title: High Serum Immunoglobulin G and M Levels Predict Freedom From Adverse Cardiovascular Events in Hypertension: A Nested Case-Control Substudy of the Anglo-Scandinavian Cardiac Outcomes Trial.
abstract: OBJECTIVE
  We aimed to determine whether the levels of total serum IgM and IgG, together with specific antibodies against malondialdehyde-conjugated low-density lipoprotein (MDA-LDL), can improve cardiovascular risk discrimination.
  
  
  RESULTS
  The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) randomized 9098 patients in the UK and Ireland into the Blood Pressure-Lowering Arm. 485 patients that had cardiovascular (CV) events over 5.5years were age and sex matched with 1367 controls. Higher baseline total serum IgG, and to a lesser extent IgM, were associated with decreased risk of CV events (IgG odds ratio (OR) per one standard deviation (SD) 0.80 [95% confidence interval, CI 0.72,0.89], p<0.0001; IgM 0.83[0.75,0.93], p=0.001), and particularly events due to coronary heart disease (CHD) (IgG OR 0.66 (0.57,0.76); p<0.0001, IgM OR 0.81 (0.71,0.93); p=0.002). The association persisted after adjustment for a basic model with variables in the Framingham Risk Score (FRS) as well as following inclusion of C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NtProBNP). IgG and IgM antibodies against MDA-LDL were also associated with CV events but their significance was lost following adjustment for total serum IgG and IgM respectively. The area under the receiver operator curve for CV events was improved from the basic risk model when adding in total serum IgG, and there was improvement in continuous and categorical net reclassification (17.6% and 7.5% respectively) as well as in the integrated discrimination index.
  
  
  CONCLUSIONS
  High total serum IgG levels are an independent predictor of freedom from adverse cardiovascular events, particularly those attributed to CHD, in patients with hypertension.
authors.affiliation: Vascular Sciences Section, NHLI, Imperial College London, United Kingdom.
authors.forename: Ramzi Y
authors.initials: RY
authors.lastname: Khamis
authors.affiliation: International Centre for Circulatory Health, NHLI, Imperial College London, United Kingdom; Institute of Cardiovascular Science, University College London, United Kingdom.
authors.forename: Alun D
authors.initials: AD
authors.lastname: Hughes
authors.affiliation: Vascular Sciences Section, NHLI, Imperial College London, United Kingdom.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Caga-Anan
authors.affiliation: International Centre for Circulatory Health, NHLI, Imperial College London, United Kingdom.
authors.forename: Choon L
authors.initials: CL
authors.lastname: Chang
authors.affiliation: Vascular Sciences Section, NHLI, Imperial College London, United Kingdom.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Boyle
authors.affiliation: Vascular Sciences Section, NHLI, Imperial College London, United Kingdom.
authors.forename: Chiari
authors.initials: C
authors.lastname: Kojima
authors.affiliation: Division of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Welsh
authors.affiliation: Division of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom.
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.affiliation: Vascular Sciences Section, NHLI, Imperial College London, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Johns
authors.affiliation: International Centre for Circulatory Health, NHLI, Imperial College London, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Sever
authors.affiliation: International Centre for Circulatory Health, NHLI, Imperial College London, United Kingdom.
authors.forename: Jamil
authors.initials: J
authors.lastname: Mayet
authors.affiliation: Vascular Sciences Section, NHLI, Imperial College London, United Kingdom. Electronic address: d.haskard@imperial.ac.uk.
authors.forename: Dorian O
authors.initials: DO
authors.lastname: Haskard
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D003327:Coronary Disease / Q000209:etiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007074:Immunoglobulin G / Q000097:blood*; D007075:Immunoglobulin M / Q000097:blood*; D008077:Lipoproteins, LDL / Q000276:immunology; D016015:Logistic Models; D008297:Male; D008315:Malondialdehyde / Q000031:analogs & derivatives / Q000276:immunology; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D016017:Odds Ratio; D010446:Peptide Fragments / Q000097:blood; D012372:ROC Curve; D012307:Risk Factors
chemical_list: D000959:Antihypertensive Agents; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D010446:Peptide Fragments; C569869:malondialdehyde-low density lipoprotein, human; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D008315:Malondialdehyde; D002097:C-Reactive Protein
keywords: Anti-oxidized-LDL antibodies; Cardiovascular risk stratification; Immunoglobulins