| 1. |
- Allahyari, Ali, et al.
(författare)
-
Application of the 2019 ESC/EAS dyslipidaemia guidelines to nationwide data of patients with a recent myocardial infarction : a simulation study
- 2020
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 41:40, s. 3900-3909
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: To estimate the proportion of patients with a recent myocardial infarction (MI) who would be eligible for additional lipid-lowering therapy according to the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidaemias, and to simulate the effects of expanded lipid-lowering therapy on attainment of the low-density lipoprotein cholesterol (LDL-C) target as recommended by the guidelines.METHODS AND RESULTS: Using the nationwide SWEDEHEART register, we included 25 466 patients who had attended a follow-up visit 6-10 weeks after an MI event, 2013-17. While most patients (86.6%) were receiving high-intensity statins, 82.9% of the patients would be eligible for expanded lipid-lowering therapy, as they had not attained the target of an LDL-C level of <1.4 mmol and a ≥50% LDL-C level reduction. When maximized use of high-intensity statins followed by add-on therapy with ezetimibe was simulated using a Monte Carlo model, the LDL-C target was reached in 19.9% using high-intensity statin monotherapy and in another 28.5% with high-intensity statins and ezetimibe, while 50.7% would still be eligible for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. When use of alirocumab or evolocumab was simulated in those who were eligible for PCSK9 inhibitors, around 90% of all patients attained the LDL-C target.CONCLUSION : Our study suggests that, even with maximized use of high-intensity statins and ezetimibe, around half of patients with MI would be eligible for treatment with PCSK9 inhibitors according to the 2019 ESC/EAS guidelines. Considering the current cost of PCSK9 inhibitors, the financial implications of the new guidelines may be substantial.
|
|
| 2. |
- Allahyari, Ali, et al.
(författare)
-
Low-density lipoprotein-cholesterol target attainment according to the 2011 and 2016 ESC/EAS dyslipidaemia guidelines in patients with a recent myocardial infarction : nationwide cohort study, 2013–17
- 2021
-
Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - : Oxford University Press. - 2058-5225 .- 2058-1742. ; 7:1, s. 59-67
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: To assess low-density lipoprotein cholesterol (LDL-C) treatment target attainment among myocardial infarction (MI) patients according to the ESC/EAS dyslipidaemia guidelines from 2011 (LDL-C <1.8 mmol/L or ≥ 50% LDL-C reduction) and 2016 (LDL-C <1.8 mmol/L and ≥50% LDL-C reduction).METHODS AND RESULTS: Using nationwide registers, we identified 44,890 patients aged 21-74 admitted for MI, 2013-2017. We included those attending follow-up visits at 6-10 weeks (n = 25,466) and 12-14 months (n = 17,117) after the event. Most patients received high-intensity statin monotherapy (84.3% [6-10 weeks] and 69.0% [12-14 months]) or statins with ezetimibe (2.7% and 10.2%). The proportion of patients attaining the 2011 LDL-C target was 63.8% (6-10 weeks) and 63.5% (12-14 months). The corresponding numbers for the 2016 LDL-C target was 31.6% (6-10 weeks) and 31.5% (12-14 months). At the 6-10-week follow-up, 37% of those not attaining the 2011 LDL-C target and 48% of those not attaining the 2016 target had an LDL-C level that was ≥0.5 mmol/L from the target. When comparing LDL-C measurements performed before vs. after the release of the 2016 guidelines, attainment of the 2016 LDL-C target increased from 30.2% to 35.0% (6-10 weeks) and from 27.6% to 37.6% (12-14 months).CONCLUSIONS: In a nationwide register, one out of three patients with a recent MI had not attained the LDL-C target of the 2011 ESC/EAS guidelines and two out of three patients had not attained the LDL-C target of the 2016 guidelines.
|
|
| 3. |
- Bennermo, Marie, et al.
