Publications
62 results found
Schmidt AF, Holmes MV, Preiss D, et al., 2018, Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in <i>PCSK9</i>
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>We characterised the phenotypic consequence of genetic variation at the <jats:italic>PCSK9</jats:italic> locus and compared findings with recent trials of pharmacological inhibitors of PCSK9.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Published and individual participant level data (300,000+ participants) were combined to construct a weighted <jats:italic>PCSK9</jats:italic> gene-centric score (GS). Fourteen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The <jats:italic>PCSK9</jats:italic> GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95%CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95%CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95%CI 0.57; 1.22) for the GS, compared to 0.85 (95%CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95%CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Genetic variation at the <jats:italic>PCSK9</jats:italic> locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid
Pazoki R, Dehghan A, Evangelou E, et al., 2018, Genetic predisposition to high blood pressure and lifestyle factors. Associations with midlife blood pressure levels and cardiovascular events, Circulation, Vol: 137, Pages: 653-661, ISSN: 0009-7322
Background:High blood pressure (BP) is a major risk factor for cardiovascular diseases (CVDs), the leading cause of mortality worldwide. Both heritable and lifestyle risk factors contribute to elevated BP levels. We aimed to investigate the extent to which lifestyle factors could offset the effect of an adverse BP genetic profile and its effect on CVD risk.Methods:We constructed a genetic risk score for high BP by using 314 published BP loci in 277 005 individuals without previous CVD from the UK Biobank study, a prospective cohort of individuals aged 40 to 69 years, with a median of 6.11 years of follow-up. We scored participants according to their lifestyle factors including body mass index, healthy diet, sedentary lifestyle, alcohol consumption, smoking, and urinary sodium excretion levels measured at recruitment. We examined the association between tertiles of genetic risk and tertiles of lifestyle score with BP levels and incident CVD by using linear regression and Cox regression models, respectively.Results:Healthy lifestyle score was strongly associated with BP (P<10–320) for systolic and diastolic BP and CVD events regardless of the underlying BP genetic risk. Participants with a favorable in comparison with an unfavorable lifestyle (bottom versus top tertile lifestyle score) had 4.9, 4.3, and 4.1 mm Hg lower systolic BP in low, middle, and high genetic risk groups, respectively (P for interaction=0.0006). Similarly, favorable in comparison with unfavorable lifestyle showed 30%, 33%, and 31% lower risk of CVD among participants in low, middle, and high genetic risk groups, respectively (P for interaction=0.99).Conclusions:Our data further support population-wide efforts to lower BP in the population via lifestyle modification. The advantages and disadvantages of disclosing genetic predisposition to high BP for risk stratification needs careful evaluation.
Pazoki R, 2018, Methods for Polygenic Traits, GENETIC EPIDEMIOLOGY: METHODS AND PROTOCOLS, Editors: Evangelou, Publisher: HUMANA PRESS INC, Pages: 145-156, ISBN: 978-1-4939-7867-0
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- Citations: 3
Ashar FN, Mitchell RN, Albert CM, et al., 2017, A Comprehensive Evaluation of the Genetic Architecture of Sudden Cardiac Arrest
<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. While several risk factors are observationally associated with SCA, the genetic architecture of SCA in the general population remains unknown. Furthermore, understanding which risk factors are causal may help target prevention strategies.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We carried out a large genome-wide association study (GWAS) for SCA (n=3,939 cases, 25,989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (1) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (2) height and BMI, and (3) electrical instability traits (QT and atrial fibrillation), suggesting etiologic roles for these traits in SCA risk.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family his
Pazoki R, Dehghan A, Evangelou E, et al., 2017, Genetic Predisposition to High Blood Pressure and Lifestyle: Associations With Midlife Blood Pressure Levels and Cardiovascular Health Outcomes, Scientific Sessions of the American-Heart-Association / Resuscitation Science Symposium, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322
Evangelou E, Warren HR, Mosen-Ansorena D, et al., 2017, Genetic analysis of over one million people identifies 535 novel loci for blood pressure
