| 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. |
- 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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| 3. |
- Näslund, Ulf, et al.
(författare)
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Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA) : a pragmatic, open-label, randomised controlled trial
- 2019
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 393:10167, s. 133-142
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Primary prevention of cardiovascular disease often fails because of poor adherence among practitioners and individuals to prevention guidelines. We aimed to investigate whether ultrasound-based pictorial information about subclinical carotid atherosclerosis, targeting both primary care physicians and individuals, improves prevention.METHODS: Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA) is a pragmatic, open-label, randomised controlled trial that was integrated within the Västerbotten Intervention Programme, an ongoing population-based cardiovascular disease prevention programme in northern Sweden. Individuals aged 40, 50, or 60 years with one or more conventional risk factors were eligible to participate. Participants underwent clinical examination, blood sampling, and ultrasound assessment of carotid intima media wall thickness and plaque formation. Participants were randomly assigned 1:1 with a computer-generated randomisation list to an intervention group (pictorial representation of carotid ultrasound plus a nurse phone call to confirm understanding) or a control group (not informed). The primary outcomes, Framingham risk score (FRS) and European systematic coronary risk evaluation (SCORE), were assessed after 1 year among participants who were followed up. This study is registered with ClinicalTrials.gov, number NCT01849575.FINDINGS: 3532 individuals were enrolled between April 29, 2013, and June 7, 2016, of which 1783 were randomly assigned to the control group and 1749 were assigned to the intervention group. 3175 participants completed the 1-year follow-up. At the 1-year follow-up, FRS and SCORE differed significantly between groups (FRS 1·07 [95% CI 0·11 to 2·03, p=0·0017] and SCORE 0·16 [0·02 to 0·30, p=0·0010]). FRS decreased from baseline to the 1-year follow-up in the intervention group and increased in the control group (-0·58 [95% CI -0·86 to -0·30] vs 0·35 [0·08 to 0·63]). SCORE increased in both groups (0·13 [95% CI 0·09 to 0·18] vs 0·27 [0·23 to 0·30]).INTERPRETATION: This study provides evidence of the contributory role of pictorial presentation of silent atherosclerosis for prevention of cardiovascular disease. It supports further development of methods to reduce the major problem of low adherence to medication and lifestyle modification.
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| 4. |
- 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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| 5. |
- Lind, Lars, et al.
(författare)
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A comparison of echocardiographic and circulating cardiac biomarkers for predicting incident cardiovascular disease
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Echocardiographic measures are known predictors of cardiovascular disease (CVD) in the general population. This study compared the predictive value of such measures to that of circulating cardiac biomarkers for a composite cardiovascular disease outcome in an aging population.Methods: In this prospective population-based cohort study, echocardiography was performed at baseline together with assessments of traditional CVD risk factors and circulating cardiac biomarkers, NT-proBNP and troponin I, in 1016 individuals all aged 70 years. Assessments were repeated at ages 75 and 80. A composite CVD outcome (myocardial infarction, heart failure or ischemic stroke) was charted over 15 years. All echocardiography variables, except for the E/A ratio, were analyzed on a continuous scale.Results: Over 10 years, left atrial (LA) diameter, left ventricular mass index (LVMI) and high E/A ratio (>1.5) increased, while left ventricular ejection fraction (LVEF) remained unchanged. Using Cox proportional hazard analyses with time-updated variables for echocardiographic measures and traditional risk factors, an enlarged LA diameter and a low LVEF were independently related to incident CVD in 222 participants. The addition of LA diameter and LVEF to traditional risk factors increased the C-statistic by 1.5% (p = 0.008). However, the addition of troponin I and NT-proBNP to traditional risk factors increased the C-statistic by 3.0% (p<0.001).Conclusion: An enlarged LA diameter and a low LVEF improved the prediction of incident CVD compared to traditional risk factors. However, given that troponin I and NT-proBNP improved prediction to a similar extent, the use of simple blood tests to improve clinical cardiovascular disease risk prediction is only further supported by this study.
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| 6. |
- 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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| 7. |
- Yndigegn, Troels, et al.
(författare)
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Design and rationale of randomized evaluation of decreased usage of beta-blockers after acute myocardial infarction (REDUCE-AMI)
- 2022
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Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press. - 2055-6837 .- 2055-6845. ; 9:2, s. 192-197
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Most trials showing benefit of beta-blocker treatment after myocardial infarction (MI) included patients with large MIs and are from an era before modern biomarker-based MI diagnosis and reperfusion treatment. The aim of the Randomized Evaluation of Decreased Usage of betabloCkErs after Acute Myocardial Infarction (REDUCE-AMI) trial is to determine whether long-term oral beta-blockade in patients with an acute MI and preserved left ventricular ejection fraction (EF) reduces the composite endpoint of death of any cause or recurrent MI.METHODS: It is a registry-based, randomized, parallel, open-label, multicenter trial performed at 38 centers in Sweden, one center in Estonia and six centers in New Zealand. About 5000 patients with an acute MI who have undergone coronary angiography and with EF ≥ 50% will be randomized to long-term treatment with beta-blockade or not. The primary endpoint is the composite endpoint of death of any cause or new non-fatal MI. There are several secondary endpoints, including all-cause death, cardiovascular death, new MI, readmission because of heart failure and atrial fibrillation, symptoms, functional status, health related quality of life after 6-10 weeks and after 1 year of treatment. Safety endpoints are bradycardia, AV-block II-III, hypotension, syncope or need for pacemaker, asthma or chronic obstructive pulmonary disease and stroke.CONCLUSION: The results from REDUCE-AMI will add important evidence regarding the effect of beta-blockers in patients with MI and preserved EF and may change guidelines and clinical practice.
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