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  • 1
    Online Resource
    Online Resource
    Prediagnosis biomarkers of insulin-like growth factor-1, insulin, and interleukin-6 dysregulation and multiple myeloma risk in the Multiple Myeloma Cohort Consortium
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 25 ( 2012-12-13), p. 4929-4937
    Details
    In: Blood, American Society of Hematology, Vol. 120, No. 25 ( 2012-12-13), p. 4929-4937
    Abstract: Insulin-like growth factor-1 (IGF-1), insulin, and IL-6 are dysregulated in multiple myeloma pathogenesis and may also contribute to multiple myeloma etiology. To examine their etiologic role, we prospectively analyzed concentrations of serologic markers in 493 multiple myeloma cases and 978 controls from 8 cohorts in the Multiple Myeloma Cohort Consortium. We computed odds ratios (ORs) and 95% confidence intervals (CIs) for multiple myeloma per 1-SD increase in biomarker concentration using conditional logistic regression. We examined heterogeneity by time since blood collection (≤ 3, 4- ≤ 6, and 〉 6 years) in stratified models. Fasting IGF binding protein-1 concentration was associated with multiple myeloma risk within 3 years (OR, 95% CI per 1-SD increase: 2.3, 1.4-3.8, P = .001) and soluble IL-6 receptor level was associated within 6 years after blood draw (OR ≤ 3 years, 95% CI, 1.4, 1.1-1.9, P = .01; OR4- ≤ 6 years, 95% CI, 1.4, 1.1-1.7, P = .002). No biomarker was associated with longer-term multiple myeloma risk (ie, 〉 6 years). Interactions with time were statistically significant (IGF binding protein-1, P-heterogeneity = .0016; sIL6R, P-heterogeneity = .016). The time-restricted associations probably reflect the bioactivity of tumor and microenvironment cells in transformation from monoclonal gammopathy of undetermined significance or smoldering multiple myeloma to clinically manifest multiple myeloma.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2012-03-417253
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
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    Online Resource
    Abstract P102: Circulating Adipocytokines and Risk of Chronic Kidney Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Circulation Vol. 125, No. suppl_10 ( 2012-03-13)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 125, No. suppl_10 ( 2012-03-13)
    Abstract: Recent studies have found a link between obesity and chronic kidney disease (CKD). However, the mechanism for this association is not well understood. Obesity-related CKD may be partially mediated by adipocytokines, including leptin, resistin, and adiponectin. In this study we investigated the association of plasma leptin, resistin and adiponectin with risk of CKD in 201 cases with CKD and 201 controls without. CKD was defined as estimated glomerular filtration rate (eGFR) 〈 60 ml/min/1.73 m2 or presence of albuminuria. Median levels of adipocytokines and odds ratios of CKD were estimated and adjusted for age, gender, race, smoking, drinking, education, physical activity, systolic blood pressure, glucose, low-density lipoprotein cholesterol, and body mass index. Compared to controls, adjusted median plasma leptin (38,385 vs. 17,303 ng/mL, p 〈 0.0001) and resistin (15.0 vs. 8.0 ng/mL, p 〈 0.0001) were significantly higher in CKD cases. The median ratio of high molecular weight adiponectin to total adiponectin was lower in cases than in controls (0.38 vs. 0.43, p=0.0001). The odds ratios (OR) for CKD comparing the highest third to the lowest two thirds of leptin was 4.7 (95% CI, 2.2, 9.8) and of resistin was 17.0 (95% CI, 8.4, 34.2). A non-significant weak inverse effect was seen when comparing the highest third to the lowest two thirds of the adiponectin ratio with an OR of 0.8 (95% CI, 0.4, 1.3). The results did not change substantially after further adjustment for history of cardiovascular disease. Our study found that increased leptin and resistin are associated with an increased risk of CKD. In conclusion, these findings suggest that adipocytokines may play a role in the etiology of CKD. Longitudinal studies are warranted to further evaluate the causal relationship of these adipocytokines with development of CKD.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.125.suppl_10.AP102
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 1466401-X
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  • 3
    Online Resource
    Online Resource
    Abstract 5100: C-Reactive Protein and Parental History Improve Global Cardiovascular Risk Prediction: The Reynolds Risk Score for Men
    Ovid Technologies (Wolters Kluwer Health) ; 2008
    In:  Circulation Vol. 118, No. suppl_18 ( 2008-10-28)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 118, No. suppl_18 ( 2008-10-28)
