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- Eggers, Kai M., 1962-, et al.
(author)
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Sex-differences in circulating biomarkers during acute myocardial infarction : An analysis from the SWEDEHEART registry
- 2021
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:4 April
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Journal article (peer-reviewed)abstract
- Background Sex-differences in the pathobiology of myocardial infarction are well established but incompletely understood. Improved knowledge on this topic may help clinicians to improve management of men and women with myocardial infarction. Methods In this registry-based cohort study (SWEDEHEART), we analyzed 175 circulating biomarkers reflecting various pathobiological axes in 856 men and 243 women admitted to Swedish coronary care units because of myocardial infarction. Two multimarker panels were applied (Proximity Extension Assay [Olink Bioscience], Multiple Reaction Monitoring mass spectrometry). Lasso analysis (penalized logistic regression), multiple testing-corrected Mann- Whitney tests and Cox regressions were used to assess sex-differences in the concentrations of these biomarkers and their implications on all-cause mortality and major adverse events (median follow-up up to 6.6 years). Results Biomarkers provided a very high discrimination between both sexes, when considered simultaneously (c-statistics 0.972). Compared to women, men had higher concentrations of six biomarkers with the most pronounced differences seen for those reflecting atherogenesis, myocardial necrosis and metabolism. Women had higher concentrations of 14 biomarkers with the most pronounced differences seen for those reflecting activation of the reninangiotensin- aldosterone axis, inflammation and for adipokines. There were no major variations between sexes in the associations of these biomarkers with outcome. Conclusions Severable sex-differences exist in the expression of biomarkers in patients with myocardial infarction. While these differences had no impact on outcome, our data suggest the presence of various sex-related pathways involved in the development of coronary atherosclerosis, the progression to plaque rupture and acute myocardial damage, with a greater heterogeneity in women.
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- Johnston, Nina, 1961-, et al.
(author)
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Are we using cardiovascular medications and coronary angiography appropriately in men and women with chest pain?
- 2011
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 32:11, s. 1331-1336
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Journal article (peer-reviewed)abstract
- Aims The main purpose of the present study was to analyse the contemporary use of cardiovascular medications and diagnostic coronary angiography in men and women with suspected coronary artery disease (CAD). Furthermore, we examined the association of outcomes (death, myocardial infarction, repeat coronary angiography, procedural complications) with angiographic findings.Methods All patients with stable chest pain (n = 12 200) referred for a first-time elective diagnostic coronary angiography during 2006-08 and registered in the Swedish Coronary Angiography and Angioplasty Register (SCAAR) were included. Significant CAD was defined as ≥50% luminal narrowing in any epicardial coronary artery.Results In the youngest age group (≤59 years), more women than men (78.8 vs. 42.3%, P< 0.001) had normal/non-significant CAD, whereas more men had either left-main or three-vessel disease (18.2 vs. 4.2%, P < 0.001). Event rates were similarly low for men and women with normal/non-significant CAD, except for a higher procedural complication rate in women. Prior to angiography, fewer women than men with high-risk features were prescribed aspirin (83 vs. 86.1%, P = 0.001).Conclusion In women, normal/non-significant CAD was highly prevalent, especially among younger women, and associated cardiovascular event rates were low. In men, findings of advanced disease were more common than in women, even younger men. Fewer high-risk women than men were initially prescribed aspirin. The observed sex differences suggest a need for improved identification of women appropriate for investigation with coronary angiography, earlier diagnostics in men, and heightened attention in the evidence-based use of aspirin in risk patients, especially women.
