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| 2. |
- Anwaar, I., et al.
(författare)
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Increasing levels of leukocyte-derived inflammatory mediators in plasma and cAMP in platelets during follow-up after acute cerebral ischemia
- 1998
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Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1015-9770 .- 1421-9786. ; 8:6, s. 310-317
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory mediators secreted by activated leukocytes play a role in the pathogenesis of atherosclerosis. They may also affect the production of vasodilatory and platelet antiaggregatory factors such as nitric oxide (NO) and prostacyclin (PGI2) from the vascular endothelium. Production of NO and PGI2, the effecs of which are mediated by cyclic 3',5'-guanosine monophosphate (cGMP) and cyclic 3',5'-adenosine monophosphate (cAMP), respectively, is disturbed in atherosclerosis, whereas increased NO levels have been found in acute cerebral ischemia. To investigate leukocyte activation and its possible influence upon endothelial function in cerebral ischemia we measured plasma neutrophil gelatinase-associated lipocalin (NGAL) and soluble tumor necrosis factor receptor protein-1 (sTNFR-1) by ELISA, and intraplatelet cAMP and cGMP by radioimmunoassay in 59 patients with acute ischemic stroke or transient ischemic attack (mean age 71 years, 27 males) and after a 1-year follow-up in 57/59 (97%) patients. NGAL (152 ± 58 vs. 126 ± 48 μg/l), sTNFR-1 (3.50 ± 2.2 vs. 2.59 ± 1.31 μg/l), and cAMP(5.12 ± 1.71 vs. 4.06 ± 0.92 pmol/109 platelets) were higher (p < 0.001) after follow-up than in acute cerebral ischemia. At follow-up sTNFR-1 and cGMP partially correlated (r = 0.31; p < 0.05), controlling for age and platelet count. In conclusion, plasma NGAL and sTNFR-1 and intraplatelet AMP increase after acute cerebral ischemia, indicating chronic inflammatory activity and endothelial activation. Plasma sTNFR-1 levels are related to intraplatelet cGMP levels.
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| 3. |
- Engström, Gunnar, et al.
(författare)
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Blood pressure increase and incidence of hypertension in relation to inflammation-sensitive plasma proteins.
- 2002
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 22:12, s. 2054-2058
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Tidskriftsartikel (refereegranskat)abstract
- Objective— The reasons for the relationship between inflammation-sensitive plasma proteins (ISPs) and incidence of cardiovascular diseases are poorly understood. This study explored the hypothesis that ISPs are associated with future hypertension and age-related blood pressure increase. Method and Results— Blood pressure and plasma levels of fibrinogen, {alpha}1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid were determined in 2262 healthy men aged 35 to 50 years, initially without treatment for hypertension. The cohort was re-examined after 15.7 (±2.2) years. Incidence of hypertension and blood pressure increase was studied in relation to number of elevated proteins (ie, in the top quartile) at baseline. Among men without treatment for hypertension at follow-up, mean (±SD) increase in systolic blood pressure was 18.8±17, 19.2±17, 19.3±17, and 22.1±18 mm Hg, respectively, for men with 0, 1, 2, and >=3 elevated proteins (P for trend=0.02, adjusted for confounders). The corresponding values for pulse pressure increase was 15.5±14, 15.8±14, 17.4±14, and 17.8±15 mm Hg, respectively (P=0.02). Incidence of hypertension (>=160/95 mm Hg or treatment) and future blood pressure treatment showed similar associations with ISPs. Increase in diastolic blood pressure showed no association with ISPs. Conclusions— Plasma levels of ISPs are associated with a future increase in blood pressure. This could contribute to the relationship between ISP levels and cardiovascular disease.
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| 4. |
- Engström, Gunnar, et al.
