The Experts below are selected from a list of 192537 Experts worldwide ranked by ideXlab platform

Paul M Ridker - One of the best experts on this subject based on the ideXlab platform.

  • polygeniC overlap between C reaCtive Protein plasma lipids and alzheimer disease
    Circulation, 2015
    Co-Authors: Rahul S Desikan, Paul M Ridker, Daniel I Chasman, Andrew J Schork, Yunpeng Wang, Wesley K Thompson, Abbas Dehghan, Linda K Mcevoy, Dominic Holland
    Abstract:

    BaCkground—EpidemiologiCal findings suggest a relationship between Alzheimer disease (AD), inflammation, and dyslipidemia, although the nature of this relationship is not well understood. We investigated whether this phenotypiC assoCiation arises from a shared genetiC basis. Methods and Results—Using summary statistiCs (P values and odds ratios) from genome-wide assoCiation studies of >200 000 individuals, we investigated overlap in single-nuCleotide polymorphisms assoCiated with CliniCally diagnosed AD and C-reaCtive Protein (CRP), triglyCerides, and high- and low-density lipoProtein levels. We found up to 50-fold enriChment of AD single-nuCleotide polymorphisms for different levels of assoCiation with C-reaCtive Protein, low-density lipoProtein, high-density lipoProtein, and triglyCeride single-nuCleotide polymorphisms using a false disCovery rate threshold <0.05. By Conditioning on polymorphisms assoCiated with the 4 phenotypes, we identified 55 loCi assoCiated with inCreased AD risk. We then ConduCted a meta-analysis of these 55 variants aCross 4 independent AD Cohorts (total: n=29 054 AD Cases and 114 824 healthy Controls) and disCovered 2 genome-wide signifiCant variants on Chromosome 4 (rs13113697; Closest gene, HS3ST1; odds ratio=1.07; 95% ConfidenCe interval=1.05–1.11; P=2.86×10−8) and Chromosome 10 (rs7920721; Closest gene, ECHDC3; odds ratio=1.07; 95% ConfidenCe interval=1.04–1.11; P=3.38×10−8). We also found that gene expression of HS3ST1 and ECHDC3 was altered in AD brains Compared with Control brains. ConClusions—We demonstrate genetiC overlap between AD, C-reaCtive Protein, and plasma lipids. By Conditioning on the genetiC assoCiation with the CardiovasCular phenotypes, we identify novel AD susCeptibility loCi, inCluding 2 genome-wide signifiCant variants Conferring inCreased risk for AD.

  • pharmaCogenetiC determinants of statin induCed reduCtions in C reaCtive Protein
    Circulation-cardiovascular Genetics, 2012
    Co-Authors: Audrey Y Chu, Franco Guilianini, Bryan J Barratt, Fredrik Nyberg, Daniel I Chasman, Paul M Ridker
    Abstract:

    BaCkground—In randomized trials, statins reduCe plasma levels of C-reaCtive Protein (CRP) and low-density lipoProtein Cholesterol (LDL-C), and the magnitude of event reduCtion relates to on-treatme...

  • rosuvastatin to prevent vasCular events in men and women with elevated C reaCtive Protein
    Obstetrical & Gynecological Survey, 2009
    Co-Authors: Paul M Ridker, Wolfgang Koenig, Eleanor Danielson, Francisco Antonio Helfenstein Fonseca, Jacques Genest, Antonio M Gotto, John J P Kastelein, Peter Libby, Alberto J Lorenzatti, Jean G Macfadyen
    Abstract:

    ABSTRACTPrevious studies have shown that statin therapy reduCes high-sensitivity C-reaCtive Protein levels as well as Cholesterol, but no prospeCtive trials have direCtly addressed the issue of whether elevated levels of high-sensitivity C-reaCtive Protein are benefiCial for apparently healthy perso

  • rosuvastatin to prevent vasCular events in men and women with elevated C reaCtive Protein
    The New England Journal of Medicine, 2008
    Co-Authors: Paul M Ridker, Borge G Nordestgaard, Wolfgang Koenig, Eleanor Danielson, Jacques Genest, Antonio M Gotto, Peter Libby, Alberto J Lorenzatti, Jean G Macfadyen, James Shepherd
    Abstract:

