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P Tornvall

Publications and source records attributed to P Tornvall.

At least 19 recordsLinked to original sources
PubMed2006

Lower serum concentration of matrix metalloproteinase-3 in the acute stage of myocardial infarction.

OBJECTIVES: The importance of matrix metalloproteinases (MMPs) in the progression and rupture of the atherosclerotic plaque is gaining increasing recognition but the mechanisms are not yet fully understood. The aim of this study was to investigate the significance of MMP-3 in the acute phase of myocardial infarction (MI) and the influence of the -1612 5A/6A MMP-3 gene promoter polymorphism on serum MMP-3 concentration. SUBJECTS: One-hundred and sixty-four patients admitted with ST-elevation MI and receiving thrombolysis treatment were included in this study. Serum MMP-3 was analysed at admission, after 48 h and at 3 months. RESULTS: Serum MMP-3 concentration was significantly increased at 3 months when compared with admission and 48 h (19.5 ng mL(-1) [14.4-24.7] vs. 15.5 ng mL(-1) [10.5-21.8] at admission, P < 0.001; and 14.7 ng mL(-1) [9.9-23.8] at 48 h, P < 0.001). Furthermore, we found the -1612 5A/6A polymorphism to influence the serum concentration of MMP-3 at all time-points: 14.1 ng mL(-1) [10.2-18.8] in 5A/5A; 19.6 ng mL(-1) [15.0-24.4] in 5A/6A; and 24.0 ng mL(-1) [20.1-32.3] in 6A/6A genotype at 3 months (P < 0.001 between all groups). Female patients had lower serum MMP-3 concentration than male patients at all time-points (14.8 ng mL(-1) [9.4-20.8] vs. 19.9 ng mL(-1) [16.0-26.9], P < 0.0001 at 3 months). CONCLUSIONS: Serum concentration of MMP-3 is significantly lower in the acute stage of MI than during recovery and is significantly influenced by -1612 5A/6A genotype and gender. Together with previous findings, these results primarily implicate MMP-3 in atherosclerosis progression rather than in acute MI.

Coronary Angiography↗
PubMed2006

Clinical and angiographic follow-up after coronary drug-eluting and bare metal stent implantation. Do drug-eluting stents hold the promise?

OBJECTIVES: To investigate the influence of drug-eluting stent (DES) implantation on clinical and angiographic restenosis. DESIGN: Registry study of data from the Swedish Coronary Angiography and Angioplasty Registry with a coronary angiographic substudy. SETTING: Multi-centre study. SUBJECTS: During October 2002 to May 2004 a total of 23 590 percutaneous coronary intervention (PCI) procedures were performed at 25 hospitals. After selection, to achieve comparable groups, a total of 5068 patients of whom 4111 had a bare metal stent (BMS) implanted and 957 had a DES implanted, remained. End-point in the registry follow-up was >50% diameter restenosis at clinically driven reangiography within 12 months after index PCI. The primary end-point in the angiographic substudy was late loss in patients' DES at 6-month angiographic follow-up. RESULTS: The rate of clinically driven restenosis, within 12 months, in patients receiving DES was less (3.9%) compared with those who received BMS (7.0%). In multivariate analysis the risk of clinical restenosis was one-third for DES compared with BMS (HR 0.36, 95% CI 0.25-0.52). In the angiographic substudy late loss was 0.07+/-0.53 mm (range -0.88 to 1.62). The amount of late loss was related to the presence of diabetes mellitus or not (0.19+/-0.45 mm vs. -0.12+/-0.58 mm), and lack of postdilatation of the stent or not (0.23+/-0.51 mm vs. -0.09+/-0.50 mm). CONCLUSIONS: The use of DES in the Swedish 'real world' is effective in reducing the clinically driven restenosis rate, when compared with patients with BMS treatment. In the angiographic follow-up the average late loss was as low as observed in recent randomized multi-centre trials.

Aged↗
PubMed2006

Effects on mortality of abciximab in ST-elevation myocardial infarction treated with percutaneous coronary intervention including stent implantation.

OBJECTIVES: To investigate the effects of abciximab on mortality in ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) including stent implantation. DESIGN: Meta-analysis of three selected randomized studies and analysis of data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). SUBJECTS: Pooled data from randomized studies containing in total 1,736 patients undergoing PCI with stent implantation because of STEMI with duration between symptom and treatment <12 h, and 7,436 patients from SCAAR treated with PCI because of STEMI (52% treated with abciximab) in Sweden 2000-2004. RESULTS: Analyses of pooled data showed that abciximab was associated with a decreased risk of reinfarction [odds ratio (OR) 0.38] and urgent target vessel revascularization (OR 0.38) at 30 days. No effect was seen on mortality at 30 days or 6 months. Multivariate analysis of data from SCAAR showed that abciximab reduced the risk of death during 14 months of follow-up (hazard ratio 0.82). CONCLUSIONS: The results are encouraging and support the ACC/AHA and ESC recommendation to use abciximab in treatment of STEMI with PCI including stent implantation. Considering that the pooled results from previous trials showed no effect of abciximab on mortality and the registry part of the present study was observational, the results encourage carrying out new randomized studies of abciximab in STEMI treated with PCI, including stent implantation, with sufficient size and length of follow-up.

Abciximab↗
PubMed2005

Severity of coronary artery stenosis is associated with a polymorphism in the CXCL16/SR-PSOX gene.

OBJECTIVE: Enhanced expression of CXCL16 has been demonstrated in atherosclerotic plaques and several properties have been attributed to CXCL16 that could influence the atherosclerotic process. CXCL16 exists in transmembrane and soluble forms. The transmembrane form acts as a scavenger receptor for oxidised LDL whereas the soluble form acts a chemoattractant for mainly CD8+ T cells. In addition, the soluble form of CXCL16 influences human aortic smooth muscle cell proliferation in vitro. In the present work, a human molecular genetic approach employing a common polymorphism within exon 4 of CXCL16 (181 Ala>Val) was used to investigate whether CXCL16 may be involved in the development of coronary artery disease. The polymorphism is located within the spacer region between the chemokine and transmembrane region and potentially influences an Ala/Val cleavage site, a site commonly used for the release of chemokines by tumour necrosis factor-alpha converting enzyme. DESIGN AND SUBJECTS: We first genotyped 387 unselected survivors of a first myocardial infarction aged <60 years and 387 sex- and age-matched controls. A subset of patients (n = 236) was evaluated by quantitative coronary angiography. Secondly, a cohort of 468 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) with stent implantation was genotyped. RESULTS: No significant difference in allele frequency between patient and controls of the 181 A>V polymorphism was detected. However, the V-allele was associated with increased severity of coronary stenoses. Secondly, the V-allele was associated with smaller minimal luminal diameter in the coronary segment subjected to intervention in a second cohort of patients undergoing PTCA with stent implantation. CONCLUSIONS: The present work provides evidence that CXCL16 is involved in processes leading to enhanced stenosis in atherosclerotic coronary arteries.

Amino Acid Sequence↗
PubMed2005

Serum matrix metalloproteinase-3 concentration is influenced by MMP-3 -1612 5A/6A promoter genotype and associated with myocardial infarction.

OBJECTIVES: Matrix metalloproteinase-3 (MMP-3) is implicated in the formation of atherosclerotic plaques, and the MMP-3 -1612 5A/6A polymorphism is associated with myocardial infarction (MI) and stable coronary artery disease (CAD). The present study examined whether the -1612 5A/6A polymorphism in the promoter region of the MMP-3 gene influences serum concentrations of MMP-3 and whether serum concentrations of MMP-3 are related to extent of coronary atherosclerosis and risk of MI. DESIGN AND SUBJECTS: This case-control study was conducted in three hospitals in the northern part of Stockholm. A total of 755 MI patients aged below 60 were screened, 433 entered and 387 completed the study. Three hundred and eighty-seven sex- and age-matched control subjects were recruited from the general population of the same county. METHODS: The MMP-3 genotype was determined by Pyrosequencing(TM) and the serum MMP-3 concentration was quantified with an immunoassay. Severity and extension of CAD was assessed by quantitative coronary angiography in a subgroup of patients (n=243). RESULTS: Patients had lower serum MMP-3 concentration than controls. There was a strong association between MMP-3 -1612 5A/6A genotype and serum concentrations of MMP-3. The presence of one or two copies of the 6A-allele was associated with a graded increase in serum MMP-3. In female patients there was an inverse correlation (r=-0.39, P<0.05) between serum MMP-3 concentration and plaque area. Conclusion. In conclusion, the serum concentration of MMP-3 is influenced by MMP-3 -1612 5A/6A genotype and associated with MI.