    Abstract: Background. CRP and family history independently associate with future cardiovascular events and have been incorporated into risk prediction models for women (the Reynolds Risk Score for women). However, no cardiovascular risk prediction algorithm incorporating these variables currently exists for men. Methods. Among 10,724 initially healthy American non-diabetic men who were followed prospectively for incident cardiovascular events over a median period of 10.8 years, we developed a cardiovascular risk prediction model that included hsCRP and parental history of myocardial infarction before age 60 years, and compared model fit, discrimination, and reclassification to prediction models limited to age, blood pressure, smoking, total cholesterol, and high-density lipoprotein cholesterol. Results. 1,294 cardiovascular events accrued during study follow-up. Predictive models incorporating hsCRP and parental history (the Reynolds Risk Score for men) had better global fit (P 〈 0.001), a superior (lower) Bayes Information Criterion (BIC)(23008 vs 23048), and larger C-indexes (0.708 vs 0.699, P 〈 0.001) than did predictive models without these variables. For the endpoint of all cardiovascular events, the Reynolds Risk Score for men reclassified 17.8 percent of the study population into higher- or lower-risk categories with markedly improved accuracy among those reclassified. In models based on the ATP-III preferred endpoint of coronary heart disease and limited to men not taking lipid-lowering therapy, 16.7 percent of the study population were reclassified to higher- or lower-risk groups, again with significantly improved global fit (P 〈 0.001), smaller BIC (13870 vs 13891), larger C-index (0.714 vs 0.704, P 〈 0.001), and almost perfect accuracy among those reclassified (99.9 percent). For this model, NRI was 8.4 percent and CNRI 15.8 percent (both P-values 〈 0.001). Conclusion. We developed an improved global risk prediction algorithm for men incorporating hsCRP and parental history that should allow better targeting of preventive therapies to maximize benefit while minimizing toxicity and cost.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.118.suppl_18.S_1145-b
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2008
    detail.hit.zdb_id: 1466401-X
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  • 4
    Online Resource
    Online Resource
    Plasma Concentration of Interleukin-6 and the Risk of Future Myocardial Infarction Among Apparently Healthy Men
    Ovid Technologies (Wolters Kluwer Health) ; 2000
    In:  Circulation Vol. 101, No. 15 ( 2000-04-18), p. 1767-1772
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 101, No. 15 ( 2000-04-18), p. 1767-1772
    Abstract: Background —Interleukin-6 (IL-6) plays a central role in inflammation and tissue injury. However, epidemiological data evaluating the role of IL-6 in atherogenesis are sparse. Methods and Results —In a prospective study involving 14 916 apparently healthy men, we measured baseline plasma concentration of IL-6 in 202 participants who subsequently developed myocardial infarction (MI) and in 202 study participants matched for age and smoking status who did not report vascular disease during a 6-year follow-up. Median concentrations of IL-6 at baseline were higher among men who subsequently had an MI than among those who did not (1.81 versus 1.46 pg/mL; P =0.002). The risk of future MI increased with increasing quartiles of baseline IL-6 concentration ( P for trend 〈 0.001) such that men in the highest quartile at entry had a relative risk 2.3 times higher than those in the lowest quartile (95% CI 1.3 to 4.3, P =0.005); for each quartile increase in IL-6, there was a 38% increase in risk ( P =0.001).This relationship remained significant after adjustment for other cardiovascular risk factors, was stable over long periods of follow-up, and was present in all low-risk subgroups, including nonsmokers. Although the strongest correlate of IL-6 in these data was C-reactive protein ( r =0.43, P 〈 0.001), the relationship of IL-6 with subsequent risk remained after control for this factor ( P 〈 0.001). Conclusions —In apparently healthy men, elevated levels of IL-6 are associated with increased risk of future MI. These data thus support a role for cytokine-mediated inflammation in the early stages of atherogenesis.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.101.15.1767
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2000
    detail.hit.zdb_id: 1466401-X
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  • 5
    Online Resource
    Online Resource
    D-Dimer, Inflammatory Markers, and Lower Extremity Functioning in Patients With and Without Peripheral Arterial Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2003
