title: Dutch Lipid Clinic Network low-density lipoprotein cholesterol criteria are associated with long-term mortality in the general population.
abstract: BACKGROUND
  Heterozygous familial hypercholesterolaemia (HeFH) is a severe autosomal dominant disease that is underdiagnosed, inadequately treated and has a severe long-term cardiovascular risk. Few studies have evaluated the long-term risk of high low-density lipoprotein cholesterol (LDL-C) concentrations.
  
  
  OBJECTIVE
  To evaluate long-term mortality in a large cohort of healthy subjects, according to LDL-C concentrations.
  
  
  METHODS
  Based on a sample of 6956 subjects visiting a preventive cardiology department, we selected adult subjects without a personal history of cardiovascular disease. From 1995 to 2011, 4930 healthy subjects were examined and followed up until 31 December 2011. All-cause deaths were collected exhaustively. A Cox-based multivariable analysis evaluated long-term total mortality risk according to Dutch Lipid Clinic Network (DLCN) LDL-C concentrations.
  
  
  RESULTS
  After a mean follow-up of 8.6 years, 123 all-cause deaths were recorded (cumulative mortality rate, 2.5%). In the final multivariable model, major risk factors such as age, sex, tobacco use and diabetes were significantly associated with mortality. After adjustment for age, sex, tobacco use, hypertension, diabetes and statin therapy, and in comparison with subjects with LDL-C<4 mmol/L (<155 mg/dL), subjects with LDL-C between 4 and <5 mmol/L (155 to <190 mg/dL) had a hazard ratio (HR) of 1.99 (95% confidence interval [CI] 1.31-3.02; P=0.001), subjects with LDL-C between 5 and <6.5 mmol/L (190 to <250 mg/dL) had an HR of 1.81 (95% CI, 1.06-3.02; P=0.030), subjects with LDL-C between 6.5 and<8.5 mmol/L (250 to <330 mg/dL) had an HR of 2.69 (95% CI, 1.06-6.88; P=0.038) and subjects with LDL-C ≥ 8.5 mmol/L (≥330 mg/dL) had an HR of 6.27 (95% CI, 0.84-46.57; P=0.073). After excluding patients on statins at baseline, subjects with LDL-C ≥ 8.5 mmol/L (≥330 mg/dL) had an HR of 8.17 (95% CI, 1.08-62.73; P=0.042).
  
  
  CONCLUSIONS
  The severity of LDL-C elevation is associated with a higher risk of death in healthy subjects. DLCN LDL-C concentrations may be used in daily practice to identify patients with HeFH who warrant aggressive treatment.
authors.affiliation: Fédération de cardiologie, TSA 50032, CHU de Rangueil, 31059 Toulouse cedex 9, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Séguro
authors.affiliation: Département d'épidémiologie, économie de la santé et santé publique, UMR1027 Inserm, université Toulouse III, 31073 Toulouse, France; Service d'épidémiologie, CHU de Toulouse, 31073 Toulouse, France.
authors.forename: Vanina
authors.initials: V
authors.lastname: Bongard
authors.affiliation: Département d'épidémiologie, économie de la santé et santé publique, UMR1027 Inserm, université Toulouse III, 31073 Toulouse, France; Service d'épidémiologie, CHU de Toulouse, 31073 Toulouse, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Bérard
authors.affiliation: Fédération de cardiologie, TSA 50032, CHU de Rangueil, 31059 Toulouse cedex 9, France.
authors.forename: Dorota
authors.initials: D
authors.lastname: Taraszkiewicz
authors.affiliation: Département d'épidémiologie, économie de la santé et santé publique, UMR1027 Inserm, université Toulouse III, 31073 Toulouse, France; Service d'épidémiologie, CHU de Toulouse, 31073 Toulouse, France.
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Ruidavets
authors.affiliation: Fédération de cardiologie, TSA 50032, CHU de Rangueil, 31059 Toulouse cedex 9, France; Département d'épidémiologie, économie de la santé et santé publique, UMR1027 Inserm, université Toulouse III, 31073 Toulouse, France. Electronic address: jean.ferrieres@univ-tlse3.fr.
authors.forename: Jean
authors.initials: J
authors.lastname: Ferrières
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL
keywords: Cholestérol LDL; Cohort study; Cohorte; Heterozygous familial hypercholesterolaemia; Hypercholestérolémie familiale hétérozygote; LDL-cholesterol; Mortality; Mortalité