An increase of interleukin-33 serum levels after coronary stent implantation is associated with coronary in-stent restenosis

AbstractThe study aim was to determine the predictive value of interleukin (IL)-33, a recently described member of the IL-1 family of cytokines, for the development of in-stent restenosis (ISR). IL-33 serum levels were measured in 387 consecutive patients undergoing percutaneous coronary intervention (PCI) of whom 193 had stable angina, 93 non-ST elevation myocardial infarction (NSTEMI), and 101 ST-elevation MI (STEMI), respectively. Blood was taken directly before and 24h after stent implantation. The presence of ISR was initially evaluated by clinical means after six to eight months. When presence of myocardial ischemia was suspected, coronary angiography was performed to confirm the suspected diagnosis of ISR. Clinical ISR was present in total in 34 patients (8.8%). IL-33 was detectable in 185 patients and was below detection limit in 202 patients. In patients with decreased IL-33 (n=95), unchanged or non-detectable levels (n=210) or increased levels of IL-33 after PCI (n=82), ISR-rate was 2.1%, 9.5% and 14.6%, respectively (p<0.05). Accordingly, patients with ISR showed a significant increase of IL-33 upon PCI (p<0.05). This association was independent from clinical presentation and risk factors as well as numbers and type of stents. In patients with both stable and unstable coronary artery disease, an increase of IL-33 serum levels after stent implantation is associated with a higher rate of in-stent restenosis

Soluble ST2 and interleukin-33 levels in coronary artery disease: relation to disease activity and adverse outcome.

ST2 is a receptor for interleukin (IL)-33. We investigated an association of soluble ST2 (sST2) and IL-33 serum levels with different clinical stages of coronary artery disease. We assessed the predictive value of sST2 and IL-33 in patients with stable angina, non-ST elevation myocardial infarction (NSTEMI) and ST elevation myocardial infarction (STEMI).We included 373 patients of whom 178 had stable angina, 97 had NSTEMI, and 98 had STEMI. Patients were followed for a mean of 43 months. The control group consisted of 65 individuals without significant stenosis on coronary angiography. Serum levels of sST2 and IL-33 were measured by ELISAs.sST2 levels were significantly increased in patients with STEMI as compared to patients with NSTEMI and stable angina as well as with controls. IL-33 levels did not differ between the four groups. During follow-up, 37 (10%) patients died and the combined endpoint (all cause death, MI and rehospitalisation for cardiac causes) occurred in 66 (17.6%) patients. sST2 serum levels significantly predicted mortality in the total cohort. When patients were stratified according to their clinical presentation, the highest quintile of sST2 significantly predicted mortality in patients with STEMI, but not with NSTEMI or stable coronary artery disease. sST2 was a significant predictor for the combined endpoint in STEMI patients and in patients with stable angina. Serum levels of IL-33 were not associated with clinical outcome in the total cohort, but the highest quintile of IL-33 predicted mortality in patients with STEMI.Serum levels of sST2 are increased in patients with acute coronary syndromes as compared to levels in patients with stable coronary artery disease and in individuals without coronary artery disease. sST2 and IL-33 were associated with mortality in patients with STEMI but not in patients with NSTEMI or stable angina

Cox proportional hazard model assessing the risk for mortality according to sST2 levels.

<p>sST2 denotes soluble ST2, CAD denotes coronary artery disease, BMI denotes body mass index.</p

Journal of Clinical Lipidology / Monocyte subset distribution in patients with stable atherosclerosis and elevated levels of lipoprotein(a)

Background Lipoprotein(a) (Lp(a)) is a proatherogenic plasma lipoprotein currently established as an independent risk factor for the development of atherosclerotic disease and as a predictor for acute thrombotic complications. In addition, Lp(a) is the major carrier of proinflammatory oxidized phospholipids (OxPL). Today, atherosclerosis is considered to be an inflammatory disease of the vessel wall in which monocytes and monocyte-derived macrophages are crucially involved. Circulating monocytes can be divided according to their surface expression pattern of CD14 and CD16 into at least 3 subsets with distinct inflammatory and atherogenic potential. Objective The aim of this study was to examine whether elevated levels of Lp(a) and OxPL on apolipoprotein B-100containing lipoproteins (OxPL/apoB) are associated with changes in monocyte subset distribution. Methods We included 90 patients with stable coronary artery disease. Lp(a) and OxPL/apoB were measured, and monocyte subsets were identified as classical monocytes (CMs; CD14++CD16), intermediate monocytes (IMs; CD14++CD16+), and nonclassical monocytes (NCMs; CD14+CD16++) by flow cytometry. Results In patients with elevated levels of Lp(a) (>50 mg/dL), monocyte subset distribution was skewed toward an increase in the proportion of IM (7.0 3.8% vs 5.2 3.0%; P = .026), whereas CM (82.6 6.5% vs 82.0 6.8%; P = .73) and NCM (10.5 5.3 vs 12.8 6.0; P = .10) were not significantly different. This association was independent of clinical risk factors, choice of statin treatment regime, and inflammatory markers. In addition, OxPL/apoB was higher in patients with elevated Lp(a) and correlated with IM but not CM and NCM. Conclusions In conclusion, we provide a potential link between elevated levels of Lp(a) and a proatherogenic distribution of monocyte subtypes in patients with stable atherosclerotic disease.(VLID)487417

sST2 and IL-33 serum levels in controls and according clinical presentation of coronary artery disease.

<p>sST2 (A) and IL-33 (B) serum levels were measured as described under “Methods”. SA denotes stable angina, NSTEMI denotes non-ST-elevation myocardial infarction, STEMI denotes ST-elevation myocardial infarction. Mean ± standard error of mean.</p

Relation of sST2 serum levels to mortality.

<p>sST2 serum levels were measured as described under “Methods”. Kaplan Meier survival curves for the highest quintile of sST2 serum levels (red, dashed line) vs. the lower four quintiles of sST2 (blue, full line) in all patients (A), patients with ST-elevation myocardial infarction (B), non-ST-elevation myocardial infarction (C) and stable angina (D).</p

Relation of IL-33 serum levels to mortality.

<p>IL-33 serum levels were measured as described under “Methods”. Kaplan Meier survival curves for the highest quintile of IL-33 serum levels (red, dashed line) vs. the lower four quintiles of IL-33 (blue, full line) in all patients (A), patients with ST-elevation myocardial infarction (B), non-ST-elevation myocardial infarction (C) and stable angina (D).</p

Baseline characteristics of study population.

<p>SA denotes stable angina, NSTEMI denotes non-ST-elevation myocardial infarction, STEMI denotes ST-elevation myocardial infarction, CAD denotes coronary artery disease, BMI denotes body mass index.</p

Multivariate Cox proportional hazards model assessing the association between G-CSF (below and above median) and major adverse cardiovascular events (death, myocardial infarction and rehospitalisation).

<p><b>-</b> denotes reference category.</p><p>Multivariate Cox proportional hazards model assessing the association between G-CSF (below and above median) and major adverse cardiovascular events (death, myocardial infarction and rehospitalisation).</p