Case-Control Studies↗
PubMed2005

Skin dose alarm levels in cardiac angiography procedures: is a single DAP value sufficient?

Maximum estimated skin doses to patients undergoing coronary angiography procedures were obtained using radiographic slow film and diode dosemeters. Conversion factors of maximum entrance skin dose versus dose-area product (MESD/DAP) for diagnostic (coronary angiography (CA); 20 patients; 2 operators) and interventional procedures (percutaneous transluminal coronary angiography (PTCA); 10 patients; 1 operator) were 4.3 (mean value of 10 CA; operator A), 3.5 (mean value of 10 CA; operator B) and 9.7 (mean value of 10 PTCA; operator B) mGy(Gycm2)(-1), respectively. The results emphasise a need for both operator- and procedure-specific conversion factors. Compared with a single, global factor for all cardiac procedures and/or operators that is commonly applied today, such a refinement is expected to improve the accuracy in skin dose estimations from these procedures. Consequently, reference DAP values used in the clinic to define patients who could suffer from a radiation induced skin injury following a cardiac procedure, should be defined for each operator/procedure. The film technique was found to be superior to the diode in defining conversion factors in this study, and allowed for a rapid and accurate estimation of MESD for each patient. With appropriate positioning of the diode, a combined film/diode technique has a potential use in the training of new angiography operators. The patient body mass index (BMI) value was a good indicator of the variation in average lung dose (critical organ) between patients. The highest lung dose/DAP value was obtained for normal sized patients (BMI: 19-26), and was close to 1.5 mGy(Gycm2)(-1) with both CA and PTCA procedures.

Angioplasty, Balloon, Coronary↗
PubMed2004

C-reactive protein and myocardial infarction during percutaneous coronary intervention.

OBJECTIVE: To evaluate the prognostic information of preprocedural C-reactive protein (CRP) levels in serum to predict myocardial infarction during percutaneous coronary interventions (PCI). DESIGN: Prospective study. SETTING: University hospital. PATIENTS: A total of 400 consecutive patients with normal serum troponin T levels (</=0.03 microg L-1) presenting with stable or unstable angina pectoris. INTERVENTIONS: PCI. MAIN OUTCOME MEASURES: C-reactive protein levels in serum measured by a high sensitive method. Myocardial infarction defined as a serum troponin T elevation the day after PCI to a level >0.05 microg L-1. RESULTS: Eighty-three patients (21%) experienced a myocardial infarction during PCI. The median value of CRP before the procedure was 1.83 (0.12-99.7) mg L-1. No difference was seen in CRP levels before PCI between patients without or with myocardial infarction during PCI. Multivariate analysis identified stent implantation (OR 2.68, 95% CI 1.18-7.28, P = 0.03), procedure time (OR 2.15, 95% CI 1.28-3.67, P < 0.005) and complications during the procedure (OR 3.62, 95% CI 1.72-7.58, P < 0.001) as independent predictors of myocardial infarction during PCI. CONCLUSION: Increased CRP levels in serum before PCI were not associated with myocardial infarction during the procedure. Furthermore, patients with an expected long procedure and a high probability of stent implantation have an increased risk of developing myocardial infarction during PCI. This finding may be useful to help the operator to decide the antithrombotic regime before, during and after the procedure and the need for observation after the procedure.

Angioplasty, Balloon, Coronary↗
PubMed2003

In vitro and in vivo lipolysis of plasma triglycerides increases the resistance to oxidative modification of low-density lipoproteins.

