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Biomedical subjects

B Lindahl

Publications and source records attributed to B Lindahl.

At least 19 recordsLinked to original sources

Work stress and low emotional support is associated with increased risk of future type 2 diabetes in women.

A case-referent study nested within a population-based health survey investigated the associations between psychosocial stress, such as work stress and low emotional support, and future development of type 2 diabetes among occupationally working middle-aged men and women. All participants in a health survey conducted during 1989-2000 (n=33,336) in Umeå in northern Sweden, were included. We identified 191 cases, who were not diabetic initially but were diagnosed with type 2 diabetes after 5.4+/-2.6 years. Two age- and sex-matched referents were selected for each case. Multivariate logistic regression analyses and interaction effects between variables were evaluated. In women, passive or tense working situations were associated with future type 2 diabetes with odds ratios 3.6 (95% confidence interval 1.1-11.7) and 3.6 (1.0-13.3), respectively, and also low emotional support 3.0 (1.3-7.0). These associations were not seen in men. In women, they remained after adjustment for BMI, civil status and educational level, and there were also tendencies for interactions between work stress and low emotional support. In conclusion, work stress and low emotional support may increase the risk of type 2 diabetes in women, but not in men. These findings contribute to our understanding of psychosocial stress as potential risk factors for type 2 diabetes in a Swedish population.

Adult↗

A combination of HbA1c, fasting glucose and BMI is effective in screening for individuals at risk of future type 2 diabetes: OGTT is not needed.

OBJECTIVE: To identify a screening model that predicts high risk of future type 2 diabetes and is useful in clinical practice. DESIGN AND METHODS: Incident case-referent study nested within a population-based health survey. We compared screening models with three risk criteria and calculated sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and attributable proportion. We used fasting plasma glucose (FPG) alone or with an oral glucose tolerance test (OGTT), glycosylated haemoglobin A (HbA1c) (normal range 3.6-5.3%), body mass index (BMI), triglycerides and family history of diabetes (FHD). SETTING: Participants in a health survey at all primary care centres (n=33,336) and subjects with diagnosed type 2 diabetes in primary and hospital care (n=6088) in Umeå during 1989-2001. SUBJECTS: Each of the 164 subjects who developed clinically diagnosed type 2 diabetes (median time to diagnosis of 5.4 years) and 304 sex- and age-matched referents without diabetes diagnosis. RESULTS: Screening models with at least one criterion present had sensitivities of 0.90-0.96, specificities of 0.43-0.57 and PPVs of 8-9%. Combinations of the criteria, FPG>or=6.1 mmol L-1 (capillary plasma), HbA1c>or=4.7% and BMI>or=27 in men and BMI>or=30 in women, had sensitivities, specificities and PPVs of 0.66%, 0.93% and 32%, and 0.52%, 0.97% and 46% respectively. Using FHD as one of three risk criteria showed comparable results. Addition of triglycerides or OGTT did not improve the prediction. CONCLUSIONS: The combination of HbA1c, FPG and BMI are effective in screening for individuals at risk of future clinical diagnosis of type 2 diabetes. OGTT or FHD is not necessary.

Adult↗

Cognitive-behavioural stress management does not improve biological cardiovascular risk indicators in women with ischaemic heart disease: a randomized-controlled trial.

