[Is morphine indicated in patients with cardiac asthma? Indications for negative effects from the use of morphine]. / Morfine geïndiceerd bij patiënten met astma cardiale? Aanwijzingen voor negatieve effecten van morfine.

According to current Dutch and European guidelines, morphine has a place in the treatment of patients with cardiac asthma. There are no studies showing an improvement in objective parameters with the use of morphine in patients with cardiac asthma. Recent large retrospective cohort studies indicate an increased mortality risk among patients given morphine in the treatment of cardiac asthma, even after correction for confounders. In addition, morphine may be linked to an increased risk of intensive care unit admission. Morphine should be used with caution in patients with cardiac asthma.

The entirely subcutaneous implantable cardioverter-defibrillator: initial clinical experience in a large Dutch cohort.

OBJECTIVES: The purpose of the study was to evaluate the efficacy and safety of the entirely subcutaneous implantable cardioverter-defibrillator (S-ICD). BACKGROUND: A new entirely S-ICD has been introduced, that does not require lead placement in or on the heart. The authors report the largest multicenter experience to date with the S-ICD with a minimum of 1-year follow-up in the first 118 Dutch patients who were implanted with this device. METHODS: Patients were selected if they had a class I or IIa indication for primary or secondary prevention of sudden cardiac death. All consecutive patients from 4 high-volume centers in the Netherlands with an S-ICD implanted between December 2008 and April 2011 were included. RESULTS: A total of 118 patients (75% males, mean age 50 years) received the S-ICD. After 18 months of follow-up, 8 patients experienced 45 successful appropriate shocks (98% first shock conversion efficacy). No sudden deaths occurred. Fifteen patients (13%) received inappropriate shocks, mainly due to T-wave oversensing, which was mostly solved by a software upgrade and changing the sensing vector of the S-ICD. Sixteen patients (14%) experienced complications. Adverse events were more frequent in the first 15 implantations per center compared with subsequent implantations (inappropriate shocks 19% vs. 6.7%, p = 0.03; complications 17% vs. 10%, p = 0.10). CONCLUSIONS: This study demonstrates that the S-ICD is effective in terminating ventricular arrhythmias. There is, however, a considerable percentage of ICD related adverse events, which decreases as the therapy evolves and experience increases.

Daytime triglyceride variability in men and women with different levels of triglyceridemia.

BACKGROUND: Triglyceride (TG) levels measured in either the fasting or non-fasting state predict the risk of cardiovascular disease (CVD). Since CVD risk assessment is affected by variability in TG, the aim of the study was to investigate intra-individual variability of non-fasting TG. METHODS: Capillary triglyceride (cTG) levels were measured in 246 free-living individuals at six time-points during the day on three separate occasions. Intra-individual variability in cTG was assessed by calculating the standard deviation of three measures at each time-point. Subjects were analyzed by gender and by fasting TG level. RESULTS: In the fasting state, intra-individual variability was similar in males and females (0.28 and 0.35 mmol/l, respectively), but increased significantly in male but not in female subjects during the day, i.e., 0.28 to 0.69, and 0.35 to 0.36 mmol/l, resp. Subjects with higher fasting TG levels had greater absolute variability in both fasting and non-fasting TG. CONCLUSIONS: The variability in non-fasting TG is greater in males and in individuals with higher levels of TG. Since greatest variability in non-fasting TG occurs very late in the day, it is unlikely to affect the assessment of CVD risk, which is based on a blood sample taken during daylight hours.

Leukocyte activation by triglyceride-rich lipoproteins.

OBJECTIVE: Postprandial lipemia has been linked to atherosclerosis and inflammation. Because leukocyte activation is obligatory for atherogenesis, leukocyte activation by triglyceride-rich lipoproteins (TRLs) was investigated. METHODS AND RESULTS: The expression of CD11b and CD66b after incubation with glucose and native and artificial TRLs (NTRL and ATRL) in vivo and in vitro was evaluated by flowcytometry. Oral fat loading tests showed an increased expression of CD11b on monocytes and neutrophils and CD66b on neutrophils. In 11 volunteers, postprandial leukocytes became enriched with meal-derived fatty acids ([1-(13)C]16:0) suggesting uptake of exogenous fat. ApoB binding on leukocytes measured by flowcytometry in 65 subjects was highest on neutrophils and monocytes suggesting adherence of apoB-containing lipoproteins. Physiological concentrations of TRLs showed 62% increased neutrophil CD11b and a dose-dependent increased monocyte CD11b up to 84% in vitro. Incubations with lipid emulsions in the hypertriglyceridemic range showed a 5-fold increased monocyte CD11b expression, which was higher than the positive control (fMLP), and a dose-dependent 2- to 3-fold increased neutrophil CD11b and CD66b. The oxidative scavenger DMTU decreased the neutrophil CD66b expression by 36%. CONCLUSIONS: Acute hypertriglyceridemia is a leukocyte activator most likely by direct interaction between TRLs and leukocytes and uptake of fatty acids. TG-mediated leukocyte activation is an alternative proinflammatory and proatherogenic mechanism of hypertriglyceridemia in part associated to the generation of oxidative stress.