(författare)
-
Genetic and environmental influences on the plasma interleukin-6 concentration in patients with a recent myocardial infarction : a case-control study
- 2011
-
Ingår i: Journal of Interferon and Cytokine Research. - : Mary Ann Liebert Inc. - 1079-9907 .- 1557-7465. ; 31:2, s. 259-264
-
Tidskriftsartikel (refereegranskat)abstract
- The aim was to study the stimuli responsible for triggering and sustaining the plasma concentration of the inflammatory marker interleukin-6 (IL-6) in patients with a first myocardial infarction before the age of 60 and healthy control subjects matched for age and sex. The plasma IL-6 concentration, antibodies against Chlamydia pneumoniae, cytomegalovirus, Epstein-Barr virus, Helicobacter pylori, herpes simplex type 1 and 2, and genotype for the IL6-174 G>C single-nucleotide polymorphism were determined 3 months after the acute event. The results showed that patients had higher IL-6 levels than control subjects, whereas there were no differences regarding individual or total number (pathogen burden) of positive antibody tests against the different pathogens or IL6 genotype distribution. The plasma IL-6 concentration was associated with the number of positive antibody tests in patients and control subjects, whereas patients irrespective of IL6 genotype had increased IL-6. Multivariate analysis, including traditional coronary heart disease risk factors, antibodies against pathogens, and IL6 genotype, explained 17% of the variation of the plasma IL-6 concentration. Neither pathogen burden nor IL6 genotype did contribute to the variation of plasma IL-6 levels, whereas smoking, body-mass index, hypertension, case-control status, and age were determinants of the plasma IL-6 concentration.
|
|
| 4. |
- Cederström, Sofia, et al.
(författare)
-
Association between high-sensitivity C-reactive protein and coronary atherosclerosis in a general middle-aged population.
- 2023
-
Ingår i: Scientific reports. - : Springer Nature. - 2045-2322. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Despite abundant knowledge about the relationship between inflammation and coronary atherosclerosis, it is still unknown whether systemic inflammation measured as high-sensitivity C-reactive protein (hsCRP) is associated with coronary atherosclerosis in a general population. This study aimed to examine the association between hsCRP and coronary computed tomography angiography (CCTA)-detected coronary atherosclerosis in a population-based cohort. Out of 30,154 randomly invited men and women aged 50 to 64years in the Swedish Cardiopulmonary Bioimage Study (SCAPIS), 25,408 had a technically acceptable CCTA and analysed hsCRP. Coronary atherosclerosis was defined as presence of plaque of any degree in any of 18 coronary segments. HsCRP values were categorised in four groups. Compared with hsCRP below the detection limit, elevated hsCRP (≥2.3mg/L) was weakly associated with any coronary atherosclerosis (OR 1.15, 95% CI 1.07-1.24), coronary diameter stenosis≥50% (OR 1.27, 95% CI 1.09-1.47),≥4 segments involved (OR 1.13, 95% CI 1.01-1.26 ) and severe atherosclerosis (OR 1.33, 95% CI 1.05-1.69) after adjustment for age, sex and traditional risk factors. The associations were attenuated after further adjustment for body mass index (BMI), although elevated hsCRP still associated with noncalcified plaques (OR 1.16, 95% CI 1.02-1.32), proposed to be more vulnerable. In conclusion, the additional value of hsCRP to traditional risk factors in detection of coronary atherosclerosis is low. The association to high-risk noncalcified plaques, although unlikely through a causal pathway, could explain the relationship between hsCRP and clinical coronary events in numerous studies.
|
|
| 5. |
|
|
| 6. |
- Karlson, Björn W., 1953, et al.
(författare)
-
Doses of rosuvastatin, atorvastatin and simvastatin that induce equal reductions in LDL-C and non-HDL-C: Results from the VOYAGER meta-analysis
- 2016
-
Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 23:7, s. 744-747
-
Tidskriftsartikel (refereegranskat)abstract
- Background Achieving the greatest reduction in atherogenic lipoproteins requires the optimum dose and potency of statin. Using data from the VOYAGER meta-analysis, we determined doses of rosuvastatin, atorvastatin and simvastatin that induce equal reductions in low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). Methods Least squares mean percentage change in LDL-C and non-HDL-C was calculated using 38,052 patient exposures to rosuvastatin 5-40mg, atorvastatin 10-80mg and simvastatin 10-80mg. Equipotent doses were estimated by linear interpolation between actual adjacent doses. Results Rosuvastatin 5mg reduced LDL-C by 39% and non-HDL-C by 35%. Equivalent reductions in LDL-C required atorvastatin 15mg or simvastatin 39mg. Equivalent reductions in non-HDL-C required atorvastatin 14 mg or simvastatin 42mg. Rosuvastatin 10mg reduced LDL-C by 44% and non-HDL-C by 40%. Equivalent reductions in LDL-C required atorvastatin 29 mg or simvastatin 72mg. Equivalent reductions in non-HDL-C required atorvastatin 27 mg or simvastatin 77mg. Rosuvastatin 20mg reduced LDL-C by 50% and non-HDL-C by 45%. Equivalent reductions in LDL-C and non-HDL-C required atorvastatin 70 mg and atorvastatin 62mg, respectively, and were not achieved with the maximum 80mg dose of simvastatin. Rosuvastatin 40mg reduced LDL-C by 55% and non-HDL-C by 50%. Comparable reductions were not achieved with the maximum 80mg doses of atorvastatin or simvastatin. Conclusions Regarding reductions in LDL-C and non-HDL-C, each rosuvastatin dose is equivalent to doses 3-3.5 times higher for atorvastatin and 7-8 times higher for simvastatin.