    InCreased levels of the inflammatory biomarker high-sensitivity C-reaCtive Protein prediCt CardiovasCular events. SinCe statins lower levels of high-sensitivity C-reaCtive Protein as well as Cholesterol, we hypothesized that people with elevated high-sensitivity C-reaCtive Protein levels but without hyperlipidemia might benefit from statin treatment. Methods We randomly assigned 17,802 apparently healthy men and women with low-density lipoProtein (LDL) Cholesterol levels of less than 130 mg per deCiliter (3.4 mmol per liter) and high-sensitivity C-reaCtive Protein levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily, or plaCebo and followed them for the oCCurrenCe of the Combined primary end point of myoCardial infarCtion, stroke, arterial revasCularization, hospitalization for unstable angina, or death from CardiovasCular Causes. Results The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduCed LDL Cholesterol levels by 50% and high-sensitivity C-reaCtive Protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and plaCebo groups, respeCtively (hazard ratio for rosuvastatin, 0.56; 95% ConfidenCe interval [CI], 0.46 to 0.69; P<0.00001), with Corresponding rates of 0.17 and 0.37 for myoCardial infarCtion (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P = 0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P = 0.002), 0.41 and 0.77 for revasCularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the Combined end point of myoCardial infarCtion, stroke, or death from CardiovasCular Causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any Cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P = 0.02). Consistent effeCts were observed in all subgroups evaluated. The rosuvastatin group did not have a signifiCant inCrease in myopathy or CanCer but did have a higher inCidenCe of physiCian-reported diabetes. ConClusions

  • Cholesterol C reaCtive Protein and CerebrovasCular events following intensive and moderate statin therapy
    Journal of Thrombosis and Thrombolysis, 2006
    Co-Authors: Jessica L Mega, Paul M Ridker, David A Morrow, Christopher P Cannon, Sabina A Murphy, Richard Cairns, Eugene Braunwald
    Abstract:

    BaCkground: While statins have been shown to reduCe CerebrovasCular events (CVE), the relationship between Cholesterol, C-reaCtive Protein (CRP), and CVE in patients treated with different statin strategies is still being explored.

Piera Gioffre - One of the best experts on this subject based on the ideXlab platform.

Russell P Tracy - One of the best experts on this subject based on the ideXlab platform.

  • serum levels of C reaCtive Protein are assoCiated with obesity weight gain and hormone replaCement therapy in healthy postmenopausal women
    American Journal of Epidemiology, 2001
    Co-Authors: Emma Barinasmitchell, Russell P Tracy, Mary Cushman, Elaine N Meilahn, Lewis H Kuller
    Abstract:

    The authors evaluated the Cross-seCtional and prospeCtive assoCiations between the serum ConCentration of C-reaCtive Protein and measures of obesity and fat distribution, hormone replaCement therapy (HRT) use, and serum sex hormones in postmenopausal women from the Healthy Women Study (Allegheny County, Pennsylvania, 1998). The authors tested the hypothesis that C-reaCtive Protein levels would be higher among HRT users and among women with greater body mass index, waist CirCumferenCe, or visCeral fat. There were 207 women in the study who were > or =8 years postmenopausal (101 HRT users and 106 HRT nonusers). The median levels of C-reaCtive Protein were 3.01 mg/liter in HRT users Compared with 1.74 mg/liter in nonusers (p = 0.002). C-reaCtive Protein levels were strongly positively Correlated with measures of body size, fatness, fat distribution, and weight gain among HRT users and nonusers. C-reaCtive Protein was also positively Correlated with serum estrone levels (r(s) = 0.38) among HRT nonusers. The highest level of C-reaCtive Protein was found among HRT users in the highest quartile of visCeral fat (4.29 mg/liter) Compared with women not on HRT and in the lowest quartile of visCeral fat (0.96 mg/liter). The use of HRT and measures of overall body fatness are important Correlates of C-reaCtive Protein among postmenopausal women.

  • the effeCts of hormone replaCement therapy and raloxifene on C reaCtive Protein and homoCysteine in healthy postmenopausal women a randomized Controlled trial
    The Journal of Clinical Endocrinology and Metabolism, 2000
    Co-Authors: Brian W Walsh, Russell P Tracy, Sofia Paul, Robert A Wild, Robert A Dean, David A Cox, Pamela W Anderson
    Abstract:

    C-ReaCtive Protein and homoCysteine are independent risk faCtors for the development of CardiovasCular disease. This study Compared the effeCts of hormone replaCement therapy (HRT) and raloxifene on serum C-reaCtive Protein and homoCysteine levels as markers of CardiovasCular risk in healthy postmenopausal women. Healthy postmenopausal women (n = 390) were enrolled in a double blind, randomized, plaCebo-Controlled, 6-month trial at eight out-patient sites in the United States. Women were randomly assigned to reCeive Continuous Combined HRT (0.625 mg/day Conjugated equine estrogen and 2.5 mg/day medroxyprogesterone aCetate), raloxifene (60 or 120 mg/day), or plaCebo for 6 months. C-ReaCtive Protein and homoCysteine were measured in baseline and 6-month serum samples. HRT inCreased C-reaCtive Protein levels by 84% (P 0.2). Raloxifene (60 and 120 mg/day) signifiCantly lowered serum levels of homoCystein...

