Health related quality of life and psychological wellbeing in patients with dilated cardiomyopathy

OBJECTIVE—To assess the health related quality of life and psychological wellbeing of patients with dilated cardiomyopathy, and relate these to clinical variables and psychological adjustment.
DESIGN—Postal questionnaire survey of 99 adult patients with dilated cardiomyopathy, selected at random from a larger database (60.6% response rate). Assessments included the short form 36 (SF-36) health survey, the hospital anxiety and depression scales, the sleep problems index, and a measure of psychological adjustment to cardiomyopathy.
RESULTS—Patients with dilated cardiomyopathy reported significant impairments in physical functioning, role limitations owing to physical and emotional problems, social functioning, mental health, perceptions of general health, sleep, and vitality. Anxiety and depression levels were higher than in population samples. Impairment in several domains of quality of life was associated with low shortening fraction, high left ventricular end diastolic diameter, and the presence of heart failure and mitral regurgitation. Patients with familial cardiomyopathy had less impairment in quality of life than those with non-familial disease. Psychological adjustment scores were associated with several aspects of quality of life and emotional wellbeing. In multivariate analysis, demographic and clinical variables accounted for 0.1-40.7% of the variance in different domains of quality of life, and psychological adjustment scores accounted for an additional 0.5-22.4% of variance.
CONCLUSIONS—Patients with dilated cardiomyopathy experience pronounced restrictions in quality of life and psychological wellbeing. These limitations are only partly accounted for by symptoms and the severity of underlying disease. Patients may benefit from efforts to improve psychological adjustment to the condition.


Keywords: dilated cardiomyopathy; quality of life; adjustment; wellbeing     

Stress responsivity and socioeconomic status: a mechanism for increased cardiovascular disease risk?

AIMS: Low socioeconomic status is associated with increased cardiovascular disease risk. We hypothesized that psychobiological pathways, specifically slow recovery in blood pressure and heart rate variability following mental stress, partly mediate social inequalities in risk. METHODS AND RESULTS: Participants were 123 men and 105 women in good health aged 47-58 years drawn from the Whitehall II cohort of British civil servants. Grade of employment was the indicator of socioeconomic status. Cardiovascular measures were monitored during performance of two behavioural tasks, and for 45 min following stress. Post-stress return of blood pressure and heart rate variability to resting levels was less complete after 45 min in the medium and low than in the high grade of employment groups. The odds of failure to return to baseline by 45 min in the low relative to the high grade of employment groups were 2.60 (95% CI 1.20-5.65) and 3.85 (1.48-10.0) for systolic and diastolic pressure, respectively, and 5.19 (1.88-18.6) for heart rate variability, adjusted for sex, age, baseline levels and reactions to tasks. Subjective ratings of task difficulty, involvement and stress did not differ by socioeconomic status. CONCLUSIONS: Lower socioeconomic status is associated with delayed recovery in cardiovascular function after mental stress. Impaired recovery may reflect heightened allostatic load, and constitute a mechanism through which low socioeconomic status enhances cardiovascular disease risk.     

Hematopoetic precursors respond to a unique B lymphocyte-derived factor in vivo

In this study we detected a factor that stimulates the proliferation of bone marrow-derived hematopoietic precursors in diffusion chambers implanted in mice. This factor, called diffusible colony-stimulating factor (D-CSF), was found in medium conditioned in the presence of spleen and peripheral blood cells from mice with B cell leukemia (BCL1). After the administration of D-CSF, the number of colonies formed in the plasma clot inside the chamber (CFU-DG) was increased, as were the number of hematopoietic precursors (CFU-MIX, CFU-S, CFU-C, and BFU-E) as judged by a subculture of diffusion chamber contents. Depletion of macrophages and T cells from the spleen cell suspension did not decrease the production of D-CSF, thereby indicating that it was derived from B cells. Neoplastic BCL1 cells appear to be the source because D-CSF could not be detected in medium conditioned with normal B cells. BCL1-conditioned medium (CM) did not enhance CFU-MIX, BFU-E, and CFU-C colony formation in vitro, which suggested that D-CSF is different from multi-CSF, EPA, or CSF. The addition of BCL1 CM to multi- CSF-, erythroid potentiating activity (EPA), and CSF (EL-4CM)- containing cultures had no effect on CFU-MIX, BFU-E, and CFU-C colony formation, thus indicating the absence of a synergistic or inhibitory activity. On the other hand, EL-4 CM, which stimulates CFU-MIX, BFU-E, and CFU-C in vitro, had no effect on CFU-DG in vivo. Biochemical characterization of BCL1 CM revealed that D-CSF is relatively heat stable and loses its bioactivity with protease treatments. It binds to lentil-lectin, according to gel-filtration chromatography has a relative molecular weight of approximately 43,000, and on reverse-phase high-performance liquid chromatography elutes with acetonitrile. These data also indicate that transformed B cells may serve as a source for hematopoietic regulators that act on hematopoietic precursors in vivo.     

