Body Mass Index and C-Reactive Protein in the Healthy Korean Aged Men

Arterial inflammation is well recognized as an essential process for atherogenesis (1). Of the markers of inflammation, with the availability of highly sensitive assay systems, C-reactive protein (CRP) levels in the low-normal range have been shown to have predictive value for subsequent clinical events among patients with cardiovascular disease (2).

Moreover, baseline levels of CRP predict the risk of future myocardial infarction, stroke, and peripheral atherosclerosis among apparently healthy middle-aged men (3) and women (4), after adjusting for other known cardiovascular risk factors. Even in the elderly, higher CRP levels were associated with cardiovascular mortality in women without cardiovascular disease (5).

In the Western countries, many studies have explored the relationship between CRP levels and determinants of cardiovascular risk factors in apparently healthy men (6-8) and women (9), and in older individuals (10). In particular, obesity is strongly associated with CRP concentration (6, 10), because adipose tissue produces proinflammatory cytokines such as interleukin-6 (IL-6), which stimulates the production of CRP (11).

In Asian populations limited studies have been conducted to determine the relationship between CRP concentration and cardiovascular risk factors. Few studies indicate that CRP levels are strongly associated with body mass index (BMI) in elderly Korean women (12), middle aged Japananese (13-15), and Asian Indian adolescents (16); however, theses studies included small numbers of elderly.

Furthermore, there has been no study which investigated whether BMI classification by WHO Asia-Pacific guideline (17) is relevant for Asian population (especially Koreans) in terms of BMI association with CRP level. Although many Korean physicians and researchers use BMI classification by WHO Asia-pacific guidelines for obesity, some researchers disagree with the classification system. Few credible published data exist in support of elevated risk of cardiovascular disease at BMI 23 to <25 in Asian population (18).

This is a cross-sectional study of Korean elderly men to determine the relationship between plasma CRP level, BMI, and other cardiovascular risk factors. We also investigated whether BMI classification by Asia-pacific guidelines for obesity is associated with CRP level.

The median age of the study subjects was 68.0 yr (interquartile range=66.0-71.0), and the median CRP value was 0.10 (interquartile range=0.07-0.19). Current smokers were more common in the underweight group, and the prevalence of hypertension and diabetes increased with higher BMI levels. Triglyceride concentration and alanine aminotransferase (ALT) level were also increased in overweight, obesity, and excessive obesity category.

As expected, univariate correlation analyses of factors relating to logCRP level showed the highest correlation with white blood cell count (Table 1). HDL-cholesterol, gamma glutamyl transferase (GGT), age and BMI also had significant correlation with log CRP level (Table 1).

Table 1
Simple linear regression anaylsis for log₁₀CRP in the 367 subjects

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In stepwise multiple linear regression analysis, age, BMI, current smoking, regular exercise, WBC count, HDL-cholesterol, GGT remained as factors independently associated with log CRP. Alcohol drinking, hypertension, diabetes mellitus, past history of stroke, past history of myocardial infarction, hemoglobin, uric acid, triglyceride, ALT were not independently significant factors. This model explained 17.9% of variance in log CRP levels (Table 2).

Table 2
Multivariate backward linear regression model predicting log₁₀CRP in the 367 subjects^*

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Subgroup analyses

Subgroup analyses were performed on those who did not smoke and who exercised regularly. This was performed because smoking and exercise were significant confounding factors with log CRP in multivariate analysis. Out of 367 men, 167 non-smoker who exercised regularly (more than once a week) were included. For this analysis, we subdivided BMI into 5 categories: <18.5, 18.5 to 19.4, 19.5 to 24.9, 25.0 to 28.9, and ≥29.0. The category was made after dividing BMI by 0.5 and then merging the combining adjacent BMI categories which showed no apparent difference in CRP levels.

When we analyzed for association between CRP levels and our new BMI subgroups by ANCOVA, the highest BMI group (BMI ≥29.0) showed significant difference in CRP concentrations from BMI group of 18.5-19.4 (p=0.038) (Fig. 1). There was a trend towards difference in CRP levels between the BMI of 25.0-28.9 and BMI of 18.5-19.4 (p=0.105). Similar analysis was conducted between CRP concentrations and BMI subgroups according to the WHO guidelines. The Asia-Pacific guideline BMI subgroup did not show any difference in CRP concentrations from each other after adjusting for covariates by ANCOVA (p>0.05).

