| 1. |
- Kimenai, Dorien M., et al.
(författare)
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Sex-Specific Versus Overall Clinical Decision Limits for Cardiac Troponin I and T for the Diagnosis of Acute Myocardial Infarction : A Systematic Review
- 2018
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Ingår i: Clinical Chemistry. - : American Association for Clinical Chemistry. - 0009-9147 .- 1530-8561. ; 64:7, s. 1034-1043
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: The overall clinical decision limits of high-sensitivity cardiac troponin I (hs-cTnI; 26 ng/L) and T (hs-cTnT; 14 ng/L) may contribute to underdiagnosis of acute myocardial infarction in women. We performed a systematic review to investigate sex-specific and overall 99th percentiles of hs-cTnI and hs-cTnT derived from healthy reference populations. CONTENT: We searched in PubMed and EMBASE for original studies, and by screening reference lists. Reference populations designed to establish 99th percentiles of hs-cTnI (Abbott) and/or hs-cTnT (Roche), published between January 2009 and October 2017, were included. Sex-specific and overall 99th percentile values of hs-cTnI and hs-cTnT were compared with overall clinical decision ranges (hs-cTnI, 23-30 ng/L; hs-cTnT, 13-25 ng/L). Twenty-eight studies were included in the systematic review. Of 16 hs-cTnI and 18 hs-cTnT studies, 14 (87.5%) and 11 (61.1%) studies reported lower femalespecific hs-cTn cutoffs than overall clinical decision ranges, respectively. Conversely, male-specific thresholds of both hs-cTnI and hs-cTnT were in line with currently used overall thresholds, particularly hs-cTnT (90% concordance). The variation of estimated overall 99th percentiles was much higher for hs-cTnI than hs-cTnT (29.4% vs 80.0% of hs-cTnI and hs-cTnT studies reported values within the current overall clinical decision range, respectively). SUMMARY: Our data show substantially lower femalespecific upper reference limits of hs-cTnI and hs-cTnT than overall clinical decision limits of 26 ng/L and 14 ng/L, respectively. The statistical approach strongly affects the hs-cTnI threshold. Downward adjustment of hs-cTn thresholds in women may be warranted to reduce underdiagnosis of acute myocardial infarction in women.
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| 2. |
- Eggers, Kai M., 1962-, et al.
(författare)
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Clinical and prognostic implications of C-reactive protein levels in myocardial infarction with nonobstructive coronary arteries
- 2021
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Ingår i: Clinical Cardiology. - : John Wiley & Sons. - 0160-9289 .- 1932-8737. ; 44:7, s. 1019-1027
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Tidskriftsartikel (refereegranskat)abstract
- Background Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a heterogeneous condition. Recent studies suggest that MINOCA patients may have a proinflammatory disposition. The role of inflammation in MINOCA may thus be distinct to myocardial infarction with significant coronary artery disease (MI-CAD). Hypothesis We hypothesized that inflammation reflected by C-reactive protein (CRP) levels might carry unique clinical information in MINOCA. Methods This retrospective registry-based cohort study (SWEDEHEART) included 9916 patients with MINOCA and 97 970 MI-CAD patients, used for comparisons. Multivariable-adjusted regressions were applied to investigate the associations of CRP levels with clinical variables, all-cause mortality and major cardiovascular events (MACE) during a median follow-up of up to 5.3 years. Results Median admission CRP levels in patients with MINOCA and MI-CAD were 5.0 (interquartile range 2.0-9.0) mg/dl and 5.0 (interquartile range 2.1-10.0 mg/dl), respectively. CRP levels in MINOCA exhibited independent associations with various cardiovascular risk factors, comorbidities and estimates of myocardial damage. The association of CRP with peripheral artery disease tended to be stronger compared to MI-CAD. The associations with female sex, renal dysfunction and myocardial damage were stronger in MI-CAD. CRP independently predicted all-cause mortality in MINOCA (hazard ratio 1.22 [95% confidence interval 1.17-1.26]), similar to MI-CAD (p interaction = 0.904). CRP also predicted MACE (hazard ratio 1.08 [95% confidence interval 1.04-1.12]) but this association was weaker compared to MI-CAD (p interaction<.001). Conclusions We found no evidence indicating the presence of a specific inflammatory pattern in acute MINOCA compared to MI-CAD. However, CRP levels were independently, albeit moderately associated with adverse outcome.
