| 1. |
- Lind, Peter, et al.
(författare)
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Risk of myocardial infarction in relation to plasma levels of homocysteine and inflammation-sensitive proteins: a long-term nested case-control study.
- 2003
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Ingår i: Angiology. - 0003-3197. ; 54:4, s. 401-410
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have found that the homocysteine plasma level is associated with cardiovascular disease. The authors previously described a relationship between concentrations of fibrinogen and other inflammation-sensitive plasma proteins, namely, alpha1-antitrypsin, ceruloplasmin, haptoglobin, and orosomucoid (alpha1-acid glucoprotein) and the incidence of myocardial infarction (MI). Whether levels of these proteins are related to homocysteine has not been clarified. The aim of this study was to investigate whether a supposed relationship between homocysteine in plasma and the occurrence of MI is modified by these inflammation-sensitive proteins. A nested case-control study was designed, comprising 241 cases of MI, with a mean age of 48 years at baseline, and 241 controls matched for age, month of examination, and duration of follow-up. The mean homocysteine concentration did not differ between cases and controls and there was no association between the baseline homocysteine level and the time lapse before the occurrence of the MI. For the cases, there was no correlation between homocysteine and any of the measured proteins, but for the controls, homocysteine was weakly but significantly negatively correlated to haptoglobin and ceruloplasmin and slightly positively correlated to albumin. For the separated groups of cases and controls there was no association between the number of inflammation-sensitive proteins in the top quartiles and homocysteine concentration. In this population-based, prospective cohort study the occurrence of MI had no relationship to homocysteine baseline plasma level. Furthermore, there was no strong association between homocysteine and the concentrations of any of these inflammation-sensitive proteins.
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| 2. |
- Liljedahl, Ulrika, et al.
(författare)
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Single nucleotide polymorphisms in the apolipoprotein B and low density lipoprotein receptor genes affect response to antihypertensive treatment
- 2004
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261 .- 1471-2261. ; 4:1, s. 16-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dyslipidemia has been associated with hypertension. The present study explored if polymorphisms in genes encoding proteins in lipid metabolism could be used as predictors for the individual response to antihypertensive treatment. METHODS: Ten single nucleotide polymorphisms (SNP) in genes related to lipid metabolism were analysed by a microarray based minisequencing system in DNA samples from ninety-seven hypertensive subjects randomised to treatment with either 150 mg of the angiotensin II type 1 receptor blocker irbesartan or 50 mg of the beta1-adrenergic receptor blocker atenolol for twelve weeks. RESULTS: The reduction in blood pressure was similar in both treatment groups. The SNP C711T in the apolipoprotein B gene was associated with the blood pressure response to irbesartan with an average reduction of 19 mmHg in the individuals carrying the C-allele, but not to atenolol. The C16730T polymorphism in the low density lipoprotein receptor gene predicted the change in systolic blood pressure in the atenolol group with an average reduction of 14 mmHg in the individuals carrying the C-allele. CONCLUSIONS: Polymorphisms in genes encoding proteins in the lipid metabolism are associated with the response to antihypertensive treatment in a drug specific pattern. These results highlight the potential use of pharmacogenetics as a guide for individualised antihypertensive treatment, and also the role of lipids in blood pressure control.
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| 3. |
- Lind, Monica, et al.
(författare)
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Estrogen supplementation modulates effects of the endocrine disrupting pollutant PCB126 in rat bone and uterus : diverging effects in ovariectomized and intact animals.
- 2004
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Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 199:2-3, s. 129-136
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Tidskriftsartikel (refereegranskat)abstract
- The aims of the present study are to compare effects of estrogen depletion (OVX) and estradiol (E2) supplementation on the tissue effects of exposure to the endocrine disrupting organochlorine 3,3',4,4',5-pentachlorobiphenyl (PCB126). For this purpose two highly estrogen-dependent tissues, bone and uterus, were studied. Forty rats exposed to PCB126 (ip) for 3 months (total dose 384 microg/kg body weight (bw)) were randomized in to OVX/sham operation or E2 supplementation (ip, 23 microg/kg, 3 days weekly) per vehicle (corn oil) groups in a 2 x 2 factorial design. Sham operated rats were treated with vehicle, PCB or PCB plus E2 (sham, sham + PCB and sham + PCB + E2, n=10 per group) whereas ovariectomized were treated with vehicle, PCB or PCB plus E2(OVX, OVX + PCB and OVX + PCB + E2, n=10 per group). As control groups served OVX or sham, and OVX + E2 (n=10 in each group). In OVX rats PCB126 + E2 treatment increased trabecular bone volume (TBV) (P<0.01), whilst the opposite was found in sham-operated rats (P<0.01). In OVX animals exposed to PCB126, E2 supplementation decreased the uterine weight and increased the uterine ERbeta mRNA level, whilst no difference was found between the PCB126 and PCB126 + E2 exposed groups in the sham-operated animals. In conclusion, estrogen modulates PCB126 induced effects on trabecular bone, as well as several uterine parameters. These results further support an important role of estrogen on the toxic effects of PCB126 on bone and uterus.
