| 1. |
- Björkbacka, Harry, et al.
(författare)
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Weak associations between human leucocyte antigen genotype and acute myocardial infarction
- 2010
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Ingår i: Journal of Internal Medicine. - : Blackwell Publishing Ltd. - 0954-6820 .- 1365-2796. ; 268:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Human leucocyte antigens (HLAs) are polymorphic molecules involved in antigen presentation. Associations between HLA type and autoimmune diseases, such as type 1 diabetes and rheumatoid arthritis, are well established but the potential association of genetic variation affecting antigen presentation with cardiovascular disease has not been systematically investigated in large cohorts. The importance of such studies is stressed by recent experimental findings of an involvement of autoimmunity in the atherosclerotic disease process. Results: An SSP-PCR method was used for HLA genotyping to determine associations of HLA-DRB1, -DQA1 and -DQB1 with cardiovascular disease in a population-based cohort of 1188 acute myocardial infarction (AMI) patients and 1191 matched healthy controls. The HLA-DRB1*0101 allele, as well as the HLA-DRB1*0101-DQA1*01-DQB1*05 haplotype, was found to be associated with increased risk for AMI (OR 1.24; 95% CI 1.00–1.54 for both). In contrast, the DRB1*07 and DQA*02 alleles (OR 0.78; 95% CI 0.65–0.95 for both), as well as the DRB1*07-DQA*02-DQB*02 haplotype, conferred protection (OR 0.79; 95% CI 0.63–0.98). An HLA risk score taking each individual’s both haplotypes into account was higher amongst cases (2.43 ± 0.92 vs. 2.29 ± 0.95, P = 0.001). The association between HLA risk score and AMI was independent of other cardiovascular riskfactors assessed. Conclusions: This study demonstrates that the associations between HLA-DRB1 and DQA1 loci and cardiovascular disease exists but that they are considerably weaker than those previously reported for other diseases with an established autoimmune aetiology such as type 1 diabetes, systemic lupus erythematosus and rheumatoid arthritis.
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| 2. |
- Dunér, Pontus, et al.
(författare)
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Immune responses against fibronectin modified by lipoprotein oxidation and their association with cardiovascular disease.
- 2009
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; Feb 14., s. 593-603
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Tidskriftsartikel (refereegranskat)abstract
- Abstract. Dunér P, To F, Alm R, Gonçalves I, Fredrikson GN, Hedblad B, Berglund G, Nilsson J, Bengtsson E (Malmö University Hospital, Lund University, Lund, Sweden). Immune responses against fibronectin modified by lipoprotein oxidation and their association with cardiovascular disease. J Intern Med 2009; doi: 10.1111/j.1365-2796.2008.02067.xObjectives. Accumulation and subsequent oxidation of LDL in the arterial wall are considered as key events in the development of atherosclerosis. We have investigated the possibility that LDL oxidation results in release of aldehydes that modify surrounding matrix proteins and that this may target immune responses against the plaque extracellular matrix and modulate the disease progression. Results. Using custom-made ELISAs we demonstrate that human plasma contains autoantibodies against aldehyde-modified fibronectin (FN) and to a lesser extent also other extracellular matrix proteins including collagen type I, type III, and tenascin-C. Immunohistochemistry and western blot analysis showed that aldehyde-modified FN is present in human atherosclerotic plaques and that aldehydes generated by oxidation of LDL formed adducts with FN in vitro. We also demonstrate that aldehyde-modification of FN results in a loss of its ability to promote basal secretion of cytokines and growth factors from cultured macrophages without affecting the ability of the cells to respond to stimulation with LPS. A prospective clinical study demonstrated that subjects that subsequently developed acute myocardial infarction or sudden cardiac death had lower baseline levels of autoantibodies against aldehyde-modified FN than matched controls. Conclusions. These observations demonstrate that oxidation of LDL in the arterial wall may lead to aldehyde-modification of surrounding extracellular matrix proteins and that these modifications may affect macrophage function and activate autoimmune responses of pathophysiological importance for the development of atherosclerosis.