A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras-transformed rat intestinal epithelial cells

BACKGROUND & AIMS: Constitutive expression of cyclooxygenase 2 (COX-2) has been found in 85% of colorectal cancers. Ras mutations are found in 50% of colorectal adenocarcinomas. The aim of this study was to determine the role of COX-2 in ras-induced transformation in rat intestinal epithelial (RIE) cells. METHODS: Cell growth was determined by cell counts. The expression of COX-2 was examined by Northern and Western analyses. For tumorigenicity assays, cells were inoculated into dorsal subcutaneous tissue of athymic nude mice. DNA-fragmentation assays were performed to detect apoptosis. RESULTS: The expression of COX-2 was increased in RIE-Ras cells at both messenger RNA (9-fold) and protein (12-fold) levels. Prostaglandin I2 levels were elevated 2.15-fold in RIE-Ras cells. Serum deprivation further increased COX-2 expression 3.8-fold in RIE-Ras cells. Treatment with a selective COX-2 antagonist (SC58125) inhibited the growth of RIE-Ras cells through inhibition of cell proliferation and by induction of apoptosis. SC-58125 treatment reduced the colony formation in Matrigel by 83.0%. Intraperitoneal administration of SC-58125 suppressed RIE-Ras tumor growth in nude mice by 60.3% in 4 weeks. SC-58125 treatment also induced apoptosis in RIE-Ras cells as indicated by increased DNA fragmentation. CONCLUSIONS: Overexpression of COX-2 may contribute to tumorigenicity of ras-transformed intestinal epithelial cells. Selective inhibition of COX-2 activity inhibits growth of ras-transformed intestinal epithelial cells and induces apoptosis. (Gastroenterology 1997 Dec;113(6):1883-91)     

The influence of psychological stress and socioeconomic status on platelet activation in men

OBJECTIVE: Circulating monocyte- and neutrophil-platelet aggregates are sensitive markers of in vivo platelet activation. Socioeconomic status is inversely associated with risk of coronary heart disease. We assessed the impact of psychological stress on leukocyte-platelet aggregates in men from higher and lower socioeconomic status groups. METHODS: Participants were 37 healthy non-smoking men aged 30-59 years, divided by occupation into higher and lower social status groups. Blood was drawn at baseline, immediately following stressful behavioural tasks, and at 30 and 75 min post-stress, and aggregates were analysed using flow cytometry. Cardiovascular and subjective stress responses were also monitored. RESULTS: There were significant increases following stress in monocyte-, neutrophil-, lymphocyte- and total leukocyte-platelet aggregates (all P<0.05). The largest responses were in monocyte-platelet (21% increase) and neutrophil-platelet (16.7% increase) aggregates. Lower socioeconomic status men had greater numbers of leukocyte-platelet aggregates throughout, but the magnitude of stress responses did not vary with social status. The increase in monocyte- and leukocyte-platelet aggregates was associated with systolic blood pressure stress responsivity. CONCLUSIONS: Psychological stress induces platelet activation as indexed by leukocyte-platelet aggregates, and correlations with cardiovascular stress reactions suggest that sympathoadrenal responses may be responsible. Platelet activation may be a mechanism through which social position influences cardiovascular disease risk.     