BACKGROUND: The majority of studies on low-density lipoprotein (LDL) particle size and susceptibility to oxidative modification have been either descriptive or interventional, but there are few mechanistic studies. MATERIALS AND METHODS: Effects of exhaustive in vitro and in vivo lipolysis of serum and plasma triglycerides, respectively, by lipoprotein lipase (LPL) were investigated in healthy normotriglyceridemic men. The LDL end-product of lipolysis of very low-density lipoprotein (VLDL) underwent compositional analysis, gradient gel electrophoresis and an assessment of resistance to copper-induced oxidative modification. RESULTS: The LDL particle contents of free fatty acid and alpha-tocopherol increased, whereas the contents of free and esterified cholesterol, alpha-carotene and coenzyme Q10 decreased upon incubation of serum with LPL in vitro. The LDL particle size decreased and the resistance to the oxidative modification of LDL increased. Lipolysis of plasma triglycerides in vivo, achieved by intravenous injection of heparin, did not alter the LDL particle size but increased the resistance to the oxidative modification of LDL. This change was accompanied by an increase in the LDL particle content of alpha-tocopherol, whereas the free fatty acid content was unaltered. CONCLUSIONS: The results show that the increased resistance to oxidative modification of LDL after lipolysis of plasma triglycerides was concomitant with an increased LDL particle content of alpha-tocopherol, and that free fatty acids did not seem to contribute to the increased resistance to oxidative modification of LDL in vivo. Furthermore, our data indicate that the resistance of LDL to oxidative modification is not dependent on particle size.

Aged↗
PubMed2003

Prognostic value of plasma C-reactive protein and fibrinogen determinations in patients with acute myocardial infarction treated with thrombolysis.

OBJECTIVES: To investigate the prognostic value of plasma C-reactive protein (CRP) and fibrinogen determinations in patients with acute myocardial infarction treated with thrombolysis. DESIGN: Longitudinal study of morbidity and mortality. SETTING: Coronary care unit at Danderyd Hospital, Stockholm, Sweden. SUBJECTS: A total of 222 patients aged 75 years or below, treated with thrombolysis because of typical symptoms of myocardial infarction and electrocardiogram showing ST-segment elevation or bundle branch block were included in the study. The patients were followed for 24-60 months (mean 40 +/- 16 months). MAIN OUTCOME MEASURES: Cardiovascular death or new myocardial infarction. RESULTS: Concentrations of CRP were significantly higher at 48 h than at 3 months, whilst the levels of fibrinogen were similar. CRP and fibrinogen concentrations measured during the acute phase of myocardial infarction were associated with cardiovascular death or a new myocardial infarction during follow-up in univariate analysis. CRP levels measured 3 months after the acute event were not associated with subsequent events whereas fibrinogen concentrations showed a borderline prognostic significance (P = 0.05). When CRP and fibrinogen were entered into multivariate analysis together with the previously established prognostic factors in the patient group (age, diabetes mellitus and left ventricular function), these markers of inflammation did not add further prognostic information. CONCLUSION: C-reactive protein and fibrinogen do not carry the same independent prognostic information after acute myocardial infarction treated with thrombolysis as in studies previously reported for patients with unstable angina or non-Q-wave myocardial infarction.

Aged↗
PubMed2003

The plasminogen activator inhibitor-1 -675 4G/5G genotype influences the risk of myocardial infarction associated with elevated plasma proinsulin and insulin concentrations in men from Europe: the HIFMECH study.

UNLABELLED: Although the potential role of plasminogen activator inhibitor-1 (PAI-1) in the development of coronary artery disease is strongly supported by its biological characteristics, results of clinical studies remain controversial. OBJECTIVES: To investigate whether plasma PAI-1 concentrations and the -675 4G/5G polymorphism located in the PAI-1 gene could constitute risk markers for myocardial infarction (MI). PATIENTS AND METHODS: We used a European case-control study, the HIFMECH study, comparing 598 men with MI and 653 age-matched controls. RESULTS: Insulin resistance explained a major part of the variation in PAI-1 (24%) whereas inflammation had only a minor contribution (0.01%). For both cases and controls plasma PAI-1 concentrations were significantly higher in the North than the South, and in both regions were higher in individuals with MI compared with control subjects [overall odds ratio (OR) for a 1 SD increase=1.54, 95% confidence interval (CI) 1.34, 1.77]. This difference was observed in all the centers studied. Overall, the difference between cases and control subjects remained significant after controlling for inflammation variables (OR=1.30, 95% CI 1.08, 1.57), but lost significance after controlling for insulin resistance variables (OR=1.17, 95% CI 0.98, 1.40). The 4G allele was associated with significantly higher PAI-1 levels in cases but not controls and, taken independently, did not modify the risk of MI (P=0.9). However, a significant interaction was observed with both insulin or proinsulin and the risk of MI (P=0.05 and 0.02, respectively), but not with triglycerides or body mass index (BMI). The insulin or proinsulin effect on risk was observed only in the carriers of the 4G/4G genotype. This interaction appeared not to be mediated by plasma PAI-1 antigen concentrations (P=0.01 and 0.02 after adjustment for PAI-1 plasma levels). The interaction with proinsulin but not insulin remained statistically significant after further adjustment for other factors associated with insulin resistance (triglycerides and BMI) and C-reactive protein (P=0.01). CONCLUSION: This study suggests that PAI-1 has a role in risk of MI in the presence of underlying insulin resistance. A significant interaction between insulin or proinsulin and the -675 4G/5G polymorphism was observed in risk for MI. The mechanisms for these interactions remain to be determined.

