Elsevier

Annals of Epidemiology

Volume 21, Issue 10, October 2011, Pages 739-748
Annals of Epidemiology

White Blood Cell Count, C-Reactive Protein, and Incident Heart Failure in the Atherosclerosis Risk in Communities (ARIC) Study

https://doi.org/10.1016/j.annepidem.2011.06.005Get rights and content

Purpose

To test the hypothesis that inflammation measured by white blood cell count (WBC) and C-reactive protein (CRP) is associated positively with incident heart failure (HF).

Methods

Using the Atherosclerosis Risk in Communities (ARIC) Study, we conducted separate Cox proportional hazards regression analyses for WBC (measured 1987–1989) and CRP (measured 1996–1998) in relation to subsequent heart failure occurrence. A total of 14,485 and 9,978 individuals were included in the WBC and CRP analyses, respectively.

Results

There were 1647 participants that developed HF during follow-up after WBC assessment and 613 developed HF after CRP assessment. After adjustment for demographic variables and traditional HF risk factors, the hazard ratio (95% confidence interval) for incident HF across quintiles of WBC was 1.0, 1.10 (0.9–1.34), 1.27 (1.05–1.53), 1.44 (1.19–1.74), and 1.62 (1.34–1.96), p trend < .001; hazard ratio across quintiles of CRP was 1.0, 1.03 (0.68–1.55), 0.99 (0.66–1.51), 1.40 (0.94–2.09), and 1.70 (1.14–2.53), p trend .002. Granulocytes appeared to drive the relation between WBCs and heart failure (hazard ratios across quintiles: 1.0, 0.93 [0.76–1.15], 1.26 [1.04–1.53], 1.67 [1.39–2.01], and 2.19 [1.83–2.61], p trend <.0001), whereas lymphocytes or monocytes were not related.

Conclusions

Greater levels of WBC (especially granulocytes) and CRP are associated with increased risk of heart failure in middle-aged adults, independent of traditional risk factors.

Introduction

Inflammation, as reflected by an elevated C-reactive protein (CRP) or white blood cell count (WBC), is considered to be important in the development of coronary heart disease (CHD) 1, 2, 3. The authors of a few population studies have suggested that greater levels of CRP may also be associated with increased risk of heart failure (HF) 4, 5, 6, 7, 8, 9. In several studies this association was independent of prevalent or incident CHD. CRP is associated positively with hypertension, obesity, diabetes, smoking, and inactivity, and inflammation accompanying these conditions could contribute to HF. Although evidence for a link between CRP and HF is growing, to our knowledge, no population study has examined the association of WBC in men and women with incident HF. WBC and CRP may be implicated in the development of HF by the immune system acting as a modulator of myocyte injury (9) and inflammatory reactions contributing to the structural and functional deteriorations observed in failing human hearts (10). Greater levels of inflammatory markers also have been associated with increased severity, mortality, and morbidity in patients with HF 11, 12, 13, 14. Here, we used data from the Atherosclerosis Risk in Communities (ARIC) Study, a cohort of middle-aged adults, to test the hypotheses that CRP and WBC are associated positively with incidence of HF.

Section snippets

Study Population and Design

The ARIC Study (15) is a prospective cohort study of 15,792 men and women ages 45–64 years in 1987 to 1989 in four U.S. communities: Forsyth County, North Carolina; Jackson, Mississippi; suburban Minneapolis, Minnesota; and Washington County, Maryland. The baseline visit (visit 1) included interviews, laboratory measurements, and clinic examinations. Additional visits were conducted in 1990–1992 (visit 2), 1993–1995 (visit 3), and 1996–1998 (visit 4). This study was approved by the

Baseline Characteristics

A total of 14,485 participants were included in the WBC (visit 1) analyses, and 9,978 were included in the CRP (visit 4) analyses. At baseline, the mean WBC (SD) was 6.09 (1.86) × 109/L. The mean age of the cohort was 54 years; 74% were white, 54% were female, and 36% had more than a high school education. As Table 1 shows, participants with greater WBC levels were more often male, had greater levels of most HF risk factors, and as expected, were more often white than black (18).

For visit 4,

Conclusions

In this analysis of a prospective, community-based, biracial sample of middle-aged adults, greater blood levels of WBC and CRP were strongly associated with increased incidence of HF. After adjustment for traditional risk factors, the associations were weakened but moderate positive associations still remained. These findings are consistent with previously published studies of the relationship between CRP and HF 4, 5, 6, 7, 8, 26. The present study extends previous findings to show that

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  • Cited by (0)

    The Atherosclerosis Risk in Communities (ARIC) Study is supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022. Dr. Astor is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (1 R01 DK076770-01). Siemens Healthcare Diagnostics provided the reagents and loan of a BNII instrument to conduct the CRP assays.

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