|
|
| 7. |
- Karlson, Björn W., 1953, et al.
(författare)
-
Variability of low-density lipoprotein cholesterol response with different doses of atorvastatin, rosuvastatin, and simvastatin: results from VOYAGER.
- 2016
-
Ingår i: European heart journal. Cardiovascular pharmacotherapy. - : Oxford University Press (OUP). - 2055-6845 .- 2055-6837. ; 2:4, s. 212-7
-
Tidskriftsartikel (refereegranskat)abstract
- Patient response to statin treatment is individual and varied. As a consequence, when using a specific-dose approach, as recommended in the 2013 American College of Cardiology/American Heart Association guideline, there will be a range of reductions in the concentration of low-density lipoprotein cholesterol (LDL-C). The aim of this study was to use individual patient data from the VOYAGER meta-analysis to determine the extent of the variability in LDL-C reduction in response to treatment across the recommended doses of different statins.
|
|
| 8. |
- Khedri, Masih, et al.
(författare)
-
Statin Treatment Intensity, Discontinuation, and Long-Term Outcome in Patients With Acute Myocardial Infarction and Impaired Kidney Function
- 2023
-
Ingår i: Journal of Cardiovascular Pharmacology. - : Wolters Kluwer. - 0160-2446 .- 1533-4023. ; 81:6, s. 400-410
-
Tidskriftsartikel (refereegranskat)abstract
- Statin dosage in patients with acute myocardial infarction (AMI) and concomitant kidney dysfunction is a clinical dilemma. We studied discontinuation during the first year after an AMI and long-term outcome in patients receiving high versus low–moderate intensity statin treatment, in relation to kidney function. For the intention-to-treat analysis (ITT-A), we included all patients admitted to Swedish coronary care units for a first AMI between 2005 and 2016 that survived in-hospital, had known creatinine, and initiated statin therapy (N = 112,727). High intensity was initiated in 38.7% and low–moderate in 61.3%. In patients with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, 25% discontinued treatment the first year; however, the discontinuation rate was similar regardless of the statin intensity. After excluding patients who died, changed therapy, or were nonadherent during the first year, 84,705 remained for the on-treatment analysis (OT-A). Patients were followed for 12.6 (median 5.6) years. In patients with eGFR 30–59 mL/min, high-intensity statin was associated with lower risk for the composite death, reinfarction, or stroke both in ITT-A (hazard ratio [HR] 0.93; 95% confidence interval, 0.87–0.99) and OT-A (HR 0.90; 0.83–0.99); the interaction test for OT-A indicated no heterogeneity for the eGFR < 60 mL/min group (P = 0.46). Similar associations were seen for all-cause mortality. We confirm that high-intensity statin treatment is associated with improved long-term outcome after AMI in patients with reduced kidney function. Most patients with reduced kidney function initiated on high-intensity statins are persistent after 1 year and equally persistent as patients initiated on low–moderate intensity.
|
|
| 9. |
- Lundman, Pia, et al.
(författare)
-
A high-fat meal is accompanied by increased plasma interleukin-6 concentrations
- 2007
-
Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 17:3, s. 195-202
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIM: Enhanced and prolonged postprandial lipaemia is associated with coronary heart disease (CHD). However, the mechanisms linking postprandial lipaemia to the increased risk of atherosclerosis and CHD remain to be determined. The aim of the present study was to examine the effects of a high-fat meal on plasma levels of the pro-inflammatory cytokine interleukin-6 (IL-6) and cellular adhesion molecules in CHD patients and control subjects. METHODS AND RESULTS: Forty-one middle-aged men with premature CHD and 26 healthy male controls were investigated. The plasma triglyceride response to the high-fat meal was significantly greater among cases than controls. The oral fat load induced a twofold increase in plasma concentrations of IL-6, an increase that was similar in CHD patients and control subjects. No changes could be detected in plasma concentrations of cellular adhesion molecules in response to postprandial lipaemia in either CHD patients or control subjects. CONCLUSION: The results of the present study suggest that a high-fat meal affects mechanisms that induce increased inflammatory activity, which is recognised as a key modulator in the development of atherosclerosis and CHD. However, the increased levels of plasma IL-6 appear not to be determined by the magnitude of the postprandial triglyceridaemia.
