[Show abstract][Hide abstract] ABSTRACT: Background:
The enzyme in matrix metalloproteinase (MMP)-9 has been suggested to be an important determinant of plaque degradation. While several studies have shown elevated levels in patients with coronary heart disease, results in prospective population based studies evaluating MMP-9 in relation to first time coronary events have been inconclusive. As of today, there are four published studies which have measured MMP-9 in serum and none using plasma. Measures of MMP-9 in serum have been suggested to have more flaws than measures in plasma.
To investigate the independent association between plasma levels of MMP-9 and first-time incidence of coronary events in an 8-year follow-up.
Material and methods:
428 men and 438 women, aged 45-69 years, free of previous coronary events and stroke at baseline, were followed-up. Adjustments were made for sex, age, socioeconomic position, behavioral and cardiovascular risk factors, chronic disease at baseline, depressive symptoms, interleukin-6 and C-reactive protein.
53 events were identified during a risk-time of 6 607 person years. Hazard ratio (HR) for MMP-9 after adjustment for all covariates were HR = 1.44 (1.03 to 2.02, p = 0.033). Overall, the effect of adjustments for other cardiovascular risk factors was low.
Levels of plasma MMP-9 are independently associated with risk of first-time CHD events, regardless of adjustments. These results are in contrast to previous prospective population-based studies based on MMP-9 in serum. It is essential that more studies look at MMP-9 levels in plasma to further evaluate the association with first coronary events.
PLoS ONE 09/2015; 10(9):e0138290. DOI:10.1371/journal.pone.0138290 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Measures of health-related quality of life (HRQoL), like the Short Form (SF)-36, have been suggested to correlate with inflammatory biomarkers. It is, however, unclear whether a joint measure of two inflammatory biomarkers would bring additional information in comparison with evaluation of one inflammatory biomarker.
To evaluate associations between SF-36 and low-grade inflammation in a Swedish population, with emphasis on a combined measure of C-reactive protein (CRP) and interleukin-6 (IL-6) as a proxy for low-grade inflammation.
In a randomly selected sample of a middle-aged Swedish general population (n = 905; aged 45-69 years, 50 % women), relations between SF-36 parameters and the biomarkers were tested. Regression and correlation analyses were adjusted for sex, age, presence of disease, lifestyle, and psychological factors.
After adjustment for sex and age, HRQoL was significantly lower in the group with a joint elevation of CRP and IL-6 in comparison with either the group with no elevation or the groups showing elevation of one of the two biomarkers. Also after full adjustments, the combined measure of elevated CRP and IL-6, with few exceptions, was associated with significantly lower HRQoL in comparison with elevations in one of them, difference ranging from 4 (Mental Health scale) to 18 scale steps (Role-Physical scale).
This study confirms that there is a relationship between HRQoL and low-grade inflammation. In particular, SF-36 scores are significantly lower in a group with joint elevation of IL-6 and CRP, in comparison with elevation of either one of them.
Quality of Life Research 07/2015; DOI:10.1007/s11136-015-1068-6 · 2.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A large number of studies have provided clear evidence for a link between the risk of coronary heart disease and psychological risk factors. Much less attention has been given to the potential protective effect of psychological resources.
The major aim of this study was to investigate the independent association between psychological resources and incidence of coronary heart disease (CHD) in an 8-year follow-up study of a Swedish community-based cohort.
The cohort consisted of 484 men and 497 women, aged 45-69 years at baseline. The incidence of first-time major event of CHD was analysed in relation to baseline levels of psychological resources, including mastery, self-esteem, and sense of coherence as well as psychological risk factors including cynicism and hostile affect, vital exhaustion, hopelessness, and depressive symptoms. In Cox proportional hazard models, adjustments were made for age, sex, eight traditional cardiovascular risk factors, and depressive symptoms.