OBJECTIVES: Psychosocial factors, such as stress and vital exhaustion, are associated with an increased risk of cardiovascular events, and women report more psychosocial ill-being after an acute myocardial infarction than men. We have earlier shown that a cognitive-behavioural intervention in women with ischaemic heart disease (IHD) improved psychosocial well-being. In the present study, we tested the hypothesis that the improvement in psychosocial well-being is associated with an improvement in biochemical indicators of cardiovascular risk. DESIGN: Randomized-controlled trial in northern Sweden. SETTING: Outpatient care. SUBJECTS: Women with IHD were randomized to either a 1-year cognitive-behavioural stress management programme or usual care. Of the 159 women who completed the study, 77 were in the intervention group, and 82 in the control group. INTERVENTIONS: A 1-year cognitive-behavioural stress management programme versus conventional care. RESULTS: Group assignment was not found to be a determinant of waist circumference, high sensitive C-reactive protein (hs-CRP), fibrinogen, von Willebrand factor (vWF), plasminogen activator inhibitor type 1 (PAI-1) activity, tissue plasminogen activator (tPA) activity, tPA antigen, tPA-PAI-1 complex, leptin, or HOMA2 insulin resistance index (HOMA2-IR) at follow up. Changes in psychosocial variables were not associated with changes in any of the biological risk indicators. CONCLUSIONS: Even if our cognitive-behavioural stress management programme had effects on proximal targets, such as stress behaviour and vital exhaustion, we found no improvement in intermediate biochemical targets related to the metabolic syndrome and IHD. Our results challenge the proposition that the relationship between psychological well-being and biological cardiovascular risk indicators is a direct cause-effect phenomenon.

Biomarkers↗

Admission N-terminal pro-brain natriuretic peptide and its interaction with admission troponin T and ST segment resolution for early risk stratification in ST elevation myocardial infarction.

OBJECTIVE: To assess the long term prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) on admission and its prognostic interaction with both admission troponin T (TnT) concentrations and resolution of ST segment elevation in fibrinolytic treated ST elevation myocardial infarction (STEMI). DESIGN AND SETTING: Substudy of the ASSENT (assessment of the safety and efficacy of a new thrombolytic) -2 and ASSENT-PLUS trials. PATIENTS: NT-proBNP and TnT concentrations were determined on admission in 782 patients. According to NT-proBNP concentrations, patients were divided into three groups: normal concentration (for patients < or = 65 years, < or = 184 ng/l and < or = 268 ng/l and for those > 65 years, < or = 269 ng/l and < or = 391 ng/l in men and women, respectively); higher than normal but less than the median concentration (742 ng/l); and above the median concentration. For TnT, a cut off of 0.1 microg/l was used. Of the 782 patients, 456 had ST segment resolution (< 50% or > or = 50%) at 60 minutes calculated from ST monitoring. MAIN OUTCOME MEASURES: All cause one year mortality. RESULTS: One year mortality increased stepwise according to increasing concentrations of NT-proBNP (3.4%, 6.5%, and 23.5%, respectively, p < 0.001). In receiver operating characteristic analysis, NT-proBNP strongly trended to be associated more with mortality than TnT and time to 50% ST resolution (area under the curve 0.81, 95% confidence interval (CI) 0.72 to 0.9, 0.67, 95% CI 0.56 to 0.79, and 0.66, 95% CI 0.56 to 0.77, respectively). In a multivariable analysis adjusted for baseline risk factors and TnT, both raised NT-proBNP and ST resolution < 50% were independently associated with higher one year mortality, whereas raised TnT contributed independently only before information on ST resolution was added to the model. CONCLUSION: Admission NT-proBNP is a strong independent predictor of mortality and gives, together with 50% ST resolution at 60 minutes, important prognostic information even after adjustment for TnT and baseline characteristics in STEMI.

Aged↗

FRISC score for selection of patients for an early invasive treatment strategy in unstable coronary artery disease.

OBJECTIVE: To develop a scoring system for risk stratification and evaluation of the effect of an early invasive strategy for treatment of unstable coronary artery disease (CAD). DESIGN: Retrospective analysis of a randomised study (FRISC II; fast revascularisation in instability in coronary disease). SETTING: 58 Scandinavian hospitals. PATIENTS: 2457 patients with unstable CAD from the FRISC II study. MAIN OUTCOME MEASURES: One year rates of mortality and death/myocardial infarction (MI). METHODS: Patients were randomly assigned to an early invasive or a non-invasive strategy. From the non-invasive cohort independent variables of death or death/MI were identified. RESULTS: Seven factors, age > 70 years, male sex, diabetes, previous MI, ST depression, and increased concentrations of troponins and markers of inflammation (interleukin 6 or C reactive protein), were associated with an independent increased risk for death or death/MI. In patients with > or = 5 of these factors the invasive strategy reduced mortality from 15.4% (20 of 130) to 5.2% (7 of 134) (risk ratio (RR) 0.34, 95% confidence interval (CI) 0.15 to 0.78, p = 0.006). Death/MI was also reduced in patients with 3-4 factors from 15.7% (80 of 511) to 10.8% (58 of 538) (RR 0.69, 95% CI 0.50 to 0.94, p = 0.02). Neither death nor death/MI was reduced in patients with 0-2 risk factors. CONCLUSION: In unstable CAD, this scoring system based on factors independently associated with an adverse outcome can be used shortly after admission to the hospital for risk stratification and for selection of patients to an early invasive treatment strategy.

Aged↗

Association between insulin resistance and GAD65-autoantibody levels--a pilot study in an adult non-diabetic population.

The aim of this pilot study was to investigate any association between insulin resistance (IR) and serum levels of autoantibodies against the glutamic acid decarboxylase (GAD65Ab) among adult non-diabetic subjects. Based on calculations of IR using the IR homeostasis model in a Swedish adult non-diabetic population (n = 756) participating in the WHO MONICA-study, an insulin sensitive group (n = 54, M/F:27/27) and an insulin resistant group (n = 46 M/F:24/22) were identified. Serum from the subjects were analysed for the presence of GAD65Ab. There was no significant difference in GAD65Ab levels between the groups. However, there was a correlation between IR and serum GAD65Ab within the insulin sensitive group (Spearman rho 0.4, p < 0.01). Our observation could indicate that IR could serve as an initiator or a progression factor in the autoimmune process in subjects predisposed to autoimmunity. This finding will be further investigated in a larger study including subjects with a continuum of IR.

Adult↗

Efficacy and safety of tenecteplase in combination with the low-molecular-weight heparin enoxaparin or unfractionated heparin in the prehospital setting: the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 PLUS randomized trial in acute myocardial infarction.

BACKGROUND: The combination of a single-bolus fibrinolytic and a low-molecular-weight heparin may facilitate prehospital reperfusion and further improve clinical outcome in patients with ST-elevation myocardial infarction. METHODS AND RESULTS: In the prehospital setting, 1639 patients with ST-elevation myocardial infarction were randomly assigned to treatment with tenecteplase and either (1) intravenous bolus of 30 mg enoxaparin (ENOX) followed by 1 mg/kg subcutaneously BID for a maximum of 7 days or (2) weight-adjusted unfractionated heparin (UFH) for 48 hours. The median treatment delay was 115 minutes after symptom onset (53% within 2 hours). ENOX tended to reduce the composite of 30-day mortality or in-hospital reinfarction, or in-hospital refractory ischemia to 14.2% versus 17.4% for UFH (P=0.080), although there was no difference for this composite end point plus in-hospital intracranial hemorrhage or major bleeding (18.3% versus 20.3%, P=0.30). Correspondingly, there were reductions in in-hospital reinfarction (3.5% versus 5.8%, P=0.028) and refractory ischemia (4.4% versus 6.5%, P=0.067) but increases in total stroke (2.9% versus 1.3%, P=0.026) and intracranial hemorrhage (2.20% versus 0.97%, P=0.047). The increase in intracranial hemorrhage was seen in patients >75 years of age. CONCLUSIONS: Prehospital fibrinolysis allows 53% of patients to receive reperfusion treatment within 2 hours after symptom onset. The combination of tenecteplase with ENOX reduces early ischemic events, but lower doses of ENOX need to be tested in elderly patients. At present, therefore, tenecteplase and UFH are recommended as the routine pharmacological reperfusion treatment in the prehospital setting.

Aged↗

No increase in the prevalence of known diabetes between 1986 and 1999 in subjects 25-64 years of age in northern Sweden.

