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Inflammation and lifestyle in cardiovascular medicine
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Despite major advances in the treatment and prevention of atherosclerosis the last several decades, cardiovascular disease still accounts for the majority of deaths in Sweden. With the population getting older, more obese and with rising numbers of diabetics, the cardiovascular disease burden may increase further in the future.

The focus in cardiovascular disease has shifted with time from calcification and narrowing of arteries to the biological processes within the atherosclerotic plaque. C-reactive protein (CRP) has emerged as one of many proteins that reflect a low grade systemic inflammation and is suitable for analysis as it is more stable and easily measured than most other inflammatory markers. Several large prospective studies have shown that CRP is not only an inflammatory marker, but even a predictive marker for cardiovascular disease. C-reactive protein is associated with several other risk factors for cardiovascular disease including obesity and the metabolic syndrome.

Our study of twenty healthy men during a two week endurance cross country skiing tour demonstrated a decline in already low baseline CRP levels immediately after the tour and six weeks later.

In a study of 200 obese individuals with impaired glucose tolerance randomised to a counselling session at their health care centre or a one month stay at a wellness centre, we found decreased levels of CRP in subjects admitted to the wellness centre. The effect remained at one, but not after three years of follow-up.

In a prospective, nested, case-referent study with 308 ischemic strokes, 61 intracerebral haemorrhages and 735 matched referents, CRP was associated with ischemic stroke in both uni- and multivariate analyses. No association was found with intracerebral haemorrhages. When classifying ischemic stroke according to TOAST criteria, CRP was associated with small vessel disease. The CRP 1444 (CC/CT vs. TT) polymorphism was associated with plasma levels of CRP, but neither with ischemic stroke nor with intracerebral haemorrhage.

A study on 129 patients with atrial fibrillation was used to evaluate whether inflammation sensitive fibrinolytic variables adjusted for CRP could predict recurrence of atrial fibrillation after electrical cardioversion. In multivariate iv models, lower PAI-1 mass was associated with sinus rhythm even after adjusting for CRP and markers of the metabolic syndrome.

In conclusion, lifestyle intervention can be used to reduce CRP levels, but it remains a challenge to maintain this effect. CRP is a marker of ischemic stroke, but there are no significant associations between the CRP1444 polymorphism and any stroke subtype, suggesting that the CRP relationship with ischemic stroke is not causal. The fibrinolytic variable, PAI-1, is associated with the risk of recurrence of atrial fibrillation after electrical cardioversion after adjustment for CRP. Our findings suggest a pathophysiological link between atrial fibrillation and PAI-1, but the relation to inflammation remains unclear.

Place, publisher, year, edition, pages
Umeå: Umeå university , 2010. , 72 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1367
Keyword [en]
C-reactive protein, cardiovascular disease, stroke, atrial fibrillation, lifestyle, interleukin-6, tumor necrosis factor-α, exercise, physical activity, obesity, the metabolic syndrome, fibrinolysis
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
URN: urn:nbn:se:umu:diva-36221ISBN: 978-91-7459-049-4 (print)OAI: oai:DiVA.org:umu-36221DiVA: diva2:352934
Public defence
2010-10-15, Forumsalen, Campus Skellefteå, Skellefteå, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2010-09-23 Created: 2010-09-22 Last updated: 2011-08-24Bibliographically approved
List of papers
1. Effects of heavy endurance physical exercise on inflammatory markers in non-athletes
Open this publication in new window or tab >>Effects of heavy endurance physical exercise on inflammatory markers in non-athletes
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2010 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 209, no 2, 601-605 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Physical activity has beneficial effects on cardiovascular disease but the mechanisms are still somewhat unclear. One possible pathway may be through the anti-inflammatory effects attributed to regular physical activity. Our primary aim was to study the effects of endurance physical exercise on C-reactive protein (CRP), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNFalpha) during the acute and recovery phases. Secondarily, we studied the impact of diet on these inflammatory markers.

METHODS: Twenty men, aged 18-55 years, participated in a 14 days cross-country skiing tour. They traveled 12-30km per day corresponding to about 10h of heavy physical activity. The participants were randomized to a diet with either 30 or 40% of energy derived from fat. Inflammatory variables were analysed at week 0, after 1 and 2 weeks and during the recovery phase at week 6 and 8.

RESULTS: CRP and TNFalpha increased significantly during the two weeks of exercise (1.4-5.0mg/l, p=0.00 and 6.8-8.4pg/ml, p=0.00). CRP levels were significantly lower during recovery (median 0.7mg/l) compared to baseline (median 1.4mg/l) and did not correlate to metabolic variables. There were no significant changes in IL-6 levels during the study period. For dietary groups significant CRP changes were observed only in the high fat group during recovery.

CONCLUSIONS: CRP and TNFalpha increased significantly but reacted differently during heavy physical activity while there seemed to be no significant changes in IL-6. No significant differences regarding inflammatory variables were found between the dietary groups.