A total of 56 CHD events had occurred after the 8-year follow-up. After adjustment for age, sex, and eight traditional risk factors, a significantly decreased risk of CHD was found for mastery (HR 0.62 per SD, p = 0.003), self-esteem (HR 0.64, p = 0.004), and sense of coherence (HR 0.70, p = 0.031). An increased risk of CHD was found for vital exhaustion (HR 1.46, p = 0.014), hopelessness (HR 1.59, p = 0.003), and depressive symptoms (HR 1.45, p = 0.009). After further adjustment for depressive symptoms, significant associations remained for mastery (HR 0.67, p = 0.034), self-esteem (HR 0.69, p = 0.048), and hopelessness (HR 1.48, p = 0.023).
The psychological resources, mastery and self-esteem, showed robust protective effects on CHD, also after adjustment for established risk factors as well as depressive symptoms. In parallel, hopelessness was an independent risk factor for CHD. The results may have implications for novel approaches in preventive efforts.
International Journal of Behavioral Medicine 01/2014; 22(1). DOI:10.1007/s12529-014-9387-5 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rydén M, Garvin P, Kristenson M, Leanderson P, Ernerudh J, Jonasson L (Linköping University, Linköping, Sweden; Örebro University Hospital, Örebro, Sweden; University of British Colombia, Vancouver, BC, Canada). Provitamin A carotenoids are independently associated with matrix metalloproteinase-9 in plasma samples from a general population. J Intern Med 2012; 272: 371–384.
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 [β-cryptoxanthine, α-carotene, β-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 (β-cryptoxanthine, α-carotene and β-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.
Journal of Internal Medicine 04/2012; 272(4):371-384. DOI:10.1111/j.1365-2796.2012.2534.x · 6.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This chapter focuses on salivary cortisol in relation to biological markers. Specifically, associations with conventional cardiovascular risk factors and metabolic abnormalities (body mass index, waist circumference, waist/hip ratio, lipid status, glucose, blood pressure, heart rate and heart rate variability), markers related to inflammation (C-reactive protein, cytokines and tumor necrosis factor-alpha) and other stress hormones (adrenaline and noradrenaline) were studied. The focus was on healthy adult populations; studies on patient populations and pregnant women were excluded. Studies on genome variations and pharmacological interventions were also excluded. After meeting all exclusion criteria, 42 papers remained. In total, 273 associations between salivary cortisol and any of the markers mentioned were studied, comprising 241 associations on metabolic abnormalities, 30 on inflammation, and 2 on stress hormones. Of the salivary cortisol measures reported for evaluations of all markers tested were 136 (49%) single time points, 100 (37%) deviations, 36 (13%) AUC, and 1 (1%) dexamethasone test. Of these, 72 (26%) were statistically significant, and 201 (74%) indicated non-significant findings.Several of the markers tested showed low or no association with any of the measurements of salivary cortisol. The number of studies exploring the association between cortisol in saliva and markers for inflammation is low, which limits the possibility of interpretation. The number of studies on adrenaline and noradrenaline is also low. To sum up, the proportion of non-significant findings was considerable. This may be due to a large number of studies with relatively small study populations. This is true for metabolic abnormalities, markers related to inflammation as well as other stress hormones. Further studies on inflammatory markers and approaches designed to study variability in other systems in relation to cortisol variability are required.
[Show abstract][Hide abstract] ABSTRACT: This chapter evaluates the association between salivary cortisol and socioeconomic variables (level of education, occupational status, income and related composite measures), ethnicity, age and sex. There were many non-significant findings for all variables, indicating that the associations with cortisol levels are relatively small. Regarding the significant results, there were some consistent trends. It is implied that high SES, regardless of how it is measured, is associated with a higher cortisol deviation throughout the day, and a higher capacity to react with increase in cortisol following a laboratory stress test. Regarding ethnicity, results consistently hint at a higher deviation throughout the day amongst Caucasians in comparison to Hispanics and Afro-Americans. Analyses on sex were not fully consistent, possibly due to influences of the menstrual cycle on cortisol levels. In addition, it has been reported that men and women respond differently to different stressors used in laboratory stress tests. For age, the significant findings found may hint at a small but general increase in cortisol levels throughout the day with increasing age.
