Mohsen Mazidi1, Dimitri P Mikhailidis2, Maciej Banach3. 1. Department of Biology and Biological Engineering, Food and Nutrition Science, Chalmers University of Technology, SE-41296 Gothenburg, Sweden. 2. Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, UK. 3. Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland. Electronic address: maciejbanach77@gmail.com.
Abstract
BACKGROUND: The health outcomes associated with extremely low or high plasma concentrations of high-density lipoprotein cholesterol (HDL-C) are not well documented mainly because of the small numbers of participants with such values included in the clinical trials. OBJECTIVE: We prospectively investigated the association between extremely low and high HDL-C with: 1) the risk of overall, coronary heart disease (CHD), cerebrovascular and cancer mortality, and, 2) their link with inflammatory factors. METHODS: Analysis was based on subjects ≥18 years old from the National Health and Nutrition Examination Surveys (NHANES). We categorized HDL-C levels as follows: [low HDL-C group ≤30 (extremely low), 30-40 (low), and ≥40 (reference)] [high HDL-C group = 40-80 (reference), 80-100 (high) and ≥100 mg/dl (extremely high). Cox proportional hazard regression models and analysis of covariance accounted for survey design, masked variance and sample weights. RESULTS: After adjustment for age, race and sex, we found that the very low HDL-C category (<30 mg/dl) had a greater risk of total mortality (risk ratio [RR]: 3.00, 95%CI: 2.20-4.09). RR for CHD and stroke mortality was 2.00 and 2.53, respectively; there was no link between cancer and level of HDL-C (p = 0.235). The association between total mortality, CHD and stroke with the level of HDL-C attenuated but remained significant even after adjustment for demographics, dietary, cardiovascular risk factors and treatment for dyslipidemia (all p < 0.001). After adjustments, subjects with extremely high HDL-C levels had a higher risk of mortalities (all p < 0.001). Mexican-American ethnicity, subjects in the low level of HDL-C (30-40 mg/dl) category had higher risk of mortalities than those with a very low level (all p < 0.001). Concentration of C-reactive protein, fibrinogen and white blood count significantly decreased as the level of the HDL-C increased; these findings were robust after adjustment for demographics, dietary, cardiovascular risk factors and treatment for dyslipidemia (all p < 0.001); further subjects with extremely high HDL-C levels have a greater levels of inflammatory factors (all p < 0.001). CONCLUSIONS: Both extremely low and high HDL-C levels were associated with greater risk of mortalities (total, CHD and stroke) and higher level of inflammatory factors, while there was no link between level of HDL-C and risk of cancer. Moreover, we found evidence of an HDL-C paradox in Mexican-American ethnicity participants.
BACKGROUND: The health outcomes associated with extremely low or high plasma concentrations of high-density lipoprotein cholesterol (HDL-C) are not well documented mainly because of the small numbers of participants with such values included in the clinical trials. OBJECTIVE: We prospectively investigated the association between extremely low and high HDL-C with: 1) the risk of overall, coronary heart disease (CHD), cerebrovascular and cancer mortality, and, 2) their link with inflammatory factors. METHODS: Analysis was based on subjects ≥18 years old from the National Health and Nutrition Examination Surveys (NHANES). We categorized HDL-C levels as follows: [low HDL-C group ≤30 (extremely low), 30-40 (low), and ≥40 (reference)] [high HDL-C group = 40-80 (reference), 80-100 (high) and ≥100 mg/dl (extremely high). Cox proportional hazard regression models and analysis of covariance accounted for survey design, masked variance and sample weights. RESULTS: After adjustment for age, race and sex, we found that the very low HDL-C category (<30 mg/dl) had a greater risk of total mortality (risk ratio [RR]: 3.00, 95%CI: 2.20-4.09). RR for CHD and stroke mortality was 2.00 and 2.53, respectively; there was no link between cancer and level of HDL-C (p = 0.235). The association between total mortality, CHD and stroke with the level of HDL-C attenuated but remained significant even after adjustment for demographics, dietary, cardiovascular risk factors and treatment for dyslipidemia (all p < 0.001). After adjustments, subjects with extremely high HDL-C levels had a higher risk of mortalities (all p < 0.001). Mexican-American ethnicity, subjects in the low level of HDL-C (30-40 mg/dl) category had higher risk of mortalities than those with a very low level (all p < 0.001). Concentration of C-reactive protein, fibrinogen and white blood count significantly decreased as the level of the HDL-C increased; these findings were robust after adjustment for demographics, dietary, cardiovascular risk factors and treatment for dyslipidemia (all p < 0.001); further subjects with extremely high HDL-C levels have a greater levels of inflammatory factors (all p < 0.001). CONCLUSIONS: Both extremely low and high HDL-C levels were associated with greater risk of mortalities (total, CHD and stroke) and higher level of inflammatory factors, while there was no link between level of HDL-C and risk of cancer. Moreover, we found evidence of an HDL-C paradox in Mexican-American ethnicity participants.
Authors: Mohsen Mazidi; Niki Katsiki; Dimitri P Mikhailidis; Dina Radenkovic; Daniel Pella; Maciej Banach Journal: J Clin Med Date: 2020-01-08 Impact factor: 4.241