Fig. 1
Box plot of CRP concentrations for nonsmoking elderly men who exercise regularly, according to new BMI classification.

^*p values were calculated by ANCOVA for log CRP after adjusting the covariates of age, hemoglobin, WBC count, uric acid, triglyceride, HDL-cholesterol, AST, GGT, alcohol drinking, history of stroke, myocardial infarction, diabetes, hypertension.

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This study examined the relationship between plasma CRP concentrations and BMI in the old Korean men. We showed that among healthy elderly men, BMI was positively associated with CRP concentrations. Similar to previous reports (6, 8, 10, 15), age, exercise level, smoking status, WBC count, HDL-cholesterol, and GGT were independently associated with CRP concentrations. There was no significant difference in CRP level between normal (BMI 18.5-22.9), overweight (BMI 23.0-24.9), or obesity subgroup (BMI 25.0-29.9) among nonsmoker who exercise regularly according to the BMI category of WHO Asia-Pacific guideline. However, when we classified the BMI differently (lower than 18.5, 18.5 to 19.4, 19.5 to 24.9, 25.0 to 28.9, 29.0 or higher), CRP concentrations showed a J shape association with BMI subgroups. CRP concentration was the lowest in BMI of 18.5-19.4, and therefore, we propose that BMI of 18.5-19.4 would be ideal for Korean older men to reduce their risk for cardiovascular disease. In the United States, an association between BMI and death from cardiovascular disease also showed a J-shaped pattern (20), and the lowest risk of death from cardiovascular disease was BMI of 20.5-24.9.

IL-6 or TNF-α levels may be a better predictor of cardiovascular events than CRP concentrations in old adults (21, 22). However, plasma IL-6 concentrations has a circadian variation. In another report, CRP concentrations rather than IL-6 was a marker which independently predicted cardiovascular disease (23). Therefore, CRP concentration provides a reliable, and feasible index of inflammation and cardiovascular risk compared to other inflammatory markers (15).

The correlations between CRP and BMI in this study were lower than that found in old individuals of Western countries (10). The possible explanation may be that our study did not include women, who usually have higher correlation between BMI and CRP levels (24). Also Asian people usually have higher proportion of body fat compared to Western people with the same BMI (24). The correlations between CRP and BMI appeared to be lower than that found in a report of middle-aged Korean adults (25). As people age, there is a gradual increase of adipose tissue in the abdomen (visceral depots) and decrease in subcutaneous fat (26). Fat-free mass is also reduced with age.

Stevens et al. (27) suggested that although greater BMI was associated with higher mortality from cardiovascular disease in men and women up to 75 yr of age, the relative risk declined with age. Furthermore, after 75 yr of age, the risk for cardiovascular disease did not increase significantly with higher BMI. Other investigators have indicated a risk for cardiovascular disease to be less in Asian people with a BMI of ≤25 (28).

Possible limitations of this study include the cross-sectional design, which can not account for acute weight change. The sample size for the excessive obesity was small, however, this was not unexpected. According to the 1998 Korea National Health and Nutrition Survey, the percentage of extreme obesity (BMI ≥30) among Korean men ≥70 yr old was 0% (29).

Highly sensitive CRP levels increased with acute infection and trauma. Thus testing should be avoided within 2 to 3-weeks after an upper respiratory infection. Although we did not exclude people with history of upper respiratory infection 2-3 weeks ago, we excluded acute infection based upon abnormal chest radiography, WBC >10,000/µL, and CRP >1 mg/dL. Despite these efforts, we still may have missed subjects with underlying infection. Another limitation of this study is the lack of generalizability. This study result is applicable to healthy Korean old men living in Korea, and it may not apply to individuals who have comorbid disease or who live in other countries.

In conclusion, our study showed that lower category of BMI (18.5-19.4) than WHO Asia-Pacific guideline for normal weight (BMI 18.5-22.9) had the lowest levels of CRP for nonsmoking elderly men who exercise regularly. Since high levels of CRP are associated with increased risk for cardiovascular disease, low BMI (18.5-19.4) levels may be advised for healthy old men in Korea.