<jats:title>Abstract</jats:title><jats:p>High blood pressure is the foremost heritable global risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits to date (systolic, diastolic, pulse pressure) in over one million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also reveal shared loci influencing lifestyle exposures. Our findings offer the potential for a precision medicine strategy for future cardiovascular disease prevention.</jats:p>
Davies G, Lam M, Harris SE, et al., 2017, Ninety-nine independent genetic loci influencing general cognitive function include genes associated with brain health and structure (N = 280,360)
<jats:p>General cognitive function is a prominent human trait associated with many important life outcomes<jats:sup>1,2</jats:sup>, including longevity<jats:sup>3</jats:sup>. The substantial heritability of general cognitive function is known to be polygenic, but it has had little explication in terms of the contributing genetic variants<jats:sup>4,5,6</jats:sup>. Here, we combined cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N=280,360; age range = 16 to 102). We found 9,714 genome-wide significant SNPs (<jats:italic>P</jats:italic><5 x 10<jats:sup>−8</jats:sup>) in 99 independent loci. Most showed clear evidence of functional importance. Among many novel genes associated with general cognitive function were<jats:italic>SGCZ</jats:italic>,<jats:italic>ATXN1</jats:italic>,<jats:italic>MAPT</jats:italic>,<jats:italic>AUTS2</jats:italic>, and<jats:italic>P2RY6</jats:italic>. Within the novel genetic loci were variants associated with neurodegenerative disorders, neurodevelopmental disorders, physical and psychiatric illnesses, brain structure, and BMI. Gene-based analyses found 536 genes significantly associated with general cognitive function; many were highly expressed in the brain, and associated with neurogenesis and dendrite gene sets. Genetic association results predicted up to 4% of general cognitive function variance in independent samples. There was significant genetic overlap between general cognitive function and information processing speed, as well as many health variables including longevity.</jats:p>
Visser AE, Pazoki R, Pulit SL, et al., 2017, No association between gluten sensitivity and amyotrophic lateral sclerosis, JOURNAL OF NEUROLOGY, Vol: 264, Pages: 694-700, ISSN: 0340-5354
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- Citations: 3
Schmidt AF, Swerdlow DI, Holmes MV, et al., 2016, PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study, Lancet Diabetes and Endocrinology, Vol: 5, Pages: 97-105, ISSN: 2213-8587
Background: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductionsin both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modesthyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way off sets theirsubstantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2diabetes and related biomarkers to gauge the likely eff ects of PCSK9 inhibitors on diabetes risk.Methods: In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials,case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol,fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, usinga standardised analysis plan, meta-analyses, and weighted gene-centric scores.Findings: Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analysesof four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lowerLDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight(1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50).Based on the collected data, we did not identify associations with HbA1c (0·03%, –0·01 to 0·08), fasting insulin (0·00%,–0·06 to 0·07), and BMI (0·11 kg/m², –0·09 to 0·30).Interpretation: PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higherfasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diab
Iotchkova V, Huang J, Morris JA, et al., 2016, Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps, Nature Genetics, Vol: 48, Pages: 1303-1312, ISSN: 1061-4036
Large-scale whole genome sequence datasets offer novel opportunities to identify genetic variation underlying human traits. Here we apply genotype imputation based on whole genome sequence data from the UK10K and the 1000 Genomes Projects into 35,981 study participants of European ancestry, followed by association analysis with twenty quantitative cardiometabolic and hematologic traits. We describe 17 novel associations, including six rare (minor allele frequency [MAF]<1%) or low frequency variants (1%<MAF<5%) with platelet count (PLT), red cell indices (MCH, MCV) and high-density lipoprotein (HDL) cholesterol. Applying fine-mapping analysis to 233 known and novel loci associated with the twenty traits, we resolve associations of 59 loci to credible sets of 20 or less variants, and describe trait enrichments within regions of predicted regulatory function. These findings augment understanding of the allelic architecture of risk factors for cardiometabolic and hematologic diseases, and provide additional functional insights with the identification of potentially novel biological targets.