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| 3. |
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| 4. |
- Eggers, Kai M., 1962-, et al.
(författare)
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Growth-differentiation factor-15 for early risk stratification in patients with acute chest pain
- 2008
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 29:19, s. 2327-2335
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Growth-differentiation factor-15 (GDF-15) has emerged as a biomarker of increased mortality and recurrent myocardial infarction (MI) in patients diagnosed with non-ST-elevation acute coronary syndrome. We explored the usefulness of GDF-15 for early risk stratification in 479 unselected patients with acute chest pain. METHODS AND RESULTS: Sixty-nine per cent of the patients presented with GDF-15 levels above the previously defined upper reference limit (1200 ng/L). The risks of the composite endpoint of death or (recurrent) MI after 6 months were 1.3, 5.1, and 12.6% in patients with normal (<1200 ng/L), moderately elevated (1200-1800 ng/L), or markedly elevated (>1800 ng/L) levels of GDF-15 on admission, respectively (P < 0.001). By multivariable analysis that included clinical characteristics, ECG findings, peak cardiac troponin I levels within 2 h (cTnI(0-2 h)), N-terminal pro-B-type natriuretic peptide, C-reactive protein, and cystatin C, GDF-15 remained an independent predictor of the composite endpoint. The ability of the ECG combined with peak cTnI(0-2 h) to predict the composite endpoint was markedly improved by addition of GDF-15 (c-statistic, 0.74 vs. 0.83; P < 0.001). CONCLUSION: GDF-15 improves risk stratification in unselected patients with acute chest pain and provides prognostic information beyond clinical characteristics, the ECG, and cTnI.
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| 5. |
- Eggers, Kai M., 1962-, et al.
(författare)
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Growth-differentiation factor-15 for long-term risk prediction in patients stabilized after an episode of non-ST-segment-elevation acute coronary syndrome
- 2010
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Ingår i: Circulation: Cardiovascular Genetics. - 1942-3268. ; 3:1, s. 88-96
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Growth-differentiation factor-15 (GDF-15) has emerged as a prognostic biomarker in patients with non-ST-segment-elevation acute coronary syndrome. This study assessed the time course and the long-term prognostic relevance of GDF-15 levels measured repetitively in patients with non-ST-segment-elevation acute coronary syndrome during 6 months after the acute event. METHODS AND RESULTS: GDF-15 and other biomarkers were measured at randomization, after 6 weeks, and after 3 and 6 months in 950 patients with non-ST-segment-elevation acute coronary syndrome included in the FRagmin and Fast Revascularization during InStability in Coronary artery disease II study. Study end points were death, recurrent myocardial infarction, and their composite during 5-year follow-up. Median GDF-15 levels decreased slightly from 1357 ng/L at randomization to 1302 ng/L at 6 months (P<0.001). GDF-15 was consistently related to cardiovascular risk factors and biochemical markers of hemodynamic stress, renal dysfunction, and inflammation. Moreover, GDF-15 was independently related to the 5-year risk of the composite end point when measured at both 3 months (adjusted hazard ratio, 1.8 [1.0 to 3.0]) and 6 months (adjusted hazard ratio, 2.3 [1.3 to 4.1]). Serial measurements of GDF-15 at randomization and 6 months helped to identify patient cohorts at different levels of risk, with patients with persistently elevated GDF-15 levels >1800 ng/L having the highest rate of the composite end point. CONCLUSIONS: GDF-15 is independently related to adverse events in non-ST-segment-elevation acute coronary syndrome both in the acute setting and for at least 6 months after clinical stabilization. Therefore, continued research on GDF-15 should be focused on the usefulness of GDF-15 for support of clinical management in acute and chronic ischemic heart disease.
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| 6. |
- Eggers, Kai M., 1962-, et al.
