Distinguishing independent and shared effects of material/structural conditions and psychosocial resources on educational inequalities in self-rated health: results from structural equation modelling.

OBJECTIVES: The aim of this study was to distinguish independent and shared effects of material/structural factors and psychosocial resources in explaining educational inequalities in self-rated health (SRH) by using structural equation modelling. STUDY DESIGN: Cross-sectional survey. METHODS: Data were derived from a questionnaire sent to a random sample of the population in five counties in Sweden in 2008. The study population (aged 25-75 years) included 15,099 men and 17,883 women. Exploratory structural equation modelling was used to analyse the pathways from educational level to SRH. RESULTS: The pathway including both material/structural factors (e.g. financial buffer and unemployment) and psychosocial resources (e.g. sense of coherence and social participation) explained about 40% of educational differences in SRH for both men and women. The pathways including only the independent effects of psychosocial resources (14% in men and 20% in women) or material/structural factors (9% and 18%, respectively) explained substantial but smaller proportions of the differences. CONCLUSIONS: The major pathway explaining educational inequalities in SRH included both material/structural factors and psychosocial resources. Therefore, to reduce educational inequalities in SRH, interventions need to address both material/structural conditions and psychosocial resources across educational groups.

Patient-reported outcomes in the Swedish National Quality Registers.

Patient-reported outcomes (PROs) are important in the healthcare system to gain understanding of patients' views on the effects of a treatment. There is an abundance of available patient-reported outcome measures (PROMs), both disease specific and generic. In the Swedish healthcare system, the national quality registers are obliged to incorporate PROs for certification at a high level. A review of the latest annual applications for funding (n = 108) shows that at present, 93 national quality registers include some form of PROM or patient-reported experience measure (PREM). Half of the registers include some type of generic measure, more than half include disease/symptom-specific measures, and around 40% include PREMs. Several different measures and combinations of measures are used, the most common of which are the EQ-5D, followed by the SF-36/RAND-36. About one-fifth of the registers report examples of how patient-reported data are used for local quality improvement. These examples include enhancing shared decision-making in clinical encounters (most common), as a basis for care plans, clinical decision aids and treatment guidelines, to improve the precision of indications for surgery (patient and healthcare professional assessments may differ), to monitor complications after the patient has left hospital and to improve patient information. In addition, funding applications reveal that most registers plan to extend their array of PROMs and PREMs in future, and to increase their use of patient-reported data as a basis for quality improvement.

Provitamin A carotenoids are independently associated with matrix metalloproteinase-9 in plasma samples from a general population.

BACKGROUND AND AIM: Carotenoids in plasma are inversely associated with cardiovascular risk. Low levels can be explained by low dietary intake but also by a number of other factors including inflammatory activity. Given that matrix metalloproteinase (MMP)-9 has an important role in inflammation and cardiovascular disease, we hypothesized that circulating MMP-9 levels would be inversely related to total or single carotenoids in a general population cohort. METHODS: A well-characterized population-based cohort of 285 Swedish men and women (45-69 years) was used for the present study. The intake of carotenoid-rich fruits and vegetables was estimated from a food frequency questionnaire. Levels of MMP-9, C-reactive protein (CRP), interleukin (IL)-6 and six major carotenoids [ß-cryptoxanthine, α-carotene, ß-carotene, lutein (+zeaxanthin) and lycopene] were determined in plasma. RESULTS: Lower plasma levels of total and single carotenoids were associated with lower dietary intake of carotenoids, older age, male sex, lower physical activity, higher alcohol consumption, higher body mass index (BMI), higher systolic and diastolic blood pressures, lower levels of total cholesterol and HDL cholesterol and higher levels of CRP, IL-6 and MMP-9. After multivariate adjustments, plasma levels of total carotenoids and provitamin A carotenoids (ß-cryptoxanthine, α-carotene and ß-carotene) remained independently associated with sex, dietary intake of carotenoids, BMI, HDL cholesterol and MMP-9, whilst associations with CRP and IL-6 were not maintained. Neither dietary intake of carotenoid-rich fruits and vegetables, nor vitamin supplement use was associated with MMP-9, CRP or IL-6 levels. CONCLUSION: Plasma carotenoids were associated with a variety of factors including age, sex, dietary intake and metabolic variables. A new finding was the independent relationship in plasma between low provitamin A carotenoids and high MMP-9, suggesting a link between these carotenoids, matrix turnover and arterial remodelling.