Polfus LM, Khajuria RK, Schick UM, et al., 2016, Erratum: Whole-Exome Sequencing Identifies Loci Associated with Blood Cell Traits and Reveals a Role for Alternative GFI1B Splice Variants in Human Hematopoiesis (American Journal of Human Genetics (2016) 99(2) (481–488)(S0002929716302208)(10.1016/j.ajhg.2016.06.016)), American Journal of Human Genetics, Vol: 99, Pages: 785-785, ISSN: 0002-9297
© 2016 American Society of Human Genetics (The American Journal of Human Genetics 99, 481–488; August 4, 2016) In the originally published version of this paper, Nora Franceschini's surname was misspelled. It has now been corrected online. The authors apologize for the error.
Polfus LM, Khajuria RK, Schick UM, et al., 2016, Whole-Exome Sequencing Identifies Loci Associated with Blood Cell Traits and Reveals a Role for Alternative <i>GFI1B</i> Splice Variants in Human Hematopoiesis, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 99, Pages: 481-488, ISSN: 0002-9297
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- Citations: 30
Pankratz N, Schick UM, Zhou Y, et al., 2016, Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits, NATURE GENETICS, Vol: 48, Pages: 867-+, ISSN: 1061-4036
Tajuddin SM, Schick UM, Eicher JD, et al., 2016, Large-scale exome-wide association analysis identifies loci for white blood cell traits and pleiotropy with immune-mediated diseases, American Journal of Human Genetics, Vol: 99, Pages: 22-39, ISSN: 1537-6605
White blood cells play diverse roles in innate and adaptive immunity. Genetic association analyses of phenotypic variation in circulating white blood cell (WBC) counts from large samples of otherwise healthy individuals can provide insights into genes and biologic pathways involved in production, differentiation, or clearance of particular WBC lineages (myeloid, lymphoid) and also potentially inform the genetic basis of autoimmune, allergic, and blood diseases. We performed an exome array-based meta-analysis of total WBC and subtype counts (neutrophils, monocytes, lymphocytes, basophils, and eosinophils) in a multi-ancestry discovery and replication sample of ∼157,622 individuals from 25 studies. We identified 16 common variants (8 of which were coding variants) associated with one or more WBC traits, the majority of which are pleiotropically associated with autoimmune diseases. Based on functional annotation, these loci included genes encoding surface markers of myeloid, lymphoid, or hematopoietic stem cell differentiation (CD69, CD33, CD87), transcription factors regulating lineage specification during hematopoiesis (ASXL1, IRF8, IKZF1, JMJD1C, ETS2-PSMG1), and molecules involved in neutrophil clearance/apoptosis (C10orf54, LTA), adhesion (TNXB), or centrosome and microtubule structure/function (KIF9, TUBD1). Together with recent reports of somatic ASXL1 mutations among individuals with idiopathic cytopenias or clonal hematopoiesis of undetermined significance, the identification of a common regulatory 3' UTR variant of ASXL1 suggests that both germline and somatic ASXL1 mutations contribute to lower blood counts in otherwise asymptomatic individuals. These association results shed light on genetic mechanisms that regulate circulating WBC counts and suggest a prominent shared genetic architecture with inflammatory and autoimmune diseases.
Eicher JD, Chami N, Kacprowski T, et al., 2016, Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals, American Journal of Human Genetics, Vol: 99, Pages: 40-55, ISSN: 1537-6605
Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets' important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors.
Chami N, Chen MH, Slater AJ, et al., 2016, Exome genotyping identifies pleiotropic variants associated with red blood cell traits, American Journal of Human Genetics, Vol: 99, Pages: 8-21, ISSN: 1537-6605
Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 × 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 × 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 × 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 × 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 × 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.