(författare)
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Morbidity and cause-specific mortality in first-time myocardial infarction with nonobstructive coronary arteries
- 2019
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Ingår i: Journal of Internal Medicine. - : Blackwell Publishing. - 0954-6820 .- 1365-2796. ; 285:4, s. 419-428
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is receiving increasing interest as a prognostically adverse entity distinct from myocardial infarction with significant coronary artery disease (MI-CAD). However, data are still limited regarding long-term cardiovascular morbidity and cause-specific mortality in MINOCA.METHODS: This is a registry-based cohort study using data from patients admitted to Swedish coronary care units. We investigated various nonfatal outcomes (recurrent MI, hospitalization for heart failure or stroke) and fatal outcomes (cardiovascular, respiratory or cancer-related mortality) in 4069 patients without apparent acute cardiovascular disease, used as non-MI controls, 7266 patients with first-time MINOCA and 69 267 patients with first-time MI-CAD.RESULTS: Almost all event rates (median follow-up 3.8 years) increased in a stepwise fashion across the three cohorts [rates of major adverse events (MAE; composite of all-cause mortality, recurrent MI, hospitalization for heart failure or stroke): n = 268 (6.6%), n = 1563 (21.5%), n = 17 777 (25.7%), respectively]. Compared to non-MI controls, MINOCA patients had an adjusted hazard ratio (HR) of 2.12 (95% confidence interval 1.84-2.43) regarding MAE. MINOCA patients had a substantial risk of cardiovascular mortality and the highest numerical risks of respiratory and cancer-related mortality. Male sex, previous heart failure and chronic obstructive pulmonary disease had a stronger prognostic impact in MINOCA than in MI-CAD. Female MINOCA patients with atrial fibrillation were at particular risk.CONCLUSIONS: Patients with first-time MINOCA have a considerable risk of adverse events. This stresses the need for a comprehensive search of the cause of MINOCA, thorough treatment of underlying disease triggers and close follow-up.
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| 7. |
- Eggers, Kai M., 1962-, et al.
(författare)
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Myocardial Infarction with Non-Obstructive Coronary Arteries : The Importance of Achieving Secondary Prevention Targets
- 2018
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Ingår i: American Journal of Medicine. - : Elsevier. - 0002-9343 .- 1555-7162. ; 131:5, s. 524-531
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Around 5-10% of all myocardial infarction patients have non-obstructive coronary arteries. Studies investigating the importance of follow-up and achievement of conventional secondary prevention targets in these patients are lacking.METHODS: In this analysis from the SWEDEHEART registry, we investigated 5830 myocardial infarction patients with non-obstructive coronary arteries (group 1) and 54,637 myocardial infarction patients with significant coronary artery disease (≥50% stenosis; group 2). Multivariable- and propensity score-adjusted statistics were used to assess the reduction in the one-year risk of major adverse events associated with prespecified secondary preventive measures: participation in follow-up at 6-10 weeks after the hospitalization; achievement of secondary prevention targets (blood pressure and low-density lipoprotein cholesterol levels in the target ranges, non-smoking, participation in exercise training).RESULTS: Patients in group 1 were less often followed up compared to patients in group 2 and less often achieved any of the secondary prevention targets. Participation in the 6-10 week follow-up was associated with a 3-20% risk reduction in group 1, similar as for group 2 according to interaction analysis. The improvement in outcome in group 1 was mainly mediated by achieving target range low-density lipoprotein cholesterol levels (24-32% risk reduction) and, to a smaller extent, by participation in exercise training (10-23% risk reduction).CONCLUSIONS: Selected secondary preventive measures are associated with prognostic benefit in myocardial infarction patients with non-obstructive coronary arteries, in particular achieving target range low-density lipoprotein cholesterol levels. Our results indicate that these patients should receive similar follow-up as myocardial infarction patients with significant coronary stenoses.
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| 8. |
- Eggers, Kai M., 1962-, et al.