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| 4. |
- Lind, Monica, et al.
(författare)
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The dioxin-like pollutant PCB 126 (3,3',4,4',5-pentachlorobiphenyl) affects risk factors for cardiovascular disease in female rats
- 2004
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Ingår i: Toxicology Letters. - : Elsevier BV. - 0378-4274 .- 1879-3169. ; 150:3, s. 293-299
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological studies suggest that exposure to persistent organic pollutants such as organochlorines might induce cardiovascular disorders and diabetes. Some of these organochlorines, such as dioxins and some dioxin-like PCBs, have been characterised as anti-estrogenic due to their inhibition of estrogenic-induced responses. In the present pilot study, 40 female rats were subjected to either exposure to the dioxin-like 3,3',4,4',5-pentachlorobiphenyl (PCB 126) or vehicle, as well as ovariectomy (OVX) or sham operation in a 2 x 2 factorial design over 12 weeks to explore potential interactions between estrogen status and PCB 126 exposure on cardiovascular risk factors. PCB 126 increased heart weight and serum cholesterol levels in both groups. PCB 126 increased blood pressure in the sham-operated animals only. In conclusion, PCB 126 exposure in female rats resulted in effects on cardiovascular risk factors, such as serum cholesterol, blood pressure, and heart weight. Of these effects of PCB 126, the increase in blood pressure was dependent on estrogen status.
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| 5. |
- Lind, Monica, et al.
(författare)
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Torsional testing and peripheral quantitative computed tomography in rat humerus
- 2001
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 29:3, s. 265-270
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Tidskriftsartikel (refereegranskat)abstract
- Peripheral quantitative computed tomography (pQCT) is a noninvasive method mainly used to evaluate the densitometric and geometric properties of bone. In the present study, we evaluate the different variables provided by pQCT examination and their ability to predict the mechanical strength properties of the rat humerus. Humeri from 68 female rats were utilized. These humeri represented bone with a wide range of mechanical and densitometric properties as well as geometric dimensions. Various characteristics, such as volumetric cortical density, total mineral content, cortical thickness, total cross-sectional area, cortical area, and polar strength strain index (SSI), were measured by pQCT. The reproducibility of these measurements was good, with a coefficient of variation (CV) ranging from 0.8% to 4.9%. Bone composition (e.g., ash weight, water content, and inorganic content) and bone dimensions (e.g., length, waist, and volume) were also determined. The mechanical properties (maximum torque, torsion at failure, and stiffness) were measured by torsional testing. Stepwise multiple linear regression was performed to identify the best explanatory variables for each mechanical parameter. Total cross-sectional area and polar SSI were equally well correlated to stiffness (r = 0.57, p < 0.001), whereas ash weight was superior to the pQCT variables to explain maximum torque (r = 0.42, p < 0.001). No other independent pQCT variable entered the two models in the stepwise regression analysis. It was found to be feasible to measure properties of the rat humerus with pQCT. Cross-sectional area and the polar SSI were shown to be the best explanatory variables for stiffness, whereas ash weight was the best predictor for maximum torque.
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| 6. |
- 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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| 7. |
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| 8. |
- 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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| 9. |
- 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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| 10. |
- Engström, Gunnar, et al.
(författare)
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Inflammation-sensitive plasma proteins, diabetes, and mortality and incidence of myocardial infarction and stroke: a population-based study.
- 2003
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 52:2, s. 442-447
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Tidskriftsartikel (refereegranskat)abstract
- This study explores the relationship of inflammation-sensitive plasma proteins (ISPs) with the prevalence of diabetes and the interrelationships between ISPs and diabetes in the prediction of death and incidence of myocardial infarction and stroke. Plasma levels of fibrinogen, α1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid were assessed in 6,050 men, aged 28–61 years. All-cause and cardiovascular mortality and incidence of myocardial infarction and stroke were monitored over 18.7 ± 3.7 years. Prevalence of diabetes (n = 321) was significantly associated with ISP levels among overweight and obese men but not among men with BMI <25 kg/m2. The association was similar for insulin resistance according to homeostasis model assessment. High ISP levels (two or more ISPs in the top quartile) increased the cardiovascular risk among diabetic men. The risk factor-adjusted relative risks for cardiovascular mortality, myocardial infarction, and stroke were 2.8 (CI 1.8–4.5), 2.2 (1.5–3.2), and 2.5 (1.4–4.6), respectively, for diabetic men with high ISP levels (reference: nondiabetic men with low ISP levels). The corresponding risks for diabetic men with low ISP levels were 1.8 (1.1–3.0), 1.3 (0.8–2.1), and 1.2 (0.6–2.5), respectively. In conclusion, in this population-based cohort, diabetes was associated with increased ISP levels among overweight and obese men but not among men with normal weight. High ISP levels increased the cardiovascular risk similarly in diabetic as compared with nondiabetic men.
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