(författare)
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Complement C3 and C4 in plasma and incidence of myocardial infarction and stroke: a population-based cohort study
- 2007
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Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - : Oxford University Press (OUP). - 1741-8275 .- 1741-8267. ; 14:3, s. 392-397
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Tidskriftsartikel (refereegranskat)abstract
- Background Complement factor C3 and C4 have been associated with atherosclerosis and cardiovascular risk factors. This study explored whether plasma levels of C3 and C4 are risk factors for the incidence of cardiovascular disease (CVD). Design A population-based prospective study of 5850 initially healthy men, 28-61 years old at baseline. Methods Plasma levels of C3 and C4 were analysed at the baseline examination. The incidence of coronary events (i.e. fatal or non-fatal myocardial infarction), ischaemic stroke and cardiovascular events (i.e. myocardial infarction, ischaemic stroke or cardiovascular death) was studied over 18 years of follow-up. Results Adjusted for age, C3 in the fourth quartile (versus the first quartile) was associated with an increased incidence of coronary events [relative risk (RR) 1.54, 95% confidence interval (CI) 1.2-1.91, cardiovascular events (RR 1.56, 95% CI 1.3-1.9), and non-significantly with the incidence of ischaemic stroke (RR 1.31, 95% CI 0.89-1.8). However, after adjustments for smoking, body mass index (BMI), cholesterol, diabetes and systolic blood pressure, these relationships were completely attenuated and non-significant. The relationships were similar for C4 concentrations within the normal range. However, for men with C4 in the top 10% of the distribution (>0.34 g/l), a significantly increased incidence of coronary events was found, which persisted after adjustments for risk factors. Conclusion C3 and C4 show substantial correlations with cardiovascular risk factors, including blood pressure, BMI, and lipids. This relationship accounts for the increased incidence of CVD in men with high C3 levels. However, very high C4 levels may be associated with the incidence of CVD, independently of traditional cardiovascular risk factors.
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| 6. |
- Engström, Gunnar, et al.
(författare)
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Fatality of acute coronary events in relation to hypertension and low-grade inflammation: a population-based cohort study.
- 2006
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Ingår i: Journal of Human Hypertension. - : Springer Science and Business Media LLC. - 1476-5527 .- 0950-9240. ; 20:2006 May 4, s. 581-586
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Tidskriftsartikel (refereegranskat)abstract
- Hypertension has been associated with increased case-fatality rates among individuals who subsequently suffer from acute coronary events. It is unknown whether inflammation modifies this relationship. This population-based study explored the effects of inflammation and hypertension on incidence of coronary event, and on the fatality of the future events. Blood pressure (BP) and five inflammation-sensitive plasma proteins (ISPs, fibrinogen, orosomucoid, alpha 1-antitrypsin, haptoglobin and ceruloplasmin) were determined in 6071 healthy men. During the mean follow-up of 19 years, 679 men had a first coronary event (non-fatal myocardial infarction or death from coronary heart disease). Of them, 197 (29%) were fatal cases (death during the first day). As expected, hypertension was associated with increased incidence of coronary events and increased proportion of fatal cases. At all levels of BP, high ISPs (>= 2 ISPs in top quartile) significantly added to the incidence of events. Men with high ISPs had the highest case-fatality rates. The difference in case-fatality rate between men with and without high ISPs was, however, significant only in men with normal BP (<130/85 mm Hg) (33 vs 19%, P<0.05), and not in men with moderate or severe hypertension (>= 160/100 mm Hg) (40 vs 35%, P=0.32). High ISPs add to the incidence of coronary events at all levels of BP. Hypertension and inflammation are both independently associated with increased case-fatality in subjects who later have an acute coronary event. The influence of ISPs on the case-fatality rate seems to be most important in men with normal BP.
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| 8. |
- Engström, Gunnar, et al.
(författare)
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Incidence of Fatal or Repaired Abdominal Aortic Aneurysm in Relation to Inflammation-Sensitive Plasma Proteins.
- 2004
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 24:2, s. 337-341
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Tidskriftsartikel (refereegranskat)abstract
- Background— Inflammation is an important pathophysiological feature of abdominal aortic aneurysms (AAA). Whether elevated levels of inflammation-sensitive plasma proteins (ISPs) predict the long-term risk of fatal or repaired AAA is largely unknown. Methods and Results— Five ISPs (fibrinogen, orosomucoid, {alpha}1-antitrypsin, haptoglobin, and ceruloplasmin) were measured in 6075 healthy men, mean age 46.8±3.7 years. After a mean time of 19 years, 63 men had a fatal or surgically/endovascularly repaired AAA. Risk of treatment or death from future AAA was studied in relation to the ISPs. The risk of future AAA increased significantly with the number of elevated ISPs (ie, in the top quartile). The proportions with future AAA were 0.4%, 1.0%, 1.3%, and 2.3% for men with none, one, two, and >=3 ISPs, respectively, in the top quartile (trend: P<0.0001). The corresponding odds ratios were 1.00 (reference), 1.9 (95% CI: 0.8 to 4.5), 2.2 (0.9 to 5.5), and 3.2 (1.4 to 7.2), respectively, adjusted for age, screening year, smoking, cholesterol, triglycerides, systolic blood pressure and physical inactivity (trend: P=0.004). Conclusion— The incidence of fatal or repaired AAA is associated with the ISP levels. In this population-based study, elevated ISPs could be observed many years before the clinical manifestation of disease.
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| 9. |
- Engström, Gunnar, et al.
(författare)
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Inflammation-sensitive plasma proteins and incidence of myocardial infarction in men with low cardiovascular risk.