Chaker L, Falla A, van der Lee SJ, et al., 2015, The global impact of non-communicable diseases on macro-economic productivity: a systematic review, EUROPEAN JOURNAL OF EPIDEMIOLOGY, Vol: 30, Pages: 357-395, ISSN: 0393-2990
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- Citations: 83
Muka T, Imo D, Jaspers L, et al., 2015, The global impact of non-communicable diseases on healthcare spending and national income: a systematic review, EUROPEAN JOURNAL OF EPIDEMIOLOGY, Vol: 30, Pages: 251-277, ISSN: 0393-2990
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- Citations: 193
Jaspers L, Colpani V, Chaker L, et al., 2015, The global impact of non-communicable diseases on households and impoverishment: a systematic review, EUROPEAN JOURNAL OF EPIDEMIOLOGY, Vol: 30, Pages: 163-188, ISSN: 0393-2990
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- Citations: 92
Sedaghat S, Pazoki R, Uitterlinden AG, et al., 2014, Association of Uric Acid Genetic Risk Score With Blood Pressure The Rotterdam Study, HYPERTENSION, Vol: 64, Pages: 1061-+, ISSN: 0194-911X
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- Citations: 29
Pazoki R, Tanck MWT, Wilde AAM, et al., 2013, Complex Inheritance for Susceptibility to Sudden Cardiac Death, CURRENT PHARMACEUTICAL DESIGN, Vol: 19, Pages: 6864-6872, ISSN: 1381-6128
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- Citations: 3
Pazoki R, de Jong JSSG, Marsman RF, et al., 2013, SNPs Identified as Modulators of ECG Traits in the General Population Do Not Markedly Affect ECG Traits during Acute Myocardial Infarction nor Ventricular Fibrillation Risk in This Condition, PLOS ONE, Vol: 8, ISSN: 1932-6203
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- Citations: 11
Eghbali SS, Amirinejad R, Obeidi N, et al., 2012, Oncogenic human papillomavirus genital infection in southern Iranian women: population-based study versus clinic-based data, VIROLOGY JOURNAL, Vol: 9
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- Citations: 17
Arking DE, Junttila MJ, Goyette P, et al., 2011, Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals, PLOS GENETICS, Vol: 7, ISSN: 1553-7390
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- Citations: 98
Pazoki R, Wilde AAM, Bezzina CR, 2010, Genetic Basis of Ventricular Arrhythmias., Curr Cardiovasc Risk Rep, Vol: 4, Pages: 454-460, ISSN: 1932-9520
Sudden cardiac death (SCD) is a leading cause of total and cardiovascular mortality, and ventricular fibrillation is the underlying arrhythmia in the majority of cases. In the young, where the incidence of SCD is low, a great proportion of SCDs occur in the context of inherited disorders such as cardiomyopathy or primary electrical disease, where a monogenic hereditary component is a strong determinant of risk. Marked advancement has been made over the past 15 years in the understanding of the genetic basis of the primary electrical disorders, and this has had an enormous impact on the management of these patients. At older ages, the great majority of SCDs occur in the context of acute myocardial ischemia and infarction. Although epidemiologic studies have shown that heritable factors also determine risk in these cases, inheritance is likely complex and multifactorial, and progress in understanding the genetic and molecular mechanisms that determine susceptibility to these arrhythmias, affecting a greater proportion of the population, has been very limited. We review the most recent insights gained into the genetic basis of both the monogenic and the more complex ventricular arrhythmias.
Bezzina CR, Pazoki R, Bardai A, et al., 2010, Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction, NATURE GENETICS, Vol: 42, Pages: 688-U64, ISSN: 1061-4036
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- Citations: 127
Nabipour I, Larijani B, Beigi S, et al., 2008, Relationship among insulinlike growth factor I concentrations, bone mineral density, and biochemical markers of bone turnover in postmenopausal women: a population-based study, MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY, Vol: 15, Pages: 934-939, ISSN: 1072-3714
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- Citations: 15
Nabipour I, Vahdat K, Jafari SM, et al., 2007, Correlation of hyperhomocysteinaemia and Chlamydia pneumoniae IgG seropositivity with coronary artery disease in a general population., Heart Lung Circ, Vol: 16, Pages: 416-422, ISSN: 1443-9506