    In:  Circulation Vol. 107, No. 25 ( 2003-07), p. 3191-3198
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 107, No. 25 ( 2003-07), p. 3191-3198
    Abstract: Background— We determined whether higher levels of D-dimer, C-reactive protein (CRP), fibrinogen, and serum amyloid A are associated independently with functional impairment in patients with and without peripheral arterial disease (PAD). Methods and Results— Participants were 370 men and women with PAD (ankle brachial index 〈 0.90) and 231 without PAD. Functional outcomes were 6-minute walk distance and 4-meter walking velocity. A summary performance score combined performance in walking speed, standing balance, and time for 5 repeated chair rises into an ordinal score ranging from 0 to 12 (12=best). Adjusting for age, sex, ankle brachial index, comorbidities, and other potential mediators and confounders, D-dimer levels were associated independently and inversely with performance on all 3 functional measures in the entire cohort and among patients with and without PAD, respectively. Adjusting for known and potential confounders, CRP levels were associated independently with 6-minute walk distance and the summary performance score among participants with PAD. No significant associations were observed between CRP and the functional measures among participants without PAD. Fibrinogen and SAA levels were not associated independently with the functional measures. Conclusions— Higher D-dimer levels are associated with poorer functioning among individuals with and without PAD. Higher CRP levels were associated with poorer 6-minute walk performance and a lower summary performance score among participants with PAD but not among those without PAD. Additional study is needed to determine whether D-dimer and CRP are involved in the pathophysiology of functional impairment or whether they are simply sensitive markers of the extent of systemic atherosclerosis.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.0000074227.53616.CC
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2003
    detail.hit.zdb_id: 1466401-X
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  • 6
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    Online Resource
    Differential Expression of Cardiac Biomarkers by Gender in Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction : A TACTICS-TIMI 18 (Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy–Thrombolysis In Myocardial Infarction 18) Substudy
    Ovid Technologies (Wolters Kluwer Health) ; 2004
    In:  Circulation Vol. 109, No. 5 ( 2004-02-10), p. 580-586
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 109, No. 5 ( 2004-02-10), p. 580-586
    Abstract: Background— Diagnosis of coronary artery disease in women is more difficult because of lower specificity of symptoms and diagnostic accuracy of noninvasive testing. We sought to examine the relationship between gender and cardiac biomarkers in patients with unstable angina (UA)/non–ST-segment elevation myocardial infarction (NSTEMI). Methods and Results— In the TACTICS-TIMI 18, OPUS-TIMI 16, and TIMI 11 studies, baseline samples were analyzed in the Thrombolysis In Myocardial Infarction (TIMI) biomarker core laboratory. We examined the relationship between gender and elevated biomarkers. Of 1865 patients from TACTICS-TIMI 18, 34% were women. Fewer women had elevated creatine kinase-MB or troponins, whereas more had elevated high-sensitivity C-reactive protein or brain natriuretic peptide. Presence of ST-segment deviation and TIMI risk scores were not significantly different. This pattern was confirmed in TIMI 11 and OPUS-TIMI 16. The prognostic value of the markers in TACTICS-TIMI 18 was similar in women and men. When a multimarker approach was examined, a greater proportion of high-risk women were identified. Marker-positive patients of both genders had improved outcome with an invasive strategy; however, marker-negative women appeared to have improved outcomes with a conservative strategy. Conclusions— In patients with UA/NSTEMI, there was a different pattern of presenting biomarkers. Men were more likely to have elevated creatine kinase-MB and troponins, whereas women were more likely to have elevated C-reactive protein and brain natriuretic peptide. This suggests that a multimarker approach may aid the initial risk assessment of UA/NSTEMI, especially in women. Further research is necessary to elucidate whether gender-related pathophysiological differences exist in presentation with acute coronary syndromes.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.0000109491.66226.26
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2004
    detail.hit.zdb_id: 1466401-X
