Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-18 (of 18 Records) |
Query Trace: Staercke C [original query] |
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Parvovirus B19 infection in sickle cell disease: An analysis from the Centers for Disease Control haemoglobinopathy blood surveillance project
Majumdar S , Bean CJ , De Staercke C , Bost J , Nickel R , Coates T , Campbell A , Thompson A . Transfus Med 2020 30 (3) 226-230 OBJECTIVE: In the multicentre Haemoglobinopathy Blood Surveillance Project, to evaluate the seroprevalence of parvovirus B19 and DNA viral load in sickle cell disease (SCD). BACKGROUND: Although the epidemiology of parvovirus B19 seropositivity in SCD has been well documented, there are few studies that have assessed possible persistent parvovirus DNAemia and associated risk factors including blood transfusion. METHODS: A qualitative analysis of parvovirus B19 serology using ELISA and quantitative parvovirus B19 DNA by RT-PCR was performed in patients with SCD. RESULTS: Of 322 patients, 113 (35%) were parvovirus IgG positive and 119 (37%) were IgM positive at enrolment. The prevalence of IgG positivity increased with age. 71/322 (22%) were parvovirus DNA positive at enrolment with a mean viral load of 15 227 +/- 55 227 SD. (range 72-329 238 IU/mL). Patients who were positive for parvovirus B19 DNA received a significantly higher red blood cell transfusion volume in the prior year compared to patients who were negative (mean RBC volume = 8310 mL vs 5435 mL, respectively; P = .0073). Seventy-seven patients had follow-up testing approximately 1 year after enrolment and 11/28 (39%) patients had persistently positive IgM. CONCLUSION: Further studies are needed to better understand the natural history of parvovirus B19 infection in SCD especially in relation to RBC transfusion as a risk factor, as well as disease outcome and severity. |
Biomarker profile in stable Fontan patients.
Saraf A , De Staercke C , Everitt I , Haouzi A , Ko YA , Jennings S , Kim JH , Rodriguez FH , Kalogeropoulos AP , Quyyumi A , Book W . Int J Cardiol 2020 305 56-62 BACKGROUND: As the population of adults with congenital heart disease (CHD) grows, cardiologists continue to encounter patients with complex anatomies that challenge the standard treatment of care. Single ventricle Fontan palliated patients are the most complex within CHD, with a high morbidity and mortality burden. Factors driving this early demise are largely unknown. METHODS AND RESULTS: We analyzed biomarker expression in 44 stable Fontan outpatients (29.2 +/- 10.7 years, 68.2% female) seen in the outpatient Emory Adult Congenital Heart Center and compared them to 32 age, gender and race matched controls. In comparison to controls, Fontan patients had elevated levels of multiple cytokines within the inflammatory pathway including Tumor Necrosis Factor-alpha (TNF-alpha) (p < 0.001), Interleukin-6 (IL-6) (p < 0.011), Growth Derived Factor-15 (GDF-15) (p < 0.0001), beta2-macroglobulin, (p = 0.0006), stem cell mobilization: Stromal Derived Factor-1 proportional, variant (SDF-1alpha) (p = 0.006), extracellular matrix turnover: Collagen IV (p < 0.0001), neurohormonal activation: Renin (p < 0.0001), renal dysfunction: Cystatin C (p < 0.0001) and Urokinase Receptor (uPAR) (p = 0.022), cardiac injury: Troponin-I (p < 0.0004) and metabolism: Adiponectin (p = 0.0037). Within 1 year of enrollment 50% of Fontan patients had hospitalizations, arrhythmias or worsening hepatic function. GDF-15 was significantly increased in Fontan patients with clinical events (p < 0.0001). In addition, GDF-15 moderately correlated with longer duration of Fontan (r = 0.55, p = 0.01) and was elevated in atriopulmonary (AP) Fontan circulation. Finally, in a multivariate model, VEGF-D and Collagen IV levels were found to be associated with a change in MELDXI, a marker of liver dysfunction. CONCLUSION: Multiple clinical and molecular biomarkers are upregulated in Fontan patients, suggesting a state of chronic systemic dysregulation. |
