Biomedical subjects
Publications and source records attributed to Lars Rydén.
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Patients with diabetes have an unfavourable prognosis after an acute myocardial infarction. The DIGAMI 2 study investigated the effect of various metabolic treatment strategies in type 2 diabetic patients with acute myocardial infarction: acutely introduced, long-term insulin treatment did not improve survival when compared with conventional management at similar levels of glucose control. However, good glucose control seems important since the glucose level was found to be a strong predictor of long-term mortality in this patient category.
BACKGROUND: Aiming at an active lifestyle, healthy food habits and non-smoking among Swedish children, the Swedish Heart Lung Foundation initiated the health educational programme 'An adventure with Pelle Pump'. A study kit, including theoretical and practical material on heart-lung function and healthy behaviour, was offered to all fourth graders in Sweden. The impact of the programme was examined by studying health behaviours and health knowledge among programme participants using non-participants as a control population. METHODS: A questionnaire on health behaviour and health knowledge was answered by a random sample of 1369 children from different social classes and living conditions. Children subjected to the programme formed the programme group (n=523) and those without exposure served as a control group (n=846). RESULTS: Children in the programme group had a significantly higher level of knowledge (P<0.001) on questions relating to health behaviour and bodily functions. The actual health behaviour was, however, not affected by the programme. CONCLUSION: Children exposed to a health education programme had, compared with a control population, 2 years after completing the programme, an increased level of knowledge; however, no difference was found in health behaviour.
This study evaluated the effects of a behaviorally oriented cardiac rehabilitation and secondary prevention program on lifestyle changes and on coronary recurrence rates. Patients recently treated with percutaneous coronary intervention (PCI) were randomized to an intervention with an aggressive focus on lifestyle changes (smoking, diet, exercise, and stress; n=46) or to a standard-care control group (n=42). Results showed that the intervention group had significantly larger overall lifestyle changes than the control group after 12, 24, 36, and 60 months. The intervention group had significantly lower rates of all coronary events (acute myocardial infarction, coronary artery bypass graft, PCI, cardiac death; 30.4% vs. 53.7%), and of cardiovascular mortality (2.2% vs. 14.6%). The need for future large-scale and long-term evaluations of lifestyle-oriented secondary prevention interventions of this kind is emphasized.
BACKGROUND: The risk of cardiovascular disease increases progressively with increasing blood glucose from levels well below the diabetic threshold. In the Reykjavík Study the relationship between heart failure and abnormal glucose regulation was already apparent at the level of impaired glucose tolerance. The aim of this study was to determine the prognosis of participants with any glucose abnormality and heart failure and to test whether the combination of these conditions may adversely affect the subsequent prognosis. DESIGN: A prospective population-based study. METHODS: Data from the first visit of 19 381 participants were used. Participants were divided into groups according to their glycaemic and heart failure level, and comparisons were made between the groups and disease-free participants serving as a reference group. The risk of mortality and morbidity was calculated with adjustments for main cardiovascular risk factors and ischaemic heart disease. RESULTS: Participants in the reference group were younger, had lower body mass indices and more seldom a history of myocardial infarction compared with diseased groups. Mortality was lowest in the reference group (P<0.0001) increasing to a maximum in participants with the combination of glucose abnormality and heart failure. Prognostically, the mortality risk associated with abnormal glucose regulation was increased but was lower than the risk of diabetes. The risk of a new myocardial infarction was highest in participants with diabetes [hazard ratio (HR) 1.6; 95% confidence interval (CI) 1.3-2.0] or diabetes in combination with heart failure (HR 1.8; CI 1.1-2.7). CONCLUSIONS: Heart failure or glucose abnormalities are related to increased morbidity and mortality. The combination of glucose abnormality and heart failure did, however, not add further to the unfavourable prognosis in the presence of ischaemic heart disease.
