patients who fell in the highest CAR tertile were up to three times more likely to die from any cause than those in the lowest tertile.

After adjusting for the same potential influencing factors, the highest CAR tertile was linked to a two times higher risk of death relative to the lowest CAR tertile.

Similar findings were observed with patients under 70, but the link between CAR and all-cause mortality failed to reach statistical significance for those 70 and older.

“Previous studies have shown that the effect of age on the progression of PD is significant, so the age variable may have an impact on the value of CAR in PD patients, which still needs to be studied with a larger sample size,” the researchers wrote.

These findings show “the all-cause mortality of PD patients with a high level of CAR is higher, which indicates that the poor overall survival of PD patients is associated with the increase of CAR,” the researchers wrote, noting their findings must be confirmed in a large multicentric clinical trial of patients with different races and nationalities, since these may affect disease progression. They also said because there is “no cut-off value for “high-level CAR,” more research is needed to explore its definition, which can be used in the future.

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