Pilot randomized controlled trial of a Mediterranean diet or diet supplemented with fish oil, walnuts, and grape juice in overweight or obese US adults
Jaacks LM , Sher S , Staercke C , Porkert M , Alexander WR , Jones DP , Vaccarino V , Ziegler TR , Quyyumi AA . BMC Nutr 2018 4 26 Background: The 2015-2020 Dietary Guidelines for Americans recommend a Mediterranean-type diet as one of three healthful eating patterns. However, only one previous trial has evaluated the effects of a Mediterranean diet intervention in a US sample population. Methods: To address this gap, we conducted a pilot, non-blinded, 8-week randomized controlled trial on the comparative efficacy of consumption of a Mediterranean diet or a diet supplemented with fish oil, walnuts, and grape juice versus controls. Participants (overweight or obese US adults; 73% female and mean age 51 years) were randomly assigned to one of three groups: (1) Mediterranean diet; (2) habitual high-fat American-type diet supplemented with fish oil, walnuts, and grape juice; or (3) habitual high-fat American-type diet (controls). Intent-to-treat analysis of within-subject differences (Student's paired t-test or Wilcoxon sign ranks test) and between-subject differences (mixed-effects models with a group-by-time interaction term, adjusted for baseline health outcome) was conducted. Results: Participants in the Mediterranean diet arm (n = 11) had significantly greater weight loss despite no significant change in total caloric intake, and lower plasma cystine, indicative of decreased oxidative stress, compared to controls (n = 9) at both 4 and 8 weeks. Compared to controls, they also had significantly lower total cholesterol and low-density lipoprotein cholesterol levels at 4 weeks. Participants in the supplement arm (n = 10) had significantly lower adiponectin levels compared to controls at 4 weeks. No significant improvements in endothelial function or inflammatory biomarkers were observed in either intervention group compared to controls. Conclusion: These results suggest that adopting a dietary pattern reflecting a Mediterranean diet improves weight and cardio-metabolic health among overweight or obese US adults, and may be more beneficial than supplementing habitual American diets with fish oil, walnuts, and grape juice. |
VKORC1-1639A allele influences warfarin maintenance dosage among Blacks receiving warfarin anticoagulation: a retrospective cohort study.
Mili FD , Allen T , Wadell PW , Hooper WC , Staercke C , Bean CJ , Lally C , Austin H , Wenger NK . Future Cardiol 2018 14 (1) 15-26 AIM: The study objectives were to investigate the association between selected CYP2C9 and VKORC1 single nucleotide polymorphisms with serious bleeding or thrombotic risk, and to estimate mean daily maintenance dose of warfarin and international normalized ratio measurements among Blacks receiving warfarin anticoagulation. METHODS: We conducted a retrospective cohort study among 230 Black adults receiving warfarin for a minimum of three consecutive months with a confirmed date of first dosage. RESULTS: A lower mean daily maintenance dosage of warfarin was required to maintain an international normalized ratio measurement within the therapeutic range among Blacks with the VKORC1-1639G>A variant alleles ([G/A vs G/G, p = 0.02], [A/A vs G/A, p = 0.008] and [A/A vs G/G, p = 0.001]). CONCLUSION: Data indicated that VKORC1-1639A variant allele influenced warfarin daily maintenance dosage among our small, likely admixed Black patient population. |
Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A patients with and without identified F8 mutations.