OBJECTIVE: Diabetes is an independent risk factor for heart failure, whereas the relation between heart failure and abnormal glucose regulation (AGR) needs further evaluation. We studied this combination in the Reykjavik Study. RESEARCH DESIGN AND METHODS: The Reykjavik Study, a population-based cohort study during 1967-1997, recruited 19,381 participants aged 33-84 years who were followed until 2002. Oral glucose tolerance tests and chest X-rays were obtained from all participants. Cases were defined in accordance with World Health Organization criteria for type 2 diabetes or AGR (impaired glucose tolerance or impaired fasting glucose) and European Society of Cardiology guidelines for heart failure. RESULTS: The overall prevalence of type 2 diabetes and heart failure was 0.5% in men and 0.4% in women, while AGR and heart failure were found in 0.7% of men and 0.6% of women. Among participants with normal glucose regulation, heart failure was diagnosed in 3.2% compared with 6.0 and 11.8% among those with AGR and type 2 diabetes, respectively. The prevalence of type 2 diabetes in the age-group 45-65 years increased in both sexes during the period (P for trend = 0.007). The odds ratio was 2.8 (95% CI 2.2-3.6) for the association between type 2 diabetes and heart failure and 1.7 (1.4-2.1) between AGR and heart failure. CONCLUSIONS: There is a strong association between any form of glucometabolic perturbation and heart failure. Future studies in this field should focus on all types of glucose abnormalities rather than previously diagnosed diabetes only.
UNLABELLED: The prevalence of type 2 diabetes mellitus is rapidly increasing. Myocardial dysfunction may be a consequence of diabetic cardiomyopathy and it contributes to the poor prognosis of diabetic patients. AIMS: This study was designed to test whether tissue Doppler imaging might be a suitable tool for early detection of myocardial dysfunction in diabetic patients. METHODS: Forty-three diabetic patients and 33 non-diabetic controls, including age-matched subgroups without evidence of coronary artery disease (n=12), were recruited if they had normal LV-function by standard 2-D echocardiography and no clinical signs of heart failure. They were investigated with tissue Doppler imaging at rest and during pharmacological stress with dipyridamole and/or dobutamine. Myocardial function was calculated as the mean value from six basal myocardial segments for peak velocity at systole (Vs), early diastole (Ve) and atrial contraction (Va). RESULTS: Compared to controls, diabetic patients had compromised Ve at rest (8.5 +/- 1.7 vs. 9.6 +/- 1.9 cm/sec, p < 0.02), as did the subgroups without coronary artery disease (9.3 +/- 1.7 vs. 10.7 +/- 1.5 cm/sec, p < 0.05). Dobutamine stress resulted in lower Vs (10.7 +/- 2.7 vs. 13.6 +/- 3.4 cm/sec, p < 0.05) and Ve (10.0 +/- 2.1 vs. 13.1 +/- 3.8 cm/sec, p < 0.05) in the diabetic patients, demonstrating an impaired increase of Vs, Vd and Va (p < 0.05, p < 0.0003 and p < 0.03, respectively). An inverse correlation was observed between Ve and age in both control and diabetic individuals. Thus, abnormal values were defined in relation to age. CONCLUSIONS: Diastolic and systolic myocardial dysfunction in patients with type 2 diabetes may be identified by quantitative tissue Doppler imaging before the onset of clinical signs of heart failure and before the appearance of traditional echocardiographic indices of systolic myocardial dysfunction.
Acute coronary syndromes are associated with a high risk for subsequent major cardiovascular events and with a risk for mortality that remains substantially increased for many months following the acute phase. Patients with type 2 diabetes mellitus are especially vulnerable and encounter excessive long-term mortality. Effective management of patients with type 2 diabetes following acute coronary syndromes requires aggressive multidisciplinary efforts for reduction of several risk factors, including meticulous control of blood glucose. The evidence for different medication and treatment strategies capable of improving the outcomes is reviewed and the currently available recommendations are summarised.