Elevated levels of circulating matrix metalloproteinase-9 are associated with a dysregulated cortisol rhythm--A case-control study of coronary artery disease.

A dysregulated cortisol pattern has been found to be associated with systemic inflammatory activity in patients with coronary artery disease (CAD). Matrix metalloproteinase (MMP)-9 is involved in both inflammation and matrix degradation and considered a main contributor to coronary plaque rupture. In this study, we hypothesized that a dysfunctional cortisol response also involved a failure to regulate systemic MMP-9 levels in CAD patients. Total MMP-9, active MMP-9 and the endogenous inhibitor TIMP-1 were measured in 30 CAD patients and 30 healthy controls. Morning and evening cortisol was measured in repeated saliva samples. Patients had higher levels of total and active MMP-9 (both p<0.01) and increased 24-h cortisol output (p<0.05) characterized by higher levels of evening cortisol (p=0.011). MMP-9 was associated with evening cortisol (p<0.001) independent of smoking and inflammatory markers. Compared with controls, patients also showed a blunted cortisol response to stress. After stress, the levels of MMP-9 became significantly reduced in controls whereas they remained unchanged in patients. The data indicate that MMP-9 is differently regulated in patients due to a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis and emphasize the role of MMP-9 as a possible link between stress and cardiovascular disease.

Correlation between rises in Chlamydia pneumoniae-specific antibodies, platelet activation and lipid peroxidation after percutaneous coronary intervention.

We recently showed that Chlamydia pneumoniae activates platelets in vitro, with an associated oxidation of low-density lipoproteins. The aim of this study was to investigate whether C. pneumoniae is released during percutaneous coronary intervention (PCI) and, thereby, causes platelet activation and lipid peroxidation. Seventy-three patients undergoing coronary angiography and following PCI or coronary artery bypass graft (CABG) and 57 controls were included in the study. C. pneumoniae antibodies, serotonin and lipid peroxidation were measured before and 24 h, 1 month and 6 months after angiography. The results show that serum C. pneumoniae IgA concentrations were significantly higher in patients than in the controls. Furthermore, in 38% of the C. pneumoniae IgG positive patients, the C. pneumoniae IgG concentration increased 1 month after PCI. The levels of C. pneumoniae IgG antibodies 1 month after PCI correlated with plasma-lipid peroxidation (r = 0.91, P < 0.0001) and platelet-derived serotonin (r = 0.62, P = 0.02). There was no elevation in the total serum IgG 1 month after PCI. In conclusion, the present results suggest that PCI treatment of coronary stenosis releases C. pneumoniae from the atherosclerotic lesions, which leads to platelet activation and lipid peroxidation.

Impaired cortisol response to acute stressors in patients with coronary disease. Implications for inflammatory activity.

OBJECTIVES: Inflammation is assumed to play a major role in the progress of atherosclerotic disease. We hypothesized that an altered hypothalamic-pituitary adrenal (HPA) axis activity was linked to a disinhibited inflammatory activity in patients with coronary artery disease (CAD). METHODS: Thirty CAD patients were assessed 12-14 weeks after a first-time acute coronary syndrome. Serum samples were assayed for C-reactive protein (CRP) and interleukin-6. Free cortisol was measured in a 24-h urine sample and in repeated saliva samples 30 min after awakening and at bedtime. The levels of inflammatory markers and cortisol were also determined before and after standardized physical and psychological stress tests. RESULTS: The CAD patients had a higher 24-h cortisol secretion and a flattened diurnal slope, resulting from significantly higher cortisol levels at bedtime, compared to clinically healthy controls. The levels of evening cortisol were strongly related to inflammatory markers in serum. When exposed to acute physical and psychological stressors, the CAD patients showed a significantly blunted cortisol response compared to controls. In addition, a stress-induced increase in CRP was only observed in the patient group. CONCLUSIONS: Patients with CAD exhibited a cortisol pattern that markedly differed from controls. The data indicate that a dysfunctional HPA axis response involves a failure to contain inflammatory activity in CAD patients, thus providing a possible link between stress and inflammation in disease.

