Arterial hypertension is a widespread risk factor for cardiovascular disease. The benefit of a co... more Arterial hypertension is a widespread risk factor for cardiovascular disease. The benefit of a consistent drug therapy is proportionally associated with the degree of blood pressure reduction. By extrapolating the data, the assumption arose “the lower the better” and was widely accepted. However, several studies found an increase in morbidity and mortality with an excessive reduction of blood pressure (J-curve). This seems to affect mainly cardiac risk, and only at lower blood pressures<60 mmHg also the cerebral risk. An important factor here is the diastolic blood pressure. Others found a linear correlation. Overall, a j-shaped connection remains controversial and is not considered equally for all organ systems. At the same time cardiovascular risk seems not to increase with additional reduction in blood pressure of <140 mm Hg to <120 mmHg. This has led to the latest guidelines of all societies recommending higher target values. Reasons for higher targets in drug therapy of arterial hypertension, are increased adverse drug reactions or increased healthcare costs with few additional benefit. The current recommendations of the ESH/ESC, AHA/ACC/ASH and the JNC 8 set a higher target value for some subgroups, but remain inconsistent among themselves.
Swiss medical weekly: official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology
Congestive heart failure is a growing public health problem worldwide, particularly in the elderl... more Congestive heart failure is a growing public health problem worldwide, particularly in the elderly population, in whom it has a substantial impact on quality of life and survival. Despite the fact that heart failure is the most common reason for hospitalisation over the age of 65 years, most clinical trials have excluded the elderly population. This is unfortunate because it may not be generally assumed that elderly patients are similar to younger ones. Nonspecific symptoms and co-morbidities in the elderly may make diagnosis of heart failure difficult. In addition, physiology changes with age, polypharmacy complicates therapy and the aim of therapy may change in the presence of co-morbidities such as cancer or dementia. Furthermore, drug interactions and adverse effects are frequent in heart failure in general, but increase significantly with age. Nevertheless, there is little evidence that treatment of heart failure should be fundamentally different in elderly patients compared with younger patients, although careful monitoring of medical therapy is of particular importance in elderly heart failure patients. Therefore, general guidelines on diagnosis and therapy of heart failure also apply to elderly patients, but therapy may need to be adjusted to cater for individual needs, potential interactions and altered elimination of drugs. This article summarises the evidence available for treatment in elderly patients with heart failure, discusses potential differences in elderly subjects compared with their younger counterparts and provides recommendations for clinical practice.
Catheterization and Cardiovascular Interventions, 2014
Coronary angiography and percutaneous coronary intervention (PCI) over the radial approach are be... more Coronary angiography and percutaneous coronary intervention (PCI) over the radial approach are becoming more frequent and are recommended by the European Association of Percutaneous Cardiovascular Interventions and European Society of Cardiology. The radial approach leads to less bleeding and improved survival in ST-segment elevation myocardial infarction. Pronounced guide catheter manipulation in cases with tortuous access routes and requirement of extra backup during complex PCI may structurally damage the guide shaft and facilitate twisting and bending. We present three cases where a twisted coronary catheter became stuck in the radial artery and describe a minimally invasive retrieval technique using a second introducer sheath of same French (F) size and greater length.
b Klinische Pharmakologie und Toxikologie, Universitätsspital Basel Summary A fatal drug interact... more b Klinische Pharmakologie und Toxikologie, Universitätsspital Basel Summary A fatal drug interaction After intake of only two 125 mg tablets of brivudine (Zostex ® ) fatal toxicity of the 5-FU-prodrug capecitabine (Xeloda ® ) occurred due to irreversible inhibition of the catalytic enzyme dihydropyrimidine dehydrogenase (DPD). Despite im- mediate withdrawal of capecitabine and appropriate supportive measures in the intensive care
Journal of thrombosis and thrombolysis, Jan 10, 2016
To derive insights into the temporal changes in oxidative, inflammatory and coagulation biomarker... more To derive insights into the temporal changes in oxidative, inflammatory and coagulation biomarkers in patients with stable angina undergoing percutaneous coronary intervention (PCI). PCI is associated with a variety of biochemical and mechanical stresses to the vessel wall. Oxidized phospholipids are present on plasminogen (OxPL-PLG) and potentiate fibrinolysis in vitro. We recently showed that OxPL-PLG increase following acute myocardial infarction, suggesting that they are involved in atherothrombosis. Plasma samples were collected before, immediately after, 6 and 24 h, 3 and 7 days, and 1, 3, and 6 months after PCI in 125 patients with stable angina undergoing uncomplicated PCI. Plasminogen levels, OxPL-PLG, and an array of 16 oxidative, inflammatory and coagulation biomarkers were measured with established assays. OxPL-PLG and plasminogen declined significantly immediately post-PCI, rebounded to baseline, peaked at 3 days and slowly returned to baseline by 6 months (p < 0.000...