(författare)
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ST2 and mortality in non-ST-segment elevation acute coronary syndrome
- 2010
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 159:5, s. 788-794
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: ST2 is a member of the interleukin-1 receptor family that is up-regulated in conditions associated with increased myocardial strain. ST2 has been shown to be independently predictive of adverse outcome in heart failure and ST-segment elevation myocardial infarction, but its prognostic value in non-ST-elevation acute coronary syndrome (NSTE-ACS) has not been established. METHODS: We measured ST2 at randomization and after 24, 48, and 72 hours in 403 NSTE-ACS patients from the GUSTO IV study, and studied its kinetics and its associations to clinical baseline factors and 1-year mortality. RESULTS: Median ST2 levels decreased from 28.4 U/mL at randomization to 21.8 U/mL at 72 hours (P < .001). Peak levels were noted 6 to 17 hours after symptom onset. Randomization ST2 levels were independently associated to N-terminal pro-B-type natriuretic peptide but otherwise exhibited only weak relations to cardiovascular risk factors and comorbidities, and biomarkers of myocardial necrosis or inflammation. ST2 was related to 1-year mortality independently of clinical risk indicators (odds ratio 2.3 [95% CI 1.1-4.6], P = .03) but lost its predictive value after additional adjustment for prognostic biomarkers, in particular N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: ST2 levels are elevated early in NSTE-ACS and predict 1-year mortality. Our data indicate that ST2 represents an interesting novel pathophysiologic pathway in the setting of ischemia-related myocardial dysfunction. However, future prospective evaluations in larger populations are needed before the clinical utility of ST2 can be determined.
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| 9. |
- Kimenai, Dorien M., et al.
(författare)
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Sex differences in investigations and outcomes among patients with type 2 myocardial infarction
- 2021
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Ingår i: Heart. - : BMJ Publishing Group Ltd. - 1355-6037 .- 1468-201X. ; 107:18, s. 1480-1486
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Type 2 myocardial infarction (MI) is a heterogenous condition and whether there are differences between women and men is unknown. We evaluated sex differences in clinical characteristics, investigations and outcomes in patients with type 2 MI.Methods: In the Swedish Web based system for Enhancement and Development of Evidence based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, we compared patients admitted to coronary care units with a diagnosis of type 1 or type 2 MI. Sex-stratified Cox regression models evaluated the association with all-cause death in men and women separately.Results: We included 57 264 (median age 73 years, 65% men) and 6485 (median age 78 years, 50% men) patients with type 1 and type 2 MI, respectively. No differences were observed in the proportion of men and women with type 2 MI who underwent echocardiography and coronary angiography, but women were less likely than men to have left ventricular (LV) impairment and obstructive coronary artery disease (CAD). Compared with type 1 MI, patients with type 2 MI had higher risk of death regardless of sex (men: adjusted HR 1.55 (95% CI 1.44 to 1.67); women: adjusted HR 1.34 (95% CI 1.24 to 1.45)). In those with type 2 MI, the risk of death was lower for women than men (adjusted HR 0.85 (95% CI 0.76 to 0.92) (men, reference)).Conclusions: Type 2 MI occurred in men and women equally and we found no evidence of sex bias in the selection of patients for cardiac investigations. Patients with type 2 MI had worse outcomes, but women were less likely to have obstructive CAD or severe LV impairment and were more likely to survive than men.
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| 10. |
- Kimenai, Dorien M., et al.
(författare)
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Sex-specific effects of implementing a high-sensitivity troponin I assay in patients with suspected acute coronary syndrome : results from SWEDEHEART registry
- 2020
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Ingår i: Scientific Reports. - : NATURE RESEARCH. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Using high-sensitivity cardiac troponin (hs-cTn) assays with sex-specific 99th percentiles may improve management of patients with suspected acute myocardial infarction (AMI). We investigated the impact of transitioning from a conventional troponin I assay to a high-sensitivity assay with sex-specific thresholds, in patients with suspected acute coronary syndrome admitted to Swedish coronary care units. Based on data from SWEDEHEART registry (females, n=4,819/males, n=7,670), we compared periods before and after implementation of hs-cTnI assay (Abbott) using sex-specific 99th percentiles. We investigated differences on discharge diagnosis, in-hospital examinations, treatments, and clinical outcome. Upon implementation of the hs-cTnI assay, proportion of patients with troponin levels above diagnostic AMI threshold increased in women and men by 24.3% versus 14.8%, respectively. Similarly, incidence of AMI increased by 11.5% and 9.8%. Diagnostic interventions and treatments increased regardless of sex. However, these associations did not persist following multivariable adjustment, probably due to the effect of temporal management trends during the observation period. Overall, no risk reduction on major adverse cardiovascular events was observed (HR: 0.91 [95% CI 0.80-1.03], P=0.126). The implementation of hs-cTnI assay together with sex-specific 99th percentiles was associated with an increase in incidence of AMI regardless of sex, but had no major impact on clinical management and prognosis.
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