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| 3. |
- Hedblad, Bo, et al.
(författare)
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COHb% as a marker of cardiovascular risk in never smokers: results from a population-based cohort study.
- 2006
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 34:6, s. 609-615
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Carbon monoxide (CO) in blood as assessed by the COHb% is a marker of the cardiovascular ( CV) risk in smokers. Non-smokers exposed to tobacco smoke similarly inhale and absorb CO. The objective in this population-based cohort study has been to describe inter-individual differences in COHb% in never smokers and to estimate the associated cardiovascular risk. Methods: Of the 8,333 men, aged 34-49 years, from the city of Malmo, Sweden, 4,111 were smokers, 1,229 ex-smokers, and 2,893 were never smokers. Incidence of CV disease was monitored over 19 years of follow up. Results: COHb% in never smokers ranged from 0.13% to 5.47%. Never smokers with COHb% in the top quartile (above 0.67%) had a significantly higher incidence of cardiac events and deaths; relative risk 3.7 (95% CI 2.0-7.0) and 2.2 (1.4-3.5), respectively, compared with those with COHb% in the lowest quartile (below 0.50%). This risk remained after adjustment for confounding factors. Conclusion: COHb% varied widely between never-smoking men in this urban population. Incidence of CV disease and death in non-smokers was related to COHb%. It is suggested that measurement of COHb% could be part of the risk assessment in non-smoking patients considered at risk of cardiac disease. In random samples from the general population COHb% could be used to assess the size of the population exposed to second-hand smoke.
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| 4. |
- Janzon, Ellis, et al.
(författare)
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Changes in blood pressure and body weight following smoking cessation in women.
- 2004
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 255:2, s. 266-272
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Few have studied the long-term effects of smoking and smoking cessation on weight gain and blood pressure increase and compared with the age-related increases experienced by most adults. This study compared the development of weight and blood pressure in female never smokers, continuing smokers and smokers who quit smoking. Design. Weight, systolic (SBP) and diastolic (DBP) blood pressure and smoking habits were assessed at baseline and re-assessed after a mean follow-up of 9.0 ± 5.8 years. Setting. Population-based cohort. Subjects. A total of 2381 female never smokers and 1550 female smokers. At the re-examination, 388 of the smokers had quit smoking. Results. Mean weight gain was 7.6 ± 6.1, 3.2 ± 5.8 and 3.7 ± 5.2 kg, respectively, in quitters, continuing smokers and never smokers (P < 0.001). In women without blood pressure treatment, mean SBP increase was 20.9 ± 16.8, 19.1 ± 15.8 and 16.1 ± 16.3 mmHg, respectively, in these groups (P < 0.001). Mean DBP increase was 6.2 ± 8.7, 5.7 ± 9.3 and 3.1 ± 8.0 mmHg, respectively (P < 0.001). After adjustments for potential confounders, the increased weight gain in quitters remained highly significant. The differences in SBP and DBP increase were attenuated after adjustments, but remained significant. Incidence of hypertension (>= 160/95 mmHg or treatment) was significantly higher in quitters [adjusted odds ratio (OR): 1.8; CI: 1.4-2.5] when compared with continuing smokers (OR: 1.3; CI: 1.07-1.6) and never smokers (reference). Conclusion. Over a long follow-up, weight gain was approximately 3-4 kg higher in quitters when compared with continuing smokers or never smokers. Although the differences in blood pressure increase were moderate, smoking cessation was associated with an increased incidence of hypertension.
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| 5. |
- Janzon, Ellis, et al.