AIMS: A global increase in diabetes is predicted due to higher body weight and less physical activity. Over the period 1986-1999, the body mass index (BMI) of the adult population of northern Sweden increased from 25.3 to 26.2 and the prevalence of obesity (BMI > or = 30) from 11% to 15%, although this was more distal than central adiposity. Our hypothesis was that this would lead to a higher prevalence of diabetes. METHODS: Four population surveys with new and independent cohorts of 2000 invited subjects, 25-64 years old, in 1986, 1990, 1994 and 1999. In the first three surveys an oral glucose tolerance test was carried out in 47%. RESULTS: Over the time period 1986-1999 there was no increase in the prevalence of known diabetes. No trends were noted in the finding of previously undiagnosed diabetes or impaired glucose tolerance over the period 1986-1994, although the confidence intervals are wide. Fasting, but not post-load, glucose levels increased with 0.040 mmol/year (95% CI 0.026; 0.055) in men and 0.033 mmol/year (0.023; 0.044) in women. CONCLUSION: In spite of a marked increase in BMI, we found no increased prevalence of known diabetes over a 13-year observation period, although our data cannot exclude minor increases in undiagnosed diabetes. The development of more distal than abdominal obesity, a diet with less saturated fat and lower glycaemic index and fewer regular smokers in the population may contribute to this. The effects of obesity may thus be attenuated by other secular trends in society and highlight potential ways of curbing the worldwide increase in diabetes.

Adult↗

ST depression in ECG at entry indicates severe coronary lesions and large benefits of an early invasive treatment strategy in unstable coronary artery disease; the FRISC II ECG substudy. The Fast Revascularisation during InStability in Coronary artery disease.

BACKGROUND: In unstable coronary artery disease, ST-segment depression indicates a poor prognosis. We evaluated whether the effect of early revascularization and the extent of coronary lesions were related to ST-segment and T wave changes on admission. METHODS AND RESULTS: 2457 patients with unstable coronary artery disease were randomized to an early invasive strategy with coronary angiography/revascularization within 7 days or to a non-invasive strategy with coronary procedures only when symptoms or severe ischaemia recurred. ST depression was present in 1114 (45.5%) patients. In the invasive group, 45% of the patients with ST depression had three-vessel disease or left main stenosis compared with 22% if no ST-segment depression was present, PP=0.004 while mortality was changed from 5.8 to 3.3%, P=0.050. In patients without ST-segment depression the corresponding rates concerning death/myocardial infarction were 10.4 and 8.9, and for mortality 2.0 and 1.2% (non-significant). CONCLUSIONS: In unstable coronary artery disease, ST-segment depression is associated with a 100% increase in the occurrence of three-vessel/left main disease and to an increased risk of subsequent cardiac events. In these patients an early invasive strategy substantially decreases death/myocardial infarction.

Aged↗

Continuous multilead ST-monitoring identifies patients with unstable coronary artery disease who benefit from extended antithrombotic treatment.

AIMS: Prolongation of anticoagulant treatment might reduce subsequent cardiac events in patients with unstable coronary artery disease. Multilead ST-segment monitoring identifies patients with a high risk of adverse outcome. The aim was to assess the value of multilead ST-monitoring in prospectively identifying patients who respond to extended anticoagulant treatment with low-molecular weight heparin when treated by a primarily non-invasive strategy. METHODS AND RESULTS: In this substudy of the FRISC II trial, ST-monitoring with a continuous 12-lead ECG or vectorcardiography was performed for 24 h in 629 patients with unstable coronary artery disease randomized to receive either the low-molecular weight heparin dalteparin, or placebo for 3 months after at least 5 days' dalteparin treatment in all patients. Ischaemic episodes were detected in 34% during ST-monitoring. In the group with ischaemic episodes, the extended dalteparin treatment was associated with a lower rate of death, myocardial infarction, or revascularization (35.2% vs 53.4%, relative risk reduction: 34%, P=0.01). In patients without ischaemic episodes, long-term dalteparin treatment had no effect. CONCLUSIONS: In patients with unstable coronary artery disease treated primarily with a non-invasive strategy, ischaemic episodes revealed while on multilead ST-monitoring identifies patients who benefit most from extended treatment with anticoagulants.

Adult↗

Impact of perioperative myocardial injury on early and long-term outcome after coronary artery bypass grafting.