Transactions of the American Ophthalmological Society, 2015
To test the hypothesis that the accumulation of oxidized phospholipids (OxPL) in the macula is to... more To test the hypothesis that the accumulation of oxidized phospholipids (OxPL) in the macula is toxic to the retina unless neutralized by a variety of mechanisms, including binding by lipoprotein(a) [Lp(a)], which is composed of apolipoprotein(a) [apo(a)] and apolipoprotein B-100 (apoB). Human maculas and eyes from two Lp(a) transgenic murine models were subjected to morphologic, ultrastructural, and immunohistochemical analysis. "Wild-type Lp(a)" mice, which express human apoB-100 and apo(a) that contains oxidized phospholipid, and "mutant LBS(-) Lp(a)" mice with a defective apo(a) lysine binding site (LBS) for oxidized phospholipid binding, were fed a chow or high-fat diet for 2 to 12 months. Oxidized phospholipid-containing lipoproteins were detected by immunoreactivity to E06, a murine monoclonal antibody binding to the phosphocholine headgroup of oxidized, but not native, phospholipids. Oxidized phospholipids, apo(a), and apoB accumulate in maculas, including...
To investigate the prognostic relevance of elevated Troponin T (cTnT) levels in patients with ST-... more To investigate the prognostic relevance of elevated Troponin T (cTnT) levels in patients with ST-segment elevation myocardial infarction (STEMI) without significant creatine kinase (CK) elevation on admission. From January 1, 2002 to December 31, 2006 patients with STEMI without significant CK elevation (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2-fold) on admission treated with percutaneous coronary intervention (PCI) were included and stratified according to cTnT plasma levels. Univariate and multivariate regression analyses were used to find independent predictors for mortality. During the 5-year period 514 patients with STEMI and normal CK plasma levels were included. 308 (59.9 %) patients had cTnT levels &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.1 μg/l and 206 (40.1 %) patients had cTnT levels ≥0.1 μg/l. Multivariate logistic regression analysis identified cTnT levels ≥0.1 μg/l and 3-vessel disease as positive, and hemoglobin levels as negative independent predictors for long-term mortality. Discordantly elevated cTnT plasma levels independently predicted higher mortality rates in the first year (HR 3.9, 95 % CI 1.7-9.1, p = 0.002) and during 5 years (HR 2.3, 95 % CI 1.4-3.9, p = 0.002) after PCI for STEMI. Discordant elevation of cTnT in the presence of normal CK plasma levels on admission is associated with increased mortality in STEMI patients undergoing primary PCI. This may be due to preceding microembolization.
Journal of thrombosis and thrombolysis, Jan 28, 2015
Oxidized phospholipids (OxPL) are abundant in atherosclerotic plaques. They are also bound to cir... more Oxidized phospholipids (OxPL) are abundant in atherosclerotic plaques. They are also bound to circulating plasminogen after myocardial infarction (MI), and their binding to plasminogen may accentuate fibrinolysis. We sought to assess whether circulating levels of plasminogen and OxPL bound to plasminogen (OxPL-PLG) increase following acute MI and whether this increase differs between atherothrombotic (Type 1) and non-atherothrombotic (Type 2) MI. We measured circulating levels of plasminogen and OxPL-PLG at 0, 6, 24, 48 h, and >3 months (stable state) following acute MI and following an angiogram for stable coronary artery disease (CAD). Forty-nine subjects met the criteria for acute MI, of whom 34 had clearly defined atherothrombotic (n = 22) or non-atherothrombotic (n = 12) MI; 15 patients met the criteria for stable CAD. Mean baseline levels of plasminogen and OxPL-PLG were lower in the acute MI group than in the stable CAD group (9.75 vs 20.2, p < 0.0001 for plasminogen an...