|
|
| 10. |
- Lundman, Pia
(författare)
-
Effects of triglycerides on the endothelium
- 2001
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hypertriglyceridaemia (HTG) is a risk factor for coronary heart disease (CHD), although the mechanisms behind the increased risk remain to be defined. It is unclear whether atherogenic or thrombogenic factors are involved, or a combination thereof the endothelium is important in maintaining normal vascular function and has a key role in atherogenesis. Endothelial dysfunction is considered to be an early marker of atherosclerosis and is associated with common risk factors for CHD and with manifest atherosclerosis. The present research programme was set up to investigate whether triglycerides have a negative effect on endothelial function and thus promote atherosclerosis, which is a proposed mechanism for how HTG acts as risk factor for CHD. In study I the effects of acute triglyceridaemia were investigated in seven healthy young men without risk factors for CHD by administration of an intravenous triglyceride-rich chylomicron-like fat emulsion. This study demonstrated that transient triglyceridaemia impaired flow-mediated endothelium-dependent vasodilation (FMD), examined by brachial artery ultrasound technique. An effect on endothelium-independent vasodilation could not be excluded in this study. In study II and study IV, 15 men with mild to moderate persistent HTG and no other risk factors for CHD and 15 age- and body mass index-matched healthy male controls were examined. Study II demonstrated that FMD of the brachial artery was impaired in chronic HTG, whereas common carotid intima media-thickness was similar in the two groups. The plasma concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) were higher in the hypertriglyceridaemic group. There was no difference in endothelium-independent vasodilation. Study IV demonstrated that chronic HTG was associated with increased concentrations of the inflammatory marker C-reactive protein, cellular adhesion molecules (sICAM-1 and sE-selectin-1) and von Willebrand factor. Study III was performed in rat femoral arterial rings in organ baths and demonstrated that a triglyceride-rich fat emulsion and free fatty acids (FFAs) (16:0,18:1 and 18:3) impaired pharmacologically stimulated endothelium-dependent vasorelaxation, whereas no effect was seen with very low density lipoproteins. There were no effects on endothelium-independent vasoreactivity with any of the substances studied. When the antioxidant vitamin C was added to the organ baths, together with the fat emulsion or FFAs, the vasodilatory responses to the endothelial agonist improved, indicating that oxidative mechanisms are involved in the observed impairment of endothelium-dependent vasorelaxation. In study V effects of acute triglyceridaemia on myocardial ischaemia were investigated in 15 men with manifest CHD, by having the patients perform an exercise stress test before and during administration of a triglyceride-rich fat emulsion or saline, in a double-blind fashion. This study demonstrated a decreased rate pressure product and a trend towards earlier ST segment depression during infusion of triglyceride-rich fat emulsion compared with saline. Conclusions: The results demonstrate that triglycerides exert negative effects or the endothelium. Acute and chronic elevation of triglycerides, or their metabolites FFAs, is associated with impairment of endothelial function and biochemical signs of endothelial activation and inflammation. This might be caused by decreased NO bioavailability, induced by oxidative mechanisms or by increased concentrations of the NO synthase inhibitor ADMA. Taken together, this emphasises the importance of hypertriglyceridaemia as a risk factor for atherosclerosis and CHD.
|
|
| 11. |
- Mörtberg, Josefin, et al.