Keyword
Exercise, C-reactive protein, Interleukin-6, Tumor necrosis factor-alpha, Inflammation
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-32638 (URN)10.1016/j.atherosclerosis.2009.10.025 (DOI)000276158000047 ()19954777 (PubMedID)
Available from: 2010-03-19 Created: 2010-03-19 Last updated: 2017-12-12Bibliographically approved
2. Effect of intensive lifestyle intervention on C-reactive protein in subjects with impaired glucose tolerance and obesity: results from a randomized controlled trial with 5-year follow-up
Open this publication in new window or tab >>Effect of intensive lifestyle intervention on C-reactive protein in subjects with impaired glucose tolerance and obesity: results from a randomized controlled trial with 5-year follow-up
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2008 (English)In: Biomarkers: biochemical indicators of exposure, response, and susceptibility to chemicals, ISSN 1366-5804, Vol. 13, no 7, 671-679 p.Article in journal (Refereed) Published
Abstract [en]

C-reactive protein (CRP) is a marker of metabolic and cardiovascular disease. To study the effects of lifestyle on CRP in a high-risk population we conducted a randomized controlled trial on 200 obese subjects (BMI > 27 kg m(-2)) with impaired glucose tolerance recruited from primary care settings. They were randomized to either a 1-month stay at a wellness centre focusing on diet, exercise and stress management (intervention group) or 30-60 min of oral and written information on lifestyle intervention (control group). A significant reduction of CRP was observed after 1 month and 1 year in the intervention group. They reduced their CRP levels more than the control group 1 year after intervention (p=0.004). In conclusion lifestyle intervention can decrease CRP in obese individuals with impaired glucose tolerance for up to 1 year. Further research is needed to evaluate whether the CRP level reduction translates into a decreased risk for cardiovascular morbidity.

National Category
Clinical Medicine
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-19330 (URN)10.1080/13547500802661266 (DOI)19096961 (PubMedID)
Available from: 2009-03-05 Created: 2009-03-05 Last updated: 2013-04-02Bibliographically approved
3. C-reactive protein is a determinant of first-ever stroke: prospective nested case-referent study
Open this publication in new window or tab >>C-reactive protein is a determinant of first-ever stroke: prospective nested case-referent study
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2009 (English)In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 27, no 6, 544-551 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND PURPOSE: C-reactive protein (CRP) is a determinant of stroke, but there are no prospective studies on CRP and first ischemic stroke divided into etiologic subtypes. Our primary aim was to study CRP as a determinant of ischemic stroke, classified according to Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria, and intracerebral hemorrhage (ICH) in a prospective study. A secondary aim was to study the relationship between the 1444C>T polymorphism, plasma levels of CRP and stroke.

METHODS: The study was a prospective population-based case-referent study nested within the Northern Sweden Cohorts. We defined 308 cases of ischemic stroke and 61 ICH. Two controls for each case were defined from the same cohort.

RESULTS: The OR for the highest (>3 mg/l) versus lowest group (<1 mg/l) of CRP was 2.58 (95% CI 1.74-3.84) for ischemic stroke and 1.63 (95% CI 0.67-3.93) for ICH. In a multivariate model including traditional risk factors, CRP remained associated with ischemic stroke (OR 2.06; 95% CI 1.29-3.29). Small-vessel disease was associated with CRP in the multivariate model (OR 3.88; 95% CI 1.10-13.7). The CRP 1444 (CC/CT vs. TT) polymorphism was associated with plasma levels of CRP but neither with ischemic stroke nor with ICH.

CONCLUSIONS: This prospective population-based study shows that CRP is significantly associated with the risk of having a first ischemic stroke, especially for small-vessel disease. No significant associations were found between the CRP 1444C>T polymorphism and any stroke subtype.

National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:umu:diva-30737 (URN)10.1159/000214217 (DOI)19390179 (PubMedID)
Available from: 2010-01-14 Created: 2010-01-14 Last updated: 2017-12-12Bibliographically approved
4. Markers of fibrinolysis as predictors for maintenance of sinus rhythm after electrical cardioversion
Open this publication in new window or tab >>Markers of fibrinolysis as predictors for maintenance of sinus rhythm after electrical cardioversion
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2011 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 127, no 3, 189-192 p.Article in journal (Refereed) Published
Abstract [en]

No fibrinolytic component alone was found to be a predictor of recurrence of atrial fibrillation. In multivariate models lower PAI-1 mass was associated with sinus rhythm even after adjusting for CRP, markers of the metabolic syndrome and treatment with atorvastatin. Our findings suggest a patophysiological link between AF and PAI-1 mass but the relation to inflammation remains unclear.

Identifiers
urn:nbn:se:umu:diva-45887 (URN)10.1016/j.thromres.2010.06.002 (DOI)21237502 (PubMedID)
Available from: 2011-08-19 Created: 2011-08-19 Last updated: 2017-12-08Bibliographically approved

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