  • assoCiations of elevated interleukin 6 and C reaCtive Protein levels with mortality in the elderly
    The American Journal of Medicine, 1999
    Co-Authors: Tamara B Harris, Luigi Ferrucci, Russell P Tracy, Chiara M Corti, Sholom Wacholder, Walter H Ettinger, Harley Heimovitz, Harvey J Cohen, Robert B Wallace
    Abstract:

    AbstraCt PURPOSE: To investigate whether interleukin-6 and C-reaCtive Protein levels prediCt all-Cause and Cause-speCifiC mortality in a population-based sample of nondisabled older people. SUBJECTS AND METHODS: A sample of 1,293 healthy, nondisabled partiCipants in the Iowa 65+ Rural Health Study was followed prospeCtively for a mean of 4.6 years. Plasma interleukin-6 and C-reaCtive Protein levels were measured in speCimens obtained from 1987 to 1989. RESULTS: Higher interleukin-6 levels were assoCiated with a twofold greater risk of death [relative risk (RR) for the highest quartile (≥3.19 pg/mL) Compared with the lowest quartile of 1.9 [95% ConfidenCe interval, CI, 1.2 to 3.1]). Higher C-reaCtive Protein levels (≥2.78 mg/L) were also assoCiated with inCreased risk (RR = 1.6; CI, 1.0 to 2.6). SubjeCts with elevation of both interleukin-6 and C-reaCtive Protein levels were 2.6 times more likely (CI, 1.6 to 4.3) to die during follow-up than those with low levels of both measurements. Similar results were found for CardiovasCular and nonCardiovasCular Causes of death, as well as when subjeCts were stratified by sex, smoking status, and prior CardiovasCular disease, and for both early ( CONCLUSIONS: Higher CirCulating levels of interleukin-6 and C-reaCtive Protein were assoCiated with mortality in this population-based sample of healthy older persons. These measures may be useful for identifiCation of high-risk subgroups for anti-inflammatory interventions.

  • relation of C reaCtive Protein and Coronary heart disease in the mrfit nested Case Control study
    American Journal of Epidemiology, 1996
    Co-Authors: Lewis H Kuller, Russell P Tracy, Jessica Shaten, Elaine N Meilahn
    Abstract:

    The authors measured the relation between C-reaCtive Protein, α 1 aCid glyCoProtein and albumin, an aCute phase Protein, and subsequent risk of myoCardial infarCtion and Coronary heart disease death in a nested Case-Control study among the Multiple Risk FaCtor Intervention Trial (MRFIT) partiCipants. There were 98 myoCardial infarCtion Cases, 148 Coronary heart disease deaths, and 491 Controls. The Cases and Controls were followed for up to 17 years for deaths and 6-7 years for myoCardial infarCtion Cases and Controls. There was a signifiCant assoCiation between available distribution of C-reaCtive Protein and subsequent Coronary heart disease mortality. For smokers at baseline, the risk of Coronary heart disease deaths in quartile 4 of C-reaCtive Protein as Compared with quartile 1 was 4.3 (95% ConfidenCe interval 1.74-10.8). The assoCiation persisted when adjusted for CharaCteristiCs related to smoking and smoking Cessation during the trial and to pulmonary funCtion. There was no relation between α 1 aCid glyCoProtein and either myoCardial infarCtion or Coronary heart disease death. Albumin was inversely related to Coronary heart disease death only for deaths that oCCurred between 7 and 13 years after baseline, Consistent with previous MRFIT analyses. This is the first prospeCtive study in healthy but high risk individuals to doCument the relation between C-reaCtive Protein and Coronary heart disease mortality.

M B Pepys - One of the best experts on this subject based on the ideXlab platform.

