|Wu, Zhijun - Shanghai Jiaotong University|
|Huang, Zhe - Kailuan Hospital|
|Jin, Wei - Shanghai Jiaotong University|
|Rimm, Eric - Harvard University|
|Lichtenstein, Alice - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Kris-etherton, Penny - Pennsylvania State University|
|Wu, Shouling - Kailuan Hospital|
|Gao, Xiang - Pennsylvania State University|
Submitted to: Clinical Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/18/2016
Publication Date: 2/1/2017
Citation: Wu, Z., Huang, Z., Jin, W., Rimm, E.B., Lichtenstein, A.H., Kris-Etherton, P.M., Wu, S., Gao, X. 2017. Peripheral inflammatory biomarkers for myocardial infarction risk: a prospective community-based study. Clinical Chemistry. doi: 10.1373/clinchem.2016.260828.
Interpretive Summary: Most previous studies that assessed the relationship between chronic inflammation and myocardial infarction (MI) risk lacked longitudinal measures of the C-reactive protein (CRP) and/or white blood cells (WBC.) Our goal was to determine whether cumulative average and longitudinal changes in these biomarkers were associated with subsequent MI risk. To accomplish this goal we examined data from a prospective, community-based study, the Kailuan Study, that included 82,544 Chinese participants (66,796 men and 15,748 women; average age 55.1 +/- 9.86 y) of the Kailuan Study. Subjects were free of cardiovascular diseases and cancer at baseline. We assessed CRP, WBC, and other clinical controls were assessed at baseline and every 2 years during the 6 year follow-up. Documented were 714 incident MI cases. Higher baseline and cumulative average levels of CRP and/or WBC were consistently associated with increased risk of MI. A longitudinal increase in CRP was also associated with a higher future risk of short-term MI events rather than long-term MI events. These data suggest that plasma CRP concentrations and WBC counts are potentially useful measures to predict MI risk.
Technical Abstract: BACKGROUND: Most previous studies regarding chronic inflammation and risk of myocardial infarction (MI) have lacked repeated measures of high-sensitivity C-reactive protein (hs-CRP) and/or white blood cell (WBC) count over time. We examined whether cumulative average and longitudinal changes in these biomarkers were associated with subsequent MI risk. METHODS: In this prospective, community-based study, we included 82544 Chinese participants [66796 men and 15748 women; mean (SD) age 55.1 (9.86) y] without prior cardiovascular diseases or cancer at baseline (2006-2007). hs-CRP, WBC and other clinical covariates were assessed at baseline and every 2 years during follow-up. RESULTS: During 6 years of follow-up (2006-2012), we documented 714 incident MI cases. Higher baseline and cumulative average concentrations of hs-CRP and/or WBC were consistently associated with increased risk of MI (Ptrend <0.001 for both). Longitudinal increase in hs-CRP (Ptrend <0.001), but not WBC, was also associated with a higher future risk of MI, after adjustment for their baseline values and other covariates. Each 1-mg/L increment per year in hs-CRP was associated with a 9.3% increase in risk for future MI [hazard ratio (HR) = 1.09, 95% CI, 1.03; 1.17]. Participants with high-grade inflammatory status (hs-CRP >/=10 mg/L and WBC >/=10 x 109/L) had a higher risk of MI occurring <3 months after hs-CRP/WBC assessments vs those with hs-CRP <0.5 mg/L and WBC <5 x 10(9)/L (HR = 6.64; 95% CI, 1.49-29.6), as compared with MI occurring >/=4 years (HR = 2.95; 95% CI, 0.90, 9.65). CONCLUSIONS: Plasma hs-CRP concentration and WBC predicted MI risk. Longitudinal increase in hs-CRP was also associated with a higher risk of MI. Inflammation plays a central role in the etiology of myocardial infarction (MI)6 and other clinical manifestation of coronary events (1). In previous studies, higher-baseline C-reactive protein (CRP) concentrations and white blood cell (WBC) counts, 2 well-standardized and cost-effective biomarkers of inflammation, were consistently associated with a higher future risk of coronary events in general populations (2-4) and coronary artery disease (CAD) patients (5-9). It remains unclear whether longitudinal changes in CRP and WBC predict MI risk (10). Knowledge of the effects of such longitudinal changes is important to our understanding of whether the observed association between inflammatory biomarkers and MI risk is causal. Documentation of a causal relationship may facilitate subsequent development of promising antiinflammatory strategies in cardiovascular disease (CVD) prevention and treatment. Although atherosclerosis has been characterized as a chronic and low-grade inflammatory process (11), recent studies have documented that immune dysregulation could predispose to MI (11, 12) and infection could trigger MI (13). These results indicated that high-grade inflammation status (e.g., CRP >/= 10 mg/L and/or WBC >/=10 x 10(9)/L) could be associated with acute coronary events. In this context, it is clinically important to examine whether high-grade inflammation predicts subsequent MI risk in a community-based cohort and whether the strength of the association is attenuated over time. However, most prior studies regarding inflammation and MI have excluded participants with high-grade inflammation status.