Analysis of factors affecting the sex difference in C -reactive protein levels

• Main Author: Shaffer, Lynn E.T
• Format: Dissertation
• Language: English
• Published: Ann Arbor ProQuest Dissertations & Theses 2009
• Subjects: Gender differences; Kinesiology; Proteins; Public health
• ISBN: 1109401949; 9781109401943

Introduction. C-reactive protein (CRP) is a marker of inflammation manufactured in the liver. Small elevations in CRP are linked to increased risk of cardiovascular disease (CVD). Despite the lower CVD risk among women, several studies suggest that women have higher CRP levels than men after controlling for other factors associated with both CRP and sex. However, these studies have not included all known and potential factors which could account for the relationship between CRP and sex, nor have they considered whether these factors represent confounding, intermediate outcomes, or another type of relationship.
Methods. This cross-sectional study utilized data from members of the fitness program at McConnell Heart Health Center in Columbus, Ohio. Information included demographics, laboratory values (CRP, glucose, lipids), MET level, medications used and comorbidities. A directed acyclic graph (DAG) delineated the relationships among various factors, sex and CRP. Implications of the DAG were incorporated into linear regression models so that confounders were controlled for while proposed causal pathways were assessed for their ability to account for the sex-CRP association. Results. Mean log CRP for females (mean=0.78, 95% CI: 0.70-0.86) was higher than for males (mean=0.40, 95% CI: 0.30-0.49). An age by sex interaction indicated that CRP rises with age among men but not women (.
beta=0.011, p=0.0155).Linear regression confirmed the sex difference in log CRP after controlling for confounders; two models accounted for the sex difference: (1) a model including sex, LDL, and MET level; and (2) a model including sex, LDL, BMI, waist circumference, √triglycerides, and interaction terms for BMI by waist, sex by √triglycerides, and sex by age. Further analysis revealed that model #1 (with MET level), as well as exogenous estrogen use and menopausal status, accounted for the sex difference among people with BMI<25, while model #2 (with the interaction terms) accounted for the sex difference among people with BMI≥30. The sex difference among individuals with 25≤BMI<30 was not explained.
Discussion. The sex difference in CRP levels can be accounted for through appropriate modeling using epidemiologic techniques. Dysfunctional adipose tissue, as indicated by elevated triglyceride levels, appears to accelerate inflammation in women compared to men.