(författare)
-
Prognostic importance of biomarkers associated with haemostatic, vascular and endothelial disturbances in acute coronary syndrome patients in relation to kidney function
- 2023
-
Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 373, s. 64-71
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with kidney failure have a high risk for cardiovascular events. We aimed to evaluate the prognostic importance of selected biomarkers related to haemostasis, endothelial function, and vascular regulation in patients with acute coronary syndrome (ACS), and to study whether this association differed in patients with renal dysfunction.METHODS: Plasma was collected in 1370 ACS patients included between 2008 and 2015. Biomarkers were analysed using a Proximity Extension Assay and a Multiple Reaction Monitoring mass spectrometry assay. To reduce multiplicity, biomarkers correlating with eGFR were selected a priori among 36 plasma biomarkers reflecting endothelial and vascular function, and haemostasis. Adjusted Cox regression were used to study their association with the composite outcome of myocardial infarction, ischemic stroke, heart failure or death. Interaction with eGFR strata above or below 60 ml/min/1.73 m 2 was tested. RESULTS: Tissue factor, proteinase-activated receptor, soluble urokinase plasminogen activator surface receptor (suPAR), thrombomodulin, adrenomedullin, renin, and angiotensinogen correlated inversely with eGFR and were selected for the Cox regression. Mean follow-up was 5.2 years during which 428 events occurred. Adrenomedullin, suPAR, and renin were independently associated with the composite outcome. Adrenomedullin showed interaction with eGFR strata (p = 0.010) and was associated with increased risk (HR 1.88; CI 1.44-2.45) only in patients with eGFR ≥60 ml/min/ 1.73 m 2. CONCLUSIONS: Adrenomedullin, suPAR, and renin were associated with the composite outcome in all. Adrenomedullin, involved in endothelial protection, showed a significant interaction with renal function and outcome, and was associated with the composite outcome only in patients with preserved kidney function.
|
|
| 12. |
- Paramel, Geena, 1985-, et al.
(författare)
-
CARD8 gene encoding a protein of innate immunity is expressed in human atherosclerosis and associated with markers of inflammation
- 2013
-
Ingår i: Clinical Science. - London, United Kingdom : Portland Press. - 0143-5221 .- 1470-8736. ; 125:8, s. 401-407
-
Tidskriftsartikel (refereegranskat)abstract
- Inflammation is a key factor in the development of atherosclerotic coronary artery disease. It is promoted through the inflammasome, a molecular machine that produces IL (interleukin)-1 beta in response to cholesterol crystal accumulation in macrophages. The CARD8 (caspase recruitment domain 8) protein modulates this process by suppressing caspase 1 and the transcription factor NF-kappa B (nuclear factor kappa B). The expression of CARD8 mRNA was examined in atherosclerotic vascular tissue and the impact on MI (myocardial infarction) of a polymorphism in the CARD8 gene determined. CARD8 mRNA was analysed by microarray of human atherosclerotic tissue and compared with transplant donor arterial tissue. Microarray analysis was performed for proximal genes associated with the rs2043211 locus in plaque. The CARD8 rs2043211 polymorphism was analysed by genotyping of two Swedish MI cohorts, FIA (First Myocardial Infarction in Northern Sweden) and SCARF (Stockholm Coronary Atherosclerosis Risk Factor). The CRP (C-reactive protein) level was measured in both cohorts, but the levels of the pro-inflammatory cytokines IL-1 beta, IL-18, TNF (tumour necrosis factor) and MCP-1 (monocyte chemoattractant protein) were measured in sera available from the SCARF cohort. CARD8 mRNA was highly expressed in atherosclerotic plaques compared with the expression in transplant donor vessel (P < 0.00001). The minor allele was associated with lower expression of CARD8 in the plaques, suggesting that CARD8 may promote inflammation. Carriers of the minor allele of the rs2043211 polymorphism also displayed lower circulating CRP and lower levels of the pro-atherosclerotic chemokine MCP-1. However, no significant association could be detected between this polymorphism and MI in the two cohorts. Genetic alterations in the CARD8 gene therefore seem to be of limited importance for the development of MI.
|
|
| 13. |
- Persson, Jonas, et al.
(författare)
-
Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease
- 2015
-
Ingår i: Journal of the American Heart Association. - : WILEY-BLACKWELL. - 2047-9980. ; 4:8
-
Tidskriftsartikel (refereegranskat)abstract
- Background-Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis. In this study, we used a sex-stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on IMT. Methods and Results-Baseline plasma adiponectin concentrationwas tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n=1777; men, n=1653) with high cardiovascular risk but no prevalent disease. Plasma adiponectin levels were inversely associated with baseline mean bifurcation IMT after adjustment for established risk factors (beta=-0.018, P<0.001) in men but not in women (beta=-0.006, P=0.185; P for interaction=0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (beta=-0.0022, P=0.047), whereas no association was seen in women (0.0007, P=0.475; P for interaction=0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% CI 0.37 to 0.87) but not in men (hazard ratio 0.82,95% CI0.54 to 1.25). Agenescore of adiponectin-raisingalleles in6loci, reported recently inalarge multi-ethnic metaanalysis, was inversely associated with baseline mean bifurcation IMT in men (beta=-0.0008, P=0.004) but not in women (beta=-0.0003, P=0.522; P for interaction=0.007). Conclusions-This report provides some evidence for adiponectin protecting against atherosclerosis, with effects being confined to men; however, compared with established cardiovascular risk factors, the effect of plasma adiponectin was modest. Further investigation involving mechanistic studies is warranted.
|
|
| 14. |
- Ritsinger, Viveca, et al.