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| 4. |
- Johnston, Nina, 1961-
(author)
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Low-Density Lipoprotein Oxidation and Renal Dysfunction : New Markers of Poor Prognosis in Patients with Unstable Coronary Artery Disease
- 2006
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Doctoral thesis (other academic/artistic)abstract
- In patients with unstable coronary artery disease (CAD) biochemical markers are emerging as useful tools in clinical management. In this thesis we studied the use of markers of low-density lipoprotein (LDL) oxidation and renal function.Our study populations consisted of unstable CAD patients included in the Fast Revascularisation during Instability in Coronary artery disease (FRISC)-II trial and healthy controls. Patients were followed for 2 years regarding death and myocardial infarction (MI).Using receiver operating characteristic curve analysis, we found that oxidized low-density lipoprotein (OxLDL), especially when combined with high-density lipoprotein, compared to traditionally measured lipids/lipoproteins, and a new lipoprotein marker, lipoprotein associated-phospholipase A2, was better at discriminating between healthy controls and CAD patients. In patients, OxLDL was found to be an independent prognostic marker associated with an increased risk of MI, of particular use in patients with no evidence of myocardial necrosis. In our study on the effects of an early invasive treatment strategy in unstable CAD patients with mild to moderate renal dysfunction (i.e. creatinine clearance <90mL/min) we found that in patients randomized to invasive treatment, the rates of death/MI and MI alone were significantly lower than in patients randomized to non-invasive treatment. In patients treated invasively, no detrimental effects were seen on renal function at follow-up at 6 months. In healthy controls, we investigated new markers of renal (cystatin C) and cardio-renal function (N-terminal probrain natriuretic peptide, [NT-proBNP]) regarding reference levels and physiological determinants. We found that cystatin C is influenced by age whereas NT-proBNP is influenced by age and gender.Our studies suggest that OxLDL and renal dysfunction are associated with a poor prognosis in unstable CAD patients and that these markers demonstrate potential for clinical use. In the search for new markers related to renal function we have contributed with reference levels of cystatin C and NT-proBNP.
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| 5. |
- Johnston, Nina, 1961-, et al.
(author)
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Sex-specific aspects on prognosis after aortic valve replacement for aortic stenosis : a SWEDEHEART registry study
- 2024
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In: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 11:2, s. 1-8
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Journal article (peer-reviewed)abstract
- Objective To compare long-term cardiovascular (CV) outcomes between men and women with aortic stenosis (AS) undergoing aortic valve replacement (AVR) by the type of valve implant.Methods The study population consisted of 14 123 non-selected patients with AS undergoing first-time AVR and included in the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry during 2008–2016. Comparisons were made between men and women and type of valve implant (ie, surgical implantation with a mechanical (mSAVR) (n=1 966) or biological valve (bioSAVR) (n=9 801)) or by a transcatheter approach (TAVR) (n=2 356). Outcomes included all-cause mortality, ischaemic stroke, major bleeding, thromboembolic events, heart failure and myocardial infarction, continuously adjusted for significant comorbidities and medical treatment.Results In the mSAVR cohort, there were no significant sex differences in any CV events. In the bioSAVR cohort, a higher risk of death (HR: 1.14; 95% CI: 1.04 to 1.26, p=0.007) and major bleeding (HR: 1.41; 95% CI: 1.18 to 1.69, p<0.001) was observed in men. In the TAVR cohort, men suffered a higher risk of death (HR: 1.24; 95% CI: 1.07 to 1.45, p=0.005), major bleeding (HR: 1.35; 95% CI: 1.00 to 1.82, p=0.022) and thromboembolism (HR: 1.35, 95% CI: 1.00 to 1.82, p=0.047).Conclusion No significant long-term difference in CV events was noted between men and women undergoing AVR with a mechanical aortic valve. In both the bioSAVR and TAVR cohort, mortality was higher in men who also had an increased incidence of several other CV events.
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| 8. |
- Johnston, Nina, 1961-, et al.
(author)
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Systematic reviews : causes of non-adherence to P2Y12 inhibitors in acute coronary syndromes and response to intervention
- 2016
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In: Open heart. - : BMJ. - 2053-3624. ; 3:2
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Research review (peer-reviewed)abstract
- To understand the factors associated with non-adherence to oral antiplatelet (OAP) therapy in acute coronary syndromes (ACS), and where interventions have modified these factors. Linked systematic reviews were undertaken in accordance with the Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines, using CINAHL Plus, MEDLINE, PsycINFO and PubMed databases. The searches were limited to studies available in English and published from 2000 onwards; last run in June 2015. Review 1: factors. Fifteen articles were identified that reported 25 different factors associated with OAP non-adherence. Factors were categorised into: Demographic, Treatment, Healthcare System Processes, Clinical, Opportunity (ie, factors outside the patients, such as cost and healthcare access) and Psychosocial. It was not possible to determine if any of these factors were more impactful than others, either overall or temporally. Review 2: interventions. Six articles were identified that described interventions targeting adherence in patients with acute coronary syndromes (ACS)/coronary artery disease (CAD). Four broad categories of intervention were identified: treatment counselling and education, educational materials, SMS reminders and telephone monitoring and reinforcement delivered different practitioners. Only reminder-based interventions had a consistently successful impact on adherence outcomes at both 3 and 12 months. A number of factors are associated with OAP non-adherence, and encouragingly, there is some evidence of the effectiveness of intervention to modify treatment adherence in patients with ACS/CAD. Future evaluations ensuring a better cohesion between the factors studied as associated with non-adherence and those targeted by intervention would further increase understanding and lead to improved results.