OBJECTIVES: This study was designed to study the influence of diabetes on the outcome of unstable coronary artery disease (CAD). BACKGROUND: Diabetes mellitus is a major contributor to CAD. Despite improvement in the management of patients with unstable coronary syndromes, this condition is still linked to a substantially increased mortality and morbidity among diabetic patients. Recent evidence advocates early revascularization in unstable coronary syndromes. Diabetic patients subjected to coronary interventions under stable conditions have a higher risk for complications and a more dismal prognosis than nondiabetic subjects. Accordingly, it is of considerable interest to obtain further information regarding the best possible management of diabetic patients with unstable CAD. METHODS: A total of 2158 patients without and 299 with diabetes mellitus were randomized to an early invasive or a noninvasive strategy. The severity of CAD was expressed as the number and extent of vessel involvement. RESULTS: Three-vessel disease was diagnosed in 42% of diabetic and 31% of nondiabetic patients (p = 0.006). The percentages of patients with ST-depression and troponin-T >0.03 microg/l at admission were comparable among diabetic and nondiabetic patients. Mortality and reinfarction after 12 months were more frequent among diabetic than nondiabetic patients in both treatment groups. Diabetes remained a strong independent predictor for death and myocardial infarction in multivariable analysis. The invasive strategy reduced event rate in nondiabetic patients from 12.0% to 8.9% (odds ratio [OR] = 0.72; confidence interval [CI] 0.54 to 0.95; p = 0.019) and in diabetic patients from 29.9% to 20.6% (OR 0.61; CI 0.36 to 1.04; p = 0.066). In a multivariate analysis including the extent of CAD, diabetes remained a strong independent predictor of the combined end point (relative risk [RR] 2.40; CI 1.47 to 3.91; p = 0.0001) and of mortality (RR 5.43; CI 2.09 to 14.12; p = 0.001). CONCLUSIONS: An invasive strategy improved outcome for both diabetic and nondiabetic patients with unstable CAD. However, diabetes mellitus remained an independent and important risk factor for death and myocardial infarction in the invasive group. Thus, factors beyond the extent of flow-limiting coronary lesions are of considerable importance for outcome in diabetic subjects with unstable coronary syndromes.
Access to medical technology differs across Europe. Differences in funding and reimbursement systems create barriers for the adoption of new and innovative medical technology. It is obvious that a joint effort between representatives from the industry and the profession has great potential to emphasise inequitable discrepancies and thereby improve the availability of accepted innovations in cardiovascular medicine. It is equally obvious that future efforts to overcome such restrictions to availability must be directed at the individual country level. The involvement of the profession, perhaps best accomplished by activation of National Cardiac Societies, will be mandatory for success. Collaboration with the industry is then a likely key factor for success. Presently there seems to be a great lack of knowledge and interest for this important aspect of a well functioning health care system and the responsibility to improve it remains with the professional societies. They need to allocate time and resources for this purpose, educate their members and lobby within their countries with the ambition to create better, more uniform and transparent procedures, and to become natural partners in the funding and reimbursement processes.
AIM: The objective behind the Euro Heart Survey on diabetes and the heart was to study the prevalence of abnormal glucose regulation in adult patients with coronary artery disease (CAD). METHODS AND RESULTS: The survey engaged 110 centres in 25 countries recruiting 4196 patients referred to a cardiologist due to CAD out of whom 2107 were admitted on an acute basis and 2854 had an elective consultation. Patient data were collected via a web-based case record form. An oral glucose tolerance test (OGTT) was used for the characterisation of the glucose metabolism. Thirty-one per cent of the patients had diabetes. An OGTT was performed on the 1920 patients without known diabetes, of whom 923 had acute and 997 had a stable manifestation of CAD, respectively. In patients with acute CAD, 36% had impaired glucose regulation and 22% newly detected diabetes. In the stable group these proportions were 37% and 14%. CONCLUSION: This survey demonstrates that normal glucose regulation is less common than abnormal glucose regulation in patients with CAD. OGTT easily discloses the glucometabolic state and should be a routine procedure. The knowledge of glucometabolic state among these patients should influence their future management because it has great potential to improve the outcome.
BACKGROUND: Management guidelines for heart failure recommend ACE-I and beta-blockers. The perception of difficult up-titration might have added to the slow uptake of beta-blockers despite their mortality and morbidity benefits. AIMS: CARMEN offered a possibility to study safety and tolerability of enalapril against carvedilol and their combination. METHODS: Five hundred and seventy-two patients were blindly up-titrated on carvedilol (target 25 mg bid) and/or enalapril (target 10 mg bid), and continued for 18 months. In the combination arm, carvedilol was up-titrated before enalapril. RESULTS: There was no group related difference in adverse events during up-titration. Withdrawal rates were 31, 30 and 30%, and serious adverse events 28, 29 and 34% in the combination, carvedilol and enalapril arms. Mortality was similar in all groups (all-cause N=14, 14 and 14; cardiovascular N=9, 13 and 14). All-cause and cardiovascular hospitalizations occurred in 26, 27 and 32%, and in 12, 16 and 22% in the combination, carvedilol and enalapril arms, respectively. CONCLUSION: The safety profile was similar in all treatment arms. In contrast to common perception, there was no difference in tolerability between the ACE-I and carvedilol. This result is even more remarkable as the high prestudy use of ACE-I (65%) might have introduced a bias by selecting ACE-I tolerant patients, who were only switched from their former ACE-I to enalapril.
