Trajectories of Blood Lipid Concentrations Over the Adult Life Course and Risk of Cardiovascular Disease and All-Cause Mortality: Observations From the Framingham Study Over 35 Years

Meredith S. Duncan; Ramachandran S. Vasan; Vanessa Xanthakis

doi:10.1161/JAHA.118.011433

Trajectories of Blood Lipid Concentrations Over the Adult Life Course and Risk of Cardiovascular Disease and All-Cause Mortality: Observations From the Framingham Study Over 35 Years

Meredith S. Duncan, Ramachandran S. Vasan, Vanessa Xanthakis

Research output: Contribution to journal › Article › peer-review

69 Scopus citations

Abstract

Background: Elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides, and non-high-density lipoprotein cholesterol (non-HDL-C) and low high-density lipoprotein cholesterol (HDL-C) concentrations correlate with atherosclerotic cardiovascular disease (ASCVD) and mortality. Therefore, understanding how lipid trajectories throughout adulthood impact ASCVD and mortality risk is essential. Methods and Results: We investigated 3875 Framingham Offspring participants (54% women, mean age 48 years) attending ≥1 examination between 1979 and 2014. We evaluated longitudinal correlates of each lipid subtype using mixed-effects models. Next, we clustered individuals into trajectories through group-based modeling. Thereafter, we assessed the prospective association of lipid trajectories with ASCVD and mortality. Male sex, greater body mass index, and smoking correlated with higher TC, LDL-C, triglycerides, non-HDL-C, and lower HDL-C concentrations. We identified 5 TC, HDL-C, and LDL-C trajectories, and 4 triglycerides and non-HDL-C trajectories. Upon follow-up (median 8.2 years; 199 ASCVD events; 256 deaths), elevated TC (>240 mg/dL), LDL-C (>155 mg/dL), or non-HDL-C (>180 mg/dL) concentrations conferred >2.25-fold ASCVD and mortality risk compared with concentrations <165 mg/dL, <90 mg/dL, and <115 mg/dL, respectively ([TC hazard ratio (HR)_ASCVD=4.17, 95% CI 1.94–8.99; TC HR_death=2.47, 95% CI 1.28–4.76] [LDL-C HR_ASCVD=5.09, 95% CI 1.54–16.85; LDL-C HR_death=4.04, 95% CI 1.84–8.89] [non-HDL-C HR_ASCVD=4.60, 95% CI 1.98–10.70; LDL-C HR_death=3.74, 95% CI 2.03–6.88]). Consistent HDL-C concentrations <40 mg/dL were associated with greater ASCVD and mortality risk than concentrations >70 mg/dL (HR_ASCVD=3.81, 95% CI 2.04–7.15; HR_death=2.88, 95% CI 1.70–4.89). Triglycerides trajectories were unassociated with outcomes. Conclusions: Using a longitudinal modeling technique, we demonstrated that unfavorable lipid trajectories over 35 years confer higher ASCVD and mortality risk later in life.

Original language	English
Article number	e011433
Journal	Journal of the American Heart Association
Volume	8
Issue number	11
DOIs	https://doi.org/10.1161/JAHA.118.011433
State	Published - Jun 4 2019

Bibliographical note

Funding Information:
This work was supported by the National Heart, Lung, and Blood Institute contracts N01-HC-25195 and HHSN268201500001I. Dr Vasan was also funded by the Evans Foundation and Jay and Louise Coffman Endowment at Boston University.

Publisher Copyright:
© 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Keywords

cardiovascular disease
life-course
lipids
longitudinal
trajectories

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1161/JAHA.118.011433

Cite this

@article{189890599a3444d8b03822ae60719813,

title = "Trajectories of Blood Lipid Concentrations Over the Adult Life Course and Risk of Cardiovascular Disease and All-Cause Mortality: Observations From the Framingham Study Over 35 Years",

