| 1. |
- Jönelid, Birgitta, 1965-
(författare)
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Importance of peripheral arterial disease as a risk marker in patients with myocardial infarction
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this thesis was to describe the true prevalence of widespread arterial disease in a cohort with patients with a recent myocardial infarction (MI) to find valuable clinical methods to detect these patients. Our aim was also to investigate biomarker relationships with peripheral artery disease (PAD) and the importance of PAD in patients’ long-term outcomes.We studied patients with a recent MI in a prospective observational study, the REBUS ((Relevance of Biomarkers for Future Risk of Thromboembolic Events in Unselected Post-myocardial Infarction Patients) trial. A total of 421 patients were included in the study, 390 of whom had their ankle-brachial index (ABI) measured and a mean-time follow up of 5.5 years. Atherosclerotic changes were assessed in three arterial beds by coronary angiography, measuring the ABI and carotid ultrasound. Ninety-two biochemical biomarkers were assessed at baseline by a proximity extension assay (PEA) chip. 263 out of 421 filled in a self-administered Walking Impairment Questionnaire (WIQ). Polyvascular (PvD) disease was defined as pathological findings in all three arterial beds.We found that PAD and PvD are underdiagnosed in patients who suffered a recent MI. We also found the ABI to be a strong and useful method to identify patients with PAD as well as patients with more widespread arterial disease, such as PvD (paper I).The results of the scoring system, the WIQ, showed it is useful for finding patients with PAD and PvD, even when completed soon after an acute MI event (paper II).We also found that biochemical biomarkers associated with the inflammatory pathway – tumour necrosis factor receptor 1 (TNFR-1), tumor necrosis factor receptor 2 (TNFR-2) and growth differentiation factor 15 (GDF-15) – were able to predict pathological ABI, i.e. PAD, in these MI patients. These results could also be validated in another observational study and cohort of MI patients, the VaMIS cohort (paper III). Pathological ABI was also found to be a strong predictor for cardiovascular events of all-cause mortality, new ACS, and a composite endpoint of all-cause mortality, new ACS, new stroke/TIA or new PAD event. When evaluating the three inflammatory biomarkers as a surrogate marker for ABI, they showed a similar association with all-cause death and the composite endpoint (paper IV).
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| 2. |
- Gard, Anton, 1985-
(författare)
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Type 2 myocardial infarction : Aspects of diagnosis, prognosis and treatment
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Unlike the coronary thromboembolic type 1 myocardial infarction (MI), a type 2 MI occurs secondary to other conditions causing an imbalance in myocardial oxygen supply and demand. Type 2 MI is associated with high mortality and evidence based treatment is lacking. It may also be difficult to differentiate type 2 MI from type 1 MI and myocardial injury, which causes uncertainty among physicians. Therefore, the aim of this thesis was to evaluate the current classification of MI types and myocardial injury with special emphasis on evaluating the therapeutic and prognostic importance of distinguishing and diagnosing type 2 MI. The validity of type 2 MI reports in the Swedish national register for MI (SWEDEHEART) was also investigated.The study populations consisted of 1328 patients with a clinical MI diagnosis from eight sites, whereof 792 had been reported to SWEDEHEART, as well as 281 patients with elevated cardiac troponins but without a clinical MI diagnosis from one site. The diagnosis of each patient was retrospectively adjudicated in accordance with the Third Universal Definition of Myocardial Infarction.Overall, the adjudicators agreed moderately when deciding the diagnosis and it was particularly difficult to distinguish type 2 MI and non-ischemic myocardial injury. Patients with type 2 MI were often treated outside cardiology departments which led to a significant underreporting to SWEDEHEART. Using the adjudicated diagnosis as a gold standard, type 2 MI registry reports had a positive predictive value of 62.5%. Receiving care outside cardiology departments was found to be associated with a lesser use of MI specific therapies and an adverse short and long term prognosis in MI patients overall. However, although clinically unrecognized type 2 MI patients received the least cardiology care in all aspects, this was still not observed to significantly affect the long term prognosis.In conclusion; the current MI classification defines type 2 MI as a very heterogeneous condition that is difficult to distinguish. This makes clinically defined type 2 MI populations, such as the one in SWEDEHEART, unreliable and it also makes it difficult to find and apply specific, prognostically relevant recommendations and therapeutic strategies for this serious condition.
