scholarly journals The Potential of ANGPTL8 Antagonism to Simultaneously Reduce Triglyceride and Increase HDL-Cholesterol Plasma Levels

2021 ◽  
Vol 8 ◽  
Author(s):  
Ren Zhang
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Complex Formation ◽  
High Density Lipoprotein ◽  
Lipoprotein Lipase ◽  
High Density Lipoprotein Cholesterol ◽  
Plasma Levels ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Endothelial Lipase

Elevated triglyceride (TG) and reduced high-density lipoprotein-cholesterol (HDL-C) plasma levels are risk factors for atherosclerosis and cardiovascular disease. Therefore, a drug that simultaneously reduces TG and increases HDL-C plasma levels has the potential to prevent and treat these diseases. Angiopoietin-like 3 (ANGPTL3) regulates plasma TG and HDL-C levels by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL), respectively. ANGPTL3 inhibition of LPL requires complex formation with ANGPTL8, which is not required for its inhibition of EL. Therefore, the entire pool of plasma ANGPTL3 can be classified as ANGPTL8-associated ANGPTL3 and ANGPTL8-free ANGPTL3, where the former inhibits LPL and the latter inhibits EL. ANGPTL8 antibodies or inhibitors that block its interactions with ANGPTL3 can disrupt or preclude the ANGPTL3-8 complex formation, resulting in fewer ANGPTL3-8 complexes (reduced LPL inhibition), but more free ANGPTL3 (enhanced EL inhibition). Therefore, ANGPTL8 antagonism increases LPL activity while decreasing EL activity, thus leading to reduced plasma TG while simultaneously increasing HDL-C levels. In humans, carriers of ANGPTL8 truncating variants consistently have lower TG but higher HDL-C levels, supporting this hypothesis.

Abstract 10041: Increased Triglyceride Levels are Associated With Endothelial Dysfunction: FMD-Japan Registry

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Masato Kajikawa ◽  
Yukihito Higashi ◽  
Tatsuya Maruhashi ◽  
Yumiko Iwamoto ◽  
Akimichi Iwamoto ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Endothelial Function ◽  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Cross Sectional

Objective: In contrast to low-density lipoprotein cholesterol, and high density lipoprotein cholesterol, which are well-established independent risk factors for cardiovascular disease, the importance of triglycerides remains controversial. In this study, we evaluated the associations between triglycerides and endothelial function in the general population. Methods and Results: We enrolled 4,908 subjects (3842 men and 1066 women; mean age, 48±12 years) who were enrolled in FMD-Japan registry. And, we investigated cross-sectional associations between triglycerides and endothelial function by measurement of flow-mediated vasodilation (FMD). The triglycerides levels were negatively associated with FMD (r=-0.10, P<0.001). Subjects were divided into six groups on the basis of the triglycerides level. FMD was significantly decreased with an increase in the triglycerides level (≤63 mg/dL, 7.0±3.5%; 64 to 83 mg/dL, 6.3±3.5%; 84 to 105 mg/dL, 6.0±3.1%; 106 to 131 mg/dL, 5.8±3.2%; 132 to 179 mg/dL, 5.7±3.1%; ≥180 mg/dL, 5.5±3.0%; P for trend<0.001). After adjustment for age, sex, cardiovascular risk factors including high density lipoprotein cholesterol, high triglycerides level groups independently remained associated with low quartile of FMD using the triglycerides ≤63 mg/dL group as the reference (Table). Conclusions: These findings supported an independent association between triglycerides and cardiovascular disease.

scholarly journals The Association Between High-Density Lipoprotein Cholesterol Level and Some Cardiovascular Risk Factors in Patients Referring to the Heart Clinic of Birjand, Iran, During 2016 - 2017

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Bita Bijari ◽  
Toba Kazemi ◽  
Adib Movahedi ◽  
Mahmoud Zardast ◽  
Reyhane Hoshyar
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Risk ◽  
High Density Lipoprotein ◽  
Cardiovascular Risk Factors ◽  
Cholesterol Level ◽  
High Density Lipoprotein Cholesterol ◽  
Density Lipoprotein ◽  
Hdl Cholesterol

Background: High-density lipoprotein cholesterol (HDL-C) as an invaluable predictor is used to determine the risk of heart diseases and evaluate the effectiveness of lipid-lowering therapies. Objectives: In this study, we aimed to investigate the association between HDL cholesterol level and some cardiovascular risk factors in the patients referring to the Heart Clinic of Birjand, Iran, during 2016 - 2017. Methods: In this cross-sectional study, 410 patients referring to the Heart Clinic of Birjand, Iran, during 2016 - 2017 were selected. Then using a questionnaire, complete demographic and biochemical data were collected and statistically analyzed for assessing the effects of some lifestyle factors such as the diet and physical activity on the serum level of HDL. Finally, all the results were analyzed by SPSS software (version 15). Results: In our study, the majority of dyslipidemic people had low levels of HDL (58.8%). Most of the participants were in a poor health condition according to BMI and physical activity, in a moderate health status in terms of smoking and cholesterol and fasting blood glucose (FBS) levels, and finally in the ideal health group in terms of the diet and blood pressure. The HDL level was significantly associated with physical activity, FBS, BMI, and blood pressure (P < 0.05). Conclusions: Considering the association between persistent cardiovascular risk factors and HDL cholesterol level, encouraging people to adopt a healthy lifestyle can help prevent cardiac diseases.

