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Comparison of interleukin-6 and C-reactive protein for the risk of developing hypertension in women
Howard D Sesso1, Lu Wang, Julie E Buring
1Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215-1204, USA. hsesso@hsph.harvard.edu
Insights
Systemic inflammation markers, interleukin-6 (IL-6) and C-reactive protein (CRP), were studied for hypertension risk. After adjusting for body mass index, CRP remained a strong predictor of hypertension, while IL-6
Area of Science:
- Cardiovascular Disease Research
- Inflammation and Immunology
- Epidemiology
Background:
- Systemic inflammation markers may influence hypertension development, but clinical evidence is limited.
- Interleukin-6 (IL-6) and C-reactive protein (CRP) are key inflammatory markers.
- Previous studies suggest a link between inflammation and hypertension, requiring further investigation.
Purpose of the Study:
- To investigate the association between IL-6 and CRP levels and the risk of developing hypertension.
- To determine if these associations persist after adjusting for confounding factors, particularly body mass index (BMI).
- To examine the independent contribution of IL-6 and CRP to hypertension risk.
Main Methods:
- A nested case-control study within the Women's Health Study.
- Included 400 women who developed hypertension and 400 age-matched normotensive controls.
- Measured baseline IL-6 and CRP levels, collected self-reported risk factors, and analyzed data using crude and multivariate models, including adjustments for BMI.
Main Results:
- Crude analyses showed strong associations between IL-6, CRP quartiles, and hypertension risk.
- Multivariate adjustment for BMI attenuated the IL-6 association significantly, making it weak.
- C-reactive protein (CRP) remained strongly associated with increased hypertension risk even after multivariate adjustment and simultaneous examination with IL-6.
Conclusions:
- Body mass index is a significant confounder in the relationship between IL-6 and hypertension.
- C-reactive protein is a strong, independent predictor of future hypertension risk in women.
- IL-6 shows a weaker association with hypertension risk compared to CRP after accounting for confounding factors.
Abstract:
Although markers of systemic inflammation may have a role in the development of hypertension, supportive clinical data remain limited. We, therefore, examined interleukin (IL)-6 and C-reactive protein (CRP) in a nested case-control study of 400 women developing hypertension and an equal number of age-matched normotensive control subjects during 10 years of follow-up as part of the Women's Health Study. All of the women initially had nonhypertensive blood pressure values and no history of diagnosis or treatment. Subjects provided self-reported risk factors, and IL-6 and CRP were measured from baseline bloods. Case subjects reported elevated systolic (>or=140 mm Hg) or diastolic (>or=90 mm Hg) blood pressure, newly diagnosed hypertension, or initiating antihypertensive treatment during follow-up. In crude-matched models, IL-6 and CRP quartiles were each strongly associated with hypertension risk (both Ps for trend <0.0001). In multivariate models, the linear trends became nonsignificant, and the relative risks (95% CIs) of hypertension for IL-6 reduced to 1.00 (ref), 1.29 (0.76 to 2.19), 2.14 (1.23 to 3.73), and 1.70 (0.92 to 3.13) and for CRP were 1.00 (ref), 2.09 (1.16 to 3.76), 2.51 (1.42 to 4.44), and 2.44 (1.29 to 4.64), primarily because of confounding by body mass index. Simultaneous adjustment for IL-6 and CRP modestly attenuated both sets of relative risks, although more for IL-6. Finally, there was no effect modification by baseline blood pressure or other risk factors (all Ps for interaction >0.05). Therefore, after multivariate adjustment and strong confounding by body mass index, IL-6 was weakly associated and CRP strongly associated with hypertension risk. In models simultaneously examining IL-6 and CRP, only CRP remained strongly associated with an increased risk of hypertension.
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