Boylan B , Rice AS , De Staercke C , Eyster ME , Yaish HM , Knoll CM , Bean CJ , Miller CH . J Thromb Haemost 2015 13 (6) 1036-42 BACKGROUND: Hemophilia A (HA) is an X-linked bleeding disorder caused by a deficiency in Factor VIII (FVIII). von Willebrand disease (VWD) is characterized by a quantitative or qualitative defect in von Willebrand Factor (VWF). Patients with VWD with severely low VWF or VWD Type 2N (VWD2N), a VWD subtype distinguished by defective VWF binding to FVIII, may have reduced FVIII levels secondary to their VWD. These patients superficially resemble patients with HA, and pose a potential for misdiagnosis. OBJECTIVES: Investigate the unexplained cause of bleeding in HA patients without known FVIII mutations by assessing plasma VWF antigen (VWF:Ag), FVIII binding capacities, and VWF genotypes. PATIENTS/METHODS: Thirty-seven of 1027 patients with HA studied as part of the Hemophilia Inhibitor Research Study lacked identifiable F8 mutations. These patients (cases) and 73 patients with identified F8 mutations (controls) were evaluated for VWF:Ag, patient's VWF capacity to bind FVIII (VWF:FVIIIB), and VWF sequence. RESULTS: Four cases had VWF:Ag <3 IU/dL and VWF mutations consistent with Type3 VWD. Six cases and one control were heterozygous for mutations previously reported to cause Type1 VWD (VWD1) (n=5 cases and 1 control) or predicted to be deleterious by Polyphen2 and SIFT prediction tools (n=1 case). One control had VWF:Ag <30 IU/dl, and seven patients (4 cases and 3 controls), including two cases who were heterozygous for a known VWD2N mutation, had reduced VWF:FVIIIB. CONCLUSIONS: These data emphasize that some patients diagnosed with HA require VWF assessments in order to achieve a comprehensive diagnosis and an optimal treatment strategy. |
Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism.
Lewis DA , Suchindran S , Beckman MG , Hooper WC , Grant AM , Heit JA , Manco-Johnson M , Moll S , Philipp CS , Kenney K , De Staercke C , Pyle ME , Chi JT , Ortel TL . Thromb Res 2015 135 (4) 659-65 INTRODUCTION: Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30% of individuals following an initial unprovoked event. There is limited understanding of the biological mechanisms that predispose patients to recurrent VTE. OBJECTIVES: To identify whole blood gene expression profiles that distinguished patients with clinically distinct patterns of VTE. PATIENTS/METHODS: We studied 107 patients with VTE separated into 3 groups: (1) 'low-risk' patients had one or more provoked VTE; (2) 'moderate-risk' patients had a single unprovoked VTE; (3) 'high-risk' patients had ≥2 unprovoked VTE. Each patient group was also compared to twenty-five individuals with no personal history of VTE. Total RNA from whole blood was isolated and hybridized to Illumina HT-12V4 Beadchips to assay whole genome expression. RESULTS: Using class prediction analysis, we distinguished high-risk patients from low-risk patients and healthy controls with good receiver operating curve characteristics (AUC=0.81 and 0.84, respectively). We also distinguished moderate-risk individuals and low-risk individuals from healthy controls with AUC's of 0.69 and 0.80, respectively. Using differential expression analysis, we identified several genes previously implicated in thrombotic disorders by genetic analyses, including SELP, KLKB1, ANXA5, and CD46. Protein levels for several of the identified genes were not significantly different between the different groups. CONCLUSION: Gene expression profiles are capable of distinguishing patients with different clinical presentations of VTE, and genes relevant to VTE risk are frequently differentially expressed in these comparisons. |
Plasma stromal cell-derived factor 1alpha/CXCL12 level predicts long-term adverse cardiovascular outcomes in patients with coronary artery disease
