Body size phenotypes and inflammation in the Women's Health Initiative Observational Study

Abstract

Individuals with "metabolically benign" obesity (obesity unaccompanied by hypertension, dyslipidemia, and diabetes) are not at elevated 10-year risk of cardiovascular disease (CVD) compared to normal weight individuals. It remains unclear whether these obese individuals or normal weight individuals with clustering of cardiometabolic factors display heightened immune activity. Therefore, we characterized levels of acute-phase reactants (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), white blood cell (WBC) count), adhesion molecules (E-selectin, vascular cell adhesion molecule-1), and coagulation products (fibrinogen, plasminogen activator inhibitor-1 (PAI-1)) among four body size phenotypes (normal weight with 0/1 vs. ≥2 metabolic syndrome components/diabetes and overweight/obesity with 0/1 vs. ≥2 metabolic syndrome components/diabetes) in cross-sectional analyses of 1,889 postmenopausal women from the Women's Health Initiative Observational Study (WHI-OS) nested case-control stroke study. Higher levels of all three inflammatory marker categories were found among women with overweight/obesity or ≥2 metabolic syndrome components or diabetes. Compared to normal weight women with 0 or 1 metabolic syndrome components, normal weight women with ≥2 metabolic syndrome components or diabetes were more likely to have ≥3 inflammatory markers in the top quartile (multivariate odds ratio (OR) 2.0, 95% confidence interval (CI): 1.3-3.0), as were overweight/obese women with 0 or 1 metabolic syndrome components (OR 2.3; 95% CI: 1.5-3.5). Overweight/obese women with ≥2 metabolic syndrome components or diabetes had the highest OR (OR 4.2; 95% CI: 2.9-5.9). Despite findings that metabolically benign obese individuals are not at increased 10-year risk of CVD compared to normal weight individuals, the current results suggest that overweight/obese women without clustering of cardiometabolic risk factors still possess abnormal levels of inflammatory markers.

Figure 1

Median Acute-Phase Marker Levels by Body Size Phenotypes Horizontal lines represent medians, while bottom and top of boxes represent 25^th and 75^th percentiles, respectively. NW=Normal weight; OO=overweight/obese; ≤1 = 0 or 1 cardiometabolic abnormalities and no diabetes; ≥2= 2 or more cardiometabolic abnormalities or diabetes Cardiometabolic abnormalities considered were: 1.) systolic/diastolic blood pressure ≥130/85 mmHg or antihypertensive medication use, 2.) fasting triglycerides ≥1.7 mmol/L, 3.) HDL <1.3 mmol/L and 4.) fasting glucose ≥7.0 mmol/L or antidiabetic med use

Figure 2

Median Adhesion Molecule Levels by Body Size Phenotypes Horizontal lines represent medians, while bottom and top of boxes represent 25^th and 75^th percentiles, respectively. NW=Normal weight; OO=overweight/obese; ≤1 = 0 or 1 cardiometabolic abnormalities and no diabetes; ≥2= 2 or more cardiometabolic abnormalities or diabetes Cardiometabolic abnormalities considered were: 1.) systolic/diastolic blood pressure ≥130/85 mmHg or antihypertensive medication use, 2.) fasting triglycerides ≥1.7 mmol/L, 3.) HDL <1.3 mmol/L and 4.) fasting glucose ≥7.0 mmol/L or antidiabetic med use

Figure 3

Median Coagulation Factor Levels by Body Size Phenotypes Horizontal lines represent medians, while bottom and top of boxes represent 25^th and 75^th percentiles, respectively. NW=Normal weight; OO=overweight/obese; ≤1 = 0 or 1 cardiometabolic abnormalities and no diabetes; ≥2= 2 or more cardiometabolic abnormalities or diabetes Cardiometabolic abnormalities considered were: 1.) systolic/diastolic blood pressure ≥130/85 mmHg or antihypertensive medication use, 2.) fasting triglycerides ≥1.7 mmol/L, 3.) HDL <1.3 mmol/L and 4.) fasting glucose ≥7.0 mmol/L or antidiabetic med use

Figure 4

Adjusted* Odds Ratios (95% Confidence Intervals) of Possessing 3 Inflammatory Markers in the Top Quartile associated with Body Size Phenotypes Metabolic abnormalities considered were: 1.) systolic/diastolic blood pressure ≥130/85 mmHg or antihypertensive medication use, 2.) fasting triglycerides ≥1.7 mmol/L, 3.) HDL <1.3 mmol/L and 4.) fasting glucose ≥5.6 mmol/L or antidiabetic med use *Adjusted for age, race-ethnicity, smoking, income, physical activity, education, hormone therapy use, NSAID use, baseline history of CVD, and stroke case-control status