(författare)
-
Design and rationale of the myocardial infarction and new treatment with metformin study (MIMET) - Study protocol for a registry-based randomised clinical trial
- 2023
-
Ingår i: Journal of diabetes and its complications. - : Elsevier. - 1056-8727 .- 1873-460X. ; 37:10
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate if addition of metformin to standard care (life-style advice) reduces the occurrence of cardiovascular events and death after myocardial infarction (MI) in patients with newly detected prediabetes.Methods: The Myocardial Infarction and new treatment with Metformin study (MIMET) is a large multicentre registry-based randomised clinical trial (R-RCT) within the SWEDEHEART registry platform expected to include 5160 patients with MI and newly detected prediabetes (identified with fasting blood glucose, HbA1c or 2-h glucose on oral glucose tolerance test) at similar to 20 study sites in Sweden. Patients 18-80 years, without known diabetes and naive to glucose lowering therapy, will be randomised 1:1 to open-label metformin therapy plus standard care or standard care alone.Outcomes: Patients will be followed for 2 years for the primary outcome new cardiovascular event (first of death, non-fatal MI, hospitalisation for heart failure or non-fatal stroke). Secondary endpoints include individual components of the primary endpoint, diabetes diagnosis, initiation of any glucose lowering therapy, cancer, and treatment safety. Events will be collected from national healthcare registries.Conclusions: The MIMET study will investigate if metformin is superior to standard care after myocardial infarction in preventing cardiovascular events in patients with prediabetes (Clinicaltrials.gov identifier: NCT05182970; EudraCT No: 2019-001487-30).
|
|
| 15. |
- Ritsinger, Viveca, et al.
(författare)
-
Diabetes, metformin and glucose lowering therapies after myocardial infarction : Insights from the SWEDEHEART registry
- 2020
-
Ingår i: Diabetes & Vascular Disease Research. - : SAGE Publications. - 1479-1641 .- 1752-8984. ; 17:6
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To explore real-life use of glucose lowering drugs and prognosis after acute myocardial infarction (AMI) with a special focus on metformin.METHODS: Patients (n = 70270) admitted for AMI 2012-2017 were stratified by diabetes status and glucose lowering treatment and followed for mortality and MACE+ (AMI, heart failure (HF), stroke, mortality) until end of 2017 (mean follow-up time 3.4 ± 1.4 years) through linkage with national registries and SWEDEHEART. Hazard ratios (HR) were calculated in adjusted Cox proportional hazard regression models.RESULTS: Mean age was 68 ± 11 years and 70% were male. Of patients with diabetes (n = 16356; 23%), a majority had at least one glucose lowering drug (81%) of whom 51% had metformin (24% monotherapy), 43% insulin and a minority any SGLT2i/GLP-1 RA (5%). Adjusted HR for patients with versus without diabetes was 1.31 (95% CI 1.27-1.36) for MACE+ and 1.48 (1.41-1.56) for mortality. Adjusted HR for MACE+ for diabetes patients on metformin was 0.92 (0.85-0.997), p = 0.042 compared to diet treated diabetes.CONCLUSION: Diabetes still implies a high complication risk after AMI. Metformin and insulin were the most common treatment used in almost half of the diabetes population. Furthermore, patients treated with metformin had a lower cardiovascular risk after AMI and needs to be confirmed in prospective controlled trials.
|
|
| 16. |
- Salzinger, Barbara, et al.