(författare)
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Smoking as a determinant of the geographical pattern of cardiac events among women in an urban population
- 2007
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Ingår i: Scandinavian Journal of Public Health. - : Sage Publications. - 1403-4948 .- 1651-1905. ; 35:3, s. 272-277
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To assess to what extent geographical differences of the female incidence of myocardial infarction in the city of Malmö in Sweden can be accounted for by smoking and to what extent intra-urban variances of smoking are related to socio-economic circumstances. Method. Area specific prevalence’s of smokers is based on a sample of 17319 women, aged 45-73 years. A comprehensive score was used to rank the 17 residential areas in terms of socioeconomic circumstances. Incidence of myocardial infarction and death is based on official statistics 1989-97. Results. The area-specific prevalence of female smokers, which ranged from 17.5 to 32.5% was inversely related to the socio-economic score in 45-54 and 55-64 years old, r = -0.65 (p<0.05) and -0.59 (p<0.05). No correlation was found for women above 65 years of age. The annual age-adjusted incidence of cardiac events in the residential areas which ranged from 151 to 414 per 100 000 person years, was strongly related to the prevalence of smokers, r = 0.75 (p < 0.001). Conclusion. Between 50-60% of the intra-urban variance of the female incidence of myocardial infarction was accounted for by smoking in this urban population. The geographical pattern of smoking was strongly related to inferior socio-economic circumstances. Key words: cardiac events, smoking women, risks and prevention
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| 6. |
- Janzon, Ellis, et al.
(författare)
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Tobacco and myocardial infarction in middle-aged women: a study of factors modifying the risk.
- 2004
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 256:2, s. 111-118
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Tidskriftsartikel (refereegranskat)abstract
- Background. Although myocardial infarction (MI) is strongly related to smoking, few have studied why some smokers are more vulnerable than others. This study explored how the risk of MI in current and former smokers is modified by other cardiovascular risk factors. Methods. Incidence of MI (fatal and nonfatal) amongst 10619 women, 48.3 ± 8.2 years old, were studied in relation to smoking, hypertension, hypercholesterolaemia, diabetes, marital status and occupational level over a mean follow-up of 14 years. Results. Of the 3738 smokers, one-third had at least one major biological risk factor besides smoking; 228 women had MI during follow-up. Smoking and hypertension showed a synergistic effect on incidence of MI. The adjusted relative risks (RR) were 12.2 (95% CI: 7.5-19.8) for smokers with hypertension, 5.3 (CI:3.3-8.1) for smokers with normal blood pressure and 2.4 (CI:1.4-4.3) for never-smokers with hypertension (reference: normotensive never-smokers). The corresponding RRs for diabetic smokers and diabetic never-smokers were 19.0 (CI: 10.2-35.4) and 8.8 (CI: 4.4-17.4), respectively (reference: nondiabetic never-smokers). In terms of attributable risks, hypertension, hypercholesterolaemia and diabetes accounted for 12.9, 11.5 and 7.2%, respectively, of MI in female smokers. Low socio-economic level and being unmarried accounted for 19.6 and 1.6%, respectively. Conclusions. Although smoking is a major risk factor for MI, the risk varies widely between women with similar tobacco consumption. The results illustrate the need of a global risk factor assessment in female smokers and suggest that female smokers should be targets both for intensified risk factor management and programmes to stop smoking.
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| 7. |
- Janzon, Ellis, et al.
(författare)
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Who are the "quitters"? a cross-sectional study of circumstances associated with women giving up smoking.
- 2005
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 33:3, s. 175-182
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Tidskriftsartikel (refereegranskat)abstract
- Background: Smoking is an important preventable risk factor for cardiovascular disease, cancer, and many other diseases. Even though tobacco consumption is declining in Sweden, it is not declining in all groups. This study explored socioeconomic and psychosocial circumstances hindering or facilitating smoking cessation in three birth cohorts of women from the general population. Methods: Between 1991 and 1996 a comprehensive questionnaire was administered to 17,319 women, 45–73 years old, from the Malmo¨ Diet and Cancer cohort. Smoking habits were compared in relation to socioeconomic and psychosocial circumstances in three birth cohorts. Results: Of these women, 44% were never smokers, 28% were ex-smokers, and 28% were smokers (regular or occasional). When compared with smokers, ex-smokers were more often married, had a higher socioeconomic position, a longer education, more smoke-free surroundings, better emotional support, higher BMI, and better self-perceived health. Ex-smokers reported less work-related stress and less shift work. A history of cardiovascular disease was not associated with smoking cessation. The socioeconomic differences between current and former smokers were higher for young women as compared with older birth cohorts. Conclusions: Continuing smokers and quitters differ with regard to socioeconomic and psychosocial circumstances and factors related to working life and environmental tobacco exposure. By determining who the quitters are through continued follow-up, useful insights can be gained to develop strategies to achieve successful cessation of smoking.
