title: Is Isolated Low High-Density Lipoprotein Cholesterol a Cardiovascular Disease Risk Factor? New Insights From the Framingham Offspring Study.
abstract: Although the inverse association between high-density lipoprotein cholesterol (HDL-C) and risk of cardiovascular disease (CVD) has been long established, it remains unclear whether low HDL-C remains a CVD risk factor when levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) are not elevated. This is a timely issue because recent studies have questioned whether HDL-C is truly an independent predictor of CVD.
  
  
  
  3590 men and women from the Framingham Heart Study offspring cohort without known CVD were followed between 1987 and 2011. Low HDL-C (<40 mg/dL in men and <50 mg/dL in women) was defined as isolated if TG and LDL-C were both low (<100 mg/dL). We also examined higher thresholds for TG (150 mg/dL) and LDL-C (130 mg/dL) and compared low versus high HDL-C phenotypes using logistic regression analysis to assess association with CVD. Compared with isolated low HDL-C, CVD risks were higher when low HDL-C was accompanied by LDL-C ≥100 mg/dL and TG <100 mg/dL (odds ratio 1.3 [1.0, 1.6]), TG ≥100 mg/dL and LDL-C <100 mg/dL (odds ratio 1.3 [1.1, 1.5]), or TG and LDL-C ≥100 mg/dL (odds ratio 1.6, [1.2, 2.2]), after adjustment for covariates. When low HDL-C was analyzed with higher thresholds for TG (≥150 mg/dL) and LDL-C (≥130 mg/dL), results were essentially the same. In contrast, compared with isolated low HDL-C, high HDL-C was associated with 20% to 40% lower CVD risk except when TG and LDL-C were elevated.
  
  
  
  CVD risk as a function of HDL-C phenotypes is modulated by other components of the lipid panel.
authors.affiliation: Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH.
authors.forename: Jacquelaine
authors.initials: J
authors.lastname: Bartlett
authors.affiliation: Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Predazzi
authors.affiliation: Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
authors.affiliation: Institute for Computational Biology, Case Western Reserve University, Cleveland, OH.
authors.forename: William S
authors.initials: WS
authors.lastname: Bush
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, New Haven, CT.
authors.forename: Yeunjung
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: Stephen
authors.initials: S
authors.lastname: Havas
authors.affiliation: CGH Medical Center, Sterling, Illinois, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Toth
authors.affiliation: Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR.
authors.forename: Sergio
authors.initials: S
authors.lastname: Fazio
authors.affiliation: Division of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, MD.
authors.forename: Michael
authors.initials: M
authors.lastname: Miller
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D015536:Down-Regulation; D050171:Dyslipidemias / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D012307:Risk Factors; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides
keywords: coronary heart disease risk; epidemiology; high-density lipoprotein cholesterol; low-density lipoprotein cholesterol; triglycerides