abstract = "Background: Elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides, and non-high-density lipoprotein cholesterol (non-HDL-C) and low high-density lipoprotein cholesterol (HDL-C) concentrations correlate with atherosclerotic cardiovascular disease (ASCVD) and mortality. Therefore, understanding how lipid trajectories throughout adulthood impact ASCVD and mortality risk is essential. Methods and Results: We investigated 3875 Framingham Offspring participants (54% women, mean age 48 years) attending ≥1 examination between 1979 and 2014. We evaluated longitudinal correlates of each lipid subtype using mixed-effects models. Next, we clustered individuals into trajectories through group-based modeling. Thereafter, we assessed the prospective association of lipid trajectories with ASCVD and mortality. Male sex, greater body mass index, and smoking correlated with higher TC, LDL-C, triglycerides, non-HDL-C, and lower HDL-C concentrations. We identified 5 TC, HDL-C, and LDL-C trajectories, and 4 triglycerides and non-HDL-C trajectories. Upon follow-up (median 8.2 years; 199 ASCVD events; 256 deaths), elevated TC (>240 mg/dL), LDL-C (>155 mg/dL), or non-HDL-C (>180 mg/dL) concentrations conferred >2.25-fold ASCVD and mortality risk compared with concentrations <165 mg/dL, <90 mg/dL, and <115 mg/dL, respectively ([TC hazard ratio (HR)ASCVD=4.17, 95% CI 1.94–8.99; TC HRdeath=2.47, 95% CI 1.28–4.76] [LDL-C HRASCVD=5.09, 95% CI 1.54–16.85; LDL-C HRdeath=4.04, 95% CI 1.84–8.89] [non-HDL-C HRASCVD=4.60, 95% CI 1.98–10.70; LDL-C HRdeath=3.74, 95% CI 2.03–6.88]). Consistent HDL-C concentrations <40 mg/dL were associated with greater ASCVD and mortality risk than concentrations >70 mg/dL (HRASCVD=3.81, 95% CI 2.04–7.15; HRdeath=2.88, 95% CI 1.70–4.89). Triglycerides trajectories were unassociated with outcomes. Conclusions: Using a longitudinal modeling technique, we demonstrated that unfavorable lipid trajectories over 35 years confer higher ASCVD and mortality risk later in life.",

keywords = "cardiovascular disease, life-course, lipids, longitudinal, trajectories",

author = "Duncan, {Meredith S.} and Vasan, {Ramachandran S.} and Vanessa Xanthakis",

note = "Funding Information: This work was supported by the National Heart, Lung, and Blood Institute contracts N01-HC-25195 and HHSN268201500001I. Dr Vasan was also funded by the Evans Foundation and Jay and Louise Coffman Endowment at Boston University. Publisher Copyright: {\textcopyright} 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.",

year = "2019",

month = jun,

day = "4",

doi = "10.1161/JAHA.118.011433",

language = "English",

volume = "8",

number = "11",

}

Trajectories of Blood Lipid Concentrations Over the Adult Life Course and Risk of Cardiovascular Disease and All-Cause Mortality : Observations From the Framingham Study Over 35 Years. / Duncan, Meredith S.; Vasan, Ramachandran S.; Xanthakis, Vanessa.

In: Journal of the American Heart Association, Vol. 8, No. 11, e011433, 04.06.2019.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Trajectories of Blood Lipid Concentrations Over the Adult Life Course and Risk of Cardiovascular Disease and All-Cause Mortality

T2 - Observations From the Framingham Study Over 35 Years

AU - Duncan, Meredith S.

AU - Vasan, Ramachandran S.

AU - Xanthakis, Vanessa

N1 - Funding Information: This work was supported by the National Heart, Lung, and Blood Institute contracts N01-HC-25195 and HHSN268201500001I. Dr Vasan was also funded by the Evans Foundation and Jay and Louise Coffman Endowment at Boston University. Publisher Copyright: © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