Interleukin-6 levels in relation to psychosocial factors: studies on serum, saliva, and in vitro production by blood mononuclear cells.

Psychosocial factors and interleukin-6 (IL-6) levels are both related to risk of morbidity and mortality. The aim of this study was to investigate how a broad range of psychosocial factors related to levels of IL-6 in different media. Fifty-nine men and women aged 30-65 were recruited from a larger study and selected to cover a broad range of psychosocial status. IL-6 levels were analyzed in serum, in saliva collected at home at three different time points during a day, and in the supernatant of cell cultures stimulated in vitro with lipopolysaccharide. After adjustments for age, gender, self-reported health problems, and lifestyle factors, IL-6-levels in serum were negatively correlated with coping and self-esteem, and positively correlated with cynicism, hostile affect, hopelessness, depression, and vital exhaustion. In saliva samples, at all time points, IL-6 levels were positively correlated to cynicism, and IL-6 levels 30 min after awakening were also positively correlated with hopelessness, depression, and vital exhaustion. After adjustment for age and gender, cynicism, depression, and vital exhaustion were negatively correlated to IL-6 levels in the supernatant of cell cultures stimulated in vitro with lipopolysaccharide, but this effect was lost after control for self-reported health problems and lifestyle factors. In conclusion, we found that IL-6 levels in serum and saliva were negatively related to psychosocial resources and positively related to psychosocial risk factors. These data strengthen the argument that IL-6 is involved in mediating the risk for disease development that has been associated with psychosocial factors.

EQ-5D in a general population survey--a description of the most commonly reported EQ-5D health states using the SF-36.

The importance of studying health-related quality of life in the general population has increasingly been emphasized. From a public health perspective, this benefits the identification of population inequalities in health status. One of the currently most popular instruments is the EQ-5D. Evaluations of the EQ-5D generally focus on the overall preference-based index. As this index has a built-in value, exploration of the information from the underlying health states is also important. In this study, the ten most commonly reported EQ-5D health states are described using the SF-36. Data collected in 1999 by questionnaires mailed to a random sample aged 20-74 in south-eastern Sweden were used (n = 9489). Almost 43% reported the best possible EQ-5D health state and 78% were accounted for by three EQ-5D health states. The EQ-5D health state classification was largely reflected by the SF-36, with the EQ-5D items mobility, usual activities, pain/discomfort and anxiety/depression tapping most clearly on the SF-36 scales physical functioning, role limitations due to physical health problems, bodily pain, and mental health, respectively. However, within the same level of EQ-5D (i.e., moderate problems) there was a rather large variation of SF-36 scale scores, particularly regarding the EQ-5D item pain/discomfort and the SF-36 scale BP.

Psychobiological mechanisms of socioeconomic differences in health.

The association between low socioeconomic status and poor health is well established. Empirical studies suggest that psychosocial factors are important mediators for these effects, and that the effects are mediated by psychobiological mechanisms related to stress physiology. The objective of this paper is to explore these psychobiological mechanisms. Psychobiological responses to environmental challenges depend on acquired expectancies (learning) of the relations between responses and stimuli. The stress response occurs whenever an individual is faced with a challenge. It is an essential element in the total adaptive system of the body, and necessary for adaptation, performance and survival. However, a period of recovery is necessary to rebalance and to manage new demands. Individuals with low social status report more environmental challenges and less psychosocial resources. This may lead to vicious circles of learning to expect negative outcomes, loss of coping ability, strain, hopelessness and chronic stress. This type of learning may interfere with the recovery processes, leading to sustained psychobiological activation and loss of dynamic capacity to respond to new challenges. Psychobiological responses and health effects in humans and animals depend on combinations of demands and expected outcomes (coping, control). In studies of humans with chronic psychosocial stress, and low SES, cortisol baseline levels were raised, and the cortisol response to acute stress attenuated. Low job control was associated with insufficient recovery of catecholamines and cortisol, and a range of negative health effects. Biological effects of choice of lifestyle, which also depends on the acquired outcome expectancies, reinforce these direct psychobiological effects on health. The paper concludes that sustained activation and loss of capacity to respond to a novel stressor could be a cause of the higher risk of illness and disease found among people with lower SES.

