title: Relations of long-term and contemporary lipid levels and lipid genetic risk scores with coronary artery calcium in the framingham heart study.
abstract: OBJECTIVE
  This study evaluated the association of timing of lipid levels and lipid genetic risk score (GRS) with subclinical atherosclerosis.
  
  
  BACKGROUND
  Atherosclerosis is a slowly progressive disorder influenced by suboptimal lipid levels. Long-term versus contemporary lipid levels may more strongly impact the development of coronary artery calcium (CAC).
  
  
  METHODS
  Framingham Heart Study (FHS) Offspring Cohort participants (n = 1,156, 44% male, 63 ± 9 years) underwent serial fasting lipids (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein, and triglycerides), Exam 1 (1971 to 1975) to Exam 7 (1998 to 2001). FHS Third Generation Cohort participants (n = 1,954, 55% male, 45 ± 6 years) had fasting lipid profiles assessed, 2002 to 2005. Computed tomography (2002 to 2005) measured CAC. Lipid GRSs were computed from significantly associated single-nucleotide polymorphisms. The association between early, long-term average, and contemporary lipids, and lipid GRS with elevated CAC was assessed using logistic regression.
  
  
  RESULTS
  In FHS Offspring, Exam 1 and long-term average as compared with Exam 7 lipid measurements, including untreated lipid levels, were strongly associated with elevated CAC. In the FHS Third Generation, contemporary lipids were associated with CAC. The LDL-C GRS was associated with CAC (age-/sex-adjusted odds ratio: 1.14, 95% confidence interval: 1.00 to 1.29, p = 0.04). However, addition of the GRS to the lipid models did not result in a significant increase in the odds ratio or C-statistic for any lipid measure.
  
  
  CONCLUSIONS
  Early and long-term average lipid levels, as compared with contemporary measures, are more strongly associated with elevated CAC. Lipid GRS was associated with lipid levels but did not predict elevated CAC. Adult early and long-term average lipid levels provide important information when assessing subclinical atherosclerosis and cardiovascular risk.
authors.affiliation: National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA 01702, USA.
authors.forename: Connie W
authors.initials: CW
authors.lastname: Tsao
authors.forename: Sarah Rosner
authors.initials: SR
authors.lastname: Preis
authors.forename: Gina M
authors.initials: GM
authors.lastname: Peloso
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Sekar
authors.initials: S
authors.lastname: Kathiresan
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Udo
authors.initials: U
authors.lastname: Hoffmann
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
mesh_terms: D050197:Atherosclerosis / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D061330:Multidetector Computed Tomography / Q000379:methods*; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors
chemical_list: D008055:Lipids