PY - 2019/6/4

Y1 - 2019/6/4

N2 - Background: Elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides, and non-high-density lipoprotein cholesterol (non-HDL-C) and low high-density lipoprotein cholesterol (HDL-C) concentrations correlate with atherosclerotic cardiovascular disease (ASCVD) and mortality. Therefore, understanding how lipid trajectories throughout adulthood impact ASCVD and mortality risk is essential. Methods and Results: We investigated 3875 Framingham Offspring participants (54% women, mean age 48 years) attending ≥1 examination between 1979 and 2014. We evaluated longitudinal correlates of each lipid subtype using mixed-effects models. Next, we clustered individuals into trajectories through group-based modeling. Thereafter, we assessed the prospective association of lipid trajectories with ASCVD and mortality. Male sex, greater body mass index, and smoking correlated with higher TC, LDL-C, triglycerides, non-HDL-C, and lower HDL-C concentrations. We identified 5 TC, HDL-C, and LDL-C trajectories, and 4 triglycerides and non-HDL-C trajectories. Upon follow-up (median 8.2 years; 199 ASCVD events; 256 deaths), elevated TC (>240 mg/dL), LDL-C (>155 mg/dL), or non-HDL-C (>180 mg/dL) concentrations conferred >2.25-fold ASCVD and mortality risk compared with concentrations <165 mg/dL, <90 mg/dL, and <115 mg/dL, respectively ([TC hazard ratio (HR)ASCVD=4.17, 95% CI 1.94–8.99; TC HRdeath=2.47, 95% CI 1.28–4.76] [LDL-C HRASCVD=5.09, 95% CI 1.54–16.85; LDL-C HRdeath=4.04, 95% CI 1.84–8.89] [non-HDL-C HRASCVD=4.60, 95% CI 1.98–10.70; LDL-C HRdeath=3.74, 95% CI 2.03–6.88]). Consistent HDL-C concentrations <40 mg/dL were associated with greater ASCVD and mortality risk than concentrations >70 mg/dL (HRASCVD=3.81, 95% CI 2.04–7.15; HRdeath=2.88, 95% CI 1.70–4.89). Triglycerides trajectories were unassociated with outcomes. Conclusions: Using a longitudinal modeling technique, we demonstrated that unfavorable lipid trajectories over 35 years confer higher ASCVD and mortality risk later in life.

AB - Background: Elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides, and non-high-density lipoprotein cholesterol (non-HDL-C) and low high-density lipoprotein cholesterol (HDL-C) concentrations correlate with atherosclerotic cardiovascular disease (ASCVD) and mortality. Therefore, understanding how lipid trajectories throughout adulthood impact ASCVD and mortality risk is essential. Methods and Results: We investigated 3875 Framingham Offspring participants (54% women, mean age 48 years) attending ≥1 examination between 1979 and 2014. We evaluated longitudinal correlates of each lipid subtype using mixed-effects models. Next, we clustered individuals into trajectories through group-based modeling. Thereafter, we assessed the prospective association of lipid trajectories with ASCVD and mortality. Male sex, greater body mass index, and smoking correlated with higher TC, LDL-C, triglycerides, non-HDL-C, and lower HDL-C concentrations. We identified 5 TC, HDL-C, and LDL-C trajectories, and 4 triglycerides and non-HDL-C trajectories. Upon follow-up (median 8.2 years; 199 ASCVD events; 256 deaths), elevated TC (>240 mg/dL), LDL-C (>155 mg/dL), or non-HDL-C (>180 mg/dL) concentrations conferred >2.25-fold ASCVD and mortality risk compared with concentrations <165 mg/dL, <90 mg/dL, and <115 mg/dL, respectively ([TC hazard ratio (HR)ASCVD=4.17, 95% CI 1.94–8.99; TC HRdeath=2.47, 95% CI 1.28–4.76] [LDL-C HRASCVD=5.09, 95% CI 1.54–16.85; LDL-C HRdeath=4.04, 95% CI 1.84–8.89] [non-HDL-C HRASCVD=4.60, 95% CI 1.98–10.70; LDL-C HRdeath=3.74, 95% CI 2.03–6.88]). Consistent HDL-C concentrations <40 mg/dL were associated with greater ASCVD and mortality risk than concentrations >70 mg/dL (HRASCVD=3.81, 95% CI 2.04–7.15; HRdeath=2.88, 95% CI 1.70–4.89). Triglycerides trajectories were unassociated with outcomes. Conclusions: Using a longitudinal modeling technique, we demonstrated that unfavorable lipid trajectories over 35 years confer higher ASCVD and mortality risk later in life.

KW - cardiovascular disease

KW - life-course

KW - lipids

KW - longitudinal

KW - trajectories

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U2 - 10.1161/JAHA.118.011433

DO - 10.1161/JAHA.118.011433

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M1 - e011433

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Trajectories of Blood Lipid Concentrations Over the Adult Life Course and Risk of Cardiovascular Disease and All-Cause Mortality: Observations From the Framingham Study Over 35 Years

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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