The relationship between inflammation, obesity and risk for hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

It has been suggested that inflammation is important in the aetiology of hypertension and that this may be most relevant among obese persons. To study this, we examined the independent relationships between obesity, inflammation-related proteins (interleukin-6 (IL-6), C-reactive protein (CRP) and fibrinogen) and risk for hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA). Hypertension status, defined as a blood pressure ≥140/90 mm Hg or a history of hypertension and use of blood pressure medications, was determined at baseline and two subsequent exams over 5 years. Among 3543 non-hypertensives at baseline, 714 individuals developed incident hypertension by Exam 3. Cox proportional hazard models were used to determine the relationship between baseline levels of IL-6, CRP and fibrinogen and future risk of hypertension. One s.d. difference in baseline concentration of IL-6, CRP or fibrinogen was associated with 20-40% greater risk of incident hypertension. This risk was attenuated after accounting for other hypertension risk factors (hazard ratio (HR) IL-6: 1.13 (95% CI: 1.04-1.23); CRP: 1.11 (95% CI: 1.02-1.21); fibrinogen 1.0 (95% CI: 0.92-1.08)). Conversely, obesity was an independent risk factor for hypertension risk, minimally impacted by other covariates, including IL-6 and CRP (HR 1.72 (95% CI: 1.36-2.16)). IL-6 and CRP did not modify the relationship between obesity and hypertension, though an adjusted twofold greater risk was observed for obese individuals with a CRP >3 mg l⁻¹ compared with CRP <1 mg l⁻¹. The relationship between inflammation-related proteins and hypertension risk was predominantly explained by other hypertension risk factors. Obesity, independent of inflammation, remained a potent risk factor for future hypertension.

Figure 1

Risk of incident hypertension by baseline circulating levels of interleukin-6, C-reactive protein and fibrinogen. Black square (95% CI)=Risk of incident hypertension comparing 1–s.d. difference (0.67 pg ml⁻¹) in interleukin-6 concentration. Black triangle (95% CI)=Risk of incident hypertension comparing 1–s.d. difference (1.17 mg l⁻¹) in C-reactive protein concentration. White dot (95% CI)=Risk of incident hypertension comparing 1–s.d. difference (0.20 mg dl⁻¹) in fibrinogen concentration. Model 1: unadjusted. Model 2: adjusted for age, gender and ethnicity. Model 3: adjusted for age, gender, ethnicity, smoking, diabetes, statin use, aspirin use, alcohol use and study site. Model 4: Model 3 + body mass index. Model 5: Model 3 + waist circumference. Abbreviations: HR, hazard ratio; CI, confidence interval. *P<0.05.

Figure 2

CRP Category among normal, overweight and obese individuals and risk for hypertension in MESA. Abbreviations: HTN, hypertension; BMI, body mass index; CRP, C-reactive protein.