  • Complement faCtor h binds to denatured rather than to native pentameriC C reaCtive Protein
    Journal of Biological Chemistry, 2008
    Co-Authors: Svetlana Hakobyan, M B Pepys, Palma Mangione, Claire L Harris, Carmen W Van Den Berg, Maria Del Carmen Fernandezalonso, Elena Goicoechea De Jorge, Santiago Rodriguez De Cordoba, German Rivas, Paul B Morgan
    Abstract:

    Binding of the Complement regulatory Protein, faCtor H, to C-reaCtive Protein has been reported and impliCated as the biologiCal basis for assoCiation of the H402 polymorphiC variant of faCtor H with maCular degeneration. Published studies utilize solid-phase or fluid-phase binding assays to show that the faCtor H Y402 variant binds C-reaCtive Protein more strongly than H402. Diminished binding of H402 variant to C-reaCtive Protein in retinal drusen is posited to permit inCreased Complement aCtivation, driving inflammation and pathology. We used well validated native human C-reaCtive Protein and pure faCtor H Y402H variants to test interaCtions. When faCtor H variants were inCubated with C-reaCtive Protein in the fluid phase at physiologiCal ConCentrations, no assoCiation oCCurred. When C-reaCtive Protein was immobilized on plastiC, either non-speCifiCally by adsorption in the presenCe of Ca2+ to maintain its native fold and pentameriC subunit assembly or by speCifiC Ca2+-dependent binding to immobilized natural ligands, no speCifiC binding of either faCtor H variant from the fluid phase was observed. In Contrast, both faCtor H variants reproduCibly bound to C-reaCtive Protein immobilized in the absenCe of Ca2+, Conditions that destabilize the native fold and pentameriC assembly. Both faCtor H variants strongly bound C-reaCtive Protein that was denatured by heat treatment before immobilization, Confirming interaCtion with denatured but not native C-reaCtive Protein. We ConClude that the reported binding of faCtor H to C-reaCtive Protein results from denaturation of the C-reaCtive Protein during immobilization. Differential binding to C-reaCtive Protein, thus, does not explain assoCiation of the Y402H polymorphism with maCular degeneration.

  • C reaCtive Protein and other CirCulating markers of inflammation in the prediCtion of Coronary heart disease
    The New England Journal of Medicine, 2004
    Co-Authors: John Danesh, M B Pepys, J G Wheeler, Gideon M Hirschfield, Gudny Eiriksdottir, Ann Rumley, Gordon D O Lowe, Vilmundur Gudnason
    Abstract:

    BaCkground C-reaCtive Protein is an inflammatory marker believed to be of value in the prediCtion of Coronary events. We report data from a large study of C-reaCtive Protein and other CirCulating inflammatory markers, as well as updated meta-analyses, to evaluate their relevanCe to the prediCtion of Coronary heart disease. Methods Measurements were made in samples obtained at base line from up to 2459 patients who had a nonfatal myoCardial infarCtion or died of Coronary heart disease during the study and from up to 3969 Controls without a Coronary heart disease event in the Reykjavik prospeCtive study of 18,569 partiCipants. Measurements were made in paired samples obtained an average of 12 years apart from 379 of these partiCipants in order to quantify within-person fluCtuations in inflammatory marker levels. Results The long-term stability of C-reaCtive Protein values (within-person Correlation CoeffiCient, 0.59; 95 perCent ConfidenCe interval, 0.52 to 0.66) was similar to that of both blood pressure an...

  • the prognostiC value of C reaCtive Protein and serum amyloid a Protein in severe unstable angina
    The New England Journal of Medicine, 1994
    Co-Authors: Giovanna Liuzzo, Luigi M Biasucci, R Grillo, A G Rebuzzi, M B Pepys, Attilio Maseri
    Abstract:

    BaCkground The pathogenesis of unstable angina is poorly understood, and prediCting the prognosis is problematiC. EvidenCe suggests that there may be aCtive inflammation, possibly in the Coronary arteries, in this syndrome. We therefore studied the prognostiC value of measurements of the CirCulating aCute-phase reaCtants C-reaCtive Protein and serum amyloid A Protein, whiCh are sensitive indiCators of inflammation. Methods We measured C-reaCtive Protein, serum amyloid A Protein, Creatine kinase, and CardiaC troponin T in 32 patients with ChroniC stable angina, 31 with severe unstable angina, and 29 with aCute myoCardial infarCtion. Results At the time of hospital admission, Creatine kinase and CardiaC troponin T levels were normal in all the patients, but the levels of C-reaCtive Protein and serum amyloid A Protein were ≥ 0.3 mg per deCiliter (exCeeding the 90th perCentile of the normal distribution) in 4 of the patients with stable angina (13 perCent), 20 of the patients with unstable angina (65 perCent)...

Achille Gaspardone - One of the best experts on this subject based on the ideXlab platform.