AIMS: Heart failure (HF) treatment guidelines of the ESC recommend ACE-inhibitors (ACE-I) as first-line treatment and beta-blockers added if patients remain symptomatic. CARMEN explored the need for combined treatment for remodelling and order of introduction by comparing the ACE-I enalapril against carvedilol and their combination. METHODS: In a parallel-group, 3-arm study of 18 months duration, 572 mild heart failure patients were randomly assigned to carvedilol (N = 191), enalapril (N = 190) or their combination (N = 191). In the latter, carvedilol was up-titrated before enalapril. Left ventricular (LV) remodelling was assessed by transthoracic echocardiography (biplane, modified Simpson) at baseline and after 6, 12 and 18 months of maintenance therapy. Primary comparisons considered the change in LV end-systolic volume index (LVESVI) from baseline to month 18 between the combination and enalapril, and between carvedilol and enalapril. RESULTS: In the first primary comparison, LVESVI was reduced by 5.4 ml/m2 (p = 0.0015) in favour of combination therapy compared to enalapril. The second primary comparison tended to favour carvedilol to enalapril (NS). In the within treatment arm analyses, carvedilol significantly reduced LVESVI by 2.8 ml/m2 (p = 0.018) compared to baseline, whereas enalapril did not. LVESVI decreased by 6.3 ml/m2 (p = 0.0001) with combination therapy. All three arms showed similar safety profiles and withdrawal rates. CONCLUSION: CARMEN is the first study to demonstrate that early combination of ACE-I and carvedilol reverses LV remodelling in patients with mild to moderate HF and LV systolic dysfunction. The results of the CARMEN study support a therapeutic strategy in which the institution of beta-blockade should not be delayed.
UNLABELLED: Congestive heart failure and type 2 diabetes have a deleterious prognosis when combined. Trimetazidine, a metabolic agent with anti-ischemic properties, reduces fatty acid beta-oxidation via decreased 3-ketoacyl-coenzyme-A thiolase activity thereby facilitating energy production via the glycolytic pathway. OBJECTIVES: To assess myocardial function by Tissue Doppler Imaging (TDI) after one month of trimetazidine (Vastarel) added-on conventional treatment in patients with type 2 diabetes and heart failure. METHODS: Twenty diabetic patients with ischemic heart failure (mean age 66 years; NYHA class II-III) were randomized to trimetazidine (60 mg daily) or placebo in a double-blind crossover design. Exercise tolerance, 2-dimensional echocardiograms, and TDI (rest and exercise) were studied before and during treatment. RESULTS: Changes in exercise tolerance did not differ in the two groups. Ejection fraction at rest and moderate exercise only improved significantly with trimetazidine when analyzed for the first treatment period. TDI velocities did not change significantly during treatment periods. CONCLUSION: In this early pilot investigation of the effects of trimetazidine in patients with diabetes and heart failure there were only weak signs of improved systolic myocardial function at rest and exercise. The present observations indicate the need of further research to explore the effect of trimetazidine during longer treatment period or with more selected patient population.
Clevidipine is an ultrashort-acting vasoselective calcium antagonist under development for short-term intravenous control of blood pressure. Studies in animals, healthy volunteers and patients have demonstrated the vascular selectivity and rapid onset and offset of antihypertensive action of clevidipine, a synthetic 1,4-dihydropyridine that inhibits L-type calcium channels. Clevidipine has a high clearance (0.05 L/min/kg) and is rapidly hydrolyzed to inactive metabolites by esterases in arterial blood. Its half-life in patients undergoing cardiac surgery is less than one min. Unlike sodium nitroprusside, a drug commonly used for the short-term control of blood pressure, which dilates both arterioles and veins, clevidipine reduces blood pressure through a selective effect on arterioles. As documented in animals and in cardiac surgical patients, clevidipine reduces peripheral resistance without any undesirable effect on cardiac filling pressure. It increases stroke volume and cardiac output. In anesthetized patients undergoing cardiac surgery clevidipine, unlike sodium nitroprusside, does not increase heart rate. In addition of having a favorable hemodynamic profile, suitable for rapid control of blood pressure, clevidipine protects against ischemia/reperfusion injuries, which are not uncommon during major surgery. In anesthetized pigs, clevidipine reduced infarct size after 45 min-long myocardial ischemia by 40%. In rats, renal function and splanchnic blood flow were better maintained when blood pressure was reduced with clevidipine than with sodium nitroprusside. Clevidipine was well tolerated in Phases I and II of clinical trials that included more than 300 individuals/patients. Since there are no known compounds with similar pharmacodynamic and pharmacokinetic properties in clinical development, it is anticipated that clevidipine, a compound tailored to the needs of anesthesiologists, has the potential to become a drug of choice for controlling blood pressure during surgical procedures.