Swiss medical weekly: official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology
European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology, 2010
The authors report the case of a 77-year-old male patient with sinus rhythm and a first-degree at... more The authors report the case of a 77-year-old male patient with sinus rhythm and a first-degree atrioventricular (AV) block who was referred for echocardiographic follow-up 18 years after aortic valve replacement. Left ventricular systolic function as well as the function of the aortic prosthesis was normal. Systolic mitral regurgitation (MR) was virtually absent, but isolated late diastolic MR was detected by colour Doppler imaging. Coincidental to the occurrence of diastolic MR, a second late diastolic forward flow in the pulmonary veins was observed. Therefore, during the prolonged left atrial relaxation caused by first-degree AV block, the left atrial pressure drops below the pressure in both adjacent chambers in late diastole, resulting in both late diastolic MR and a second diastolic pulmonary venous forward flow.
Sustained elevation of resting heart rate (RHR) is thought to promote the initiation and progress... more Sustained elevation of resting heart rate (RHR) is thought to promote the initiation and progression of coronary artery disease (CAD). The aim of this paper is to test the hypothesis whether elevated RHR correlates with the presence and the extent of CAD in patients evaluated for CAD. The association between RHR and CAD findings and myocardial perfusion SPECT (MPS) was tested in 1,465 patients. Patients with atrial fibrillation, pacemaker rhythm and treatment with negative chonotropic drugs were excluded. Standard scores for MPS evaluation were used. CAD findings of myocardial ischaemia or scar were present in 408 patients (28%). The prevalence of CAD finding at MPS was not higher among patients with RHR above the median value of 79 bpm compared to patients with lower RHR (28% vs 28%; p = 1.00). The extent of myocardial ischaemia and scar did not increase with higher quartiles of RHR. In contrast, the presence of other established cardiovascular risk factors such as diabetes, male gender, more advanced age and presence of CAD symptoms such as angina and dyspnoea were independent predictors of CAD findings (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05 for all). Elevated RHR is not associated with the presence and the extent of CAD in patients evaluated for suspected but previously unknown CAD, suggesting that the impact of a higher RHR on mortality may be linked with other factors than only CAD itself.
Arterial hypertension is a widespread risk factor for cardiovascular disease. The benefit of a co... more Arterial hypertension is a widespread risk factor for cardiovascular disease. The benefit of a consistent drug therapy is proportionally associated with the degree of blood pressure reduction. By extrapolating the data, the assumption arose “the lower the better” and was widely accepted. However, several studies found an increase in morbidity and mortality with an excessive reduction of blood pressure (J-curve). This seems to affect mainly cardiac risk, and only at lower blood pressures&amp;amp;lt;60 mmHg also the cerebral risk. An important factor here is the diastolic blood pressure. Others found a linear correlation. Overall, a j-shaped connection remains controversial and is not considered equally for all organ systems. At the same time cardiovascular risk seems not to increase with additional reduction in blood pressure of &amp;amp;lt;140 mm Hg to &amp;amp;lt;120 mmHg. This has led to the latest guidelines of all societies recommending higher target values. Reasons for higher targets in drug therapy of arterial hypertension, are increased adverse drug reactions or increased healthcare costs with few additional benefit. The current recommendations of the ESH/ESC, AHA/ACC/ASH and the JNC 8 set a higher target value for some subgroups, but remain inconsistent among themselves.
Swiss medical weekly: official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology
Congestive heart failure is a growing public health problem worldwide, particularly in the elderl... more Congestive heart failure is a growing public health problem worldwide, particularly in the elderly population, in whom it has a substantial impact on quality of life and survival. Despite the fact that heart failure is the most common reason for hospitalisation over the age of 65 years, most clinical trials have excluded the elderly population. This is unfortunate because it may not be generally assumed that elderly patients are similar to younger ones. Nonspecific symptoms and co-morbidities in the elderly may make diagnosis of heart failure difficult. In addition, physiology changes with age, polypharmacy complicates therapy and the aim of therapy may change in the presence of co-morbidities such as cancer or dementia. Furthermore, drug interactions and adverse effects are frequent in heart failure in general, but increase significantly with age. Nevertheless, there is little evidence that treatment of heart failure should be fundamentally different in elderly patients compared with younger patients, although careful monitoring of medical therapy is of particular importance in elderly heart failure patients. Therefore, general guidelines on diagnosis and therapy of heart failure also apply to elderly patients, but therapy may need to be adjusted to cater for individual needs, potential interactions and altered elimination of drugs. This article summarises the evidence available for treatment in elderly patients with heart failure, discusses potential differences in elderly subjects compared with their younger counterparts and provides recommendations for clinical practice.