Long chain polyunsaturated fatty acids may account for higher low-density lipoprotein oxidation susceptibility in Lithuanian compared to Swedish men.

OBJECTIVES: Mortality in coronary heart disease among middle-aged men is four times higher in Lithuania than in Sweden. Traditional risk factors cannot account for this difference. We earlier reported that low-density lipoprotein (LDL) in Lithuanian men showed a lower resistance to oxidation, measured as LDL lag time during copper oxidation, than that in Swedish men. Serum concentrations of several fat-soluble antioxidant vitamins were lower among Lithuanian men. The aim of this study was to investigate whether differences in LDL fatty acid composition could account for the difference in LDL oxidation susceptibility between men in the two countries. METHODS: This cross-sectional study included randomly selected healthy 50-year-old men from Vilnius, Lithuania (n=50) and Linköping, Sweden (n=50). Main outcome measures were fatty acids in LDL, phospholipid (PL) and cholesterol ester (CE) fractions of LDL and LDL oxidation susceptibility. RESULTS: The mean proportions of PL 20:5n3 (eicosapentaenoic acid, EPA) were higher in Vilnius men (2.09 +/- 1.05 vs. 1.53 +/- 0.58%, p= 0.004). LDL lag time was shorter in Vilnius men, mean +/- SD (75.4 +/- 13.6 vs. 89.5 +/- 13.1 mins, p<0.0001) than in Linköping men. Mean serum gamma-tocopherol was lower in Vilnius men (0.07 +/- 0.05 vs. 0.12 +/- 0.04 microg/mmol, p<0.0001) but alpha-tocopherol did not differ. In a multiple regression analysis controlled for city, high PL-EPA, low alpha-tocopherol, and high plasma triglycerides significantly contributed to a short LDL lag time, r2=0.53. CONCLUSIONS: Fat quality, i.e. poly unsaturated fatty acids, especially LDL-EPA, plasma triglycerides and antioxidative vitamins may partly account for the increased LDL oxidation susceptibility found in Vilnius men compared with Linköping men.

Risk factors for coronary heart disease in different socioeconomic groups of Lithuania and Sweden--the LiVicordia Study.

AIMS: Lithuanian middle-aged men have a fourfold higher risk for coronary heart disease (CHD) mortality compared with Swedish men. In Sweden, CHD mortality is twice as high in blue- compared with white-collar workers. Whether the same risk factors that characterized Lithuanian men, compared with Swedish men, could be found in low socioeconomic groups within the cities was investigated. METHODS: The LiVicordia study compared both traditional and new possible risk factors for CHD among 150 50-year-old men in Linköping, Sweden and Vilnius, Lithuania. A comparison was made of the prevalence of these risk factors in high and low socioeconomic groups within the cities and, after controlling for the city, variations across socioeconomic groups in the total sample. RESULTS: Small differences were found in traditional risk factors between cities. However, Vilnius men were shorter, had lower serum levels of antioxidant vitamins, more psychosocial strain, and lower cortisol response to a standardized laboratory stress test. These characteristics were also found among men in low social classes in both cities. In linear regression models, short stature, low serum beta-carotene, low social integration, coping and self-esteem, high vital exhaustion, high baseline and low cortisol response to stress were related to low social class. CONCLUSIONS: The same set of risk factors, mainly relating to oxidative and psychosocial stress, that characterized Vilnius men was also found in men in low social classes within the cities. The results suggest that a common set of risk factors may help to explain health differences both between and within countries.

Ultrasound determined carotid and femoral atherosclerosis in Lithuanian and Swedish men: the LiVicordia study.

