Identification of pathophysiological and prognostic biomarkers in different types of myocardial infarction

The pathophysiological mechanisms of myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) are largely unknown. Analogous, differences in pathobiology between ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) are incompletely understood. The overall aim of this thesis was to explore whether concentrations of cardiovascular biomarkers during the acute and stable phase may offer novel pathophysiological insights, comparing MINOCA (coronary stenoses <50%) to myocardial infarction with obstructive coronary arteries (MI-CAD; stenoses ≥50%) and controls, or STEMI to NSTEMI. Also, the prognostic implications of biomarkers were explored. The study populations consisted of subjects included in the quality registry SWEDEHEART at hospitalization in two cohorts (n=18,943 and n=1082), in the SMINC study at three-month follow-up (n=292), and finally in the PLATO trial during hospitalization (n=11,660) and at one-month follow-up (n=2862). Cardiovascular biomarkers were analyzed with proximity extension assay (91 biomarkers), multiple reaction monitoring assay (84 biomarkers) and standard laboratory chemistry. Lasso analysis (penalized logistic regression model) and multiple linear regression were used to select biomarkers that discriminated MINOCA from MI-CAD patients or controls, and the former was also used to compare STEMI to NSTEMI patients. Adjusted Cox regression was mainly used for prognostic evaluations. The combined pattern of several inflammatory biomarkers suggested that MINOCA had a more pronounced chronic inflammatory activity compared to MI-CAD and controls. High sensitivity C-reactive protein (hs-CRP) concentrations were also initially higher in MINOCA than MI-CAD during the hospital stay, although later temporal changes of hs-CRP indicated less acute phase reaction in MINOCA. As reflected by high sensitivity cardiac troponin T (hs-cTnT) and natriuretic peptides, there was a lower degree of myocardial injury in MINOCA than MI-CAD during ...