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  • 1
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    Online Resource
    Hypobetalipoproteinemia Is Associated With Low Levels of Hemostatic Risk Factors in the Framingham Offspring Population
    Ovid Technologies (Wolters Kluwer Health) ; 1997
    In:  Circulation Vol. 95, No. 4 ( 1997-02-18), p. 825-830
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 95, No. 4 ( 1997-02-18), p. 825-830
    Abstract: Background Given the importance of thrombosis in causation of acute coronary syndromes, it is possible that the beneficial effect of low lipid levels on the risk of coronary events is achieved by lowering thrombotic potential of the blood. Hypobetalipoproteinemia is characterized by plasma concentrations of apolipoprotein B and LDL cholesterol that are one third of those observed in the general population. The aim of this study was to utilize subjects with hypobetalipoproteinemia to examine the relation between thrombotic potential and low levels of LDL cholesterol. Methods and Results Hemostatic risk factors were measured in 1878 individuals (1003 women and 875 men) participating in cycle 5 of the Framingham Offspring Study. The subjects were divided into five groups on the basis of LDL cholesterol level. Subjects with hypobetalipoproteinemia (LDL cholesterol 〈 70 mg/dL) had the lowest levels of fibrinogen, plasminogen activator inhibitor–1 antigen, and tissue plasminogen activator antigen. As LDL cholesterol increased, there was a significant increase in the levels of the hemostatic risk factors, with the exception of von Willebrand factor antigen. Adjustment with multivariate regression analyses for the covariates age, sex, body mass index, diabetes mellitus, smoking, alcohol intake, triglyceride level, and use of antihypertensive medication did not materially alter the results. Conclusions Decreasing levels of LDL cholesterol are associated with decreasing levels of hemostatic risk factors. Subjects with hypobetalipoproteinemia have the lowest levels of hemostatic risk factors and may be protected against thrombotic complications of atherosclerotic cardiovascular disease because of reduced thrombotic potential. One mechanism by which lipid-lowering therapy may decrease clinical cardiac events is through a reduction in thrombotic tendency.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.95.4.825
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1997
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  • 2
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    Abstract 291: Association of Single Nucleotide Polymorphisms in Inflammatory Candidate Genes with Circulating Inflammatory Biomarker Concentrations: The Framingham Heart Study
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Circulation Vol. 116, No. suppl_16 ( 2007-10-16)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 116, No. suppl_16 ( 2007-10-16)
    Abstract: Background : Chronic subclinical inflammation is a prominent feature of atherosclerotic disease. The genetic background for this pro-inflammatory state is not well-established. Circulating biomarker concentrations have become attractive candidates to measure disease activity and prognosis. Methods : We examined 2356 single-nucleotide polymorphisms (SNPs) in 235 inflammatory pathway genes in association with 11 circulating inflammatory biomarkers in about 1800 Framingham Offspring cohort participants [CD40 ligand, CRP, intercellular adhesion molecule-1, interleukin-6 (IL6), urinary isoprostanes, monocyte chemoattractant protein-1 (MCP1), myeloperoxidase, P-selectin, tumor necrosis factor alpha, tumor necrosis factor receptor-2, fibrinogen]. We created residuals of log transformed biomarker concentrations adjusting for 16 potential confounders. Only SNPs with call rate ≥0.98 and HWE p 〉 0.01, which had at least 5 minor allele carriers entered analyses. False discovery rate (FDR) and q-value methods were applied. Results : We observed similar results with FDR and q-value methods. A total of 45 associations were significant at a cutoff q value of 0.25. The top SNPs were observed in the SELP gene in association with P-selectin concentrations (rs6136 [nonsynonymous], p= 5.17*10 −39 , rs3753305 [intronic], p= 6.17*10 −9 ) and the ICAM1 gene in relation to ICAM-1 concentrations (rs1799969 [coding-nonsynonymous], p= 1.32*10 −8 ). Lowest p-values for trans-acting SNPs were observed for APCS (rs1374486 [function unknown], p= 1.01*10 −7 , and rs6695377 [function unknown], p= 1.85*10 −7 ) with MCP-1 concentrations and for IL6R (rs8192284 [coding-nonsynonimous,intronic], p= 3.36*10 −5 ) with IL6 concentrations. In addition, we could replicate reported findings for rs1799969, and rs5498 in the ICAM-1 gene in relation to ICAM-1 concentrations as well as associations of SNPs rs2857654, rs1024611, and rs2857657 in the CCL-2 gene with MCP-1 concentrations. Conclusions : The results of this candidate gene approach support the relevance of genetic variation for circulating inflammatory biomarker traits. Some former findings were confirmed and novel potential candidates are reported. Our findings merit replication in other cohorts.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.116.suppl_16.II_39