Coronary heart disease mortality is four times higher in Lithuanian compared to Swedish middle-aged men. Using the same equipment (Acuson XP10 with 5 MHz linear transducer) and staff, we compared the amount of atherosclerosis in carotid and femoral arteries in 100 randomly sampled 50-year-old men in each of the cities Vilnius, Lithuania and Linköping, Sweden. Atherosclerotic plaques were more abundant in Vilnius men compared to Linköping men (53 versus 28% in the common carotid artery, 73 versus 37% in the common femoral artery, P < 0.001 for both). Plaques were thicker and more extended in arteries of Vilnius men, and an ultrasound atherosclerosis score was higher in both carotid and femoral arteries (P < 0.001 for all). More Vilnius men had a maximal intima-media thickness of the common femoral artery above 1 mm (P<0.005). Stiffness in the common carotid artery was higher in Vilnius men (P<0.001). In a linear regression model of the pooled material, after adjustment for city was made, smoking, systolic blood pressure, low density lipoprotein cholesterol and beta-carotene (inversely) significantly contributed to a high total ultrasound score (r2 = 0.32). These findings show that the higher coronary mortality noted in Lithuanian men goes together with a higher prevalence of early peripheral atherosclerosis.

Adipose tissue fatty acids in men from two populations with different cardiovascular risk: the LiVicordia study.

The LiVicordia study was set up to investigate possible causes for coronary heart disease mortality in middle-aged Lithuanian men being four times higher than in Swedish men. In a previous part of this study we found lower total and low density lipoprotein (LDL) cholesterol in the Lithuanian men in spite of them having a higher fat intake than in the Swedish men. Their LDL was also more susceptible to oxidation in vitro than was that of the Swedish men. Fat quality can influence LDL oxidation. In order to obtain data on long-term fat quality intake we measured the fatty acid composition of abdominal wall adipose tissue by gas chromatography in men aged 50 years from Vilnius, Lithuania (n=50) and Linköping, Sweden (n=50). Men from Vilnius had a significantly higher percentage of adipose tissue long chain polyunsaturated fatty acids (PUFA) (20:4n6, 20:5n3, 22:5n5, 22:6n3) and lower percentage of saturated fatty acids, especially myristic acid (14:0), 3.4+/-0.7 versus 4.6+/-0.8, p<0.0001. The percentage content of adipose tissue linoleic acid (18:2n6) was 11.5+/-2.1 versus 11.0+/-1.4 (n.s.) and of linolenic acid (18:3n3) 0.7+/-0.3 versus 0.6+/-0.2 (n.s.) in men from Vilnius and Linköping, respectively. It is concluded that the adipose tissue content of essential fatty acids is similar in men from Vilnius and men from Linköping and therefore the intake is also likely to be similar. The higher contents of long chain highly unsaturated fatty acids in men from Vilnius may be of importance in the oxidation process of LDL.

Increased plasma 7 beta-hydroxycholesterol concentrations in a population with a high risk for cardiovascular disease.

The mortality in coronary heart disease among 50- to 54-year-old men is 4 times higher in Lithuania than in Sweden. It was recently suggested that traditional risk factors could not explain this mortality difference. LDL of Lithuanian men showed, however, a lower resistance to oxidation than that of Swedish men. In addition, the plasma concentration of gamma-tocopherol, lycopene, and beta-carotene were lower in Lithuanian men. In the present investigation, we determined plasma oxysterols in men from Lithuania and Sweden and found that the plasma concentration of 7 beta-hydroxycholesterol was higher in Lithuanian men, 12+/-5 versus 9+/-8 (SD) ng/mL (P=0.0011). This oxysterol is a cholesterol autoxidation product and there is no indication that it should have an enzymatic origin. Mean LDL oxidation lag time was shorter in Lithuanian men (75+/-14 versus 90+/-13 minutes, P<0.0001) and the concentration of LDL linoleic acid was lower (249+/-56 versus 292+/-54 microgram/mg of LDL protein, P<0.0001). Lipid corrected gamma-tocopherol was 0.07+/-0.02 mg/mL in Vilnius men and 0.12+/-0. 04 mg/mL (P<0.0001) in Linköping men. There was a negative correlation between the concentration of 7 beta-hydroxycholesterol and lag time (R=-0.31, P=0.0023). It is suggested that the higher 7 beta-hydroxycholesterol concentration in Lithuanian men is an indication of an increased in vivo lipid peroxidation.

Increased psychosocial strain in Lithuanian versus Swedish men: the LiVicordia study.

