Hiroaki Ikezaki1,2, Virginia A Fisher3,4, Elise Lim3,4, Masumi Ai1,5, Ching-Ti Liu3,4, L Adrienne Cupples3,4, Katsuyuki Nakajima6,7, Bela F Asztalos1, Norihiro Furusyo2, Ernst J Schaefer8,9. 1. Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University and Tufts University School of Medicine, Boston, MA. 2. Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan. 3. Department of Biostatistics, Boston University School of Public Health, Boston, MA. 4. the Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA. 5. Department of Insured Medical Care Management, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. 6. Department of Biochemistry, Gunma University, Maebashi, Japan. 7. Department of Clinical Chemistry, Gunma University, Maebashi, Japan. 8. Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University and Tufts University School of Medicine, Boston, MA; ernst.schaefer@tufts.edu. 9. Clinical Affairs Department, Boston Heart Diagnostics, Framingham, MA.
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.
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.
Authors: José Castela Forte; Pytrik Folkertsma; Rahul Gannamani; Sridhar Kumaraswamy; Sarah Mount; Tom J de Koning; Sipko van Dam; Bruce H R Wolffenbuttel Journal: J Pers Med Date: 2021-12-07