[Show abstract][Hide abstract] ABSTRACT: Hepatocyte growth factor (HGF) is an angiogenic, cardioprotective factor important for tissue and vascular repair. High levels of HGF are associated with chronic inflammatory diseases, such as coronary artery disease (CAD) and periodontitis, and are suggested as a marker of the ongoing atherosclerotic event in patients with CAD. Periodontal disease is more prevalent among patients with CAD than among healthy people. Recent studies indicate a reduced biological activity of HGF in different chronic inflammatory conditions. Biologically active HGF has high affinity to heparan sulfate proteoglycan (HSPG) on cell-membrane and extracellular matrix. The aim of the study was to investigate the serum concentration and the biological activity of HGF with ELISA and surface plasmon resonance (SPR), respectively, before and at various time points after percutaneous coronary intervention (PCI) in patients with CAD, and to examine the relationship with periodontal condition. The periodontal status of the CAD patients was examined, and the presence of P. gingivalis in periodontal pockets was analyzed with PCR. The HGF concentration was significantly higher, at all time-points, in patients with CAD compared to the age-matched controls (P< 0.001), but was independent of periodontal status. The HGF concentration and the affinity to HSPG adversely fluctuated over time, and the biological activity increased one month after intervention in patients without periodontitis. We conclude that elevated concentration of HGF but with reduced biological activity might indicate a chronic inflammatory profile in patients with CAD and periodontitis.
Results in Immunology 12/2011; 2:7-12. DOI:10.1016/j.rinim.2011.12.002
[Show abstract][Hide abstract] ABSTRACT: To assess whether there are socioeconomic (SES) differences in outpatient visits within groups of comparable morbidity (medical disease and self-rated health) and whether psychosocial factors can explain these differences.
Baseline data for SES, presence of disease, self-rated health (SRH), and psychosocial factors were collected during 2003-04 from 923 men and women aged 45-69 years in southeast Sweden. Outcome data were all registered outpatient healthcare visits to physicians during 2004-08. Cumulative incidences and standardised rate ratios (SSR) were calculated for strata of comparable morbidity for all visits, for visits due to cardiovascular disorders (CVD)/diabetes and for musculoskeletal problems.
Low SES was associated with more outpatient visits due to musculoskeletal problems (SRR for education 1.52, 95% CI 1.35-1.73; for occupation 1.40, 95% CI 1.26-1.56) and accentuated in groups with poor SRH. The SES effect was significant for visits to primary care and to hospitals, for men and women, and independent of present disease, SRH, and psychosocial factors. Low SES was significantly associated with more total outpatient visits at primary healthcare centres. In contrast, for outpatient visits due to CVD/diabetes, high SES was related to more visits to hospitals among people with good SRH at baseline.
We found a consistent pattern for outpatient visits related to musculoskeletal problems where people with low SES counted more visits and this was most prominent in groups of poor SRH. The results demonstrate the need to apply different morbidity measures when studying inequalities in healthcare utilisation.
Scandinavian Journal of Public Health 12/2011; 39(8):805-12. DOI:10.1177/1403494811423430 · 1.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To test the association between psychosocial factors and circulating levels of matrix metalloproteinase-9 (MMP-9) in a normal population sample. Psychosocial factors have been associated with inflammatory markers and are of prognostic significance for coronary artery disease (CAD). The degrading enzyme MMP-9 is upregulated in inflammatory processes and hypothesized to play a role in the rupture of atherosclerotic plaques.
A total of 402 participants (50% women), aged 45 to 69 years, were drawn randomly from a normal population. Psychosocial instruments covered depression (Center for Epidemiological Studies Depression Questionnaire, CES-D), vital exhaustion, hostile affect, cynicism, mastery, self-esteem, sense of coherence (SOC), emotional support, and social integration. Plasma MMP-9 was measured by an enzyme-linked immunosorbent assay method. Linear regression models were adjusted for age, sex, known CAD, rheumatoid arthritis, cancer, cardiovascular risk factors including C-reactive protein and ongoing medication.