Ghasemzadeh N , Hritani AW , De Staercke C , Eapen DJ , Veledar E , Al Kassem H , Khayata M , Zafari AM , Sperling L , Hooper C , Vaccarino V , Mavromatis K , Quyyumi AA . Atherosclerosis 2015 238 (1) 113-8 OBJECTIVE: Stromal derived factor-1alpha/CXCL12 is a chemoattractant responsible for homing of progenitor cells to ischemic tissues. We aimed to investigate the association of plasma CXCL12 with long-term cardiovascular outcomes in patients with coronary artery disease (CAD). METHODS: 785 patients aged: 63 +/- 12 undergoing coronary angiography were independently enrolled into discovery (N = 186) and replication (N = 599) cohorts. Baseline levels of plasma CXCL12 were measured using Quantikine CXCL12 ELISA assay (R&D systems). Patients were followed for cardiovascular death and/or myocardial infarction (MI) for a mean of 2.6 yrs. Cox proportional hazard was used to determine independent predictors of cardiovascular death/MI. RESULTS: The incidence of cardiovascular death/MI was 13% (N = 99). High CXCL12 level based on best discriminatory threshold derived from the ROC analysis predicted risk of cardiovascular death/MI (HR = 4.81, p = 1 x 10(-6)) independent of traditional risk factors in the pooled cohort. Addition of CXCL12 to a baseline model was associated with a significant improvement in c-statistic (AUC: 0.67-0.73, p = 0.03). Addition of CXCL12 was associated with correct risk reclassification of 40% of events and 10.5% of non-events. Similarly for the outcome of cardiovascular death, the addition of the CXCL12 to the baseline model was associated with correct reclassification of 20.7% of events and 9% of non-events. These results were replicated in two independent cohorts. CONCLUSION: Plasma CXCL12 level is a strong independent predictor of adverse cardiovascular outcomes in patients with CAD and improves risk reclassification. |
Endothelium-derived hyperpolarizing factor mediates bradykinin-stimulated tissue plasminogen activator release in humans
Rahman AM , Murrow JR , Ozkor MA , Kavtaradze N , Lin J , De Staercke C , Hooper WC , Manatunga A , Hayek S , Quyyumi AA . J Vasc Res 2014 51 (3) 200-8 AIMS: Bradykinin (BK) stimulates tissue plasminogen activator (t-PA) release from human endothelium. Although BK stimulates both nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) release, the role of EDHF in t-PA release remains unexplored. This study sought to determine the mechanisms of BK-stimulated t-PA release in the forearm vasculature of healthy human subjects. METHODS: In 33 healthy subjects (age 40.3 +/- 1.9 years), forearm blood flow (FBF) and t-PA release were measured at rest and after intra-arterial infusions of BK (400 ng/min) and sodium nitroprusside (3.2 mg/min). Measurements were repeated after intra-arterial infusion of tetraethylammonium chloride (TEA; 1 micromol/min), fluconazole (0.4 micromol.min(-1).l(-1)), and N(G)-monomethyl-L-arginine (L-NMMA, 8 micromol/min) to block nitric oxide, and their combination in separate studies. RESULTS: BK significantly increased net t-PA release across the forearm (p < 0.0001). Fluconazole attenuated both BK-mediated vasodilation (-23.3 +/- 2.7% FBF, p < 0.0001) and t-PA release (from 50.9 +/- 9.0 to 21.3 +/- 8.9 ng/min/100 ml, p = 0.02). TEA attenuated FBF (-14.7 +/- 3.2%, p = 0.002) and abolished BK-stimulated t-PA release (from 22.9 +/- 5.7 to -0.8 +/- 3.6 ng/min/100 ml, p = 0.0002). L-NMMA attenuated FBF (p < 0.0001), but did not inhibit BK-induced t-PA release (nonsignificant). CONCLUSION: BK-stimulated t-PA release is partly due to cytochrome P450-derived epoxides and is inhibited by K(+)Ca channel blockade. Thus, BK stimulates both EDHF-dependent vasodilation and t-PA release. |
Evidence for the transmission of parvovirus B19 in patients with bleeding disorders treated with plasma-derived factor concentrates in the era of nucleic acid test screening.
Soucie JM , De Staercke C , Monahan PE , Recht M , Chitlur MB , Gruppo R , Hooper WC , Kessler C , Kulkarni R , Manco-Johnson MJ , Powell J , Pyle M , Riske B , Sabio H , Trimble S . Transfusion 2013 53 (6) 1217-25 BACKGROUND: Parvovirus B19 (B19V) is a small, nonenveloped virus that typically causes a benign flu-like illness that occurs most frequently in childhood. The virus is resistant to current viral inactivation steps used in the manufacture of antihemophilic factor concentrates and B19V transmission through these products has been documented. Since 2000, B19V nucleic acid test (NAT) screening of plasma pools has been implemented to further decrease the viral burden in these products, but no study has examined populations using these products to assess the impact of the screening on B19V transmission. STUDY DESIGN AND METHODS: Blood specimens obtained from participants of a surveillance system established in federally supported specialized bleeding disorders clinics were used in a B19V seroprevalence study. RESULTS: A total of 1643 specimens from 1043 participants age 2 to 7 years born after B19V NAT screening was implemented were tested. Age-specific prevalence rates were generally higher for subjects exposed to either plasma-derived products alone or in combination with other products compared to subjects with no exposure to antihemophilic products. Overall, compared to participants unexposed to blood or blood products, those exposed to plasma-derived products alone were 1.7 times more likely to have antibodies to B19V (p = 0.002). CONCLUSION: These results are consistent with continued B19V transmission through plasma-derived factor concentrates. Effective viral inactivation and detection processes are needed to protect users of these products from infection with B19V or other new or emerging viruses. |