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
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  • 3
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    Clinical Correlates of Circulating Visfatin Levels in a Community-Based Sample
    American Diabetes Association ; 2007
    In:  Diabetes Care Vol. 30, No. 5 ( 2007-05-01), p. 1278-1280
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 30, No. 5 ( 2007-05-01), p. 1278-1280
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc06-2353
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2007
    detail.hit.zdb_id: 1490520-6
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  • 4
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    Effect of marathon running on inflammatory and hemostatic markers
    Elsevier BV ; 2001
    In:  The American Journal of Cardiology Vol. 88, No. 8 ( 2001-10), p. 918-920
    Details
    In: The American Journal of Cardiology, Elsevier BV, Vol. 88, No. 8 ( 2001-10), p. 918-920
    Type of Medium: Online Resource
    ISSN: 0002-9149
    URL: Article
    DOI: 10.1016/S0002-9149(01)01909-9
    RVK:
    XA 18500
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2001
    detail.hit.zdb_id: 2019595-3
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  • 5
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    Biomarkers of the Osteoprotegerin Pathway : Clinical Correlates, Subclinical Disease, Incident Cardiovascular Disease, and Mortality
    Ovid Technologies (Wolters Kluwer Health) ; 2010
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 30, No. 9 ( 2010-09), p. 1849-1854
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 30, No. 9 ( 2010-09), p. 1849-1854
    Abstract: Objective— Experimental evidence identified the osteoprotegerin (OPG)/receptor activator of nuclear factor–κB (RANK)/RANK ligand (RANKL) pathway as a candidate system modulating vascular remodeling and cardiovascular disease (CVD). Methods and Results— Serum concentrations of OPG and RANKL were measured in 3250 Framingham Study participants (54% women, 61±9 years). During a mean follow-up of 4.6 years, 143 (of 3084 free of CVD at baseline) participants developed a first CVD event, and 235 died. In multivariable models, OPG was associated with increased hazards for incident CVD and mortality (hazard ratio, 1.27; 95% CI, 1.04 to 1.54; and hazard ratio, 1.25; 95% CI, 1.07 to 1.47, per 1-SD increment in log-OPG, respectively). Log-OPG was positively related to multiple CVD risk factors, including age, smoking, diabetes, systolic blood pressure, and prevalent CVD. In a subsample (n=1264), the prevalence of coronary artery calcification, measured by computed tomography, increased nonsignificantly with OPG quartiles. RANKL concentrations displayed inverse associations with multiple CVD risk factors, including smoking, diabetes, and antihypertensive treatment, and were not related to coronary artery calcification or incident CVD or mortality. Conclusion— Our prospective data reinforce OPG as marker for CVD risk factor burden and predictor for CVD and mortality in the community.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/ATVBAHA.109.199661
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2010
    detail.hit.zdb_id: 1494427-3
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  • 6
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    Factor VII Gene Polymorphism, Factor VII Levels, and Prevalent Cardiovascular Disease : The Framingham Heart Study
    Ovid Technologies (Wolters Kluwer Health) ; 2000
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 20, No. 2 ( 2000-02), p. 593-600
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 20, No. 2 ( 2000-02), p. 593-600
    Abstract: Abstract —Elevated factor VII levels have been associated with increased cardiovascular risk in some studies. The arginine/glutamine (Arg/Gln) polymorphism of the factor VII gene has been previously shown to modify factor VII levels. However, the presence of a gene/environment interaction on factor VII levels or a link with cardiovascular disease (CVD) remains uncertain. We studied subjects from the Framingham Heart Study to determine (1) the extent to which this genetic polymorphism affects factor VII levels; (2) whether interactions exist between this polymorphism and environmental factors on factor VII levels; and (3) the association between the polymorphism and CVD. Genotype data and factor VII antigen levels were available in 1816 subjects. Factor VII levels differed significantly among genotypes in an additive fashion: Gln homozygous, 82.7±2.5%; heterozygous, 92.2±0.7%; and Arg homozygous, 100.5±0.4% ( P 〈 0.0001). The polymorphism was the strongest, single predictor of factor VII levels, explaining 7.7% of the total variance of factor VII levels, whereas other traditional risk factors combined explained an additional 11.5% of the variance. There was an interaction ( P =0.02) between the genotype and total cholesterol on factor VII levels, such that the correlation coefficient and slope (factor VII level/total cholesterol) were greatest in Gln/Gln subjects. Among 3204 subjects characterized for genotype and CVD, there was no significant relationship between the genotype and CVD ( P =0.12). In the Framingham Heart Study, the Arg/Gln polymorphism was significantly associated with factor VII antigen levels. The strength of the association suggests that genetic variation plays an important role in determining factor VII levels. However, despite being associated with factor VII levels, the Arg/Gln polymorphism was not associated with prevalent CVD.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/01.ATV.20.2.593
