Association between C-reactive protein, metabolic cardiovascular risk factors, obesity and oral contraceptive use in young adults

OBJECTIVE: This study sought to determine the relationship between levels of the inflammatory marker, C-reactive protein (CRP), cardiovascular risk factors and oral contraceptive use in young adults.

DESIGN: Cross-sectional study of a community cohort.

SUBJECTS: A total of 822 men and women aged 26 y.

MEASUREMENTS: CRP, body mass index (BMI), blood pressure, lipid and lipoprotein levels, smoking status, socioeconomic status, health status, and hormonal contraceptive use in women.

RESULTS: Multiple regression analysis showed that obesity was independently related to CRP with an increase in ratio CRP of 1.03 (95% CI 1.01, 1.05) for men and 1.07 (1.05, 1.09) for women associated with a 1 kg/m² increase in BMI. In women, combined oral contraceptive use was associated with a ratio change in CRP of 1.52 (1.27, 1.82) compared with nonusers. Other independent determinants of CRP in men and women were apolipoprotein B level, systolic blood pressure and apolipoprotein A1 in men. Univariate analysis showed that the relationship between CRP and BMI, systolic blood pressure and apolipoprotein B was significantly stronger in women than men.

CONCLUSION: These findings suggest that obesity is associated with inflammation independent of other cardiovascular risk factors that may contribute to an increased risk for cardiovascular disease in men and women. Elevated CRP related to combined oral contraceptive use may influence the rate of cardiovascular events in young women.

Inflammation appears to mediate all stages of atherosclerosis. C-reactive protein (CRP), a marker of low-grade chronic inflammation,¹ is associated with an increased risk of cardiovascular events in apparently healthy men and women² and has recently been shown to provide additional prognostic information to low-density lipoprotein cholesterol in women.³ Although it has been shown that other cardiovascular risk factors are associated with elevated CRP,^4, 5 the inter-relationship between and relative importance of such risk factors remain uncertain.

Obesity, which is an increasing problem in childhood and early adulthood,⁶ is associated with multiple cardiovascular risk factors and a higher risk of cardiovascular events.^7, 8 It has been suggested that low-grade inflammation may contribute to the association of obesity with cardiovascular disease.⁹ Previous studies in middle-aged and elderly people have shown an association between body mass index (BMI) and CRP level.^4, 10 These findings have been confirmed in young adults who generally have a low prevalence of confounding subclinical disease.⁹

Important insights have been gained into the relationship between obesity and inflammation. Adipose tissue synthesizes tumour necrosis factor-α (TNF-α) and interleukin 6 (Il-6) which are associated with chronic inflammation and elevated CRP levels.¹¹ However, there are also relationships between CRP and smoking, insulin resistance, high-density lipoprotein (HDL) cholesterol, triglycerides, blood pressure and markers of endothelial dysfunction.^4, 11 This raises the possibility that the relationship between inflammation and obesity is influenced by confounding factors.

An evolving area of interest concerns the effect of oestrogens/progestogens on indices of inflammation in women.¹² Recent studies have shown that hormone replacement therapy in postmenopausal women is associated with elevated CRP^13, 14 with a potential adverse cardiovascular risk. Early reports suggested that there may be a link between oral contraceptives and CRP^15, 16 and an open label study has suggested increases in CRP in young women treated with third-generation combined oral contraceptives.¹⁷ There have been long-standing concerns about the possible cardiovascular risks associated with combined oral contraceptive use¹⁸ but limited understanding of possible mechanisms of arterial disease in a predominantly younger age group of women. There is little information regarding the significance of oestrogen/progestogen-mediated increases in CRP in young women.

The aim of this study was to determine the inter-relationship and relative importance of predictors of CRP levels in young men and women. The study assessed the relationship between CRP, obesity, metabolic and other cardiovascular risk factors including hormonal contraceptive use in women, in a cohort of young adults.