BACKGROUND: Both Chlamydia pneumoniae infection and hyperhomocysteinaemia have been assumed to increase the atherosclerotic risk independently of each other and independently of the classic risk factors. The correlation between hyperhomocysteinaemia, C. pneumoniae infection and coronary artery disease (CAD) have not been investigated in the general population. METHODS: In an ancillary study to the Persian Gulf Healthy Heart Study, a cohort study of men and women aged >or=25 years, a random sample of 1699 (48.9% males, 51.1% females) subjects were evaluated. Total homocysteine, high sensitivity C-reactive protein (CRP) and IgG antibodies to C. pneumoniae were determined by ELISA. Minnesota coding criteria of a 12-lead resting electrocardiogram was used for evaluation of CAD. RESULTS: A total of 12.4% of the subjects had electrocardiogram-defined (Minnesota-coding criteria) coronary artery disease. Hyperhomocysteinaemia (>14 micromol/l) and IgG seropositivity were found in 50.8% and 37.7%, respectively. Neither of hyperhomocysteinaemia nor C. pneumoniae IgG seropositivity showed a significant association with CAD after adjusting of sex and age. Concurrent elevated CRP level (>8.2mg/l) and C. pneumoniae seropositivity (chronic C. pneumoniae infection) had a significant association with CAD [OR=1.73, CI (1.09-2.75); p=0.01] after adjusting for age, sex, systolic and diastolic blood pressures, BMI, and serum levels of LDL-cholesterol, fasting blood sugar and triglyceride as covariates in a logistic regression model. This odds ratio increased to 2.11, CI (1.18-4.12; p=0.02) when concurrent hyperhomocysteinaemia and chronic C. pneumoniae infection, as a single covariate entity; was adjusted for multiple risk factors in another logistic regression model. CONCLUSION: Concurrent hyperhomocysteinaemia and chronic C. pneumoniae infection, as a single entity, was independently associated with coronary artery disease in the general population. This synergism may have imp
Pazoki R, Nabipour I, Seyednezami N, et al., 2007, Effects of a community-based healthy heart program on increasing healthy women's physical activity: a randomized controlled trial guided by Community-based Participatory Research (CBPR), BMC PUBLIC HEALTH, Vol: 7
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Vahdat K, Jafari SM, Pazoki R, et al., 2007, Concurrent increased high sensitivity C-reactive protein and chronic infections are associated with coronary artery disease: a population-based study., Indian J Med Sci, Vol: 61, Pages: 135-143, ISSN: 0019-5359
BACKGROUND: An elevated serum level of C-reactive protein (CRP) is an independent predictor of coronary artery disease (CAD). Chronic infections have also been implicated in the pathogenesis of CAD. AIMS: To investigate how concomitant chronic infection and CRP related to electrocardiogram-defined CAD in a general population. SETTING AND DESIGN: A population-based cross-sectional study, which was conducted in three Iranian ports in the northern Persian Gulf. MATERIALS AND METHODS: For evaluation of CAD, we used Minnesota coding criteria of a 12-lead resting electrocardiogram in 1,754 subjects, aged 25 years and over, selected by cluster random sampling. Sera were analyzed for IgG antibodies to Chlamydia pneumoniae (C. pneumoniae), Herpes simplex virus type 1 (HSV-1), Helicobacter pylori (H. pylori) and cytomegalovirus (CMV) using ELISA. Measurement of CRP by a high-sensitivity CRP assay was done. STATISTICAL ANALYSIS: Multiple logistic regression analysis was used. RESULTS: None of the infectious agents (CMV, H. pylori, C. pneumoniae and HSV-1) showed a significant association with electrocardiogram-defined CAD after adjusting for sex and age. Elevated CRP levels did not show significant association with electrocardiogram-defined CAD independent of seropositivity to one of the four infectious agents, but concurrent elevated CRP levels (>10.0 mg/L) and anti-C. pneumoniae [OR = 1.68 (CI, 1.24-2.59; P=0.04)], H. pylori [OR = 1.98 (CI, 1.26-3.13; P=0.003)], CMV [OR = 1.66 (CI, 1.10-2.49; P=0.01)] or HSV-1 [OR=1.79 (CI, 1.18-2.72; P=0.006)] IgG antibodies were associated with prevalence of electrocardiogram-defined CAD in the general population, after adjustment for multiple risk factors, including age, sex and the components of the metabolic syndrome. CONCLUSIONS: Beyond traditional cardiovascular risk factors, concomitant chronic infection and elevated CRP are significantly correlated with electrocardiogram-defined CAD.
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