Psychosocial factors in coronary heart disease -- scientific evidence and recommendations for clinical practice

Psychosocial risk factors like low socio-economic status, lack of social support and social isolation, chronic work or family stress, as well as negative emotions, e. g. depression and hostility, contribute significantly to the development and adverse outcome of coronary heart disease (CHD). Negative effects of psychosocial risk factors are conveyed via behavioural pathways including unhealthy lifestyle, e. g. food choice, smoking, sedentary life, inadequate utilisation of medical resources, and psychobiological mechanisms like disturbed autonomic and hormonal regulation: all these factors contribute to metabolic dysfunction and inflammatory and haemostatic processes, which are directly involved in the pathogenesis of CHD. Interventions to improve pychosocial factors are available and have demonstrated positive effects on risk factors and - at least in part - on CHD morbidity and mortality. The prevention of CHD should therefore include screening for psychosocial risk factors and adequate interventions. Recommedations for the screening of risk factors, behavioural change and further management of psychosocial risk factors in clinical practice are pointed out.     

Sociodemographic factors associated with calcium intake in premenopausal women: a cross-sectional study

OBJECTIVE: To describe associations between sociodemographic factors and calcium intake in premenopausal women. DESIGN: Cross-sectional study. SETTING: Population-based. SUBJECTS: A total of 467 randomly selected, predominantly Caucasian Tasmanian women aged 25-44 y, response rate 63%. MAIN OUTCOME MEASURES: calcium intake, sociodemographic factors, anthropometrics, osteoporosis knowledge and self-efficacy. RESULTS: Education level, calcium-specific osteoporosis knowledge and self-efficacy were all independently associated with calcium intake (P<0.05). The odds of achieving the recommended dietary intake for calcium increased with higher levels of calcium-specific self-efficacy and knowledge, and decreased in smokers or if the household's main financial provider was unemployed (P<0.05). CONCLUSIONS: Women who have lower levels of education, who are in households where the main financial provider is unemployed, who are smokers, and those with low levels of calcium-specific self-efficacy and knowledge are at risk of not achieving adequate calcium intake. This information will assist targeting of public health strategies aimed at improving the calcium intake of premenopausal women.     

Use of proximal aortic cuffs as an adjunctive procedure during endovascular aortic aneurysm repair

The purpose of this study was to evaluate the incidence and durability of additional proximal cuffs during endovascular abdominal aortic aneurysm repair (EVAR). A retrospective review of 90 EVAR patients was conducted. Postoperative survival, proximal sealing zone-related complications, and secondary procedures were analyzed. Additional proximal cuffs were used in 11%. Their use did not affect postoperative survival (p = .58), type I endoleak rate (4.4%; p = .19), or the need for sealing zone-related secondary procedures (6.3%; p = .38) compared with patients without cuff placement but was related to a higher cumulative graft migration rate (2.2% overall p = .02). Two patients (2.5%; p = .79) underwent conversion to open surgery, both for proximal sealing zone-related complications. Application of proximal cuffs appears to be an effective intraoperative adjunctive procedure to achieve a proximal seal during EVAR, with favorable midterm results. However, the risk of late endograft migrations may be elevated in this group.     

Thoracic wall involvement by Hodgkin disease and non-Hodgkin lymphoma: CT evaluation

Thoracic computed tomographic (CT) scans of 250 patients with newly diagnosed or recurrent lymphoma revealed thoracic wall involvement in 24 patients (11 with Hodgkin disease, 13 with non-Hodgkin lymphoma). Thoracic wall involvement occurred without contiguous mediastinal or parenchymal involvement in 17 patients. Of these, 13 patients had masses beneath the pectoralis muscles or within the breast, and four had masses arising from the ribs. Five additional patients had mediastinal masses with thymic involvement and parasternal extension through the thoracic wall. Pulmonary parenchymal lymphoma with thoracic wall invasion was noted in the remaining two patients. In five of nine patients receiving radiation therapy, treatment plans were modified by CT demonstration of thoracic wall lymphoma.     