Effect of meditation on endothelial function in black Americans with metabolic syndrome: a randomized trial
Vaccarino V , Kondwani KA , Kelley ME , Murrah NV , Boyd L , Ahmed Y , Meng YX , Gibbons GH , Hooper WC , De Staercke C , Quyyumi AA . Psychosom Med 2013 75 (6) 591-9 OBJECTIVES: Psychological stress may play a role in metabolic syndrome. A consequence of metabolic syndrome is endothelial dysfunction, which is also influenced by psychological stress. We sought to compare the effect of consciously resting meditation (CRM), a sound based meditation, with a control intervention of health education (HE) on endothelial function in the setting of metabolic syndrome. METHODS: Sixty-eight black Americans with metabolic syndrome risk factors (age, 30-65 years) were randomized to either CRM (n = 33) or HE (n = 35); interventions were matched for frequency and duration of sessions and lasted 12 months. Endothelial function was assessed by brachial artery flow-mediated dilation at baseline and at 6 and 12 months. Arterial elasticity, metabolic risk factors, and psychosocial and behavioral variables were secondary end points. RESULTS: Although flow-mediated dilation improved in the CRM group for 12 months, this increase was not significantly higher than that in the HE group (p = .51 for the interaction between group and time). Non-endothelium-dependent dilation and arterial elasticity did not change in either group. Most metabolic syndrome risk factors showed beneficial trends in the CRM group only. A risk factor score counting the number of metabolic syndrome components decreased in the CRM group only (p = .049 for the interaction between treatment group and time). CONCLUSIONS: Among black Americans with metabolic syndrome risk factors, CRM, did not improve endothelial function significantly more than a control intervention of HE. CRM resulted in favorable trends in metabolic syndrome risk factors, which were examined as secondary outcomes. |
Evidence for the continued transmission of parvovirus B19 in patients with bleeding disorders treated with plasma-derived factor concentrates
Soucie JM , Monahan PE , Kulkarni R , De Staercke C , Recht M , Chitlur MB , Gruppo R , Hooper WC , Kessler C , Manco-Johnson MJ , Powell J , Pyle M , Riske B , Sabio H , Trimble S . Transfusion 2013 53 (5) 1143-4 Gajardo and colleagues1 contend that our finding of continued increased prevalence of parvovirus B19 (B19V) antibodies among users of plasma-derived factor concentrates relative to people with bleeding disorders unexposed to any blood or factor product2 may have been influenced by exposure to product not subjected to B19V nucleic acid test (NAT) screening or to exposure to low-purity products during the study period. The authors also disagree with our characterization of B19V as resistant to viral inactivation steps used in the manufacture of antihemophilic factor concentrates. | We understand and discuss in our article that B19V NAT screening was not initiated at the same time for all products. Nonetheless, we provided evidence, based on our finding of higher B19V prevalence in later years of the study period, that our findings were not likely due to transmissions that occurred solely in earlier years. For example, among 2- to 4-year-old children exposed to plasma-derived products, 77% of the specimens tested were drawn between 2006 and 2009—well after studies showed relatively complete adoption of screening.3 Others have reported the detection of B19V in products purchased in 2008.4 | The authors suggest that our study findings may also have been influenced by users of less highly purified products such as activated prothrombin complex concentrates. However, only 7% of subjects in our study were exposed to these products. |
Accumulation of retained nonfunctional arteriovenous grafts correlates with severity of inflammation in asymptomatic ESRD patients
