CRP as a 'risk thermometer': Study links inflammation marker to overall mortality

A prospective study from Shanghai was published in BMJ Open: the higher the level of C-reactive protein (CRP) in the blood of people from the general population, the higher their risk of dying from any cause, as well as from certain groups of causes (cardiovascular, oncological, etc.). This is not a diagnosis for tomorrow, but rather that low-intensity inflammation, which reflects CRP, provides additional prognostic information on top of the usual risk factors.

Background

• What is CRP and why is it important? CRP is an acute-phase reactant in the liver; its “high-sensitivity” measurement (hs-CRP) captures low-grade chronic inflammation associated with atherosclerosis and other diseases of old age. Classic hs-CRP categories for CV risk stratification are <1, 1–3, ≥3 mg/L (low/moderate/high risk); current guidelines use hs-CRP ≥2 mg/L as a risk enhancer in people in the intermediate category.
• Why look at all-cause mortality, not just CVD. Inflammation is a common mechanism for many outcomes (CV events, cancer, COPD, infections, frailty). Cohort data from different countries showed that elevated hs-CRP predicts all-cause mortality and often CV and cancer mortality separately, even after adjusting for age, smoking, BMI, and comorbidities.
• What's new about the Shanghai cohort? This is a prospective study of the general urban population with baseline CRP/hs-CRP measurement, long-term follow-up, and analysis of cause-specific mortality. The authors confirm that higher CRP is associated with an increased risk of all-cause mortality, as well as CV and cancer mortality, independent of traditional risk factors, strengthening the role of CRP as a simple "thermometer of systemic risk."
• Confounding factors that can easily lead to error. CRP is affected by obesity, abdominal fat, smoking, infections, medications, and seasonality; baseline levels also vary for genetic reasons. Therefore, proper adjustment/stratification and exclusion of acute conditions are important.
• Why does the clinic and healthcare need this?
  • In the general population, CRP is a cheap and accessible marker that can add prognostic information to risk calculators and aid in lifestyle modification and treatment conversations (lipids, blood pressure, glycemia).
  • There is growing evidence that repeated/cumulative measurements of hs-CRP are more informative than a single measurement (more consistently reflecting chronic inflammation).
• Limitations of the approach. CRP is nonspecific and not a target of therapy in itself; its reduction often reflects successful risk factor modification (weight loss, smoking cessation, statin/antihypertensive therapy, etc.) rather than “treatment of CRP.” Because of residual confounding, causality should be interpreted with caution.
• Why Asian validation is important. Much of the early work is from Europe/America; confirming associations in a major Chinese city helps generalize findings across ethnicities/diets/disease patterns and refine thresholds and nonlinearities in risk curves.

What did they do?

The authors followed a large urban cohort of Shanghai residents: at baseline, they measured CRP/hs-CRP and other health and lifestyle indicators, and then prospectively tracked mortality and its causes. They then calculated how the risk of death changed in groups with increasing CRP, adjusting for age, gender, smoking, BMI, and comorbidities. This design allows us to understand whether CRP has independent prognostic value.

What we found - in simple words

• People with higher CRP had a higher risk of all-cause mortality during the follow-up period. Similar signals emerged for cause-specific mortality (cardiovascular, cancer, and “other”), consistent with chronic systemic inflammation “fueling” many diseases of old age.
• The associations of CRP with mortality risk persisted after controlling for key confounding factors, suggesting an independent prognostic role for the marker. Similar patterns have been previously seen in other Asian cohorts (including the “oldest” elderly) and in disease-specific studies.

Why is this important?

• Simple, cheap, understandable. CRP is a widely available test. If it does provide an additional layer of prognosis beyond age, blood pressure, lipids, and glucose, it could be used as a screening “systemic risk thermometer” — especially where sophisticated biomarker panels are not available.
• General population benefit. It’s not just about cardiovascular risk: elevated CRP is also associated with cancer outcomes and some chronic conditions, making the marker a universal indicator of ill-being, albeit a non-specific one.

How to Use It (and What Not to Expect)

• Not a "horror story", but a reason to check risk factors. A one-time elevated CRP is a signal to look for and adjust modifiable risks: weight, smoking, blood pressure, lipids, glycemia, physical activity level, sleep and stress. It can help set priorities in prevention.
• CRP is not a diagnosis or treatment target in itself. It reflects inflammation, but does not indicate the cause. Normalizing CRP with diet, exercise, and treatment of underlying conditions is a consequence of a comprehensive approach, not an end in itself.

Limitations and accuracy of conclusions

This is an observational study: it shows association, not causation. CRP is non-specific — it is affected by infections, chronic diseases, obesity, smoking, even season. Therefore, the authors do not call for basing clinical decisions on CRP alone, but suggest considering it as an addition to classic risk scales. Similar warnings are heard in other cohorts.

What's next?

Required:

1. Multicenter validations in other regions and ethnic groups;
2. Checking nonlinearity (are there CRP “thresholds” after which the risk grows faster);
3. Tests to see if adding CRP to standard calculators improves stratification accuracy (reclassification/NRI) and whether prognosis changes with targeted reduction of inflammatory background.

Source: Prognostic value of C-reactive protein predicting all-cause and cause-specific mortality: a prospective cohort study in Shanghai, China, BMJ Open 15(8):e101532, 2025. https://doi.org/10.1136/bmjopen-2025-101532