Case-Control Studies↗
PubMed2001

[A controlled trial with prolonged follow up: percutaneous intervention in acute myocardial infarction is equivalent to thrombolytic therapy].

Previous studies comparing percutaneous coronary intervention (PCI) with thrombolysis for treatment of myocardial infarction with ST-elevation have in meta-analyses but not in randomized trials shown that PCI is more effective. Despite a large volume of primary PCI performed in Sweden no controlled trials have been carried out. The present study included 96 patients with myocardial infarction with ST-segment elevation treated with primary PCI 1995-1998. The main indications were shock (15 cases), contraindication to thrombolysis (24 cases), as an alternative to thrombolysis (57 cases), with a mortality in the respective groups of 67, 25 and 10 percent. Controls matched for age and infarct location and treated with thrombolysis could be identified for 55 of the patients treated with PCI. After four years 40 percent and 52 percent of the patients treated with PCI and thrombolysis respectively reached the combined endpoint of death/myocardial infarction/revascularization/angina pectoris (not significant). In conclusion, the study shows that primary PCI in patients with myocardial infarction with ST-segment elevation can be performed safely also in Sweden.

Aged↗
PubMed2001

A triglyceride-rich fat emulsion and free fatty acids but not very low density lipoproteins impair endothelium-dependent vasorelaxation.

OBJECTIVE: To investigate the effects of triglycerides and free fatty acids on endothelium-dependent and endothelium-independent vasorelaxation. METHODS: Femoral arterial rings from rats were studied in organ baths. The vascular segments were constricted with phenylephrine after 20 min of preincubation with the triglyceride-rich fat emulsion Intralipid, free fatty acids (16:0, 18:1, 18:3) bound to bovine serum albumin, or very low density lipoproteins. Endothelium-dependent and endothelium-independent relaxations were determined after administration of acetylcholine and nitric oxide donors, respectively. RESULTS: Preincubation with Intralipid caused a concentration-dependent impairment of endothelium-dependent but not endothelium-independent relaxation. Very low density lipoproteins did not affect vascular function. All free fatty acids impaired endothelium-dependent relaxation, whereas endothelium-independent relaxation was unaffected. Administration of the antioxidant vitamin C partly reversed the impairment of the endothelium-dependent relaxation induced by Intralipid and free fatty acids. CONCLUSIONS: The present study demonstrates that the triglyceride-rich fat emulsion Intralipid and individual FFAs impair endothelium-dependent relaxation of arterial rings from rat, whereas triglycerides in the form of VLDL do not affect endothelial function. The finding that the antioxidant vitamin C partly reverses this impairment indicates the involvement of oxidative mechanisms.

Acetylcholine↗
PubMed2001

Mild-to-moderate hypertriglyceridemia in young men is associated with endothelial dysfunction and increased plasma concentrations of asymmetric dimethylarginine.

