Margareta Kristenson

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.

Antioxidant state and mortality from coronary heart disease in lithuanian and swedish men: concomitant cross sectional study of men aged 50

Abstract 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 (141v 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 (ß carotene 377v 510 nmol/l, P<0.01; lycopene 327 v 615 nmol/l, P<0.001; and lipid adjusted tocopherol 0.25v 0.46 µmol/mmol, P<0.001. 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. Key messages Mortality from coronary heart disease in 50-54 year old men is four times higher in Lithuania than in Sweden Differences in traditional risk factors for coronary heart disease in 50 year old men in LinkÖping (Sweden) and Vilnius (Lithuania) were small–systolic blood pressure was higher in men from Vilnius, but total and low density lipoprotein cholesterol concentrations were lower and smoking habits similar The resistance of low density lipoprotein to oxidation was lower in men from Vilnius and remained after adjustment for antioxidant vitamin concentrations Plasma concentrations of the antioxidant vitamins, ß carotene, lycopene, and lipid adjusted tocopherol were lower in men from Vilnius; tocopherol did not differ Mechanisms related to antioxidant state may be important in explaining the much higher mortality from coronary heart disease in Lithuanian compared with Swedish middle aged men

Increased Plasma 7β-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.

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.

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 Linkoping, 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 Linkoping, 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 Linkoping men. We suggest that this finding may provide a basis for possible new explanations of the differences in CHD mortality between Lithuania and Sweden.

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).

Circulating Matrix Metalloproteinase-9 Is Associated with Cardiovascular Risk Factors in a Middle-Aged Normal Population

Background Elevated levels of circulating matrix metalloproteinase-9 (MMP-9) have been demonstrated in patients with established coronary artery disease (CAD). The aim of this study was to analyse levels of MMP-9 in a population free from symptomatic CAD and investigate their associations with cardiovascular (CV) risk factors, including C-reactive protein (CRP). Methods A cross-sectional study was performed in a population based random sample aged 45–69 (n = 345, 50% women). MMP-9 levels were measured in EDTA-plasma using an ELISA-method. CV risk factors were measured using questionnaires and standard laboratory methods. Results Plasma MMP-9 was detectable in all participants, mean 38.9 ng/mL (SD 22.1 ng/mL). Among individuals without reported symptomatic CAD a positive association (p<0.001) was seen, for both men and women, of MMP-9 levels regarding total risk load of eight CV risk factors i.e. blood pressure, dyslipidemia, diabetes, obesity, smoking, alcohol intake, physical activity and fruit and vegetable intake. The association was significant also after adjustment for CRP, and was not driven by a single risk factor alone. In regression models adjusted for age, sex, smoking, alcohol intake and CRP, elevated MMP-9 levels were independently positively associated with systolic blood pressure (p = 0.037), smoking (p<0.001), alcohol intake (p = 0.003) and CRP (p<0.001). The correlation coefficient between MMP-9 and CRP was r = 0.24 (p<0.001). Conclusions In a population without reported symptomatic CAD, MMP-9 levels were associated with total CV risk load as well as with single risk factors. This was found also after adjustment for CRP.

Role of preexisting disease in patients' perceptions of health-related quality of life after intensive care.

Objectives:To find out how patients perceive their health-related quality of life after they have been treated in an intensive care unit and whether preexisting disease influenced their perception. Design:Follow-up, quantitative, dual-site study. Setting:Combined medical and surgical intensive care units of one university and one general hospital in Sweden. Patients:Among the 1,938 patients admitted, 562 were considered eligible (>24 hrs in the intensive care unit, and age >18 yrs). The effect of preexisting disease was assessed by use of a large reference group, a random sample (n = 10,000) of the main intake area of the hospitals. Interventions:None. Measurements and Main Results:During 2000–2002, data were collected from the intensive care unit register and from a questionnaire mailed to the patients 6 months after their discharge from hospital. Subjects in the reference group were sent postal questionnaires during 1999. Of the patients in the intensive care unit group, 74% had preexisting diseases compared with 51% in the reference group. Six months after discharge, health-related quality of life was significantly lower among patients than in the reference group. When comparisons were restricted to the previously healthy people in both groups, the observed differences were about halved, and when we compared the patients in the intensive care unit who had preexisting diseases with subjects in the reference group who had similar diseases, we found little difference in perceived health-related quality of life. In some dimensions of health-related quality of life, we found no differences between patients in the intensive care unit and the subjects in the reference population. Conclusions:Preexisting diseases significantly affect the extent of the decline of health-related quality of life after critical care, and this effect may have been underestimated in the past. As most patients who are admitted to an intensive care unit have at least one preexisting disease, it is important to account for these effects when examining outcome.

The prevalence of the metabolic syndrome and its risk factors in a middle-aged Swedish population - mainly a function of overweight?

Background: The prevalence of obesity, one risk factor for developing the metabolic syndrome (MS), has increased during the last decades. It has therefore been assumed that the prevalence of MS would also increase. Aims: The aim was to analyse the prevalence of MS and its risk factors in a middle-aged Swedish population. Methods: Data were obtained between 2003 and 2004 from a random population based sample of 502 men and 505 women, 45–69 years old. Measures of plasma glucose, serum lipids, blood pressure, weight, height, waist circumference and self-reported data concerning presence of disease, medication and lifestyle were obtained. Results: The prevalence of MS was 14.8% among men and 15.3% among women, with an increase by age among women only, 10% to 25% (p = 0.029). Among individuals with MS the most frequent risk factor was large waist circumference, present in 85% of men and 99% of women, followed by high blood pressure, high triglycerides, high glucose and HDL cholesterol (38% and 47% respectively). Conclusion: The prevalence of MS was 15%, increasing with age only among women. Overweight was a dominant characteristic, and only half of the individuals with MS had glucose/HDL cholesterol levels beyond defined cut points of the syndrome.

Life span and disability: a cross sectional comparison of Russian and Swedish community based data

Abstract Objectives To compare levels of disability (in terms of physical function and self rated health) among middle aged and elderly people in Russia and Sweden, a country with high life expectancy. Design Cross sectional study. Setting General population of the Russian Federation and of two counties in southern Sweden. Participants Randomly selected men and women in Sweden (n = 9489) and Russia (n = 1599). Main outcome measures Official life table data; self rated health and physical functioning (subscale of the SF-36). Results The official life table data showed large differences in mortality—for example, 36% of Russian men aged 45-49 years would survive the next 25 years compared with 75% of Swedish men. The survey data showed, for both sexes, similar levels of self rated health and physical functioning in the two countries up to the age of about 45 years, but after that, the age related decline in both outcomes was much faster in Russia than in Sweden. By combining the national life tables with survey data on physical functioning we estimated that in the age group 45-49 years, 99% of Russian and 97% of Swedish men would be free of disability; of these, if these data were for a cohort, only 17% of Russians would be alive and free of disability 25 years later compared with 65% of Swedes. The difference in survival was similar in women. Conclusions Large differences exist in survival without disability between elderly Russians and Swedes. The short life span in Russia reflects high levels of ill health and disability and is associated with a rapid age related decline in physical functioning.