Congestive heart failure (CHF) is a serious disease with a poor prognosis. Diabetes is an independent risk factor for CHF, probably in part due to disturbances in myocardial metabolism. Glucagon-like peptide-1 (GLP-1) causes glucose-dependent secretion of insulin, improving glycaemic control. In turn, this may improve myocardial metabolism and myocardial function. The aim of the present study was to assess the feasibility and safety of three days' infusion of recombinant GLP-1 in an open observational study in six patients with type 2 diabetes and CHF. The study included assessment of myocardial function. There were no major complications of the infusion, and all patients completed the study protocol. Some improvement was observed in glycaemic state, and there was an insignificant trend towards improved myocardial function. It is concluded that GLP-1 deserves further evaluation in such patients.
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AIMS: The prognosis after an acute myocardial infarction is worse for patients with diabetes mellitus than for those without. We investigated whether differences in the use of evidence-based treatment may contribute to the differences in 1-year survival in a large cohort of consecutive acute myocardial infarction patients with and without diabetes mellitus. METHODS: We included patients below the age of 80 years from the Register of Information and Knowledge about Swedish Heart Intensive care Admissions (RIKS-HIA), which included all patients admitted to coronary care units at 58 hospitals during 1995-1998. In all 5193 patients had the combination of acute myocardial infarction and diabetes mellitus while 20440 had myocardial infarction but no diabetes diagnosed. Multivariate logistical regression analyses were performed to evaluate the influence of diabetes mellitus on the use of evidence-based treatment and its association with survival during the first year after the index hospitalisation. RESULTS: The prevalence of diabetes mellitus was 20.3% (males 18.5%; females 24.4%). The 1-year mortality was substantially higher among diabetic patients compared with those without diabetes mellitus (13.0 vs. 22.3% for males and 14.4 vs. 26.1% for female patients, respectively) with an odds ratio (OR) (95% confidence interval (CI)) in three different age groups: <65 years 2.65 (2.23-3.16); 65-74 years 1.81 (1.61-2.04) and >75 years 1.71 (1.50-1.93). During hospital stay patients with diabetes mellitus received significantly less treatment with heparins (37 vs. 43%; p<0.001), intravenous beta blockade (29 vs. 33%; p<0.001), thrombolysis (31 vs. 41%; p<0.001) and acute revascularisation (4 vs. 5%; p<0.003). A similar pattern was apparent at hospital discharge. After multiple adjustments for dissimilarities in baseline characteristics between the two groups, patients with diabetes were significantly less likely to be treated with reperfusion therapy (OR 0.83), heparins (OR 0.88), statins (OR 0.88) or to be revascularised within 14 days from hospital discharge procedures (OR 0.86) while the use of ACE-inhibitors was more prevalent among diabetic patients compared to non-diabetic patients (OR 1.45). The mortality reducing effects of evidence-based treatment like reperfusion, heparins, aspirin, beta-blockers, lipid-lowering treatment and revascularisation were, in multivariate analyses, of equal benefit in diabetic and non-diabetic patients. INTERPRETATION: Diabetes mellitus continues to be a major independent predictor of 1-year mortality following an acute myocardial infarction, especially in younger age groups. This may partly be explained by less use of evidence-based treatment although treatment benefits are similar in both patients with and without diabetes mellitus. Thus a more extensive use of established treatment has a potential to improve the poor prognosis among patients with acute myocardial infarction and diabetes mellitus.