Direct versus calculated LDL cholesterol and C-reactive protein in cardiovascular disease risk assessment in the Framingham Offspring Study

Hiroaki Ikezaki, Virginia A. Fisher, Elise Lim, Masumi Ai, Ching Ti Liu, L. Adrienne Cupples, Katsuyuki Nakajima, Bela F. Asztalos, Norihiro Furusyo, Ernst J. Schaefer

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Increases in circulating LDL cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) concentrations are significant risk factors for cardiovascular disease (CVD). We assessed direct LDL-C and hsCRP concentrations compared to standard risk factors in the Framingham Offspring Study. METHODS: We used stored frozen plasma samples (-80 °C) obtained after an overnight fast from 3147 male and female participants (mean age, 58 years) free of CVD at cycle 6 of the Framingham Offspring Study. Overall, 677 participants (21.5%) had a CVD end point over a median of 16.0 years of follow-up. Total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C), direct LDL-C (Denka Seiken and Kyowa Medex methods), and hsCRP (Dade Behring method) concentrations were measured by automated analysis. LDL-C was also calculated by both the Friedewald and Martin methods. RESULTS: Considering all CVD outcomes on univariate analysis, significant factors included standard risk factors (age, hypertension, HDL-C, hypertension treatment, sex, diabetes, smoking, and TC concentration) and nonstandard risk factors (non-HDL-C, direct LDL-C and calculated LDL-C, TG, and hsCRP concentrations). On multivariate analysis, only the Denka Seiken direct LDL-C and the Dade Behring hsCRP were still significant on Cox regression analysis and improved the net risk reclassification index, but with modest effects. Discordance analysis confirmed the benefit of the Denka Seiken direct LDL-C method for prospective hard CVD endpoints (new-onset myocardial infarction, stroke, and/or CVD death). CONCLUSIONS: Our data indicate that the Denka Seiken direct LDL-C and Dade Behring hsCRP measurements add significant, but modest, information about CVD risk, compared to standard risk factors and/or calculated LDL-C.

Original languageEnglish
Pages (from-to)1102-1114
Number of pages13
JournalClinical Chemistry
Volume65
Issue number9
DOIs
Publication statusPublished - Jan 1 2019

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C-Reactive Protein
Risk assessment
LDL Cholesterol
Cardiovascular Diseases
Cholesterol
HDL Cholesterol
Triglycerides
Hypertension
Factor analysis
Medical problems
Regression analysis
Statistical Factor Analysis
Multivariate Analysis
Smoking
Stroke
Myocardial Infarction
Regression Analysis
Plasmas

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Biochemistry, medical

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Direct versus calculated LDL cholesterol and C-reactive protein in cardiovascular disease risk assessment in the Framingham Offspring Study. / Ikezaki, Hiroaki; Fisher, Virginia A.; Lim, Elise; Ai, Masumi; Liu, Ching Ti; Adrienne Cupples, L.; Nakajima, Katsuyuki; Asztalos, Bela F.; Furusyo, Norihiro; Schaefer, Ernst J.

In: Clinical Chemistry, Vol. 65, No. 9, 01.01.2019, p. 1102-1114.

Research output: Contribution to journalArticle

Ikezaki, H, Fisher, VA, Lim, E, Ai, M, Liu, CT, Adrienne Cupples, L, Nakajima, K, Asztalos, BF, Furusyo, N & Schaefer, EJ 2019, 'Direct versus calculated LDL cholesterol and C-reactive protein in cardiovascular disease risk assessment in the Framingham Offspring Study', Clinical Chemistry, vol. 65, no. 9, pp. 1102-1114. https://doi.org/10.1373/clinchem.2019.304600
Ikezaki, Hiroaki ; Fisher, Virginia A. ; Lim, Elise ; Ai, Masumi ; Liu, Ching Ti ; Adrienne Cupples, L. ; Nakajima, Katsuyuki ; Asztalos, Bela F. ; Furusyo, Norihiro ; Schaefer, Ernst J. / Direct versus calculated LDL cholesterol and C-reactive protein in cardiovascular disease risk assessment in the Framingham Offspring Study. In: Clinical Chemistry. 2019 ; Vol. 65, No. 9. pp. 1102-1114.
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AU - Ikezaki, Hiroaki

AU - Fisher, Virginia A.

