[Prevalence and severity of pulmonary embolism are dependent on clinical and paraclinical parameters : Analysis of 1,943 consecutive patients with CT pulmonary angiography]. / Prävalenz und Schwere der Lungenarterienembolie in Abhängigkeit von klinischen und paraklinischen Parametern : Analyse von 1943 konsekutiven Patienten mit CT-Pulmonalisangiographie.

BACKGROUND: Patients with pulmonary embolism (PE) have heterogeneous symptoms. Clinical scores and age-adjusted D­dimer should help clinicians to establish the correct diagnosis. METHODS: A cohort of 1,943 consecutive patients with positive D­dimer levels who were referred for CT pulmonary angiography (CTPA) over a period of 5 years to rule PE in or out were retrospectively analyzed. RESULTS: On CTPA n = 362 (19 %) had PE. The prevalence of PE increased stepwise with increasing D­dimer levels (prevalence of PE with 10 percentiles of D­dimers was: 3 %, 4 %, 7 %, 8 %, 8 %, 21 %, 20 %, 27 %, 37 %, 52 %; p < 0.001). D­dimers > 2.0 were significantly associated with PE (OR 7.17 95 % CI 5.27-9.76, p < 0.001). Chest discomfort and tachypnea showed no association with PE. Dyspnoea, pleuritic pain, and general fatigue showed significant associations with age: pleuritic chest pain was more frequent in patients aged < 76 years than in patients aged > 76 years (15 % vs 3 %; p < 0.001) and was highly significantly associated with PE (OR 4.99 95 % CI 2.83-8.81; p < 0.001). General fatigue was more prevalent in patients aged > 76 years (44 % vs 24 %; p < 0.001). PE patients with D­dimers > 6.0 mg/l were hemodynamically more compromised than patients with D­dimers < 6.0 mg/l: tachycardia 32 % vs 20 %, p = 0.015; right ventricular strain on echocardiography: 38 % vs 23 %, p = 0.003; right ventricular strain on ECG: 27 % vs 13 %; p  = 0.001; resuscitation 4 % vs 0 %, p = 0.003; lytic therapy 6 % vs 1 %, p = 0.014. CONCLUSION: The symptoms of PE patients are often vague. Particularly in older patients, fatigue may be the only symptom. The absolute level of D­dimers, particularly > 2.0 mg/l, is a strong predictor of PE. A D­dimer level > 6.0 mg/l is associated with more severe hemodynamic impairment in patients with PE.

[Analgesia in intensive care medicine]. / Analgesie in der Intensivmedizin.

BACKGROUND: The administration of sedatives and analgesics on the intensive care unit (ICU) is routine daily practice. The correct discrimination between delirium, pain and anxiety or confusion is essential for the strategy and selection of medication. The correct pain therapy and sedation are essential for patient quality of life on the ICU and for the prognosis. OBJECTIVE: The aim of this article is to present state of the art recommendations on the classification of pain and pain therapy on the ICU. MATERIAL AND METHODS: An online search was carried out in PubMed for publications on the topics of "pain" and "ICU". RESULTS: Critical care patients are frequently subjected to many procedures and situations which can cause pain. The perception of pain is, among other things, influenced by the degree of orientation, anxiety and the degree of sedation. The administration of analgesics and non-pharmacological approaches are effective in reducing the stress perceived by patients. DISCUSSION: The main aim is improvement in the awareness of nursing and medical personnel for pain inducers and pain perception in ICU patients. The classification of pain must be made objectively. Therapeutic targets must be defined and in addition to the correct selection of pain medication, non-pharmacological approaches must also be consistently implemented.

Robust association of the APOE epsilon4 allele with premature myocardial infarction especially in patients without hypercholesterolaemia: the Aachen study.

BACKGROUND: Genetic influence on the manifestation of coronary artery disease (CAD) and myocardial infarction (MI) has been shown previously. From many candidate genes the APOE (apolipoprotein E) with the major alleles epsilon2/epsilon3/epsilon4 is in the focus of interest. MATERIALS AND METHODS: In 1817 patients admitted for their first left heart catheterization at a premature age (males < 55 and females < 65) the association of APOE alleles with MI was analysed. Genotyping was done by 5' exonuclease assay (TaqMan). RESULTS APOE was significantly associated with hypercholesterolaemia (epsilon4 72% vs. epsilon3 66% vs. epsilon2 51%; P < 0.0001), and premature MI (epsilon4 57% vs. epsilon3 50% vs. epsilon2 41%; P < 0.0001; hazard ratio 1.41, 95%CI 1.14-1.75). In patients without hypercholesterolaemia, the APOE allele epsilon4 was highly predictive for the presence of premature MI (epsilon4 55% vs. epsilon3 45% vs. epsilon2 28%; P < 0.0001; hazard ratio 1.75, 95%CI 1.19-2.57). CONCLUSION: The APOEepsilon4 allele shows a robust association with premature MI independent of hypercholesterolaemia.

