Abstract
BackgroundSo far it is unclear whether the association between serum uric acid (SUA), inflammatory cytokines and risk of atherosclerosis is causal or an epiphenomenon. The aim of the project is to investigate the independent prognostic relationship of inflammatory markers and SUA levels with adverse cardiovascular outcomes in a patient population with stable coronary heart disease (CHD).MethodsSUA, C-reactive protein (CRP) and interleukin (IL)-6 were measured at baseline in a cohort of 1,056 patients aged 30–70 years with CHD. Cox proportional hazards model was used to determine the prognostic value of these markers on a combined CVD endpoint during eight year follow-up after adjustment for covariates.ResultsFor 1,056 patients with stable coronary heart disease aged 30–70 years (mean age 58.9 years, SD 8.0) follow-up information and serum measurements were complete and n = 151 patients (incidence 21.1 per 1000 patients years) experienced a fatal or non-fatal CVD event during follow-up (p-value = 0.05 for quartiles of SUA, p = 0.002 for quartiles of CRP, p = 0.13 for quartiles of IL-6 in Kaplan-Meier analysis). After adjustment for age, gender and hospital site the hazard ratio (HR) for SUA increased from 1.37 to 1.65 and 2.27 in the second, third, and top quartile, when compared to the bottom one (p for trend <0.0005). The HR for CRP increased from 0.85 to 0.98 and 1.64 in the respective quartiles (p for trend 0.02). After further adjustment for covariates SUA still showed a clear statistically significant relationship with the outcome (p for trend 0.045), whereas CRP did not (p for trend 0.10).ConclusionThe data suggest that compared to inflammatory markers such as CRP and IL-6 serum uric acid levels may predict future CVD risk in patients with stable CHD with a risk increase even at levels considered normal.
Highlights
Low grade inflammation plays a major role in coronary heart disease (CHD) and especially C-reactive protein (CRP) and interleukin-6 (IL-6, a major pro-inflammatory cytokine) are relevant molecules in this process [1]
The aim of the present project is to investigate the relationship of inflammatory markers with serum uric acid level in a patients population with stable coronary heart disease (CHD) at baseline and investigate the independent prognostic relationship of inflammatory markers and serum uric acid levels for subsequent fatal-and non-fatal cardiovascular disease (CVD) events under special consideration of potential confounding factors such as markers of cardiac and renal dysfunction and hypertension
1 referent 0.66 (0.37–1.16) 0.67 (0.38–1.17) 1.27 (0.76–2.10) p for trend 0.17 aconsidered main model - beside the main factors, the following potential confounders were included in multivariable analyses: smoking status, history of myocardial infarction, history of diabetes mellitus, severity of CHD, intake of ACE-inhibitors, intake of allopurinol, HDL-cholesterol, LDL-cholesterol
Summary
Low grade inflammation plays a major role in coronary heart disease (CHD) and especially C-reactive protein (CRP) and interleukin-6 (IL-6, a major pro-inflammatory cytokine) are relevant molecules in this process [1]. A simultaneous investigation of serum urate acid levels and inflammatory parameters considering a large number of potentially related factors such as renal function and established cardiovascular risk factors to further disentangle the causality of these interrelated factors in a long-term observational study is lacking. It is unclear whether the association between serum uric acid (SUA), inflammatory cytokines and risk of atherosclerosis is causal or an epiphenomenon. The aim of the project is to investigate the independent prognostic relationship of inflammatory markers and SUA levels with adverse cardiovascular outcomes in a patient population with stable coronary heart disease (CHD)
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