Lipid and lipoprotein measurements and the risk of ischemic vascular events: Framingham Study

Aleksandra Pikula, Alexa S. Beiser, Jing Wang, Jayandra J. Himali, Margaret Kelly-Hayes, Carlos S. Kase, Qiong Yang, Sudha Seshadri, Philip A. Wolf

Research output: Contribution to journalArticle

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Abstract

Objectives: 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 6 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 5,875, aged 64 6 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.

Original languageEnglish (US)
Pages (from-to)472-479
Number of pages8
JournalNeurology
Volume84
Issue number5
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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HDL Cholesterol
Lipoproteins
Blood Vessels
Stroke
Lipids
Myocardial Infarction
Cholesterol
LDL Cholesterol
Triglycerides
Random Allocation
Biomarkers
Genome
Confidence Intervals

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Pikula, A., Beiser, A. S., Wang, J., Himali, J. J., Kelly-Hayes, M., Kase, C. S., ... Wolf, P. A. (2015). Lipid and lipoprotein measurements and the risk of ischemic vascular events: Framingham Study. Neurology, 84(5), 472-479. https://doi.org/10.1212/WNL.0000000000001202

Lipid and lipoprotein measurements and the risk of ischemic vascular events : Framingham Study. / Pikula, Aleksandra; Beiser, Alexa S.; Wang, Jing; Himali, Jayandra J.; Kelly-Hayes, Margaret; Kase, Carlos S.; Yang, Qiong; Seshadri, Sudha; Wolf, Philip A.

In: Neurology, Vol. 84, No. 5, 01.01.2015, p. 472-479.

Research output: Contribution to journalArticle

Pikula, A, Beiser, AS, Wang, J, Himali, JJ, Kelly-Hayes, M, Kase, CS, Yang, Q, Seshadri, S & Wolf, PA 2015, 'Lipid and lipoprotein measurements and the risk of ischemic vascular events: Framingham Study', Neurology, vol. 84, no. 5, pp. 472-479. https://doi.org/10.1212/WNL.0000000000001202
Pikula A, Beiser AS, Wang J, Himali JJ, Kelly-Hayes M, Kase CS et al. Lipid and lipoprotein measurements and the risk of ischemic vascular events: Framingham Study. Neurology. 2015 Jan 1;84(5):472-479. https://doi.org/10.1212/WNL.0000000000001202
Pikula, Aleksandra ; Beiser, Alexa S. ; Wang, Jing ; Himali, Jayandra J. ; Kelly-Hayes, Margaret ; Kase, Carlos S. ; Yang, Qiong ; Seshadri, Sudha ; Wolf, Philip A. / Lipid and lipoprotein measurements and the risk of ischemic vascular events : Framingham Study. In: Neurology. 2015 ; Vol. 84, No. 5. pp. 472-479.
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abstract = "Objectives: 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 6 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 5,875, aged 64 6 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.",
author = "Aleksandra Pikula and Beiser, {Alexa S.} and Jing Wang and Himali, {Jayandra J.} and Margaret Kelly-Hayes and Kase, {Carlos S.} and Qiong Yang and Sudha Seshadri and Wolf, {Philip A.}",
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AU - Pikula, Aleksandra

AU - Beiser, Alexa S.

AU - Wang, Jing

AU - Himali, Jayandra J.

AU - Kelly-Hayes, Margaret

AU - Kase, Carlos S.

AU - Yang, Qiong

AU - Seshadri, Sudha

AU - Wolf, Philip A.

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N2 - Objectives: 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 6 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 5,875, aged 64 6 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.

AB - Objectives: 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 6 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 5,875, aged 64 6 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.

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