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2000
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  • 7
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    Association of Blood Pressure With Fibrinolytic Potential in the Framingham Offspring Population
    Ovid Technologies (Wolters Kluwer Health) ; 2000
    In:  Circulation Vol. 101, No. 3 ( 2000-01-25), p. 264-269
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 101, No. 3 ( 2000-01-25), p. 264-269
    Abstract: Background —Hypertension is an established risk factor for acute coronary events. Because fibrinolytic and hemostatic factors are also associated with cardiovascular disease, we examined the relations of systolic and diastolic blood pressures (SBP and DBP) to levels of plasminogen activator inhibitor antigen, tissue plasminogen activator antigen, fibrinogen, factor VII, von Willebrand factor, fibrinogen, and plasma viscosity in subjects of the Framingham Offspring Study. Methods and Results —We studied 1193 men and 1459 women after the exclusion of subjects with known cardiovascular disease and those receiving anticoagulant or antihypertensive therapy. Linear regression models were used to evaluate SBP and DBP as predictors of fibrinolytic and hemostatic factor levels in separate sex models, with adjustment for age, body mass index, smoking, diabetes, total cholesterol, HDL, triglycerides, alcohol intake, and estrogen use (in women). In both sexes, levels of plasminogen activator inhibitor and tissue plasminogen activator antigen were positively related to SBP and DBP ( P 〈 0.001). Plasma viscosity was positively related to SBP ( P =0.008) and DBP ( P =0.001) in women only. There was no association between SBP or DBP and fibrinogen, factor VII, or von Willebrand factor in either sex. Conclusions —These data suggest that impaired fibrinolysis may play an important role in the pathogenesis of cardiovascular disease in hypertensive patients.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.101.3.264
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2000
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  • 8
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    Visceral and Subcutaneous Adipose Tissue Volumes Are Cross-Sectionally Related to Markers of Inflammation and Oxidative Stress : The Framingham Heart Study
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Circulation Vol. 116, No. 11 ( 2007-09-11), p. 1234-1241
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 116, No. 11 ( 2007-09-11), p. 1234-1241
    Abstract: Background— Excess adiposity is associated with greater systemic inflammation. Whether visceral adiposity is more proinflammatory than subcutaneous abdominal adiposity is unclear. Methods and Results— We examined the relations of abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), assessed by multidetector computerized tomography, to circulating inflammatory and oxidative stress biomarkers in 1250 Framingham Heart Study participants (52% women; age 60±9 years). Biomarkers were examined in relation to increments of SAT and VAT after adjustment for age, sex, smoking, physical activity, menopause, hormone replacement therapy, alcohol, and aspirin use; additional models included body mass index and waist circumference. SAT and VAT were positively and similarly (with respect to strength of association) related to C-reactive protein, fibrinogen, intercellular adhesion molecule-1, interleukin-6, P-selectin, and tumor necrosis factor receptor-2 (multivariable model R 2 0.06 to 0.28 [SAT] and 0.07 to 0.29 [VAT] ). However, compared with SAT, VAT was more highly associated with urinary isoprostanes and monocyte chemoattractant protein-1 (SAT versus VAT comparison: isoprostanes, R 2 0.07 versus 0.10, P =0.002; monocyte chemoattractant protein-1, R 2 0.07 versus 0.08, P =0.04). When body mass index and waist circumference were added to the models, VAT remained significantly associated with only C-reactive protein ( P =0.0003 for women; P =0.006 for men), interleukin-6 ( P =0.01), isoprostanes ( P =0.0002), and monocyte chemoattractant protein-1 ( P =0.008); SAT only remained associated with fibrinogen ( P =0.01). Conclusions— The present cross-sectional data support an association between both SAT and VAT with inflammation and oxidative stress. The data suggest that the contribution of visceral fat to inflammation may not be completely accounted for by clinical measures of obesity (body mass index and waist circumference).
