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Immune cells drive atherosclerotic lesion progression and plaque destabilization. Coronary heart disease patients undergoing noncardiac surgery are at risk for perioperative major adverse cardiac and cerebrovascular events (MACCE). It is unclear whether differential leukocyte subpopulations contribute to perioperative MACCE and thereby could aid identification of patients prone to perioperative cardiovascular events. First, we performed a hypothesis-generating post hoc analysis of the LeukoCAPE-1 study (n = 38). We analyzed preoperative counts of 6 leukocyte subpopulations in coronary heart disease patients for association with MACCE (composite of cardiac death, myocardial infarction, myocardial ischemia, myocardial injury after noncardiac surgery, thromboembolic stroke) within 30 d after surgery. Regulatory T cells (Tregs) were the only leukocyte subgroup associated with MACCE. We found reduced Tregs in patients experiencing MACCE versus no-MACCE (0.02 [0.01; 0.03] vs. 0.04 [0.03; 0.05] Tregs nl−1, P = 0.002). Using Youden index, we derived the optimal threshold value for association with MACCE to be 0.027 Tregs nl−1. Subsequently, we recruited 233 coronary heart disease patients for the prospective, observational LeukoCAPE-2 study and independently validated this Treg cutoff for prediction of MACCE within 30 d after noncardiac surgery. After multivariate logistic regression, Tregs < 0.027 cells nl−1 remained an independent predictor for MACCE (OR = 2.54 [1.22; 5.23], P = 0.012). Tregs improved risk discrimination of the revised cardiac risk index based on ΔAUC (area under the curve; ΔAUC = 0.09, P = 0.02), NRI (0.26), and IDI (0.06). Preoperative Treg levels below 0.027 cells nl−1 predicted perioperative MACCE and can be measured to increase accuracy of established preoperative cardiac risk stratification in coronary heart disease patients undergoing noncardiac surgery.

BACKGROUND To evaluate the diagnostic and prognostic value of sensitive troponin I (TnI) in patients with acute dyspnea and/or peripheral edema suspected of having acute heart failure (AHF). METHODS This single centre prospective clinical study evaluates 372 patients presenting with acute dyspnea and/or peripheral edema to the emergency department (ED). Measurements of TnI and NT-proBNP were performed at the initial presentation in the ED. All patients were followed up to 5 years. The diagnostic value of TnI compared to NT-proBNP for AHF diagnosis as well as long-term prognostic values for all cause mortality and AHF related rehospitalization were evaluated. RESULTS TnI plus NT-proBNP improved the diagnosis of AHF (improvement of accuracy (75%, 95% CI 71% - 79%), specificity (68%, 95% CI 62% - 74%), PPV (54%, 95% CI 47% - 62%), and NRI +0.15) compared to NT-proBNP alone (p = 0.0001). TnI levels showed independent prognostic value for all-cause mortality and AHF related rehospitalization after 1 and 5 years (range of AUCs 0.64 - 0.72; p = 0.03 or lower). Highest TnI levels of the 4th quartile revealed an up to 5.5 times higher risk of death within 1 and 5 years (range of HRs: 2.5 - 5.5; p = 0.0001). TnI added significantly to multivariable Cox prediction models even after adjusting for NT-proBNP, particularly in AHF patients (range of HRs: 2.1 - 2.7; p ≤ 0.05). CONCLUSIONS TnI improves AHF diagnosis when combined with NT-proBNP. TnI identifies patients with high 1- and 5-year all-cause mortality and AHF-related rehospitalization risk and adds prognostic value to NT-proBNP.

Aims To evaluate the diagnostic and prognostic value of osteopontin in patients with acute dyspnoea and/or peripheral oedema suspected of having acute congestive heart failure (aCHF). Methods and results A total of 401 patients presenting with acute dyspnoea and/or peripheral oedema to the emergency department were prospectively enrolled and followed up for up to 5 years. Blood samples for biomarker measurements were collected on admission to the emergency department. Osteopontin combined with NT-proBNP vs. NT-proBNP alone for diagnosis of aCHF was tested. Additionally, osteopontin vs. NT-proBNP for prognostic outcomes (i.e. all-cause mortality, aCHF-related rehospitalization, and both in combination) was tested. The diagnostic and prognostic capacity of osteopontin was tested by C-statistics, reclassification indices, and multivariable Cox prediction models. Osteopontin plus NT-proBNP improved the diagnostic capacity for aCHF diagnosis [accuracy 76%, 95% confidence interval (CI) 72–80%; specificity 74%, 95% CI 69–79%, net reclassification improvement (NRI) +0.10] compared with NT-proBNP alone in the emergency department (P = 0.0001). Osteopontin independently predicted all-cause mortality and aCHF-related rehospitalization after 1 and 5 years. Compared with NT-proBNP, osteopontin was of superior prognostic value, specifically in aCHF patients and for the prognostic outcome of aCHF-related rehospitalization. Conclusion Osteopontin improves aCHF diagnosis when combined with NT-proBNP. Osteopontin identifies aCHF patients with high 1- and 5-year mortality and rehospitalization risk, and adds prognostic value to NT-proBNP. Trial registration NCT00143793