Wasse H , Cardarelli F , De Staercke C , Hooper WC , Long Q . Nephrol Dial Transplant 2013 28 (4) 991-7 BACKGROUND: The contribution of multiple retained nonfunctional arteriovenous grafts (AVGs) to the burden of chronic inflammation in chronic hemodialysis patients has not been well studied. Here, we sought to evaluate the association between plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and albumin and the number of retained nonfunctional AVGs. METHODS: This cross-sectional study enrolled 91 prevalent patients undergoing in-center hemodialysis without evidence of infection or inflammation. A baseline blood sample was obtained at study enrollment. A general linear model (GLM) was used to compare levels of biomarkers of systemic inflammation across groups defined by the number of retained, nonfunctional AVGs. RESULTS: A total of 43 patients had one or more retained thrombosed AVG and had significantly greater plasma log-CRP levels compared with patients without a previous AVG (P= 0.036), regardless of the current AV access type. Using a GLM, we found that for every additional retained thrombosed AVG, plasma log-CRP, log-IL-6 and TNF-alpha concentrations increased significantly by 0.30 mg/L (P= 0.011), 0.18 pg/mL (P= 0.046) and 0.72 pg/mL (P= 0.046), respectively, following adjustment. CONCLUSIONS: Hence, the severity of inflammation increases with the number of retained nonfunctional AVG's, suggesting that AVG accumulation may contribute to the cardiovascular morbidity and mortality associated with chronic inflammation in asymptomatic end-stage renal disease (ESRD) patients. Further study is indicated to determine whether patients with one or more thrombosed, retained AVG may benefit from periodic screening with CRP monitoring to identify those patients who may benefit from AVG resection. |
Elevated C-reactive protein is associated with severe periodic leg movements of sleep in patients with restless legs syndrome
Trotti LM , Rye DB , Staercke CD , Hooper WC , Quyyumi A , Bliwise DL . Brain Behav Immun 2012 26 (8) 1239-43 BACKGROUND: Restless legs syndrome (RLS) is a common sleep disorder in which urges to move the legs are felt during rest, are felt at night, and are improved by leg movement. RLS has been implicated in the development of cardiovascular disease. Periodic leg movements (PLMs) may be a mediator of this relationship. We evaluated systemic inflammation and PLMs in RLS patients to further assess cardiovascular risk. METHODS: 137 RLS patients had PLM measurements taken while unmedicated for RLS. Banked plasma was assayed for high sensitivity C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha). RESULTS: Mean (SD) PLM index was 19.3 (22.0). PLMs were unrelated to TNF-a and IL-6, but were modestly correlated with logCRP (r(129)=0.19, p=0.03). Those patients with at least 45PLMs/h had an odds ratio of 3.56 (95% CI 1.26-10.03, p=0.02, df=1) for having elevated CRP compared to those with fewer than 45PLMs/h. After adjustment for age, race, gender, diabetes, hypertension, hyperlipidemia, inflammatory disorders, CRP-lowering medications, and body mass index, the OR for those with 45PLMs/h was 8.60 (95% CI 1.23 to 60.17, p=0.03, df=10). CONCLUSIONS: PLMs are associated with increased inflammation, such that those RLS patients with at least 45PLMs/h had more than triple the odds of elevated CRP than those with fewer PLMs. Further investigation into PLMs and inflammation is warranted. |
Matrix metalloproteinases, tissue inhibitors of metalloproteinases, and heart failure outcomes
Bhalla V , Georgiopoulou VV , Azeem AA , Marti CN , Cole RT , Laskar SR , De Staercke C , Hooper WC , Smith AL , Kalogeropoulos AP , Butler J . Int J Cardiol 2011 151 (2) 237-9 Heart failure (HF) prevalence continues to increase and is associated with a high mortality, morbidity, and cost burden for the society. [1, 2] The most common cause of HF in the United States is coronary artery disease. [3] Left ventricular (LV) dysfunction, irrespective of the cause of heart failure (HF), leads to perturbed wall stress resulting in remodeling and HF progression. Matrix metalloproteinases (MMP) are a family of proteolytic enzymes that are involved in the protein degradation in the extracellular matrix and play an important role in remodeling. [4, 5] Multiple classes of MMPs have been identified in human myocardium.