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.107.710509
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
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  • 9
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    Platelet Glycoprotein IIIa Pl A Polymorphism, Fibrinogen, and Platelet Aggregability : The Framingham Heart Study
    Ovid Technologies (Wolters Kluwer Health) ; 2001
    In:  Circulation Vol. 104, No. 2 ( 2001-07-10), p. 140-144
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 104, No. 2 ( 2001-07-10), p. 140-144
    Abstract: Background — Recent data suggest that the Pl A2 allele of the platelet glycoprotein IIIa receptor may be a genetic risk factor for cardiovascular disease. We previously reported that the Pl A2 allele was associated with increased platelet aggregability, as indicated by lower epinephrine threshold concentrations. Paradoxically, however, it has been reported that Pl A2 -positive platelets have reduced fibrinogen binding. Because fibrinogen mediates platelet aggregability, we hypothesized that plasma fibrinogen levels may interact with Pl A genotype in modulating platelet aggregability. Methods and Results — Glycoprotein IIIa Pl A genotype, fibrinogen level, and platelet aggregability were ascertained in 1340 subjects enrolled into the Framingham Offspring Study. Platelet aggregability was evaluated by the Born method. Higher fibrinogen levels were associated with increased epinephrine-induced aggregation ( P =0.002) and a trend for ADP-induced aggregation ( P =0.07). The fibrinogen effect was genotype specific, however, in that the increase in platelet aggregability with higher fibrinogen was present for the Pl A1/A1 genotype ( P =0.0005 and P =0.03 for epinephrine- and ADP-induced aggregation, respectively) but not for the Pl A2 -positive genotype ( P 〉 0.90). Conclusion — Higher fibrinogen levels were associated with increased platelet aggregability. However, the association between fibrinogen and platelet aggregability was genotype specific. This interaction may be responsible for the conflicting findings regarding Pl A genotype and platelet aggregability. Further study of this gene-environment interaction may provide insight into cardiovascular disease risk.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.104.2.140
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2001
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  • 10
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    Association between obesity and a prothrombotic state: the Framingham Offspring Study
    Georg Thieme Verlag KG ; 2004
    In:  Thrombosis and Haemostasis Vol. 91, No. 04 ( 2004), p. 683-689
    Details
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 91, No. 04 ( 2004), p. 683-689
    Abstract: Although obesity is associated with increased cardiovascular risk, the mechanism has not been fully explained. Since thrombosis is a critical component of cardiovascular disease, we examined the relationship between obesity and hemostatic factors. We studied 3230 subjects (55% females, mean age 54 years) without a history of cardiovascular disease in cycle 5 of the Framingham Offspring Study. Obesity was assessed by body mass index and waist-to-hip ratio. Fasting blood samples were obtained for fibrinogen, plasminogen activator inhibitor (PAI-1) antigen, tissue plasminogen activator (tPA) antigen, factor VII antigen, von Willebrand factor (VWF), and plasma viscosity. Body mass index was directly associated with fibrinogen, factor VII, PAI-1 and tPA antigen in both men and women (p 〈 0.001) and with VWF and viscosity in women. Similar associations were present between waist-to-hip ratio and the hemostatic factors. With minor exceptions for VWF and viscosity, all associations persisted after controlling for age, smoking, total and HDL cholesterol, triglycerides, glucose level, blood pressure, and use of antihypertensive medication. The association between increased body mass index and waist-to-hip ratio and prothrombotic factors and impaired fibrinolysis suggests that obesity is a risk factor whose effect is mediated in part by a prothrombotic state.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    URL: Article
    DOI: 10.1160/TH03-01-0014
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2004
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