(författare)
-
Associations between inflammatory and angiogenic proteomic biomarkers, and cardiovascular events and mortality in relation to kidney function
- 2024
-
Ingår i: Clinical Kidney Journal. - : Oxford University Press. - 2048-8505 .- 2048-8513. ; 17:3
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe links between chronic kidney disease (CKD) and the high burden of cardiovascular disease remain unclear. We aimed to explore the association between selected inflammatory and angiogenic biomarkers, kidney function and long-term outcome in patients with an acute coronary syndrome (ACS) and to test the hypothesis that CKD status modifies this association.MethodsA total of 1293 ACS patients hospitalized between 2008 and 2015 were followed until 31 December 2017. Plasma was collected on days 1–3 after admission. A total of 13 biomarkers were a priori identified and analysed with two proteomic methods, proximity extension assay or multiple reaction monitoring mass spectrometry. Boxplots and multiple linear regression models were used to study associations between biomarkers and kidney function and adjusted standardized Cox regression with an interaction term for CKD was used to assess whether CKD modified the association between biomarkers and major adverse cardiovascular events and death (MACE+).ResultsThe concentrations of nine biomarkers—endothelial cell-specific molecule-1 (ESM-1), fibroblast growth factor 23 (FGF-23), fractalkine (CX3CL1), interleukin-1 receptor antagonist (IL-1RA), interleukin-18 (IL-18), monocyte chemotactic protein-1 (MCP-1), placenta growth factor (PlGF), transmembrane immunoglobulin 1 (TIM-1) and vascular endothelial growth factor A (VEGFA)—were inversely associated with kidney function. ESM-1, FGF-23 and TIM-1 showed associations with MACE+. Only FGF23 remained independently associated after adjustment for the other biomarkers (hazard ratio per standard deviation increase 1.34; 95% Bonferroni corrected confidence interval 1.19–1.50). None of the biomarkers showed an interaction with CKD.ConclusionsThe concentrations of 9 of the 13 prespecified inflammatory and angiogenic proteomic biomarkers increased when kidney function declined. Only FGF-23 demonstrated an independent association with MACE+, and this association was not modified by CKD status. These findings further support FGF-23 as an independent prognostic marker in ACS patients with and without CKD.
|
|
| 17. |
- Swanberg, Maria, et al.
(författare)
-
MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction
- 2005
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 37:5, s. 486-494
-
Tidskriftsartikel (refereegranskat)abstract
- Antigen presentation to T cells by MHC molecules is essential for adaptive immune responses. To determine the exact position of a gene affecting expression of MHC molecules, we finely mapped a previously defined rat quantitative trait locus regulating MHC class II on microglia in an advanced intercross line. We identified a small interval including the gene MHC class II transactivator (Mhc2ta) and, using a map over six inbred strains combined with gene sequencing and expression analysis, two conserved Mhc2ta haplotypes segregating with MHC class II levels. In humans, a -168A --> G polymorphism in the type III promoter of the MHC class II transactivator (MHC2TA) was associated with increased susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction, as well as lower expression of MHC2TA after stimulation of leukocytes with interferon-gamma. We conclude that polymorphisms in Mhc2ta and MHC2TA result in differential MHC molecule expression and are associated with susceptibility to common complex diseases with inflammatory components.
|
|
| 18. |
- Szummer, Karolina, et al.
(författare)
-
Association between statin treatment and outcome in relation to renal function in survivors of myocardial infarction
- 2011
-
Ingår i: KIDNEY INTERNATIONAL. - : Nature Publishing Group. - 0085-2538 .- 1523-1755. ; 79:9, s. 997-1004
-
Tidskriftsartikel (refereegranskat)abstract
- As statins are recommended at discharge to all patients following myocardial infarction (MI), we studied their use and efficacy in renal disease by analyzing the data, in the nationwide SWEDEHEART registry, of 42,814 consecutive survivors of MI with available creatinine/dialysis data but without statin therapy on admission. The estimated glomerular filtration rate (eGFR) was determined by the Modification of Diet in Renal Disease Study formula and the patients classified into the five traditional stages of kidney disease. The 1-year survival in relation to prescription of statin at discharge was assessed in a Cox regression analysis adjusted by a propensity score that described each individuals likelihood of being treated with a statin, established by 36 baseline characteristics and in-hospital therapies. Statin use at discharge decreased with increased renal impairment from 81% in eGFR stage 1 to 31% in eGFR stage 5. After adjusting for the propensity score and discharge medication, statin use was associated with a significant reduction in overall risk of death (hazard ratio 0.63), with a statistically significant interaction between statin therapy and the stage of renal function. Thus, statin use at discharge was associated with improved 1-year survival of patients in stages 2-4 (mild-to-severe) of renal insufficiency. This effect appears attenuated in those with stage 5 renal failure.
|
|
| 19. |
- Szummer, Karolina, et al.