[5, 6] Certain MMPs, specifically MMP-2, MMP-3, and MMP-9 have been shown to have high expression in the left ventricle. [7, 8] Tissue inhibitors of metalloproteinases (TIMPS) are low-molecular-weight molecules that bind to MMPs forming MMP-TIMP complexes that exhibit an inhibitory control on MMPs. Several studies have delineated the relationship between MMPs and TIMPs, and that the changes in the MMP/TIMP ratio correlate with left ventricular hypertrophy and dilation. [9, 10] Loss of inhibitory control of TIMP on MMP correlates with progression of left ventricular remodeling via increased MMP activity, extra-cellular matrix proteolysis, and myocardial remodeling changes. [11] There have been conflicting reports on MMPs and TIMPs levels association with HF outcomes. [12-17] These studies have generally not assessed the multiple members of the MMP and TIMP family simultaneously and have assessed varying HF outcomes. In this study, we sought to assess the association between multiple MMPs and TIMPs with clinical outcomes, health status, and exercise capacity among HF patients. |
25-hydroxyvitamin D concentration is inversely associated with serum MMP-9 in a cross-sectional study of African American ESRD patients
Wasse H , Cardarelli F , De Staercke C , Hooper C , Veledar E , Guessous I . BMC Nephrol 2011 12 24 BACKGROUND: Circulating 25-hydroxyvitamin D [25(OH)D] concentration is inversely associated with peripheral arterial disease and hypertension. Vascular remodeling may play a role in this association, however, data relating vitamin D level to specific remodeling biomarkers among ESRD patients is sparse. We tested whether 25(OH)D concentration is associated with markers of vascular remodeling and inflammation in African American ESRD patients. METHODS: We conducted a cross-sectional study among ESRD patients receiving maintenance hemodialysis within Emory University-affiliated outpatient hemodialysis units. Demographic, clinical and dialysis treatment data were collected via direct patient interview and review of patients records at the time of enrollment, and each patient gave blood samples. Associations between 25(OH)D and biomarker concentrations were estimated in univariate analyses using Pearson's correlation coefficients and in multivariate analyses using linear regression models. 25(OH) D concentration was entered in multivariate linear regression models as a continuous variable and binary variable (<15 ng/ml and ≥15 ng/ml). Adjusted estimate concentrations of biomarkers were compared between 25(OH) D groups using analysis of variance (ANOVA). Finally, results were stratified by vascular access type. RESULTS: Among 91 patients, mean (standard deviation) 25(OH)D concentration was 18.8 (9.6) ng/ml, and was low (<15 ng/ml) in 43% of patients. In univariate analyses, low 25(OH) D was associated with lower serum calcium, higher serum phosphorus, and higher LDL concentrations. 25(OH) D concentration was inversely correlated with MMP-9 concentration (r = -0.29, p = 0.004). In multivariate analyses, MMP-9 concentration remained negatively associated with 25(OH) D concentration (P = 0.03) and anti-inflammatory IL-10 concentration positively correlated with 25(OH) D concentration (P = 0.04). CONCLUSIONS: Plasma MMP-9 and circulating 25(OH) D concentrations are significantly and inversely associated among ESRD patients. This finding may suggest a potential mechanism by which low circulating 25(OH) D functions as a cardiovascular risk factor. |
Association between depression and inflammation--differences by race and sex: the META-Health Study
Morris AA , Zhao L , Ahmed Y , Stoyanova N , De Staercke C , Hooper WC , Gibbons G , Din-Dzietham R , Quyyumi A , Vaccarino V . Psychosom Med 2011 73 (6) 462-8 OBJECTIVE: To test whether the association between depression and inflammation differs by race and sex. Depressive symptoms have been associated with higher levels of C-reactive protein (CRP). However, few studies have examined this association in samples including a significant number of African Americans, or examined whether the association differs by race and sex. METHODS: Depressive symptoms and CRP were assessed in 512 African American and white participants, age 30 to 65 years, as part of the community-based Morehouse and Emory Team up to Eliminate Health Disparities (META-Health) Study. Depression was determined by responses to the Beck Depression Inventory II (BDI-II). Multivariable linear regression models were used to adjust for demographic and metabolic risk factors. RESULTS: African American men had higher total BDI-II scores than white men (p = .03), whereas there was no difference in women. There was a significant race-sex-depression interaction in predicting CRP levels (p = .02). White women with mild to severe depressive symptoms had higher levels of CRP compared with those with minimal to no depressive symptoms (p < .05). There were no differences in levels of CRP by severity of depressive symptoms in white men or African Americans of either sex. Higher BDI-II scores were related to higher CRP levels in white women after adjusting for age and level of education (beta = 0.227, p = .006). However, the association was eliminated after further adjustment for metabolic risk factors (beta = 0.077, p = .35). CONCLUSIONS: Although depressive symptoms are associated with inflammation, the association varies by race and sex. |