VKORC1 haplotypes and their impact on the inter-individual and inter-ethnical variability of oral anticoagulation

In order to elucidate the role of VCORC1 sequence variants in warfarin sensitivity, we established a complete SNP map of the VKORC1 gene locus in 200 blood donors from Western Germany. Nearly all of the genetic variability of the VKORC1 gene in Europeans is reflected by three main haplotypes. Recently described polymorphisms associated with low warfarin dose requirement (dbSNP:rs9934438; dbSNP:rs17878363) were found in complete linkage disequilibrium with the VKORC1*2 haplotype. In two patient cohorts of European origin with either increased coumarin sensitivity (n= 14) or partial coumarin resistance (n=36) the VKORC1*2 frequency varied highly significant between the two groups and also when compared to 200 blood donor controls (coumarin sensitive 96%, coumarin resistant 7%, controls 42%) thus demonstrating a strong association between these two phenotypes and the VKORC1 haplotype (p = 1.6 x 10(-8) for coumarin sensitive and p = 1.9 x 10(-8) for coumarin resistant). Analysis of database derived VKORC1 genotypes of African Americans and Chinese revealed that haplotype frequencies in these populations differ significantly from the European sample (for VKORC1*2: Europeans 42%, Chinese 95%, African Americans 14%). These observations suggest VKORC1 as principal genetic modulator of the ethnic differences in warfarin response. Since hereditary pharmacodynamic (VKORC1) and pharmacokinetic (CYP2C9) factors account for up to 50% of the inter-individual variability of the warfarin response, these genetic markers may serve as clinically relevant predictors of warfarin dosing in future studies.     

Site-directed mutagenesis of coumarin-type anticoagulant-sensitive VKORC1: evidence that highly conserved amino acids define structural requirements for enzymatic activity and inhibition by warfarin

Coumarin and homologous compounds are the most widely used anticoagulant drugs worldwide. They function as antagonists of vitamin K, an essential cofactor for the posttranslational gamma-glutamyl carboxylation of the so-called vitamin K-dependent proteins. As vitamin K hydroquinone is converted to vitamin K epoxide (VKO) in every carboxylation step, the epoxide has to be recycled to the reduced form by the vitamin K epoxide reductase complex (VKOR). Recently, a single coumarin-sensitive protein of the putative VKOR enzyme complex was identified in humans (vitamin K epoxide reductase complex subunit 1, VKORC1). Mutations in VKORC1 result in two different phenotypes: warfarin resistance (WR) and multiple coagulation factor deficiency type 2 (VKCFD2). Here,we report on the expression of site-directed VKORC1 mutants, addressing possible structural and functional roles of all seven cysteine residues (Cys16, Cys43, Cys51, Cys85, Cys96, Cys132, Cys135), the highly conserved residue Ser/Thr57, and Arg98, known to cause VKCFD2 in humans. Our results support the hypothesis that the C132-X-X-C135 motif in VKORC1 comprises part of the redox active site that catalyzes VKO reduction and also suggest a crucial role for the hydrophobic Thr-Tyr-Ala motif in coumarin binding. Furthermore, our results support the concept that different structural components of VKORC1 define the binding sites for vitamin K epoxide and coumarin.     

Aortic aneurysm repair is associated with a lower inflammatory response compared with surgery for inflammatory bowel disease

BACKGROUND: Since the plasma cytokine profile reflects the body's inflammatory response to injury, this study was designed to prospectively observe the plasma cytokine levels in response to the degree of different sorts of abdominal surgical trauma. METHODS: Plasma levels of TNF-alpha, type I TNF receptor (p55), type II TNF receptor (p75), IL-6, IL-8, IL-10, phospholipase A(2) (PLA(2)), and haptoglobin were measured peri-operatively in patients undergoing bowel resection for inflammatory bowel disease or diverticulitis (IBD) (n = 9), elective repair of abdominal aortic aneurysm (AAA) (n = 9), or laparoscopic cholecystectomy (lap chole) (n = 9). RESULTS: The IBD patients showed a significant (p < 0.05) post-operative elevation in plasma IL-6, p55, p75, and PLA(2) levels, but no significant change in TNF-alpha, IL-8, IL-10 or haptoglobin levels. The AAA patients had a significant post-operative rise in IL-10 levels and a significant decrease in plasma haptoglobin levels, but no significant change of TNF-alpha, IL-6, IL-8, p55, p75, or PLA(2) concentrations. The lap chole patients demonstrated no significant change in any of these parameters. CONCLUSION: These data show that IL-6, IL-10, p55, and p75 are markers to measure the degree of inflammatory stress associated with abdominal operative procedures and demonstrate the relative lack of a cytokine response to laparoscopic cholecystectomy.