The main conclusions of the thesis can be summarized as follows:
Part 1, coronary artery disease
- Higher SXscore is associated with higher atherosclerotic burden as assessed by NIRS and RF-IVUS in a single non-stenotic coronary artery segment in patients with CAD.
- A multiplex panel of 26 inflammatory biomarkers (acute phase proteins, cytokines, and chemokines) and renal markers did not render a useful blood biomarker of high NIRS-derived LCBI. Conversely, circulating serum PCSK9 levels were positively associated with LCBI. This association was independent of established cardiac risk factors, statin use and serum LDL-C.
- Plasma IL-8, plasma Cer(d18:1/16:0) and serum PCSK9 levels were independently associated with adverse cardiovascular outcomes during a median follow-up period of 4.7 years in patients with CAD.
- After 1 year intensive rosuvastatin therapy clinically relevant reductions in CRP levels were observed in a series of patients with established CAD. The observed CRP changes were correlated with changes in IVUS-derived plaque characteristics in ACS patients, but not in SAP. CRP changes were uncorrelated with changes in LDL-C levels.
Part II, heart failure:
- Serially assessments NT-proBNP and Hs-TnT were positively associated with serially assessed NYHA class in patients with stable CHF. Repeatedly measured NT-proBNP and CRP both add individually to serial NYHA-class assessments for monitoring CHF patients in terms of discriminative ability compared to a model with only serial NYHA class measurements.
- The dynamic, temporal patterns of serially measured NT-proBNP and CRP are strong and independent predictors of adverse clinical events in patients with stable CHF. Not only the evolution of biomarkers level, but also their instantaneous rate of change in NT-proBNP and CRP levels as well as the area under the curve of the trajectory of NT-proBNP, were associated with adverse outcome.
- The temporal pattern of circulating miR-22-3p is a strong and independent predictor of prognosis in CHF patients.
- Repeatedly assessed glomerular function (creatinine, eGFR and CysC), and tubular function (NAG and KIM-1) independently predicts adverse clinical outcomes in CHF patients. Both renal compartments chronically deteriorate, but not in parallel, during clinically silent progression of CHF

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H. Boersma (Eric) , I. Kardys (Isabella) , K.M. Akkerhuis (Martijn)
Erasmus University Rotterdam
Department of Cardiology