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Direct Versus Calculated LDL Cholesterol and C-Reactive Protein in Cardiovascular Disease Risk Assessment in the
Hiroaki Ikezaki1,2, Virginia A Fisher3,4, Elise Lim3,4
1Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University and Tufts University School of Medicine, Boston, MA.
Insights
Direct LDL-C and hsCRP measurements offer modest but significant insights into cardiovascular disease (CVD) risk beyond standard factors. These biomarkers improve CVD risk prediction in the Framingham Offspring Study population.
Area of Science:
- Cardiovascular Disease Research
- Biomarker Analysis
- Epidemiology
Background:
- Elevated low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) are established cardiovascular disease (CVD) risk factors.
- The study investigated the predictive value of direct LDL-C and hsCRP compared to traditional risk factors.
Purpose of the Study:
- To assess the incremental value of direct LDL-C and hsCRP measurements in predicting cardiovascular disease (CVD) events.
- To compare the predictive performance of direct LDL-C and hsCRP against standard CVD risk factors and calculated LDL-C.
Main Methods:
- Analysis of plasma samples from 3147 participants in the Framingham Offspring Study, free of CVD at baseline.
- Measurement of direct LDL-C (Denka Seiken and Kyowa Medex), hsCRP (Dade Behring), and calculated LDL-C (Friedewald and Martin methods).
- Cox regression analysis and net reclassification index used to evaluate risk prediction over a median follow-up of 16.0 years.
Main Results:
- Univariate analysis identified standard risk factors and non-HDL-C, direct LDL-C, calculated LDL-C, TG, and hsCRP as significant predictors of CVD.
- Multivariate analysis revealed that only Denka Seiken direct LDL-C and Dade Behring hsCRP remained significant predictors.
- These biomarkers modestly improved the net risk reclassification index for hard CVD endpoints.
Conclusions:
- Direct LDL-C (Denka Seiken) and hsCRP (Dade Behring) measurements provide significant, albeit modest, additional information for CVD risk assessment.
- These biomarkers offer enhanced predictive value compared to standard risk factors and calculated LDL-C, particularly for hard CVD endpoints.
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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