Catheterization and Cardiovascular Interventions, 2014
Coronary angiography and percutaneous coronary intervention (PCI) over the radial approach are be... more Coronary angiography and percutaneous coronary intervention (PCI) over the radial approach are becoming more frequent and are recommended by the European Association of Percutaneous Cardiovascular Interventions and European Society of Cardiology. The radial approach leads to less bleeding and improved survival in ST-segment elevation myocardial infarction. Pronounced guide catheter manipulation in cases with tortuous access routes and requirement of extra backup during complex PCI may structurally damage the guide shaft and facilitate twisting and bending. We present three cases where a twisted coronary catheter became stuck in the radial artery and describe a minimally invasive retrieval technique using a second introducer sheath of same French (F) size and greater length.
b Klinische Pharmakologie und Toxikologie, Universitätsspital Basel Summary A fatal drug interact... more b Klinische Pharmakologie und Toxikologie, Universitätsspital Basel Summary A fatal drug interaction After intake of only two 125 mg tablets of brivudine (Zostex ® ) fatal toxicity of the 5-FU-prodrug capecitabine (Xeloda ® ) occurred due to irreversible inhibition of the catalytic enzyme dihydropyrimidine dehydrogenase (DPD). Despite im- mediate withdrawal of capecitabine and appropriate supportive measures in the intensive care
Journal of thrombosis and thrombolysis, Jan 10, 2016
To derive insights into the temporal changes in oxidative, inflammatory and coagulation biomarker... more To derive insights into the temporal changes in oxidative, inflammatory and coagulation biomarkers in patients with stable angina undergoing percutaneous coronary intervention (PCI). PCI is associated with a variety of biochemical and mechanical stresses to the vessel wall. Oxidized phospholipids are present on plasminogen (OxPL-PLG) and potentiate fibrinolysis in vitro. We recently showed that OxPL-PLG increase following acute myocardial infarction, suggesting that they are involved in atherothrombosis. Plasma samples were collected before, immediately after, 6 and 24 h, 3 and 7 days, and 1, 3, and 6 months after PCI in 125 patients with stable angina undergoing uncomplicated PCI. Plasminogen levels, OxPL-PLG, and an array of 16 oxidative, inflammatory and coagulation biomarkers were measured with established assays. OxPL-PLG and plasminogen declined significantly immediately post-PCI, rebounded to baseline, peaked at 3 days and slowly returned to baseline by 6 months (p < 0.000...
Transactions of the American Ophthalmological Society, 2015
To test the hypothesis that the accumulation of oxidized phospholipids (OxPL) in the macula is to... more To test the hypothesis that the accumulation of oxidized phospholipids (OxPL) in the macula is toxic to the retina unless neutralized by a variety of mechanisms, including binding by lipoprotein(a) [Lp(a)], which is composed of apolipoprotein(a) [apo(a)] and apolipoprotein B-100 (apoB). Human maculas and eyes from two Lp(a) transgenic murine models were subjected to morphologic, ultrastructural, and immunohistochemical analysis. "Wild-type Lp(a)" mice, which express human apoB-100 and apo(a) that contains oxidized phospholipid, and "mutant LBS(-) Lp(a)" mice with a defective apo(a) lysine binding site (LBS) for oxidized phospholipid binding, were fed a chow or high-fat diet for 2 to 12 months. Oxidized phospholipid-containing lipoproteins were detected by immunoreactivity to E06, a murine monoclonal antibody binding to the phosphocholine headgroup of oxidized, but not native, phospholipids. Oxidized phospholipids, apo(a), and apoB accumulate in maculas, including...