The metabolic syndrome in relation to complement component 3 and postprandial lipemia in patients from an outpatient lipid clinic and healthy volunteers.

We investigated the relationship between complement component 3 (C3), fasting and postprandial lipemia and the metabolic syndrome (MetabS). Herefore fasting and postprandial samples after an acute oral fat load were obtained in 40 MetabS+ (50+/-8 years) and 70 MetabS- (48+/-7 years) subjects. Fasting C3 was higher in MetabS+ (1.21+/-0.33g/L versus 0.91+/-0.14g/L, P<0.001). Postprandially, MetabS+ had a higher total and incremental triglyceride response (TG-AUC: +77%; P<0.001 and TG-dAUC: +48%; P<0.05, respectively) and a higher total free fatty acid (FFA-AUC: +13%, P<0.05) and C3 response (C3-AUC: +26%, P<0.001) when compared to MetabS-. In both groups, fasting C3 was strongly associated with fasting TG, TG-AUC, TG-dAUC and insulin sensitivity (HOMA) (R=0.68, 0.67, 0.41 and 0.67, respectively, for the whole group; P<0.001 for each). Fasting C3 showed a dose-dependent relation with the number of MetabS components and, following exclusion of these components, it was after TG-AUC, the second best determinant of the MetabS (adjusted R(2)=0.47, P<0.001). In conclusion, C3 and postprandial lipema are closely associated with the metabolic syndrome and with several metabolic variables linked to insulin resistance. C3 may be a useful marker to identify subjects with the metabolic syndrome.

Effects of a stanol-enriched diet on plasma cholesterol and triglycerides in patients treated with statins.

BACKGROUND: Plant stanols have been recommended in combination with individualized dietary interventions to reduce plasma cholesterol concentrations. It is unclear whether plant stanols in combination with dietary guidance in patients already using optimal doses of statins will further reduce fasting and postprandial lipids compared with standard care. STUDY DESIGN: This single-blind, randomized study investigated the effect of plant stanols in margarines, combined with a lipid-lowering dietary intervention, in patients already on lipid-lowering medications at maximal doses not reaching their target lipid levels. Nutrition education was based on the stages of change theory. The control group (which served as the standard care control group) was also taking optimal doses of statins. This group received a margarine without plant stanols and a leaflet with Dutch nutrition guidelines. Fasting lipids were measured once in venous samples and postprandial lipemia was assessed by self-measured triglycerides in an outpatient setting. All subjects were given a capillary triglyceride measuring device (Accutrend GCT, Roche Diagnostics, Mannheim, Germany) and were instructed to measure their capillary triglycerides at six fixed time-points throughout the day on three different days. The mean area under the triglyceride curve represented total daylong triglyceridemia, which has been shown to reflect postprandial triglyceridemia. Twenty patients were included, 11 in the intervention group and 9 in the control group. RESULTS: In the plant stanol group, low-density lipoprotein cholesterol decreased significantly by 15.6% compared with a reduction of only 7.7% in the control group. The daylong triglyceridemia was similar in both groups at the beginning and at the end of the study, and no change was observed by the intervention. CONCLUSION: Intensive dietary intervention with addition of plant stanols results in clinically relevant reduction of low-density lipoprotein cholesterol in patients optimally treated with statins, compared with similar patients on statins receiving only standard care. The use of a plant stanol-enriched margarine did not decrease postprandial triglyceridemia in these patients.

Lipaemia, inflammation and atherosclerosis: novel opportunities in the understanding and treatment of atherosclerosis.

Atherosclerosis is the major cause of death in the world. Fasting and postprandial hyperlipidaemia are important risk factors for coronary heart disease (CHD). Recent developments have undoubtedly indicated that inflammation is pathophysiologically closely linked to atherogenesis and its clinical consequences. Inflammatory markers such as C-reactive protein (CRP), leucocyte count and complement component 3 (C3) have been linked to CHD and to hyperlipidaemia and several other CHD risk factors. Increases in these markers may result from activation of endothelial cells (CRP, leucocytes, C3), disturbances in adipose tissue fatty acid metabolism (CRP, C3), or from direct effects of CHD risk factors (leucocytes). It has been shown that lipoproteins, triglycerides, fatty acids and glucose can activate endothelial cells, most probably as a result of the production of reactive oxygen species. Similar mechanisms may also lead to leucocyte activation. Increases in triglycerides, fatty acids and glucose are common disturbances in the metabolic syndrome and are most prominent in the postprandial phase. People are in a postprandial state most of the day, and this phase is proatherogenic. Inhibition of the activation of leucocytes, endothelial cells, or both, is an interesting target for intervention, as activation is obligatory for adherence of leucocytes to the endothelium, thereby initiating atherogenesis. Potential interventions include the use of unsaturated long-chain fatty acids, polyphenols, antioxidants, angiotensin converting enzyme inhibitors and high-dose aspirin, which have direct anti-inflammatory and antiatherogenic effects. Furthermore, peroxisome proliferator activating receptor gamma (PPARgamma) agonists and statins have similar properties, which are in part independent of their lipid-lowering effects.