Cardiorespiratory Fitness, C-Reactive Protein, and All-Cause Mortality in Men and Women: The Cooper Center Longitudinal Study

January 24, 2023
published in:
Journal of Investigative Medicine
Stephen W. Farrell, PhD, FACSM
, et al.

As you may be aware, cardiorespiratory fitness (CRF) as well as inflammation are two hot topics in the health and fitness research field.

CRF is best thought of as the ability of the body to use oxygen at the cell level, and can be objectively measured via maximal treadmill exercise testing in a clinical setting. C-Reactive Protein (CRP) is a common and inexpensive blood test that measures inflammation levels within the body. The higher the CRP level, the greater the amount of inflammation present. Both CRF and CRP are important predictors of mortality. Our research team examined the relationship between CRF, CRP, and all-cause mortality in men and women. Our primary goal was to look at all possible combinations of CRF and CRP at baseline, then examine subsequent all-cause mortality risk. Our results were recently published in the Journal of Investigative Medicine.

We followed 30,077 healthy adults (31% women) with an average age of 49 years, who completed a comprehensive health examination at the Cooper Clinic between 2000 and 2016.

The exam included a maximal treadmill exercise test to measure CRF as well as blood analysis for CRP. The participants were divided into Fit and Unfit CRF categories based on their age, sex, and treadmill performance. Participants were also divided into Normal and Elevated categories of CRP. We examined mortality risk for Fit and Unfit participants within each of the two CRP categories. Several factors that might have affected our observations were taken into account. These included age, sex, body mass index, resting blood pressure, blood cholesterol and glucose levels, triglyceride: HDL ratio, and smoking.

There were a total of 576 deaths during an average of 10 years of follow-up. About 60% of deaths were from cardiovascular disease and cancer, which is consistent with U.S. population data as a whole during that same time period.

Unfit individuals were 50% more likely to die during follow-up compared to those who were Fit. Similarly, those with elevated CRP levels were 51% more likely to die during follow-up compared to those with normal CRP levels.

The more novel finding in this study was that Fit individuals had lower mortality risk than Unfit individuals within each category of CRP. This was especially true for those in the elevated CRP category. Therefore, regardless of the level of inflammation present, higher levels of CRF helped protect against mortality. The highest mortality risk was seen among those who were Unfit with elevated CRP levels. These results are shown below in the Figure.

Figure. All-cause mortality risk for Fit and Unfit within each CRP category

As you see in the Figure, among those with Normal CRP levels, mortality risk was 38% higher for those who were Unfit compared to those who were Fit. Among those with Elevated CRP levels, mortality risk was 77% higher for those who were Unfit compared to those who were Fit.  

Action Points  

Since both CRF and CRP are important predictors of mortality, it is important to have these health markers measured. While CRP is measured in a clinical setting, CRF can be either measured in a clinical setting via a maximal treadmill exercise test, or estimated outside of a clinical setting utilizing methods such as the Rockport 1 Mile Walking Test or the Cooper 12-Minute Run Test.

Individuals who are found to have low CRF should strive to meet current public health guidelines for physical activity, that is, accumulate at least 150 minutes each week of moderate intensity aerobic physical activity and perform resistance training at least two days each week. For individuals who are very sedentary, it may take several weeks to gradually build up to recommended physical activity levels. Individuals found to have elevated CRP should consult with their health care provider regarding strategies to decrease inflammation. These lifestyle strategies typically include avoiding tobacco in all forms, performing regular physical activity, losing weight if overweight, and consuming a heart healthy diet such as the DASH Eating Plan or the Mediterranean Diet. From a pharmacological perspective, in addition to lowering blood LDL-cholesterol and triglyceride levels, statin drugs have also been shown to reduce inflammation. Since aspirin also has anti-inflammatory properties, you might also speak with your primary health care provider to see if you are a good candidate for low-dose aspirin therapy.  


Farrell, S.W., et al. Cardiorespiratory fitness, C-reactive protein, and all-cause mortality in men and women. Journal of Investigative Medicine. Published online ahead of print. January 24, 2023.

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