Orthostatic hypotension and risk of cardiovascular disease in elderly people: the Rotterdam study

OBJECTIVES: To determine the prognostic role of orthostatic hypotension for cardiovascular disease (CVD) and all‐cause mortality in elderly people. DESIGN: Prospective study. SETTING: Community based. PARTICIPANTS: Five thousand sixty‐four subjects from the Rotterdam study aged 55 and older. MEASUREMENTS: Orthostatic hypotension was measured using a Dinamap automatic blood pressure recorder. Orthostatic hypotension is defined as a decline in systolic blood pressure of 20 mmHg or more or a decline in diastolic blood pressure of 10 mmHg or more from supine to standing position at any of three measurements taken 1, 2, and 3 minutes after standing. RESULTS: At baseline, 901 subjects had orthostatic hypotension. During follow‐up, 668 subjects had coronary heart disease (CHD) (mean follow‐up 6.0 ± 3.5 years), and 1,835 subjects died (mean follow‐up period 7.8 ± 3.8 years). Orthostatic hypotension increased the risk of CHD (hazard ratio (HR)=1.31, 95% confidence interval (CI)=1.08–1.57) and all‐cause mortality (HR=1.22, 95% CI=1.09–1.36), in models adjusted for age and sex. The risk was slightly lower after additional adjustment for cardiovascular risk factors. In analyses stratified for age, the HRs for all‐cause mortality were 1.80 (95% CI 1.25–2.60), 1.13 (0.89–1.42), and 1.27 (95% CI=1.11–1.44), in the first, second, and third tertile of age, respectively. CONCLUSION: Orthostatic hypotension increases the risk of CHD and all‐cause mortality in elderly people. The risk of CVD and mortality is strongest in younger and very old subjects.     

Social Role Participation and Satisfaction With Life: A Study Among Patients With Ankylosing Spondylitis and Population Controls

Objective

Participation in society of persons with chronic diseases receives increasing attention. However, little is known about which components of participation are most relevant to life satisfaction. This study examines the association between several aspects of social role participation and satisfaction with life (SWL) in patients with ankylosing spondylitis (AS) compared to population controls.

Methods

In a cross‐sectional study, participants completed the Social Role Participation Questionnaire (SRPQ) and SWL scale. The SRPQ assesses several dimensions of participation (importance, satisfaction with performance, and satisfaction with time and physical difficulty) in 11 roles representing 3 domains (interpersonal relations, leisure, and work). For individuals with AS and controls, the association between role domains and SWL was examined using linear regression for each participation dimension separately, in the total and the employed population, adjusting for age, sex, education, and income.

Results

A total of 246 AS patients (mean ± SD age 51 ± 12 years, 62% males, mean ± SD disease duration 17 ± 12 years) and 510 controls (mean ± SD age 42 ± 15 years, 70% males) were included. AS patients were more frequently (extremely) dissatisfied with life (17.9% versus 8.6%; P < 0.05). In the total and the employed population, less physical difficulty and higher satisfaction with interpersonal relations and leisure were associated with higher SWL, and this was somewhat stronger in patients than in controls (P < 0.1). In employed controls, but not in employed patients, satisfaction with work was independently associated with SWL.

Conclusion

These findings highlight the importance of supporting persons with AS in ameliorating social role participation, particularly in areas like close relationships and leisure activities, which are typically ignored when treating AS.

     

Primary genotypic resistance of HIV-1 to CCR5 antagonists in CCR5 antagonist treatment-naive patients

Resistance to CCR5 antagonists can be driven by mutations in gp120. Sequences from 323 anti-CCR5 naive patients were analyzed for the presence of previously described in-vivo or in-vitro resistance mutations to CCR5 antagonists located in the V3 loop of gp120. The V3 loop region was rather polymorphic, and 7.3% of patients showed viruses with combinations of mutations in V3 loop previously described to be involved in maraviroc resistance, a licensed CCR5 antagonist.     

Differential expression of galectin-3 in medullary thyroid carcinoma and C-cell hyperplasia

OBJECTIVE AND DESIGN: Galectin-3 is a beta-galactoside-binding protein that plays a role in cell adhesion and tumour progression. It was shown recently to diagnose malignant follicular thyroid lesions accurately. The reliability of this marker in the differential diagnosis between medullary thyroid carcinoma and C-cell hyperplasia was studied by immunohistochemistry. PATIENTS: Tissue specimens were obtained from 34 patients belonging to families with medullary thyroid carcinoma who underwent prophylactic thyroidectomy for RET gene mutation and/or abnormally increased plasma calcitonin levels. RESULTS: Galectin-3 was expressed in 23 of 25 cases of medullary thyroid carcinoma and in none of the nine cases of C-cell hyperplasia only, giving a sensitivity of 92% and a specificity of 100% for the diagnosis of carcinoma. A significant association was found between higher galectin-3 expression and occurrence of lymph node metastases (P < 0.05). CONCLUSIONS: Galectin-3 is a reliable diagnostic marker of medullary thyroid carcinoma, and its use may provide relevant information for prognosis and therapy.     

Detection of high frequencies of HIV-1 cross-subtype reactive CD8 T lymphocytes in the peripheral blood of HIV-1-infected Kenyans

OBJECTIVES: To quantitate rapidly the frequency of HIV-1 subtype-specific and broadly HIV-1 cross-subtype-reactive CD8 T cells in the peripheral blood of HIV-1-infected individuals from a geographical region of multiple subtype endemicity. METHODS: Autologous B-lymphoblastoid cell lines infected with recombinant vaccinia-viruses expressing gag, env and nef gene products from HIV-1 subtypes A-H were used as antigen-presenting cells to stimulate CD8 T cells from cryopreserved peripheral blood mononuclear cells. Cross-subtype and subtype-specific CD8 cell responses were assessed by flow cytometry for the upregulation of IFN-gamma gene expression in specifically activated CD8 T cells. RESULTS: Strikingly high frequencies of circulating CD8 T cells (up to 11.3% of peripheral CD8 T cells) with specificity for HIV-1 were detectable using this methodology. Both subtype-specific and broadly cross-subtype-reactive CD8 T cells were detected as assessed by IFN-gamma production after stimulation. The pattern of cross-subtype reactivity appeared to be random when the results were assessed as a population, but analysis of the full-length sequence of the infecting virus for each individual showed some skewing of the CD8 cell response towards the infecting subtype. CONCLUSION: High frequencies of HIV-1 cross-subtype-reactive peripheral CD8 T cells can be detected in individuals from a multiple subtype endemic region, providing an incentive for vaccine advancement in such locations. The future assessment of the subtype specificity of cellular immune responses requires full-length sequencing of the infecting virus in conjunction with a comprehensive analysis of phenotypic and functional parameters.