title: Ideal cardiovascular health influences cardiovascular disease risk associated with high lipoprotein(a) levels and genotype: The EPIC-Norfolk prospective population study.
abstract: Lipoprotein(a) (Lp[a]) is a strong genetic risk factor for cardiovascular disease (CVD). The American Heart Association has prioritised seven cardiovascular health metrics to reduce the burden of CVD: body mass index, healthy diet, physical activity, smoking status, blood pressure, diabetes and cholesterol levels (together also known as ideal cardiovascular health). Our objective was to determine if individuals with high Lp(a) levels could derive cardiovascular benefits if characterized by ideal cardiovascular health.
  
  
  
  A total of 14,051 participants of the EPIC-Norfolk study were stratified according to the cardiovascular health score (based on the number of health metrics with an ideal, intermediate or poor status). Of them, 1732 had a CVD event during a mean follow-up of 11.5 years. Cox proportional hazards models were used to describe the association between the cardiovascular health score and Lp(a) level or genotype (as estimated by the rs10455872 variant) with the risk of CVD.
  
  
  
  We observed little or no differences in serum Lp(a) levels across the seven cardiovascular health metric categories. Among participants with high serum Lp(a) levels ≥50 mg/dl), those in the highest (i.e. healthiest) cardiovascular health score category (10-14) had an adjusted hazard ratio for cardiovascular disease of 0.33 (95% CI = 0.17-0.63, p = 0.001) compared to participants in the lowest (i.e. unhealthiest) cardiovascular health score category(0-4). Similar results were obtained when we replaced Lp(a) with rs10455872.
  
  
  
  Although Lp(a) levels are only slightly influenced by cardiovascular health metrics, an ideal cardiovascular health could substantially reduce CVD risk associated with high Lp(a) levels or genotype.
authors.affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Canada; Department of Medicine, Faculty of Medicine, Université Laval, Québec, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Perrot
authors.affiliation: Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Rutger
authors.initials: R
authors.lastname: Verbeek
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Manjinder
authors.initials: M
authors.lastname: Sandhu
authors.affiliation: Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: S Matthijs
authors.initials: SM
authors.lastname: Boekholdt
authors.affiliation: Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.affiliation: MRC Epidemiology Unit, Cambridge, United Kingdom.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Canada; Department of Medicine, Faculty of Medicine, Université Laval, Québec, Canada. Electronic address: benoit.arsenault@criucpq.ulaval.ca.
authors.forename: Benoit J
authors.initials: BJ
authors.lastname: Arsenault
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control; D016009:Chi-Square Distribution; D004739:England / Q000453:epidemiology; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006304:Health Status; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D005819:Genetic Markers; D017270:Lipoprotein(a)
keywords: Cardiovascular diseases; Genetics; Ideal cardiovascular health; Lifestyle; Lipoprotein(a)