To investigate the prognostic relevance of elevated Troponin T (cTnT) levels in patients with ST-... more To investigate the prognostic relevance of elevated Troponin T (cTnT) levels in patients with ST-segment elevation myocardial infarction (STEMI) without significant creatine kinase (CK) elevation on admission. From January 1, 2002 to December 31, 2006 patients with STEMI without significant CK elevation (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2-fold) on admission treated with percutaneous coronary intervention (PCI) were included and stratified according to cTnT plasma levels. Univariate and multivariate regression analyses were used to find independent predictors for mortality. During the 5-year period 514 patients with STEMI and normal CK plasma levels were included. 308 (59.9 %) patients had cTnT levels &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.1 μg/l and 206 (40.1 %) patients had cTnT levels ≥0.1 μg/l. Multivariate logistic regression analysis identified cTnT levels ≥0.1 μg/l and 3-vessel disease as positive, and hemoglobin levels as negative independent predictors for long-term mortality. Discordantly elevated cTnT plasma levels independently predicted higher mortality rates in the first year (HR 3.9, 95 % CI 1.7-9.1, p = 0.002) and during 5 years (HR 2.3, 95 % CI 1.4-3.9, p = 0.002) after PCI for STEMI. Discordant elevation of cTnT in the presence of normal CK plasma levels on admission is associated with increased mortality in STEMI patients undergoing primary PCI. This may be due to preceding microembolization.
Journal of thrombosis and thrombolysis, Jan 28, 2015
Oxidized phospholipids (OxPL) are abundant in atherosclerotic plaques. They are also bound to cir... more Oxidized phospholipids (OxPL) are abundant in atherosclerotic plaques. They are also bound to circulating plasminogen after myocardial infarction (MI), and their binding to plasminogen may accentuate fibrinolysis. We sought to assess whether circulating levels of plasminogen and OxPL bound to plasminogen (OxPL-PLG) increase following acute MI and whether this increase differs between atherothrombotic (Type 1) and non-atherothrombotic (Type 2) MI. We measured circulating levels of plasminogen and OxPL-PLG at 0, 6, 24, 48 h, and >3 months (stable state) following acute MI and following an angiogram for stable coronary artery disease (CAD). Forty-nine subjects met the criteria for acute MI, of whom 34 had clearly defined atherothrombotic (n = 22) or non-atherothrombotic (n = 12) MI; 15 patients met the criteria for stable CAD. Mean baseline levels of plasminogen and OxPL-PLG were lower in the acute MI group than in the stable CAD group (9.75 vs 20.2, p < 0.0001 for plasminogen an...
Swiss medical weekly: official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology
European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology, 2010
The authors report the case of a 77-year-old male patient with sinus rhythm and a first-degree at... more The authors report the case of a 77-year-old male patient with sinus rhythm and a first-degree atrioventricular (AV) block who was referred for echocardiographic follow-up 18 years after aortic valve replacement. Left ventricular systolic function as well as the function of the aortic prosthesis was normal. Systolic mitral regurgitation (MR) was virtually absent, but isolated late diastolic MR was detected by colour Doppler imaging. Coincidental to the occurrence of diastolic MR, a second late diastolic forward flow in the pulmonary veins was observed. Therefore, during the prolonged left atrial relaxation caused by first-degree AV block, the left atrial pressure drops below the pressure in both adjacent chambers in late diastole, resulting in both late diastolic MR and a second diastolic pulmonary venous forward flow.
Sustained elevation of resting heart rate (RHR) is thought to promote the initiation and progress... more Sustained elevation of resting heart rate (RHR) is thought to promote the initiation and progression of coronary artery disease (CAD). The aim of this paper is to test the hypothesis whether elevated RHR correlates with the presence and the extent of CAD in patients evaluated for CAD. The association between RHR and CAD findings and myocardial perfusion SPECT (MPS) was tested in 1,465 patients. Patients with atrial fibrillation, pacemaker rhythm and treatment with negative chonotropic drugs were excluded. Standard scores for MPS evaluation were used. CAD findings of myocardial ischaemia or scar were present in 408 patients (28%). The prevalence of CAD finding at MPS was not higher among patients with RHR above the median value of 79 bpm compared to patients with lower RHR (28% vs 28%; p = 1.00). The extent of myocardial ischaemia and scar did not increase with higher quartiles of RHR. In contrast, the presence of other established cardiovascular risk factors such as diabetes, male gender, more advanced age and presence of CAD symptoms such as angina and dyspnoea were independent predictors of CAD findings (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05 for all). Elevated RHR is not associated with the presence and the extent of CAD in patients evaluated for suspected but previously unknown CAD, suggesting that the impact of a higher RHR on mortality may be linked with other factors than only CAD itself.
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Papers by Gregor Leibundgut