(författare)
-
Cockcroft-Gault is better than the Modification of Diet in Renal Disease study formula at predicting outcome after a myocardial infarction : Data from the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART)
- 2010
-
Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 159:6, s. 979-986
-
Tidskriftsartikel (refereegranskat)abstract
- Background The aim was to examine whether the Modification of Diet in Renal Disease (MDRD) or the Cockcroft-Gault (CG) formula is better at predicting prognosis in myocardial infarction (MI) patients. Methods All consecutive MI patients entered in a nationwide registry between 2003 and 2006 with glomerular filtration rate (eGFR) estimated by both the MDRD and CG formula (N = 36,137) were analyzed. Results Cockcroft-Gault classified a larger proportion of patients as having at least a moderate (39.8% vs 31.1%, P<.001) or at least a severe renal dysfunction (7.6% vs 4.4%, P<.001) compared with the MDRD. The largest difference between the estimations was seen when patients were divided according to gender, age, and weight, where CG estimated a lower eGFR in women, the elderly, and those with low body weight. In a receiver operating characteristic analysis, CG had a stronger association to 1-year mortality (area under the curve 0.78, 95% CI 0.77-0.79) than MDRD (area under the curve 0.73, 95% CI 0.72-0.74). Within each renal function stage classified with the MDRD, there were patients identified with the CG as having both a worse renal function and a higher mortality. After multivariable adjustment, CG predicted 1-year mortality better than the MDRD (renal failure vs normal renal function: hazard ratio 3.00, 95% CI 2.42-3.71 with the CG; hazard ratio 2.56, 95% CI 2.10-3.11 with the MDRD). Conclusion Cockcroft-Gault is better than the MDRD equation at predicting mortality after a MI. This is mainly explained by differences in the coefficients and variables included in the eGFR equations, and less to differences in various subgroups of patients.
|
|
| 20. |
|
|
| 21. |
- Szummer, Karolina, et al.
(författare)
-
Influence of Renal Function on the Effects of Early Revascularization in Non-ST-Elevation Myocardial Infarction Data From the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART)
- 2009
-
Ingår i: CIRCULATION. - 0009-7322 .- 1524-4539. ; 120:10, s. 851-U55
-
Tidskriftsartikel (refereegranskat)abstract
- Background-It is unknown whether patients with non-ST-elevation myocardial infarction derive a similar benefit from an early invasive therapy at different levels of renal function. Methods and Results-A total of 23 262 consecutive non-ST-elevation myocardial infarction patients andlt;= 80 years old were included in a nationwide coronary care unit register between 2003 and 2006. Glomerular filtration rate (eGFR) was estimated with the Modification of Diet in Renal Disease Study formula. Patients were divided into medically or invasively treated groups if revascularized within 14 days of admission. A propensity score for the likelihood of invasive therapy was calculated. A Cox regression model with adjustment for propensity score and discharge medication was used to assess the association between early revascularization and 1-year mortality across renal function stages. There was a gradient, with significantly fewer patients treated invasively with declining renal function: eGFR andgt;= 90 mL . min(-1) . 1.73 m(-2), 62%; eGFR 60 to 89 mL . min(-1) . 1.73 m(-2), 55%; eGFR 30 to 59 mL . min(-1) . 1.73 m(-2), 36%; eGFR 15 to 29 mL . min(-1) . 1.73 m(-2), 14%; and eGFR andlt; 15 mL . min(-1) . 1.73 m(-2)/ dialysis, 15% (P andlt; 0.001). After adjustment, the overall 1-year mortality was 36% lower (hazard ratio 0.64, 95% confidence interval 0.56 to 0.73, P andlt; 0.001) with an invasive strategy. The magnitude of survival difference was similar in normal-to-moderate renal function groups. The lower mortality observed with invasive therapy declined with lower renal function, with no difference in mortality in patients with kidney failure (eGFR andlt; 15 mL . min(-1) . 1.73 m(-2)) or in those receiving dialysis (hazard ratio 1.61, 95% confidence interval 0.84 to 3.09, P=0.15). Conclusions-Early invasive therapy is associated with greater 1-year survival in patients with non-ST-elevation myocardial infarction and mild-to-moderate renal insufficiency, but the benefit declines with lower renal function, and is less certain in those with renal failure or on dialysis.
|
|
| 22. |
|
|
| 23. |
|
|