Risk factors for cardiovascular diseases and development of prehypertension

2018 ◽  
pp. 37-43
Author(s):  
В.В. Шерстнев ◽  
М.А. Грудень ◽  
В.П. Карлина ◽  
В.М. Рыжов ◽  
А.В. Кузнецова ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Serum Levels ◽  
Left Ventricular ◽  
Optimal Blood Pressure

Цель - исследование взаимосвязи факторов риска сердечно-сосудистых заболеваний и развития предгипертонии. Методика. Проведен сравнительный и корреляционный анализы показателей модифицируемых и немодифицируемых факторов риска сердечно-сосудистых заболеваний у обследованных лиц в возрасте 30-60 лет с «оптимальным» артериальным давлением, (n = 63, АД <120/80 мм рт.ст.) и лиц с предгипертонией (n = 52, АД = 120-139/80-89 мм рт.ст.). Результаты. Показано, что лица с предгипертонией по сравнению с группой лиц, имеющих «оптимальное» артериальное давление характеризуются статистически значимо повышенным содержанием холестерина и холестерина липопротеидов низкой плотности, интеллектуальным характером трудовой деятельности, а также значимыми сочетаниями факторов риска: повышенный уровень холестерина липопротеидов низкой плотности с интеллектуальным характером трудовой деятельности; повышенное содержание креатинина с уровнем триглициридов; наследственная отягощенность по заболеваниям почек и интеллектуальным характером трудовой деятельности; наследственная отягощенность по сахарному диабету и гипертрофия левого желудочка сердца. У лиц с предгипертонией документированы перестройки структуры взаимосвязи (количество, направленность и сила корреляций) между показателями факторов риска в сравнении с лицами, имеющими «оптимальное» артериальное давление. Заключение. Выявленные особенности взаимосвязей факторов риска сердечно-сосудистых заболеваний при предгипертонии рассматриваются как проявление начальной стадии дизрегуляционной патологии и нарушения регуляции физиологических систем поддержания оптимального уровня артериального давления. The aim of the study was to investigate the relationship between risk factors for cardiovascular disease and development of prehypertension. Methods. Comparative and correlation analyses of modifiable and non-modifiable risk factors for cardiovascular disease were performed in subjects aged 30-60 with «optimal» blood pressure (n = 63, BP <120/80 mm Hg) and prehypertension (n = 52, BP = 120-139 / 80-89 mm Hg). Results. The group with prehypertension compared with the «optimal» blood pressure group had significantly increased serum levels of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, sedentary/intellectual type of occupation, and significant combinations of risk factors. The risk factor combinations included an increased level of LDL cholesterol and a sedentary/intellectual occupation; increased serum levels of creatinine and triglycerides; hereditary burden of kidney disease and a sedentary/intellectual occupation; hereditary burden of diabetes mellitus and cardiac left ventricular hypotrophy. In subjects with prehypertension compared to subjects with «optimal» blood pressure, changes in correlations (correlation number, direction, and strength) between parameters of risk factors were documented. Conclusion. The features of interrelationships between risk factors for cardiovascular disease observed in prehypertension are considered a manifestation of early dysregulation pathology and disordered regulation of physiological systems, which maintain optimal blood pressure.

scholarly journals High-intensity activity is more strongly associated with metabolic health in children compared to sedentary time: a cross-sectional study of the I.Family cohort

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Jonatan Fridolfsson ◽  
Christoph Buck ◽  
Monica Hunsberger ◽  
Joanna Baran ◽  
Fabio Lauria ◽  
...  
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Insulin Resistance ◽  
Blood Pressure ◽  
Body Mass Index ◽  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Density Lipoprotein ◽  
Cross Sectional ◽  
Intensity Physical Activity

Abstract Background Physical activity (PA) during childhood is important for preventing future metabolic syndrome (MetS). To examine the relationship between PA and MetS in more detail, accurate measures of PA are needed. Previous studies have only utilized a small part of the information available from accelerometer measured PA. This study investigated the association between measured PA and MetS in children with a new method for data processing and analyses that enable more detailed interpretation of PA intensity level. Methods The association between PA pattern and risk factors related to MetS was investigated in a cross- sectional sample of children (n = 2592, mean age 10.9 years, 49.4% male) participating in the European multicenter I. Family study. The risk factors examined include body mass index, blood pressure, high-density lipoprotein cholesterol, insulin resistance and a combined risk factor score (MetS score). PA was measured by triaxial accelerometers and raw data was processed using the 10 Hz frequency extended method (FEM). The PA output was divided into an intensity spectrum and the association with MetS risk factors was analyzed by partial least squares regression. Results PA patterns differed between the European countries investigated, with Swedish children being most active and Italian children least active. Moderate intensity physical activity was associated with lower insulin resistance (R2 = 2.8%), while vigorous intensity physical activity was associated with lower body mass index (R2 = 3.6%), MetS score (R2 = 3.1%) and higher high-density lipoprotein cholesterol (R2 = 2.3%). PA of all intensities was associated with lower systolic- and diastolic blood pressure, although the associations were weaker than for the other risk factors (R2 = 1.5% and R2 = 1.4%). However, the multivariate analysis implies that the entire PA pattern must be considered. The main difference in PA was observed between normal weight and overweight children. Conclusions The present study suggests a greater importance of more PA corresponding to an intensity of at least brisk walking with inclusion of high-intense exercise, rather than a limited time spent sedentary, in the association to metabolic health in children. The methods of data processing and statistical analysis enabled accurate analysis and interpretation of the health benefits of high intensity PA that have not been shown previously.

Sign in / Sign up

Export Citation Format

Share Document