APOE alleles are not associated with calcific aortic stenosis.

OBJECTIVES: To analyse the association of APOE alleles with aortic stenosis (AS) in a large study population. METHODS: Patients with AS (n = 538) and a control group of the same age without heart disease (n = 536) were recruited. Left heart catheterisation was performed and mean gradient, aortic valve area, presence of stenotic coronary artery disease (CAD) and cardiovascular risk factors (hypercholesterolaemia, hypertension, smoking, diabetes mellitus and family history of CAD) were assessed. The frequency of the APOE major alleles e2, e3 and e4 was assessed by genotyping the polymorphisms APOE334 and APOE472 with a 5' exonuclease assay (TaqMan). RESULTS: Mean gradient across the aortic valve in cases was 50 (SD 20) mm Hg corresponding to a mean aortic valve area of 0.84 (SD 0.34) cm(2). 270 patients with AS had stenotic CAD. Among patients with AS, the prevalence of hypercholesterolaemia (64% v 40%, p < 0.001), smoking (43% v 27%, p < 0.001), diabetes (27% v 17%, p < 0.01), family history of CAD (30% v 21%, p 0.10). CONCLUSION: APOE e4 is not associated with AS, reflecting the different genetic backgrounds of CAD and AS.

The interleukin-6 promoter polymorphism is associated with elevated leukocyte, lymphocyte, and monocyte counts and reduced physical fitness in young healthy smokers.

Smoking and interleukin-6 are important factors in driving inflammation. This study assessed the relationship between smoking, interleukin-6 genotype, physical fitness, and peripheral blood count in healthy young men. For this interleukin-6 promoter polymorphism -174 genotype-phenotype association study 1,929 healthy German male aviators recruited at the central German Air Force Institute of Aviation Medicine were stratified by smoking habits. Cardiovascular fitness was expressed as maximal physical working capacity (PWCmax) in watts per kilogram body weight as assessed by maximal exercise testing by cycle ergometry up to physical exhaustion. Smokers had higher leukocyte and lymphocyte counts than nonsmokers and lower PWCmax. In the overall study population the C allele of the interleukin-6 polymorphism was weakly associated with elevated leukocytes and lymphocytes; in nonsmokers the interleukin-6 polymorphism was not associated with altered phenotypes, but in smokers the interleukin-6 C allele was associated with higher leukocytes, lymphocytes, and monocytes and with lower PWCmax. Smoking is thus associated with elevated leukocytes and lymphocytes and with reduced physical fitness. Gene carriers with the interleukin-6 C allele may suffer particularly from cigarette smoking.

Cardiovascular risk factors in patients with aortic stenosis predict prevalence of coronary artery disease but not of aortic stenosis: an angiographic pair matched case-control study.

BACKGROUND: Traditional cardiovascular risk factors have been associated with aortic stenosis and coronary artery disease. As these two conditions often co-exist, the association of cardiovascular risk factors with aortic stenosis may reflect confounding. OBJECTIVE: To compare the cardiovascular risk profile in patients with severe aortic stenosis undergoing elective coronary angiography with that of patients without aortic stenosis or calcification undergoing coronary angiography for suspected coronary artery disease. METHODS: 523 patients referred for elective diagnostic left heart catheterisation because of severe aortic stenosis formed the case population; 3925 patients without valve disease referred for elective diagnostic left heart catheterisation formed the base control population. Of the latter, 523 were pair matched to the case population for sex, age, and prevalence of relevant coronary artery disease, forming a pair matched control population. Cardiovascular risk factors (male sex, hypertension, hypercholesterolaemia, smoking, diabetes mellitus, family history of coronary artery disease) were assessed in all the patients. RESULTS: None of the cardiovascular risk factors was more prevalent in patients with aortic stenosis than in the base control population or in the pair matched control population. However, male sex, hypercholesterolaemia, smoking, diabetes mellitus, and a family history of coronary artery disease were significantly associated with the presence of additional coronary artery disease in patients with aortic stenosis. CONCLUSIONS: Cardiovascular risk factors are commonly present in patients with aortic stenosis. However, when compared with controls matched for age, sex, and angiographically defined coronary artery disease, no risk factor was significantly associated with the prevalence of aortic stenosis. Thus other factors are likely to be more important in the pathogenesis of aortic stenosis.

Relation of body mass index, physical fitness, and the cardiovascular risk profile in 3127 young normal weight men with an apparently optimal lifestyle.

Obesity is a well-accepted cardiovascular risk factor associated with hypertension and hyperlipidaemia. A body mass index (BMI) within the range of 18.5-25 kg/m(2) is considered normal. To prevent cardiovascular diseases regular physical activity and abstinence from smoking are strongly recommended. Since it is not evident that a lower optimal threshold exists concerning cardiovascular risk factors if other lifestyle conditions are apparently optimised, we studied the relation between BMI and vascular risk factors in 3127 hyperhealthy Caucasian males. They were aged between 18 and 23 y, were nonsmokers, without regular alcohol intake, and had at least 3 h of sports activity per week. Their BMI was below 25 kg/m(2). Low BMI revealed to be significantly associated with high physical fitness, low blood pressure, and low serum lipids. The lower the BMI was, the more favourable these parameters were. Thus, the threshold for an optimal BMI concerning cardiovascular risk factors might be far below 25 kg/m(2) even if other lifestyle conditions are apparently optimal.