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| 9. |
- Jönelid, Birgitta, et al.
(author)
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Biochemical biomarkers associated with peripheral artery disease contribute to prediction of outcome during long-term follow up after myocardial infarction
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Other publication (other academic/artistic)abstract
- AbstractBackground: Few studies have investigated biomarkers and their association to cardiovascular (CV) outcomes in patients with myocardial infarction (MI) and peripheral artery disease (PAD). Tumor necrosis factor receptor 1(TNFR-1), tumor necrosis factor receptor 2(TNFR-2) and growth differentiation factor 15 (GDF-15) are inflammatory biomarkers found to predict PAD.Aim: To evaluate whether pathological ankle brachial index (ABI) and the group of biomarkers TNFR-1, TNFR-2 and GDF-15 analyzed early after a MI, were associated with all-cause mortality and the risk of new cardiovascular events during long-term follow up. Method: 388 patients with MI included in the REBUS (Relevance of Biomarkers for future risk of Thromboembolic Events in Unselected Post-myocardial Infarction Patients) study were examined with ABI to diagnose PAD (defined as an ABI score <0.9 or > 1.4 on at least one side). TNFR-1, -2 and GDF-15 was measured using the Proseek Multiplex CVD III ⁹⁶˟⁹⁶ proximity extension assay (www.olink.com/products/cvd-i and iii-panel). The composite results for these 3 biomarkers were dichotomized into two groups (i.e high and low values) We evaluated pathological ABI and the group with higher biomarkers values with the association to long-term outcome, and if the group of biomarkers for inflammation could further improve prediction of recurrence of cardiovascular events (mortality, new acute coronary syndrome (ACS) and the composite of mortality, new ACS, stroke/TIA and PAD) after an MI. Results: The mean follow-up time was 5.5 years. After adjustment for established CV risk factors, pathological ABI was associated with a higher risk of new ACS, HR 1.97, 95 % CI 1.12-3.49, p = 0.019, and the composite endpoint; HR 1.97, 95 % CI 1.29-3.01, p=0.002, compared to patients with normal ABI. The group with the higher biomarker value was associated with a higher risk for all-cause mortality; HR 1.84, 95 % CI 1.00-3.38, p=0.049 and the composite endpoint; HR 1.62, 95 % CI 1.03-2.53, p=0.035. In the ROC analyses pathological ABI added to established CV risk factors improved the AUC for a new ACS from 0.753 (95% C.I. 0.684-0.822, p<0.001) to 0.763 (95% C.I. 0.697-0.830, p<0.001). When the group with higher biomarker values was added to established CV risk factors AUC for all-cause mortality increased from 0.789 (95% C-I. 0.729-0.849, p<0.001) to 0.805 (95% C.I. 0.746-0.863, p<0.001).Conclusion: Despite a high proportion of revascularization and guideline-recommended secondary medical treatment, both pathological ABI and the group with higher values of the inflammatory biomarkers (TNFR-1, TNFR-2, GDF-15) predictive for PAD were associated with the risk of new CV events and mortality in patients with a recent MI. The group of inflammatory biomarkers provide additional information to established risk factors in prediction of CV outcome in this cohort with recent MI.
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| 10. |
- Jönelid, Birgitta, 1965-
(author)
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Importance of peripheral arterial disease as a risk marker in patients with myocardial infarction
- 2019
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Doctoral thesis (other academic/artistic)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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