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  • 7
    Online Resource
    Online Resource
    High-Dose Atorvastatin Enhances the Decline in Inflammatory Markers in Patients With Acute Coronary Syndromes in the MIRACL Study
    Ovid Technologies (Wolters Kluwer Health) ; 2003
    In:  Circulation Vol. 108, No. 13 ( 2003-09-30), p. 1560-1566
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 108, No. 13 ( 2003-09-30), p. 1560-1566
    Abstract: Background— Inflammation promotes acute coronary syndromes and ensuing clinical complications. Although statins reduce inflammatory markers in asymptomatic adults or in patients with stable angina, the effect of statins on the markedly heightened inflammation in patients with acute coronary syndromes is unknown. Methods and Results— We measured C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) in 2402 subjects enrolled the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study. Subjects with unstable angina or non–Q-wave myocardial infarction were randomized to atorvastatin 80 mg/d or placebo within 24 to 96 hours of hospital admission and treated for 16 weeks. The effect of treatment on inflammatory markers was assessed by ANCOVA after adjustment for presenting syndrome, country, and initial level of marker. All 3 markers were markedly elevated at randomization and declined over the 16 weeks in both treatment groups. Compared with placebo, atorvastatin significantly reduced CRP, −83% (95% CI, −84%, −81%) versus −74% (95% CI, −75%, −71%) ( P 〈 0.0001) and SAA, −80% (95% CI, −82%, −78%) versus −77% (−79%, −75%) ( P =0.0006) but not IL-6, −55% (95% CI, −57%, −53%) versus −53% (95% CI, −55%, −51%) ( P =0.3). Reductions in CRP and SAA were observed in patients with unstable angina and non–Q-wave myocardial infarction, with initial LDL cholesterol 〈 3.2 or ≥3.2 mmol/L (125 mg/dL), age ≥65 or 〈 65 years, and in men and women. By 16 weeks, CRP was 34% lower with atorvastatin than with placebo. Conclusions— High-dose atorvastatin potentiated the decline in inflammation in patients with acute coronary syndromes. This supports the value of early statin therapy in these patients.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.0000091404.09558.AF
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2003
    detail.hit.zdb_id: 1466401-X
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  • 8
    Online Resource
    Online Resource
    Low-Density Lipoprotein Particle Concentration and Size as Determined by Nuclear Magnetic Resonance Spectroscopy as Predictors of Cardiovascular Disease in Women
    Ovid Technologies (Wolters Kluwer Health) ; 2002
    In:  Circulation Vol. 106, No. 15 ( 2002-10-08), p. 1930-1937
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 106, No. 15 ( 2002-10-08), p. 1930-1937
    Abstract: Background— Nuclear magnetic resonance (NMR) offers an alternative, spectroscopic means of quantifying LDL and of measuring LDL particle size. Methods and Results— We conducted a prospective nested case-control study among healthy middle-aged women to assess LDL particle size (NMR) and concentration (NMR) as risk factors for future myocardial infarction, stroke, or death of coronary heart disease. Median baseline levels of LDL particle concentration (NMR) were higher (1597 vs 1404 nmol/L; P = 0.0001) and LDL particle size (NMR) was lower (21.5 vs 21.8 nm; P =0.046) among women who subsequently had cardiovascular events (n=130) than among those who did not (n= 130). Of these 2 factors, LDL particle concentration (NMR) was the stronger predictor (relative risk for the highest compared with the lowest quartile=4.17, 95% CI 1.96–8.87). This compared with a relative risk of 3.11 (95% CI 1.55–6.26) for the ratio of total cholesterol to HDL cholesterol and a relative risk of 5.91 (95% CI 2.65–13.15) for C-reactive protein. The areas under the receiver operating characteristic curves for LDL particle concentration (NMR), total cholesterol to HDL cholesterol ratio, and C-reactive protein were 0.64, 0.64, and 0.66, respectively. LDL particle concentration (NMR) correlated with several traditionally assessed lipid and nonlipid risk factors, and thus adjustment for these tended to attenuate the magnitude of association between LDL particle concentration (NMR) and risk. Conclusions— In this cohort, LDL particle concentration measured by NMR spectroscopy was a predictor of future cardiovascular risk. However, the magnitude of predictive value of LDL particle concentration (NMR) was not substantively different from that of the total cholesterol to HDL cholesterol ratio and was less than that of C-reactive protein.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.0000033222.75187.B9
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2002