Relation between the angiotensinogen (AGT) M235T gene polymorphism and blood pressure in a large, homogeneous study population.

The aim of this study was to assess the association of the angiotensinogen M235T polymorphism with arterial blood pressure (BP) at rest and under physical stress in a homogeneous large-scale study population. In all, 1903 men who passed routine medical examination for military flying duty were recruited. BP and heart rate were measured at rest, during, and after bicycle ergometry. Genotyping for the AGT M235T polymorphism was carried out by PCR and RFLP technique. The AGT T235 allele was associated with a significantly higher diastolic BP (n=1903; MM 81+/-8, MT 83+/-7, TT 83+/-8; P=0.003). Pulse pressure (PP) at rest differed significantly between AGT genotypes (n=1903; MM 51+/-10 mmHg, MT 49+/-10 mmHg, TT 49+/-10 mmHg; P=0.001). During physical activity, BP values showed no significant difference between genotypes. In healthy young men, the AGT T235 allele is significantly associated with elevated diastolic BP but also reduced PP at rest. During physical activity, the AGT polymorphism had no impact on blood pressure, indicating the existence of other counteracting mechanisms, which might balance the influence of this gene.

The vitamin D receptor gene variant and physical activity predicts fasting glucose levels in healthy young men.

AIMS: Vitamin D can influence lipolysis and insulin secretion. A common genetic polymorphism of the vitamin D receptor (VDR), which has been found to be associated with bone mineral density, has been reported to be also associated with Type 2 diabetes mellitus (DM). To test the influence of the VDR polymorphism on fasting glucose in healthy young men before the onset of Type 2 DM, we studied a homogeneous population of aircrew members. METHODS: A total of 1539 individuals were recruited during routine medical qualification for flying duty. Physical activity was assessed in all individuals and categorized into low physical activity ( 3 h per week). The BsmI VDR polymorphism was analysed by polymerase chain reaction. On the day of blood testing the individuals were fasting for at least 8 h overnight. Serum glucose was measured within 60 min after sampling venous blood. RESULTS: In young males with low physical activity (n = 752) gene carriers with the VDR genotype BB (n = 137) have significantly (P < 0.001) higher levels of fasting glucose (5.61 +/- 0.49 mmol/l) than gene carriers with the genotype Bb (n = 370; 5.44 +/- 0.44 mmol/l) or bb (n = 245; 5.38 +/- 0.44 mmol/l). Of BB gene carriers, 47% had fasting glucose levels > 5.55 mmol/l compared with 36% of Bb gene carriers and 34% of bb gene carriers (P = 0.018). This effect is absent in gene carriers with high physical activity (n = 787). CONCLUSIONS: The VDR genotype is associated with altered fasting glucose levels in young men with low physical activity. If this association is confirmed in other populations it might be worthwhile studying the particular benefits of an exercise programme in dependents of the VDR genotype.

Vitamin D receptor gene polymorphism BsmI is not associated with the prevalence and severity of CAD in a large-scale angiographic cohort of 3441 patients.

BACKGROUND: Recent studies found a relationship between Vitamin D and atherosclerosis. A common genetic polymorphism of the Vitamin D receptor (VDR) has been associated with coronary artery disease (CAD) in small study populations. To assess its influence on the prevalence and severity of CAD we studied a large-scale population. METHODS: A total of 3441 consecutive patients were referred for diagnostic coronary angiography. The BsmI Vitamin D receptor polymorphism was analyzed by polymerase chain reaction. Angiography was used to define phenotypes with clear coronary arteries (n = 775), coronary sclerosis (diameter stenosis < 50%; n = 579), CAD (diameter stenosis > 50% in at least one vessel; n = 1524). Patients with CAD at a young age (females aged less than 65 years, males aged less than 55 years; n = 563) were specially defined as premature CAD. The risk profile of traditional cardiovascular risk factors was obtained for every patient. RESULTS: The genotype frequencies of the VDR BsmI polymorphism did not differ between all four phenotypes (P = 0.756). The allele frequencies for the B allele were 0.43 vs. 0.44 vs. 0.42 vs. 0.45 in the four phenotypic groups (P = 0.827). All traditional cardiovascular risk factors (hypercholesterolaemia, smoking, hypertension, diabetes mellitus, severe obesity, male gender) were significantly (P < 0.001) associated with the angiographic phenotype. CONCLUSIONS: The VDR gene variant BsmI was not associated with prevalence and severity of CAD in a large-scale cohort phenotyped by angiography.