AIMS: To establish the influence of perioperative myocardial injury on short- and long-term survival after coronary artery bypass grafting (CABG). METHODS AND RESULTS: The correlation of postoperative serum aspartate aminotransferase and creatine kinase MB to early cardiac-related death and to late survival was evaluated in 4911 patients who underwent CABG consecutively during a 6-year period. There were 93 early deaths (1.9%), 73 of them cardiac-related (1.5% of 4911). After a mean follow-up of 5 years, 409 additional deaths (8.5% of 4818) had occurred. Elevated enzyme levels on day 1 postoperatively highly increased the risk of early cardiac death (serum aspartate aminotransferase >or=2.35 microkat.l(-1): odds ratio 9.2; serum creatine kinase MB >or=61 microg.l(-1): odds ratio 6.0), and increased the risk of late death by approximately 50% (serum aspartate aminotransferase >or=2.35 microkat.l(-1): relative hazard 1.5; serum creatine kinase MB >or=61 microg.l(-1): relative hazard 1.4). This increased risk of death was independent of other risk factors and remained constant over time. CONCLUSIONS: Enzyme elevation after CABG implied an increased risk of both early and late death. The long-term effect persisted many years after surgery.

Aged↗

Physical activity of subjects aged 50-64 years involved in the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE: To describe physical activity of participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: A cross-sectional analysis of baseline data of a European prospective cohort study. SUBJECTS: This analysis was restricted to participants in the age group 50-64 years, which was represented in all EPIC centres. It involved 236 386 participants from 25 centres in nine countries. In each EPIC centre, physical activity was assessed by standardised and validated questions. Frequency distribution of type of professional activity and participation in non-professional activities, and age-adjusted means, medians and percentiles of time dedicated to non-professional activities are presented for men and women from each centre. RESULTS: Professional activity was most frequently classified as sedentary or standing in all centres. There was a wide variation regarding participation in different types of non-professional activities and time dedicated to these activities across EPIC centres. Over 80% of all EPIC participants engaged in walking, while less than 50% of the subjects participated in sport. Total time dedicated to recreational activities was highest among the Dutch participants and lowest among men from Malmö (Sweden) and women from Naples (Italy). In all centres, total time dedicated to recreational activity in the summer was higher than in the winter. Women from southern Europe spent the most time on housekeeping. CONCLUSIONS: There is a considerable variation of physical activity across EPIC centres. This variation was especially evident for recreational activities in both men and women.

Cross-Sectional Studies↗

Markers of myocardial damage in acute coronary syndromes--therapeutic implications.

Patients admitted with suspicion of an acute coronary syndrome (ACS) still constitute a diagnostic, prognostic and therapeutic challenge for the treating physician. The final diagnosis ranges from a noncardiac diagnosis to a full-blown myocardial infarction (MI). Biochemical markers of myocardial damage are essential for diagnosis and, especially troponin T and troponin I, have been shown to be valuable for early risk stratification and for selection of treatment in ACS. Patients identified to be at low risk of future cardiac events might be discharged early, and unnecessary investigations and treatments avoided. On the contrary, a more intense treatment can be started in patients identified to be at high risk. Unstable angina patients with, compared to without, elevation of troponin, have a more activated coagulation system and more frequently complex lesions and visible thrombus in their coronary arteries. Accordingly, antithrombotic and antiplatelet therapies, i.e. l.m.w heparin and GP IIb/IIIa receptor antagonists, have been proved to have beneficial effects in troponin positive patients, but little or no beneficial effects in troponin negative patients. Also, the beneficial effects of an invasive compared to a noninvasive approach seem to be much more pronounced in troponin positive patients. In patients with ST-elevation MI, an elevated troponin T level at admission are associated with an increased mortality. However, the therapeutic implications of this finding remain speculative. Patients admitted with chest pain and left bundle branch block (LBBB) and who develop an MI have a poor prognosis. Current guidelines in acute myocardial infarction state that these patients should receive thrombolysis. Despite that, only a minority of these patients do receive thrombolysis, most probably because of the great diagnostic uncertainty. Rapid testing with a cardiac marker, e.g. myoglobin, would most probably increase the proportion of patients with chest pain and LBBB who receive appropriate reperfusion treatment.