After full adjustment, there were independent associations of elevated MMP-9 levels with CES-D (+2.9 ng/ml per SD, p = .02), hostile affect (+3.0 ng/ml per SD, p = .02), cynicism (+3.5 ng/ml per SD, p = .006), and SOC (-2.5 ng/ml per SD, p = .046). A principal component analysis extracted three components. The first was mainly extracted from CES-D, vital exhaustion, self-esteem, mastery, and SOC; the second was mainly extracted from hostile affect and cynicism. Both were independently associated with MMP-9 (p = .02, p = .04) when run in the same model.
MMP-9 levels were associated with psychosocial factors in a middle-aged normal population sample, independently of traditional risk factors. The findings may constitute a possible link between psychosocial factors and cardiovascular risk.
Psychosomatic Medicine 03/2009; 71(3):292-300. DOI:10.1097/PSY.0b013e3181960e7f · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two previous epidemiological studies on the incidence of total malignancies in Sweden after the Chernobyl accident have shown consistently increased risks. The first study used an analogue map on (137)Cs from 1986 to classify individuals in terms of the parish they lived in. In the second study, dwelling coordinates were matched to a digital map from the year 2000 to assess the individual exposure. To establish the accuracy of the exposure assessment using the larger unit of parish, instead of coordinates, we decided to compare the methods.
On the analogue map eleven isolines on the deposition of (137)Cs (kBq/m(2)) were used to classify all individuals in each of the 450 parishes. Using the digital map, by contrast, each dwelling with its inhabitants could be matched to (137)Cs deposition at a coordinate level. A population-weighted average of (137)Cs deposition was calculated for each parish. In total, 1,126,960 individuals and 450 parishes were included and analysed into six different exposure categories.
Using the new parish exposure index, 111 out of the 450 parishes were reclassified as a result of the increased resolution of the digital map (86 parishes) or unequal distribution of the population compared with the deposition (25 parishes). Seventy-five per cent of the parishes remained in the same exposure category as on the analogue map.
Using dwelling coordinates for exposure assessment may not always be superior to parish classification. Nor is it always a cost-effective way of estimating the exposure, especially if the exposure in a parish is relatively homogenous or if parishes can be merged into broader categories with little intra-parish difference.
Science of The Total Environment 09/2008; 405(1-3):324-9. DOI:10.1016/j.scitotenv.2008.07.019 · 4.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
European Journal of Clinical Microbiology 07/2008; 27(7):503-11. DOI:10.1007/s10096-008-0465-y · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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).
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.
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).
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.
PLoS ONE 03/2008; 3(3):e1774. DOI:10.1371/journal.pone.0001774 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: When cortisol measurements are to be studied in large populations, cost-effective analyses are needed. This study aimed at testing whether one pooled cortisol value over three consecutive days is as reliable as using the arithmetic mean of the samples from the same measure points.
Thirty participants aged between 45 and 69 collected saliva in salivettes immediately after awakening (t(1)), 30 min after awakening (t(2)) and in the evening (t(3)) during 3 consecutive days. A fixed volume from each of the samples (t(1), t(2 )and t(3)) was pooled prior to laboratory analysis. Mean levels over 3 days for t(1), t(2 )and t(3) were compared to corresponding levels of pooled vials. Cortisol levels were analysed using a radio immunoassay.
All measures tested had high correlations between mean values and pooled samples, exemplified with diurnal deviation r(dif t2-t3) = 0.974 (CI 0.946;0.987), and awakening response r(dif t2-t1) = 0.982 (CI 0.963;0.991). There were no statistical differences between the pooled values and the arithmetic means.
Pooling samples gave as reliable results as arithmetic means did. Pooling samples prior to laboratory analysis is a cost-effective method for measuring general diurnal cortisol variation in field research projects.
Scandinavian journal of clinical and laboratory investigation 03/2008; 68(6):508-12. DOI:10.1080/00365510701832229 · 1.90 Impact Factor