- 2003
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 23:12, s. 2247-2251
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Tidskriftsartikel (refereegranskat)abstract
- Objective— Myocardial infarction (MI) is sometimes experienced by individuals without any traditional risk factor. This prospective study explored whether incidence of MI in nonsmoking, nondiabetic men with normal blood pressure and serum lipids is related to inflammation-sensitive plasma proteins (ISPs). Methods and Results— Five ISPs ({alpha}1-antitrypsin, haptoglobin, ceruloplasmin, fibrinogen, orosomucoid) were analyzed in 6075 men, 47±3.6 years old. A low-risk group (no traditional risk factor, n=1108) and a high-risk group (>=2 major risk factors, n=1011) were defined. Incidence of MI (n=227) was monitored over 18.1±4.3 years of follow-up. In the low-risk group, the age-adjusted relative risks (RRs) were 1.00 (reference), 1.9 (95% CI, 0.8 to 4.2), 1.8 (95% CI, 0.6 to 5.4), and 2.9 (95% CI, 1.05 to 8.1), respectively, for men with 0, 1, 2 and >=3 ISPs in the top quartile (trend: P=0.03). In this group, the increased risk was observed only after >=10 years of follow-up. In the high-risk group, the age-adjusted RRs were 1.00, 1.4 (95% CI, 0.9 to 2.2), 1.9 (95% CI, 1.2 to 3.1), and 2.0 (95% CI, 1.3 to 3.1), respectively, for men with 0, 1, 2, and >=3 ISPs in the top quartile (trend: P=0.0004). Conclusion— Incidence of MI in nonsmoking, nondiabetic men with normal blood pressure and lipids was related to ISPs. The causes for this relationship remain to be explored.
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| 10. |
- Engström, Gunnar, et al.
(författare)
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Inflammation-sensitive plasma proteins are associated with future weight gain.
- 2003
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 52:8, s. 2097-2101
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Tidskriftsartikel (refereegranskat)abstract
- Cross-sectional studies have associated obesity and other components of the so-called metabolic syndrome with low-grade inflammation. The temporal and causal relations of this association have not been fully explored. This study explored whether elevated levels of inflammation-sensitive plasma proteins (ISPs) (fibrinogen, orosomucoid, {alpha}1-antitrypsin, haptoglobin, and ceruloplasmin) are associated with future weight gain. Five ISPs were measured in 2,821 nondiabetic healthy men (38–50 years of age) who were reexamined after a mean follow-up of 6.1 years. Future weight gain was studied in relation to the number of elevated ISPs (i.e., in the top quartile). The proportion with a large weight gain (75th percentile >=3.8 kg) was 21.0, 25.9, 26.8, and 28.3%, respectively, among men with none, one, two, and three or more ISPs in the top quartile (P for trend 0.0005). This relation remained significant after adjustments for weight at baseline, follow-up time, height (at baseline and follow-up), physical inactivity (at baseline and follow-up), smoking (at baseline and follow-up), high alcohol consumption, and insulin resistance. The relations were largely similar for all individual ISPs. Elevated ISP levels predict a large weight gain in middle-aged men. This relation could contribute to the relation between inflammation, the metabolic syndrome, and cardiovascular disease. Several cross-sectional studies have reported positive correlations between body fatness and inflammation-sensitive plasma proteins (ISPs) and other inflammatory markers (1–4). Weight reduction in obese subjects has been associated with reduced inflammation (5–7). It has been proposed that proinflammatory cytokines formed in the adipose tissue, e.g., interleukin (IL)-6 and tumor necrosis factor-{alpha} (TNF-{alpha}), increase the hepatic synthesis of ISPs (4,8–10). However, the temporal and causal relations between obesity and elevated ISPs are incompletely understood. Even though inflammation is mainly considered an effect of obesity or weight increase, it also has been suggested that there could be a reverse relation, i.e., that inflammation could promote weight gain (11). A 3-year follow-up of the Atherosclerosis Risk in Communities (ARIC) study reported that a large weight gain was more common in subjects with elevated fibrinogen, white blood cells, von Willebrand factor, or factor VIII, i.e., four putative markers of inflammation (12). The Malmö Preventive Study cohort includes ~6,000 men with data on five ISPs (fibrinogen, haptoglobin, {alpha}1-antitrypsin, orosomucoid, and ceruloplasmin). Previous studies from this cohort have shown cross-sectional relations between ISP levels and BMI, blood pressure, and insulin resistance (1,13,14). Follow-up studies have shown that these proteins are associated with an increased incidence of cardiovascular diseases and an increased incidence of high blood pressure (15,16). The present study sought to explore whether these proteins predicted weight gain over a mean follow-up of 6 years.
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