AU - Lim, Elise

AU - Ai, Masumi

AU - Liu, Ching Ti

AU - Adrienne Cupples, L.

AU - Nakajima, Katsuyuki

AU - Asztalos, Bela F.

AU - Furusyo, Norihiro

AU - Schaefer, Ernst J.

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N2 - BACKGROUND: Increases in circulating LDL cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) concentrations are significant risk factors for cardiovascular disease (CVD). We assessed direct LDL-C and hsCRP concentrations compared to standard risk factors in the Framingham Offspring Study. METHODS: We used stored frozen plasma samples (-80 °C) obtained after an overnight fast from 3147 male and female participants (mean age, 58 years) free of CVD at cycle 6 of the Framingham Offspring Study. Overall, 677 participants (21.5%) had a CVD end point over a median of 16.0 years of follow-up. Total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C), direct LDL-C (Denka Seiken and Kyowa Medex methods), and hsCRP (Dade Behring method) concentrations were measured by automated analysis. LDL-C was also calculated by both the Friedewald and Martin methods. RESULTS: Considering all CVD outcomes on univariate analysis, significant factors included standard risk factors (age, hypertension, HDL-C, hypertension treatment, sex, diabetes, smoking, and TC concentration) and nonstandard risk factors (non-HDL-C, direct LDL-C and calculated LDL-C, TG, and hsCRP concentrations). On multivariate analysis, only the Denka Seiken direct LDL-C and the Dade Behring hsCRP were still significant on Cox regression analysis and improved the net risk reclassification index, but with modest effects. Discordance analysis confirmed the benefit of the Denka Seiken direct LDL-C method for prospective hard CVD endpoints (new-onset myocardial infarction, stroke, and/or CVD death). CONCLUSIONS: Our data indicate that the Denka Seiken direct LDL-C and Dade Behring hsCRP measurements add significant, but modest, information about CVD risk, compared to standard risk factors and/or calculated LDL-C.

AB - BACKGROUND: Increases in circulating LDL cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) concentrations are significant risk factors for cardiovascular disease (CVD). We assessed direct LDL-C and hsCRP concentrations compared to standard risk factors in the Framingham Offspring Study. METHODS: We used stored frozen plasma samples (-80 °C) obtained after an overnight fast from 3147 male and female participants (mean age, 58 years) free of CVD at cycle 6 of the Framingham Offspring Study. Overall, 677 participants (21.5%) had a CVD end point over a median of 16.0 years of follow-up. Total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C), direct LDL-C (Denka Seiken and Kyowa Medex methods), and hsCRP (Dade Behring method) concentrations were measured by automated analysis. LDL-C was also calculated by both the Friedewald and Martin methods. RESULTS: Considering all CVD outcomes on univariate analysis, significant factors included standard risk factors (age, hypertension, HDL-C, hypertension treatment, sex, diabetes, smoking, and TC concentration) and nonstandard risk factors (non-HDL-C, direct LDL-C and calculated LDL-C, TG, and hsCRP concentrations). On multivariate analysis, only the Denka Seiken direct LDL-C and the Dade Behring hsCRP were still significant on Cox regression analysis and improved the net risk reclassification index, but with modest effects. Discordance analysis confirmed the benefit of the Denka Seiken direct LDL-C method for prospective hard CVD endpoints (new-onset myocardial infarction, stroke, and/or CVD death). CONCLUSIONS: Our data indicate that the Denka Seiken direct LDL-C and Dade Behring hsCRP measurements add significant, but modest, information about CVD risk, compared to standard risk factors and/or calculated LDL-C.

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