OBJECTIVES: The aim of this study was to investigate endothelial function and common carotid intima-media thickness (IMT) in healthy young men with mild-to-moderate hypertriglyceridemia. Plasma asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, was measured to further elucidate the mechanisms involved. BACKGROUND: Hypertriglyceridemia is a risk factor for coronary heart disease although the mechanisms behind the increased risk remain to be defined. Acute elevation of plasma triglycerides induced by an intravenous fat load is associated with impaired endothelial function. The results of studies examining acute effects induced by a high-fat meal or effects of chronic hypertriglyceridemia on endothelial function are more inconsistent. METHODS: Flow-mediated vasodilation and nitroglycerin-induced vasodilation of the brachial artery and common carotid IMT were measured noninvasively by ultrasound technique in 15 hypertriglyceridemic (HTG) subjects and 15 matched controls, mean age 34 years. Plasma concentrations of ADMA were measured by high-performance liquid chromatography. RESULTS: Flow-mediated vasodilation was decreased in the HTG group (p < 0.0001), whereas nitroglycerin-induced vasodilation and carotid IMT did not differ significantly. Asymmetric dimethylarginine concentrations were higher in the HTG group (p < 0.05). CONCLUSIONS: Hypertriglyceridemia in young men is associated with endothelial dysfunction and increased plasma concentration of ADMA but not with increased IMT of the common carotid artery. The corollary is that chronic hypertriglyceridemia results in endothelial dysfunction, possibly due to increased ADMA concentration, and that endothelial dysfunction might precede increased IMT among the early manifestations of atherosclerosis.

Adult↗
PubMed2000

Accumulation of apolipoprotein C-I-rich and cholesterol-rich VLDL remnants during exaggerated postprandial triglyceridemia in normolipidemic patients with coronary artery disease.

BACKGROUND: Exaggerated postprandial triglyceridemia is common in normolipidemic patients with coronary artery disease (CAD). Alterations in the composition of triglyceride-rich lipoproteins (TRLs) are likely to underlie this metabolic disturbance. However, the composition of very-low-density lipoproteins (VLDLs), which are the most abundant postprandial TRLs, has never been defined in CAD patients. METHODS AND RESULTS: We examined postprandial changes in the number and composition of VLDLs in middle-aged, normolipidemic CAD patients and control subjects. TRLs from 14 patients and 14 control subjects aged 45 to 55 years were subfractionated by density gradient ultracentrifugation into Svedberg flotation rate (Sf) fractions >400, 60 to 400, and 20 to 60. The VLDLs were separated from chylomicron remnants by immunoaffinity chromatography. In CAD patients, the postprandial concentrations of triglycerides and large (Sf 60 to 400) VLDL particles were elevated. In addition, their postprandial large VLDLs were enriched in apolipoprotein (apo) C-I and their postprandial small (Sf 20 to 60) VLDL remnants were enriched with apo C-I and cholesterol. CONCLUSIONS: Perturbed handling of postprandial triglycerides in normolipidemic CAD patients involves the accumulation of apo C-I-rich large VLDL particles and the generation of small, apo C-I- and cholesterol-rich VLDL remnants.

Apolipoprotein B-100↗
PubMed2000

Diabetes mellitus is a strong negative prognostic factor in patients with myocardial infarction treated with thrombolytic therapy.

OBJECTIVES: To assess the long-term prognostic values of baseline demographic data, occurrence of vectorcardiographic signs of reperfusion, left ventricular function and coronary angiographic features. DESIGN: Longitudinal study of morbidity and mortality. SETTING: Coronary care unit at Danderyd Hospital, Stockholm, Sweden. SUBJECTS: A total of 222 patients (mean age 61 years) with a suspected acute myocardial infarction treated with thrombolysis were investigated and followed for 2-5 years (mean 1216 days). MAIN OUTCOME MEASURES: Death or a new myocardial infarction. RESULTS: Age above 55 years (P < 0.05), a previous diagnosis of diabetes mellitus (P < 0.005), hypertension (P < 0.05), heart failure (P < 0.001) and myocardial infarction (P < 0.05), a previous use of beta-blockers (P < 0.05) and an ejection fraction below 60% (P < 0.01) were predictors for death or a new myocardial infarction in univariate analysis. Sex, a previous history of smoking or angina pectoris, vectorcardiographic signs of reperfusion or degree of coronary artery disease had no prognostic values. In multivariate analysis including age above 55 years, a previous diagnosis of diabetes mellitus, hypertension and myocardial infarction, and an ejection fraction below 60%, only age (P < 0.05), diabetes mellitus (P < 0. 01) and ejection fraction (P < 0.05) were predictors for death or a new myocardial infarction. CONCLUSIONS: The results of the present study emphasize the importance of diabetes mellitus as a long-term prognostic risk factor in patients with myocardial infarction treated with thrombolysis. Further studies are needed to determine the mechanisms behind this increased risk.

Aged↗