title: Lipid and lipoprotein measurements and the risk of ischemic vascular events: Framingham Study.
abstract: OBJECTIVE
  To examine the relationship between plasma lipid measurements and incident ischemic vascular events (ischemic stroke [IS], and as a positive control, myocardial infarction [MI]) in a community cohort.
  
  
  METHODS
  In 6,276 stroke-free Framingham participants (aged 64 ± 10 years, 56% female), we related plasma lipid levels (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], and TC/HDL-C ratio) measured at the original cohort 15th (1977-1979) and 20th examination cycles (1986-1990) and (TC, HDL-C, TC/HDL-C ratio, triglycerides [TG], and low-density lipoprotein cholesterol [LDL-C]) measured at the offspring fourth examination (1995-1998), to 10-year risk of incident IS and MI. Utilizing genome-wide genotyping in the same subjects, we used mendelian randomization methods to assess whether observed associations were incidental or causal.
  
  
  RESULTS
  During a mean follow-up of 9 years, 301 participants experienced incident IS. In multivariable-adjusted analyses, HDL-C ≤40 mg/dL and TC/HDL ratio ≥5 were associated with increased risk of IS (hazard ratio [95% confidence interval]: 1.59 [1.23-2.05], p < 0.001 and 1.47 [1.15-1.87], p < 0.001), but not TC or LDL-C. In adjusted analysis, a strong association between TG and IS was diminished. In the MI-free sample (n = 5,875, aged 64 ± 10 years, 58% female; 403 MI events), all lipid markers were associated with MI risk. A genetic risk score comprising 47 known determinants of circulating HDL-C was not associated with IS.
  
  
  CONCLUSIONS
  In a middle-aged to elderly community sample, we observed that low HDL-C and high TC/HDL-C ratio, but not LDL-C or TG were associated with risk of incident IS. We observed the usual associations between lipids and risk of MI. Our findings suggest an important, but less likely causal, role of HDL-C over other lipid biomarkers for optimal stroke risk stratification.
authors.affiliation: From the Boston University Schools of Medicine and Public Health (A.P., A.S.B., J.W., J.J.H., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Boston; and Framingham Heart Study (A.P., A.S.B., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Framingham, MA. aleksandra.pikula@uhn.ca.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Pikula
authors.affiliation: From the Boston University Schools of Medicine and Public Health (A.P., A.S.B., J.W., J.J.H., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Boston; and Framingham Heart Study (A.P., A.S.B., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Framingham, MA.
authors.forename: Alexa S
authors.initials: AS
authors.lastname: Beiser
authors.affiliation: From the Boston University Schools of Medicine and Public Health (A.P., A.S.B., J.W., J.J.H., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Boston; and Framingham Heart Study (A.P., A.S.B., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Framingham, MA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: From the Boston University Schools of Medicine and Public Health (A.P., A.S.B., J.W., J.J.H., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Boston; and Framingham Heart Study (A.P., A.S.B., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Framingham, MA.
authors.forename: Jayandra J
authors.initials: JJ
authors.lastname: Himali
authors.affiliation: From the Boston University Schools of Medicine and Public Health (A.P., A.S.B., J.W., J.J.H., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Boston; and Framingham Heart Study (A.P., A.S.B., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Framingham, MA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Kelly-Hayes
authors.affiliation: From the Boston University Schools of Medicine and Public Health (A.P., A.S.B., J.W., J.J.H., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Boston; and Framingham Heart Study (A.P., A.S.B., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Framingham, MA.
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Kase
authors.affiliation: From the Boston University Schools of Medicine and Public Health (A.P., A.S.B., J.W., J.J.H., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Boston; and Framingham Heart Study (A.P., A.S.B., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Framingham, MA.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.affiliation: From the Boston University Schools of Medicine and Public Health (A.P., A.S.B., J.W., J.J.H., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Boston; and Framingham Heart Study (A.P., A.S.B., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Framingham, MA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.affiliation: From the Boston University Schools of Medicine and Public Health (A.P., A.S.B., J.W., J.J.H., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Boston; and Framingham Heart Study (A.P., A.S.B., M.K.-H., C.S.K., Q.Y., S.S., P.A.W.), Framingham, MA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wolf
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D014280:Triglycerides / Q000097:blood*
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides