Abstract
BACKGROUND: Exposure to lipopolysaccharide (LPS), a potent proinflammatory glycolipid derived from gut microbiota, may be linked to the development of coronary heart disease (CHD). However, evidence from human studies is limited.
OBJECTIVES: We aimed to investigate prospective relationships between 2 plasma biomarkers of LPS exposures-LPS-binding protein (LBP) and soluble cluster of differentiation 14 (sCD14)-in relation to incident CHD among United States males and females.
METHODS: A prospective nested 1:1 matched case-control study of CHD was conducted among participants in the Nurses' Health Study II (NHSII) and Health Professionals Follow-up Study (HPFS). Plasma concentrations of LBP and sCD14 were measured in 496 HPFS male CHD case-control pairs and 212 NHSII female pairs.
RESULTS: Among controls, plasma concentrations of LBP exhibited positive correlations with age, body mass index, and C-reactive protein (CRP) concentrations and an inverse correlation with high-density lipoprotein cholesterol concentrations. For sCD14, positive correlations with age and CRP were only observed in HPFS controls. Neither elevated LBP nor sCD14 concentrations were significantly associated with incident CHD in HPFS. In NHSII, higher sCD14 concentrations, but not LBP, were significantly associated with higher risk of CHD, with a risk ratio of 3.01 [95% confidence interval (CI): 1.28, 7.11] when comparing extreme quintiles. Collectively, CRP and the total cholesterol/ high-density lipoprotein cholesterol ratio explained 27.9% (95% CI: 7.1%, 66.1%; P = 0.01) of the positive association between sCD14 and CHD in NHSII females. These associations were not modified by physical activity, alcohol intake, body mass index, inflammation markers, family history of CHD, or the presence of hypertension, hyperlipidemia, or type-2 diabetes.
CONCLUSION: Higher concentrations of sCD14 may be associated with an increased risk of CHD in females, whereas LBP concentrations are not associated with CHD in either sex. These data do not support that LPS exposure in initially healthy individuals is a contributing CHD risk factor, although the potential sex difference should be explored further.