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| 3. |
- Hjort, Marcus, 1988-
(författare)
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Identification of pathophysiological and prognostic biomarkers in different types of myocardial infarction
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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 hospital stay, but also a faster recovery in MINOCA and less persistent myocardial damage and dysfunction. Compared to controls however, there was a higher degree of residual myocardial dysfunction in MINOCA three months later. Corresponding with this, higher in-hospital hs-cTnT concentrations in MINOCA independently predicted poor one-year outcomes, in particular cardiovascular mortality and heart failure. Finally, samples three months post-MINOCA displayed lower concentrations of tissue-type plasminogen activator than post-MI-CAD patients, suggesting less persistent coagulation activation.In STEMI and NSTEMI patients, biomarkers indicated greater myocardial damage and dysfunction in the acute phase in STEMI, together with more pronounced inflammatory activity. They also displayed a more diverse pathophysiological pattern in NSTEMI. All of the biomarkers that separated STEMI from NSTEMI were however similarly prognostic for mortality and adverse events between the two MI groups.In conclusion, extensive biomarker investigations combined with advanced statistical analyses displayed intriguing aspects of pathobiology in MINOCA and differences between STEMI and NSTEMI. Some of these biomarkers were also related to clinical outcome.
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| 4. |
- Kesek, Milos, 1957-
(författare)
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Traces of Repolarization Inhomogeneity in the ECG
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Repolarization inhomogeneity is arrhythmogenic. QT dispersion (QTd) is an easily accessible ECG-variable, related to the repolarization and shown to carry prognostic information. It was originally thought to reflect repolarization inhomogeneity. Lately, arguments have been risen against this hypothesis. Other measures of inhomogeneity are being investigated, such as nondipolar components from principal component analysis (PCA) of the T-wave. In all here described populations, continuous 12-lead ECG was collected during the initial hours of observation and secondary parameters used for description of a large number of ECG-recordings.Paper I studied QTd in 548 patients with chest pain with a median number of 985 ECG-recordings per patient. Paper II explored a spatial aspect of QTd in 276 patients with unstable coronary artery disease. QTd and a derived localized ECG-parameter were compared to angiographical measures. QTd, expressed as the mean value during the observation was a powerful marker of risk. It was however not effective in identifying high-risk patients. Variations in QTd contained no additional prognostic information. In unstable coronary artery disease, QTd was increased by a mechanism unrelated to localization of the disease.Two relevant conditions for observing repolarization inhomogeneity might occur with conduction disturbances and during initial course of ST-elevation myocardial infarction (STEMI). Paper III compared the PCA-parameters of the T-wave in 135 patients with chest pain and conduction disturbance to 665 patients with normal conduction. Nondipolar components were quantified by medians of the nondipolar residue (TWRabsMedian) and ratio of this residue to the total power of the T-wave (TWRrelMedian). Paper IV described the changes in the nondipolar components of the T-wave in 211 patients with thrombolyzed STEMI. TWRabsMedian increased with increasing conduction disturbance and contained a moderate amount of prognostic information. In thrombolyzed STEMI, TWRabsMedian was elevated and has an increased variability. A greater decrease in absolute TWR during initial observation was seen in patients with early ST-resolution. Nondipolar components do however not reflect identical ECG-properties as the ST-elevation and their change does not occur at the same time.
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| 5. |
- Täufer Cederlöf, Elin
(författare)
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Pregnancy Complications and Cardiovascular Disease
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Women with a history of pregnancy complications have an increased risk of cardiovascular disease (CVD) later in life. The overall aims were to investigate pregnancy complications as cardiovascular risk factors; whether they have predictive value for the spread of atherosclerosis in older women, whether they are associated with atherosclerotic CVD after adjusting for major confounders, both at the population-level and in women with structural heart disease; and to investigate cardiovascular biomarkers in women with spontaneous preterm birth.Among 307 postmenopausal women with and without CVD, the self-reported frequency of pregnancy complications was assessed, and three vascular beds were examined (peripheral, carotid and coronary arteries). The self-reported complications were evaluated as possible predictors of spreading atherosclerosis. Exposures to pregnancy complications of a population-based cohort, including 2 134 239 women from the national Medical Birth Register from 1973 to 2014, were evaluated as a risk factor for atherosclerotic cardiovascular outcomes (hospitalizations and mortality) after adjustment for major confounders. The associations were further analyzed in 2554 women from the same cohort identified as having structural heart disease, and also for hospitalizations for heart failure and arrhythmias.A first screening phase used comparative mass spectrometry to examine differences in protein expression in mid-pregnancy plasma samples, from the Uppsala Biobank for Pregnant Women, from a subset of women with spontaneous preterm birth in first pregnancy and controls. Seven protein biomarkers differed significantly between cases and controls. In a second validation phase, plasma samples and data on cardiovascular risk factors were collected from 65 women who agreed to participate in a follow-up visit 4–15 years after pregnancy. Concentrations of the selected biomarkers were analyzed, as well as lipid profiles from samples from both pregnancy (Biobank) and follow-up.In conclusion, an association between pregnancy complications and the spread of atherosclerosis in older women was not found. Pregnancy complications were associated with an increased risk of atherosclerotic cardiovascular outcomes, both at the population level and in women with structural heart disease, after adjustment for major confounding factors. Compared with women without preterm birth, those with spontaneous preterm birth had higher concentrations of fibrinogen and triglycerides, both at mid-pregnancy and a decade after pregnancy.
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