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| 8. |
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| 9. |
- Nordin Fredrikson, Gunilla, et al.
(författare)
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Association between IgM against an aldehyde-modified peptide in apo B-100 and progression of carotid disease.
- 2007
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Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 38, s. 1495-1500
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose— Autoantibodies against antigens in oxidized low-density lipoprotein are common in people; experimental studies suggest that these immune responses have a functional role in the disease process. The aim of this study was to evaluate the relationship between the immune response against one defined oxidized low-density lipoprotein antigen, the aldehyde-modified peptide corresponding amino acids 3136 and 3155 (MDA-p210) in apolipoprotein (apo) B-100, and progression of carotid intima media thickness (IMT).Methods— IgM and IgG against MDA-p210 were determined by enzyme-linked immunosorbent assay at baseline and after 12 months of treatment with placebo, metoprolol, fluvastatin, or metoprolol/fluvastatin in 751 individuals participating in the BCAPS. Carotid IMT was assessed by ultrasonography at baseline and after 18 and 36 months of treatment.Results— Antibody levels did not change in response to treatment, but high baseline MDA-p210 IgM levels were associated with a more rapid progression of carotid disease both at 18 (r=0.09, P<0.05) and 36 months (r=0.12, P<0.005). At 36 months, the difference in IMT progression rate per year between those with high MDA-p210 IgM levels and those with low was 0.011 mm (95% CI=0.005 to 0.018 mm, P<0.0001). Treatment with fluvastatin markedly decreased the progression of IMT among subjects with high but not with low MDA-p210 IgM levels. There was no association between MDA-p210 IgG and carotid IMT progression.Conclusions— IgM against the aldehyde-modified peptide corresponding amino acids 3136 and 3155 in apo B-100 is common in subjects with asymptomatic carotid disease, and high levels are associated with a more rapid progression of carotid IMT. The observation that the effect of fluvastatin was restricted to subjects with high MDA-p210 IgM levels may reflect the increased rate of disease progression in this group.
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| 10. |
- Nordin Fredrikson, Gunilla, et al.
(författare)
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Identification of autoantibodies in human plasma recognizing an apoB-100 LDL receptor binding site peptide
- 2006
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Ingår i: Journal of Lipid Research. - 1539-7262 .- 0022-2275. ; 47:9, s. 2049-2054
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to test the hypothesis that autoantibodies recognize amino acid sequences in the LDL receptor binding region of apolipoprotein B-100 (apoB-100). Autoantibodies against an unmodified or malondialdehyde (MDA)-modified LDL receptor binding site peptide were determined by ELISA in baseline plasma samples of 78 cases with coronary events and 149 matched controls recruited from the prospective Malmo Diet Cancer Study. IgG and IgM recognizing this peptide were detected in all subjects but did not differ between cases and controls. Inverse associations were observed between IgG against the native binding site and plasma oxidized LDL (r = -0.21, P < 0.005), but there were no significant associations with total or LDL cholesterol levels. In univariate analyses, inverse associations were found between baseline carotid intima-media thickness and IgG against the MDA-modified binding site (r = -0.14, P < 0.05), but this association was lost when controlling for other major cardiovascular risk factors. Specificity studies demonstrated that the binding of autoantibodies to these sequences could be inhibited by oxidized but not by native LDL. Autoantibodies recognizing the LDL receptor binding site in apoB-100 are frequently expressed. Their association with plasma oxidized LDL suggests that they have been generated in response to breakdown products of LDL oxidation, but their influence on cholesterol metabolism and the development of atherosclerosis appears limited.
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