OBJECTIVE: Coronary heart disease (CHD) mortality is four times higher in 50-year-old Lithuanian men than in 50-year-old Swedish men. The difference cannot be explained by standard risk factors. The objective of this study was to examine differences in psychosocial risk factors for CHD in the two countries. METHODS: The LiVicordia study is a cross-sectional survey comparing 150 randomly selected 50-year-old men in each of the two cities: Vilnius, Lithuania, and Linköping, Sweden. As part of the study, a broad range of psychosocial characteristics, known to predict CHD, were investigated. RESULTS: In the men from Vilnius compared with those from Linköping, we found a cluster of psychosocial risk factors for CHD; higher job strain (p <.01), lower social support at work, lower emotional support, and lower social integration (p values <.001). Vilnius men also showed lower coping, self-esteem, and sense of coherence (p values < .001), higher vital exhaustion, and depression (p values < .001). Quality of life and perceived health were lower and expectations of ill health within 5 to 10 years were higher in Vilnius men (p values < .001). Correlations between measurements on traditional and psychosocial risk factors were few and weak. CONCLUSIONS: The Vilnius men, representing the population with a four-fold higher CHD mortality, had unfavorable characteristics on a cluster of psychosocial risk factors for CHD in comparison with the Linköping men. We suggest that this finding may provide a basis for possible new explanations of the differences in CHD mortality between Lithuania and Sweden.

Attenuated cortisol response to a standardized stress test in Lithuanian versus Swedish men: the LiVicordia study.

Cardiovascular mortality rates of middle-aged men are 4 times higher in Lithuania than in Sweden The difference is not explained by standard risk factors, but our previous findings of pronounced psychosocial stress in Lithuanian men offer a possible explanation. We investigated cortisol and cardiovascular reactivity to a standardized laboratory stress test in population-based random samples of 50-year-old men from Vilnius, Lithuania and Linköping, Sweden. Repeated measures analysis of variance showed that cortisol responses differed between cities (p's < .0001). Mean change of serum cortisol from baseline to 30 min was 18.1 and 88.4 nmol/1 for Vilnius and Linkoping men, respectively (p < .001). In a multivariate analysis, a low peak cortisol response was significantly related to high baseline cortisol, current smoking, and vital exhaustion. The findings suggest a physiological mechanism of chronic psychosocial stress, which may contribute to increased risk for cardiovascular death.

Antioxidant state and mortality from coronary heart disease in Lithuanian and Swedish men: concomitant cross sectional study of men aged 50.

OBJECTIVE: To investigate possible risk factors and mechanisms behind the four times higher and diverging mortality from coronary heart disease in Lithuanian compared with Swedish middle aged men. DESIGN: Concomitant cross sectional comparison of randomly selected 50 year old men without serious acute or chronic disease. Methods and equipment were identical or highly standardised between the centres. SETTING: Linköping (Sweden) and Vilnius (Lithuania). SUBJECTS: 101 and 109 men aged 50 in Linköping and Vilnius respectively. MAIN OUTCOME MEASURES: Anthropometric data, blood pressure, smoking, plasma lipid and lipoprotein concentrations, susceptibility of low density lipoprotein to oxidation, and plasma concentrations of fat soluble antioxidant vitamins. RESULTS: Systolic blood pressure was higher (141 v 133 mm Hg, P < 0.01), smoking habits were similar, and plasma total cholesterol (5.10 v 5.49 mmol/l, P < 0.01) and low density lipoprotein cholesterol (3.30 v 3.68 mmol/l, P < 0.01) lower in men from Vilnius compared with those from Linköping. Triglyceride, high density lipoprotein cholesterol, and Lp(a) lipoprotein concentrations did not differ between the two groups. The resistance of low density lipoprotein to oxidation was lower in the men from Vilnius; lag phase was 67.6 v 79.5 minutes (P < 0.001). Also lower in the men from Vilnius were mean plasma concentrations of lipid soluble antioxidant vitamins (beta carotene 377 v 510 nmol/l, P < 0.01; lycopene 327 v 615 nmol/l, P < 0.001; and lipid adjusted gamma tocopherol 0.25 v 0.46 mumol/mmol, P < 0.001. alpha Tocopherol concentration did not differ). Regression analysis showed that the lag phase was still significantly shorter by 10 minutes in men from Vilnius when the influence of other known factors was taken into account. CONCLUSIONS: The high mortality from coronary heart disease in Lithuania is not caused by traditional risk factors alone. Mechanisms related to antioxidant state may be important.