In this cross-sectional analysis of US men and women, the lowest concentrations of CRP and fibrinogen were found among normal weight individuals. As BMI ranges increased from overweight to obesity classes 1, 2, and 3, CRP concentration increased by 0.11
0.03 mg/dl, 0.21
0.03 mg/dl, 0.43
0.09 mg/dl, and 0.73
0.09 mg/dl, respectively, and fibrinogen levels increased by 11.5
3.9 mg/dl, 25.6
5.0 mg/dl, 40.0
7.6 mg/dl and 93.5
10.1 mg/dl, respectively. The strongest association between obesity and change in biomarker concentration was observed among those in obesity class 3.
We observed a strong association between increasing weight class and increasing CRP concentrations. Compared to normal weight individuals, there was a 2-fold increase in mean CRP levels in overweight individuals; a 4-fold increase in obesity class 1 individuals; and an 8-fold and 14-fold increase among obesity class 2 and obesity class 3 individuals, respectively. Using data from NHANES III (1988–1994), Ford similarly found that CRP concentrations increased across six weight categories (BMI
18.5, 18.5 to <25, 25 to <30, 30 to <35, 35 to <40, and ≥40 kg/m2
). Ford also found that the odds ratio for elevated CRP levels above the 85th percentile for BMI of 25 to<30 was 1.51 (95% CI 1.23, 3.86); 3.19 (95% CI 2.60, 3.91) for BMI of 30 to <35; 6.11 (95% CI 4.67, 7.98) for BMI 35 to <40; and 9.30 (95% CI 6.43–13.46) for those with BMI ≥40 compared to those with BMI <25 kg/m2
Similarly, Visser and colleagues found that, with increasing BMI, the presence of elevated CRP levels, defined as CRP
0.22 mg/dl, increases for both overweight and obese (≥30 kg/m2
) groups. Visser and colleagues also found that overweight men and overweight women were 1.41 (95% CI 1.09, 1.81) and 2.23 (95% CI 1.86, 2.67) times more likely to have elevated CRP levels compared to normal-weight counterparts.20
The normal range for fibrinogen is between 200 and 400 mg/dl.32
In our adjusted regression analysis between fibrinogen levels and weight class, being in the overweight, obesity class 1, obesity class 2, and obesity class 3 groups placed individuals increasingly near the upper limit of normal fibrinogen levels. Elevated fibrinogen levels have been previously shown to associate with insulin resistance and atherosclerosis.34
We also examined fibrinogen concentrations across weight class according to diabetes status. Our findings suggest that increasing severity of obesity is associated with increased risk for diabetes. The results also support the idea that inflammation may play a role in the development of insulin resistance,35
underlying the importance of having a normal BMI to prevent the disease onset.
In addition to what has been presented in past studies, this study quantifies the estimated change in biomarker concentrations across different weight classes. As anticipated, those individuals in the highest weight class, obesity class 3, had significantly higher CRP and fibrinogen concentrations relative to the normal BMI group as well as the other weight groups. This trend did not change with adjustments for age, gender, arthritis status, race/ethnicity, or smoking, suggesting that the observed CRP–obesity relationship is not due to other factors possibly affecting CRP levels and/or weight status. When we stratified by diabetes status, we also found that individuals in obesity class 3 had higher biomarker levels than those in obesity classes 1 and 2. This was also observed when we compared CRP levels between diabetics and non-diabetics in obesity class 3 to those in the overweight and normal weight categories. Extending our analyses, we also stratified by hypertension status, reporting the mean biomarker concentrations within each weight class for a representative US population. The general trend supports our primary hypothesis that inflammation severity, indicated by elevated biomarker levels, directly correlates to weight class.
Inflammation in the presence of obesity is thought to arise primarily in adipose tissue as a result of chronic disruption of metabolic homeostasis, which leads to increased cytokine production and the activation of inflammatory signaling pathways in the body.12
A recent clinical study by Madsen and colleagues investigated the effects of short-term and long-term weight loss on levels of CRP and fibrinogen among obese subjects and found that long-term weight loss was associated with decreased CRP and fibrinogen concentrations.37
A systematic review found that for each 1 kg of weight loss, mean CRP levels were reduced by 0.13 mg/l.38
Moderate, short-term weight loss, however, was shown to have no effect on fibrinogen levels,23
suggesting that long-term weight loss solutions through lifestyle changes or surgical intervention may be more useful for reducing inflammation and related disease risks.
Limitations of this study include the lack of repeated measurements of biomarker levels as well as the absence of information regarding any previous medical or surgical treatment for obesity. Additionally, the extent of our study on inflammatory biomarkers was limited by the availability of biomarker measurements in the NHANES dataset; we did not have the opportunity to access other markers of inflammation such as interleukin-6 or TNF-alpha. The population used for our CRP analyses also differed from the population used for the fibrinogen analysis because fibrinogen data was only collected among those who were 40 years of age and older between 1999 and 2002 while CRP measurements were taken among those who were 20 years of age and older between 1999 and 2004. There is also the possibility for information and recall bias in this study because data on hypertension, arthritis, and diabetic status were collected by means of self-report. However, in this study, possible information and recall biases were minimized by taking into account additional data collected on hypertension and diabetes medication usage as well as any relevant examination or laboratory data. Additionally, the under- or over-reporting of hypertension and diabetes should be similar across BMI categories. Despite these limitations, this study utilizes a large, comprehensive data set that serves as a representative sample of the US population, allowing for greater generalizability of the study results. Multiple markers of inflammation were also assessed, which increased the possibility of capturing a more complete description of inflammatory status among individuals. Future studies are needed to determine if the changes in inflammatory markers further differ among obese individuals, and whether inflammatory biomarker levels decrease at a different rate and by different amounts in obesity class 1 vs. obesity class 2 or 3. If trends from this current study are persistent in such future studies, we anticipate that changes in levels of inflammatory biomarkers will differ according to weight class. Thus, the current findings of an association of CRP and fibrinogen and body weight, if causal, would imply that weight reduction leads to reduced prevalence of inflammation with attendant public health benefits.