Acute Disease↗

The low-molecular-weight heparin dalteparin as adjuvant therapy in acute myocardial infarction: the ASSENT PLUS study.

Rapid reperfusion of an infarct-related artery reduces the extent of myocardial damage and improves survival in acute myocardial infarction (AMI). Currently, anticoagulant treatment with unfractionated heparin (UFH) is used as adjuvant therapy to fibrinolytic treatment. The low-molecular-weight heparin (LMWH) dalteparin is at least as effective as UFH in unstable coronary artery disease. The ASSENT PLUS trial was carried out to evaluate whether dalteparin is as effective as UFH as an adjunct to recombinant tissue-plasminogen activator (rt-PA) and aspirin in obtaining patency and Thrombolysis in Myocardial Infarction (TIMI)-3 flow in patients with AMI. The primary assessment of this phase II trial was TIMI flow, determined by coronary angiography. Patients with ST-elevation MI were randomized to receive aspirin and either rt-PA and UFH for 48 h, or rt-PA and dalteparin for 4 to 7 days. Evaluation was by TIMI flow after 4 to 7 days and clinical events (death, reinfarction, or revascularization) up to 30 days. There was a clear trend toward greater TIMI 3 flow with dalteparin compared with UFH. There was significantly less TIMI 0-1 flow or thrombus in the dalteparin group. Bleeding rates were similar. The occurrence of reinfarction was reduced during dalteparin treatment. These findings suggest that dalteparin could be substituted for UFH as an adjunct to rt-PA/aspirin in the management of patients with AMI.

Anticoagulants↗

Mechanisms behind the prognostic value of troponin T in unstable coronary artery disease: a FRISC II substudy.

OBJECTIVES: This study was designed to elucidate possible mechanisms for the prognostic value of troponin T (tnT). BACKGROUND: The reasons for the adverse prognosis associated with elevation of troponins in unstable coronary artery disease are poorly understood. METHODS: Patients enrolled in the Fast Revascularization during InStability in CAD (FRISC-II) trial were included. Clinical characteristics, findings at echocardiography and coronary angiography, and prognosis were evaluated in relation to different tnT levels. RESULTS: Absence of significant coronary stenosis was more frequent and three-vessel disease or left main stem stenosis was less frequent in patients without, compared with, detectable tnT. The occurrence of visible thrombus increased with rising levels of tnT. In the group with the highest levels of tnT, occlusion of the left circumflex artery was more common than in the three other tnT groups, as was a left ventricular ejection fraction below 0.45. The one-year risk of death in the noninvasive arm of the study increased by increasing levels of tnT (1.6% to 4.6%), whereas the risk of myocardial infarction showed an inverted U-shaped curve and was lower in the lowest (5.5%) and highest (8.4%) tnT groups than in the two intermediate groups (17.5% and 16.2%). CONCLUSIONS: Any detectable elevation of tnT raises the probability of significant coronary stenosis and thrombus formation and is associated with an increased risk of reinfarction and death. However, at a more pronounced elevation of troponin, a higher proportion of patients has a persistent occlusion of the culprit vessel and reduced left ventricular function, associated with a high mortality but a modest risk of reinfarction.

Aged↗

Detection of myocardial damage - are the troponins the ultimate solution?

Biochemical markers of myocardial damage are together with the clinical history, the physical examination and the 12-lead ECG key elements in the clinical evaluation of patients presenting with symptoms suggestive of an acute coronary syndrome (ACS). In this situation the detection of myocardial damage, even very minor, is of importance, not only for diagnosis, but also for risk assessment and selection of treatment. The new markers of myocardial damage. troponin T and I, have been shown to offer some advantages over the conventional markers in ACS and there is also an increasing interest for troponins in other clinical situations, e.g. after surgery and percutaneous coronary intervention. This paper will discuss the role of troponins in these different clinical situations.

Biomarkers↗