Estimation of fruit and vegetable intake using a two-item dietary questionnaire: a potential tool for primary health care workers

BACKGROUND AND AIM: High fruit and vegetable intake is associated with health benefits for cancer and cardiovascular disease. An increase is therefore integral in recommendations for the prevention of chronic disease. However, measuring intake requires either extensive dietary assessment or the measurement of specific bio-markers which is neither cheap nor feasible for the routine assessment of an individual's diet in a community or primary care setting. Within the context of a study evaluating a dietary counselling programme to increase fruit and vegetable intake our aim was to assess the use of a simple tool to estimate fruit and vegetable intake. METHODS AND RESULTS: We studied associations between bio-markers [plasma ascorbic acid, beta-carotene and alpha-tocopherol 24-hour urinary potassium excretion] and a two-item fruit and vegetable consumption questionnaire in 271 subjects (105 men and 166 women), aged 18 to 70 years. After controlling for age, sex, vitamin supplement use, smoking and body mass, those reporting a daily intake of > or = 5 portions of fruit and vegetables had higher potassium excretion (difference 15.6 [95% confidence interval: 6.2 to 25.0] mmol/24 h), urinary potassium/creatinine ratio (1.2 [0.5 to 2.0]) and plasma vitamin C (10.0 [-0.9 to 20.8] mumol/L) than those reporting < or = 2.5 portions per day. beta-carotene (p = 0.04), vitamin C (p = 0.01) and potassium excretion (p < 0.001) were associated with fruit rather than vegetable intake. The two-item questionnaire had high specificity; over 3/4 of participants who reported low intake also had bio-markers below the upper third of the distribution. CONCLUSION: Self report of fruit and vegetable intake through a simple questionnaire is confirmed by bio-markers for those eating less than five portions of fruit and vegetables a day. Although the tool is amenable to improvements for the detection of vegetable portions, it may prove useful for monitoring dietary preventive approaches in primary care without the use of invasive and costly biochemical measurements.     

Hypertension is not the link between job strain and coronary heart disease in the Whitehall II study

BACKGROUND: Hypertension is assumed to be one of the mechanisms through which job strain (a combination of high work demands and low job control) increases coronary heart-disease risk. However, direct tests of this hypothesis are lacking. METHODS: We examined whether hypertension mediated the association between job strain and incident coronary heart disease among 5630 men and 2456 women free of coronary heart disease at study entry. Job strain was assessed at phase 1 (1985 to 1988); hypertension and systolic and diastolic blood pressure (BP) were assessed at phases 1, 3 (1992 to 1993), and 5 (1997 to 1999); and incident coronary heart disease was assessed from the end of phase 1 to phase 7 (2003 to 2004) (698 events; median follow-up, 16.1 years). RESULTS: After adjustment for age, sex, ethnicity, and employment grade, job strain was associated with an increased incidence of coronary heart disease. Further adjustments, for hypertension, systolic BP, and diastolic BP at phase 1 and across phases 1, 3, and 5, and the slope of hypertension and BP over time, had little effect on this association, although measures of hypertension and BP were strongly related to incident coronary heart disease. CONCLUSIONS: Data, including repeated casual measurements of hypertension and BP, suggest that the development of chronic hypertension is not a key mechanism linking job strain and coronary heart disease. Further research on ambulatory measurements is needed to determine whether episodic BP elevations have a role in this association.     

CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis

CD4(+)CD25(+) regulatory T cells (Treg) play a crucial role in the regulation of immune responses. Although many mechanisms of Treg suppression in vitro have been described, the mechanisms by which Treg modulate CD8(+) T cell differentiation and effector function in vivo are more poorly defined. It has been proposed, in many instances, that modulation of cytokine homeostasis could be an important mechanism by which Treg regulate adaptive immunity; however, direct experimental evidence is sparse. Here we demonstrate that CD4(+)CD25(+) Treg, by critically regulating IL-2 homeostasis, modulate CD8(+) T-cell effector differentiation. Expansion and effector differentiation of CD8(+) T cells is promoted by autocrine IL-2 but, by competing for IL-2, Treg limit CD8(+) effector differentiation. Furthermore, a regulatory loop exists between Treg and CD8(+) effector T cells, where IL-2 produced during CD8(+) T-cell effector differentiation promotes Treg expansion.