Introduction

Inflammation is taking a more central position in the chain of events leading to coronary heart disease (CHD), almost shouldering aside blood lipid levels. C-reactive protein (CRP) plasma levels are generally accepted as markers of subclinical inflammation, and elevated values are associated with a 2- to 5-fold increased risk of a cardiac event, such as myocardial infarction (MI). Raised CRP levels are also linked with smoking, obesity, increased insulin sensitivity, and type 2 diabetes.

Regular exercise decreases CRP levels as well as the risk of CHD. Does this mean that exercise reduces subclinical inflammation, one of the known causes of CHD? Two reports have suggested that this may be the case, and a new study in women from different ethnic backgrounds now provides further evidence.

Method

The Cross-Cultural Activity Participation Study (CAPS) was designed to get information on physical activity in three different ethnic groups of women -- African American (AA), Native American (NA), and Caucasian (CA). Fasting CRP levels were determined, along with interview-based health histories, body mass index estimates (BMI), waist measurement, and resting blood pressure. Cardiorespiratory fitness was quantified as the duration of maximum treadmill exercise using a standard protocol, with the result expressed in 'metabolic equivalent tasks (METs). ¹

For the purpose of analyses, log transformations of CRP values were made, as the values were skewed. Fitness varied significantly by race, so race-specific treadmill times were used to create three race-specific percentiles. BMI and waist measurements were categorized into 3 groups (18-24.9, 25-29.9 and >30) and 2 groups (<88 cm, =/>88 cm), respectively. Fitness was classified as follows: 'fit' >6.5 METs, 'unfit' =/<6.5 METs. A CRP level above 0.19 mg/dL was regarded as 'high-risk'.

Results

There were 44 AA, 45 NA, and 46 CA women in the total collective. Their mean age was 53.8 years, their mean BMI 27.6, and they had relatively few CHD risk factors (smoking status, high blood pressure, raised cholesterol, etc).

Among all the women, CRP levels were found to correlate significantly with fitness, BMI, waist girth, insulin level, and triglycerides.

The AA women were, on average, less fit, and had higher mean CRP levels, than the Caucasians and to a lesser extent, the NA women:

	AA women	NA women	CA women
Age-adjusted fitness (METs)	7.2*^	9.1*	10.0
CRP (mg/dL)	0.43*^	0.25*	0.23

* p<0.05 vs. CA women     ^ p<0.05 vs. NA women

CRP levels increased significantly with BMI and girth. After adjusting for BMI, smoking, diabetes, and estrogen status (parameters that might be expected to affect the association), lower CRP values were correlated with higher treadmill times for NA and CA women, but not for AA women.

For all women in the study, the odds of high-risk CRP levels (>0.19 mg/dL) were 0.67 for fit (>0.65 METs), vs. unfit women. This odds ratio was not significant, however (95% CI, 0.19 to 2.4).

Comment

The authors describe this as a pilot study -- a relatively small sample size and cross-sectional design. However, the findings confirm many of the observations in women of different ethnic background that have been reported more extensively for males. It seems probable that a larger sample would provide statistically significant evidence of the inverse relationship between fitness and high-risk CRP levels, and for the relationship between fitness and CRP in AA women.

Why are CRP levels lower in fit individuals? Raised CRP values are seen in people with infectious viral pathogens, while fitness is reported to enhance natural killer cell activity, leading to resistance to such infections. Alternatively, fitness is associated with improved insulin sensitivity, reduced body fat and lowered LDL-cholesterol; these three factors may possibly be non-infectious triggers for elevated CRP.

CRP determination is emerging as an important step in helping predict coronary artery health (and, of course, atherosclerosis in general). Not only does it give an indication of possible subclinical inflammatory lesions, but it also reflects cardiorespiratory fitness. Further studies will reveal the exact relationship between the 4 elements: fitness -- CRP -- inflammation -- CHD. Is CRP a mediator, or just a by-product?