Bleeding events are associated with an increase in markers of inflammation in acute coronary syndromes: an ACUITY trial substudy
Campbell CL , Steinhubl SR , Hooper WC , Jozic J , Smyth SS , Bernstein D , De Staercke C , Syros G , Negus BH , Stuckey T , Stone GW , Mehran R , Dangas G . J Thromb Thrombolysis 2011 31 (2) 139-45 Bleeding events have been associated with adverse early and late outcomes in virtually all clinical settings. The mechanism behind this observation remains poorly understood. We sought to determine if the reason might be the provocation of an inflammatory response by bleeding events. In a formal substudy of the ACUITY trial, plasma samples of a range of biomarkers were collected at baseline, discharge, 30 days, and 1 year from 192 patients with acute coronary syndromes (ACS) and were analyzed in a central core laboratory. Temporal changes in biomarker levels were assessed in patients who experienced in-hospital hemorrhagic events, recurrent ischemic events, or neither. Sixteen patients were excluded from the study (7 with incomplete samples, 5 undergoing coronary artery bypass grafting (CABG) during index hospitalization; 1 had both bleeding and ischemic events). Median high sensitivity C-reactive protein (hs-CRP) levels (mg/l) increased significantly more from admission to discharge among the 9 patients who experienced an in-hospital major bleed compared to either the 9 patients who had a recurrent ischemic event (+6.0 vs. +0.70, P = 0.04) or the 151 patients who had no event (+6.0 vs. +0.60, P = 0.003). Compared to patients with no in-hospital events, median interleukin-6 (IL-6) levels (pg/ml) increased from admission to hospital discharge non-significantly in those with a bleeding event (+0.92 vs. +2.46, P = 0.55) and in those who experienced an in-hospital recurrent ischemic event (+0.92 vs. +3.60, P = 0.09). These data suggest that major bleeding is associated with development of a pro-inflammatory state. If confirmed, this mechanism may in part explain the poor prognosis of patients experiencing an acute hemorrhagic event. |
New gene variants associated with venous thrombosis - a replication study in United States Whites and Blacks
Austin H , De Staercke C , Lally C , Bezemer ID , Rosendaal FR , Hooper WC . J Thromb Haemost 2011 9 (3) 489-95 BACKGROUND: We evaluated 10 SNPs identified in 3 European case-control studies as risk factors for venous thrombosis. OBJECTIVES: We sought to replicate the positive findings from this report among Whites and to evaluate the association of these SNPs with venous thrombosis for the first time among Blacks. PATIENTS/METHODS: These SNPs were evaluated in a case-control study of deep vein thrombosis and pulmonary embolism that included 1,076 cases and 1,239 controls. About 50% of subjects were African Americans. We measured plasma FXI on a subset of subjects. RESULTS: Among Whites, positive findings for rs13146272 in the CYP4V2 gene, for rs3087505 in the KLKB1 gene, and for rs3756008 and rs2036914 in the F11 gene were found. We did not find significant associations for rs2227589 in the SERPINC1 gene and for rs1613662 in the GP6 gene. Among Blacks rs2036914 in F11 and rs670659 in RGS7 were related to venous thrombosis, but the study had limited statistical power for many SNPs. Among Blacks plasma FXI was related to two SNPs and the OR relating to the 90(th) percentile of the control distribution of plasma FXI was 2.6 (95% CI: 1.4, 5.0). CONCLUSIONS: Our study supports the finding that genetic variants in the F11 gene are risk factors for venous thrombosis both among Whites and Blacks, although the findings in Blacks require confirmation. A meta-analysis of 5 case-control studies indicates that rs2227589 in the SERPINC1 gene, rs13146272 in the CYP4V2 gene, and rs1613662 in the GP6 gene are risk factors for venous thrombosis among Whites. |
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