    detail.hit.zdb_id: 1466401-X
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  • 9
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    Online Resource
    Plasma Concentration of Cystatin-C and Mannose Binding Protein and the Risk of Developing Peripheral Vascular Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2001
    In:  Circulation Vol. 103, No. suppl_1 ( 2001-03), p. 1351-1351
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 103, No. suppl_1 ( 2001-03), p. 1351-1351
    Abstract: P05 Background- Cystatin-C, a cysteine protease inhibitor, and mannose binding lectin, an innate defense protein involved in microbial clearance, have both been hypothesized to mediate atherosclerotic plaque progression. However, little prospective data are available evaluating whether levels of these proteins in healthy individuals are associated with incident cardiovascular disease. Methods and Results-Employing a prospective, nested, case control study design, baseline levels of cystatin-C and mannose binding protein were evaluated among 133 apparently healthy men who subsequently developed symptomatic peripheral arterial disease (cases) and among 133 age and smoking matched controls who remained free of reported vascular disease during a 5 year follow-up period. Overall, median baseline levels of cystatin-C were virtually identical among case and control subjects (0.83mg/L, p=0.84). Similarly, median baseline levels of mannose binding protein among cases and controls were 2.32mg/L and 2.2mg/L,(p=0.69). We found no evidence of association between either cystatin-C or mannose binding protein and the development of peripheral vascular disease in analyses evaluating for linear trends or for threshold effects (all p values 〉 0.05). Conclusion-In contrast to prior retrospective and cross-sectional studies, we found no evidence in this prospective evaluation that baseline levels of cystatin-C or mannose binding protein are associated with increased risk of future vascular disease.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.103.suppl_1.9998-5
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2001
    detail.hit.zdb_id: 1466401-X
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  • 10
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    Online Resource
    Multiple Biomarkers and the Risk of Incident Hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Hypertension Vol. 49, No. 3 ( 2007-03), p. 432-438
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 49, No. 3 ( 2007-03), p. 432-438
    Abstract: An understanding of mechanisms underlying the development of essential hypertension is critical for designing prevention and treatment strategies. Selected biomarkers may be elevated before the onset of hypertension, but previous studies are limited by cross-sectional designs or a focus on single biomarkers. We prospectively studied 1456 nonhypertensive individuals who had baseline measurement of 9 biomarkers: C-reactive protein (inflammation); fibrinogen (inflammation and thrombosis); plasminogen activator inhibitor-1 (fibrinolytic potential); aldosterone, renin, B-type natriuretic peptide, and N-terminal proatrial natriuretic peptide (neurohormonal activity); homocysteine (renal function and oxidant stress); and urinary albumin/creatinine ratio (glomerular endothelial function). Incident hypertension, defined as blood pressure ≥140/90 mm Hg or antihypertensive therapy, developed in 232 participants over a mean follow-up of 3 years. After adjustment for clinical risk factors, the biomarker panel was significantly associated with incident hypertension ( P =0.002). Three (of 9) biomarkers were significantly related to incident hypertension on backward elimination (multivariable-adjusted odds ratios, per SD increment in biomarker): C-reactive protein (1.26; 95% CI: 1.05 to 1.51), plasminogen activator inhibitor-1 (1.28; 95% CI: 1.05 to 1.57), and urinary albumin/creatinine ratio (1.21; 95% CI: 1.02 to 1.43). The incidence of hypertension was 4.5, 6.4, and 9.9 per 100 person years for participants with 0, 1, and ≥2 elevated biomarkers, respectively (elevation defined as ≥1 SD above the mean). The threshold of ≥2 elevated biomarkers for predicting hypertension was associated with high specificity (0.92) but low sensitivity (0.15). Biomarkers of inflammation, reduced fibrinolytic potential, and low-grade albuminuria are jointly associated with the incidence of hypertension. These data support the premise that abnormalities in multiple biological pathways antedate the onset of overt hypertension.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/01.HYP.0000256956.61872.aa
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 2094210-2
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