Atherogenic Dyslipidemia: Cardiovascular Risk and Dietary Intervention

Atherogenic dyslipidemia comprises a triad of increased blood concentrations of small, dense low-density lipoprotein (LDL) particles, decreased high-density lipoprotein (HDL) particles, and increased triglycerides. A typical feature of obesity, the metabolic syndrome, insulin resistance, and type 2 diabetes mellitus, atherogenic dyslipidemia has emerged as an important risk factor for myocardial infarction and cardiovascular disease. A number of genes have now been linked to this pattern of lipoprotein changes. Low-carbohydrate diets appear to have beneficial lipoprotein effects in individuals with atherogenic dyslipidemia, compared to high-carbohydrate diets, whereas the content of total fat or saturated fat in the diet appears to have little effect. Achieving a better understanding of the genetic and dietary influences underlying atherogenic dyslipidemia may provide clues to improved interventions to reduce the risk of cardiovascular disease in high-risk individuals

Two-fluid modeling of cratering in a particle bed by a subsonic turbulent jet

The Two-Fluid Method is capable of modeling large-scale (i.e., lab scale or larger) multiphase (particle-fluid) flows by treating both the fluid and particle phase as interpenetrating continua and solving mass and momentum balances for each phase. To solve for the flow of the solids phase the momentum balance requires constitutive relations in the form of normal and shear stresses – i.e., pressures and viscosities. However, the stresses that account for frictional contacts in dense particle systems, and are relevant to this work, are empirically based. A study of the effects of adjusting the frictional model formulation (the empirical parameters of the model), by changing the overall frictional stress magnitude and the relative magnitude of the frictional viscosity to the frictional pressure, on the behavior of the bed is presented here. It was found that the magnitude of the frictional viscosity relative to the frictional pressure affects the crater growth prediction almost as much as the magnitude of the overall frictional stress. Additionally, a frictional model formulation is validated for sand particles, and predictions are compared with existing experimental data for the crater formation of a sand bed under a vertical, impinging jet of gas (Metzger et al. J Areo Eng (2008) v22, p24–32). In the low jet velocity regime (subsonic, turbulent jet), the model predicts the salient features previously measured for the growth rate of the crater of time, the profile of the crater, and the response of the crater to turning the jet off. In the high jet velocity regime (compressible, near sonic jet flow) the prediction agrees qualitatively with prior experimental observations

Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies

BACKGROUND: Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality. METHODS: We assessed the -1131T>C (rs662799) promoter polymorphism of the apolipoprotein A5 (APOA5) gene in relation to triglyceride concentration, several other risk factors, and risk of coronary heart disease. We compared disease risk for genetically-raised triglyceride concentration (20,842 patients with coronary heart disease, 35,206 controls) with that recorded for equivalent differences in circulating triglyceride concentration in prospective studies (302 430 participants with no history of cardiovascular disease; 12,785 incident cases of coronary heart disease during 2.79 million person-years at risk). We analysed -1131T>C in 1795 people without a history of cardiovascular disease who had information about lipoprotein concentration and diameter obtained by nuclear magnetic resonance spectroscopy. FINDINGS: The minor allele frequency of -1131T>C was 8% (95% CI 7-9). -1131T>C was not significantly associated with several non-lipid risk factors or LDL cholesterol, and it was modestly associated with lower HDL cholesterol (mean difference per C allele 3.5% [95% CI 2.6-4.6]; 0.053 mmol/L [0.039-0.068]), lower apolipoprotein AI (1.3% [0.3-2.3]; 0.023 g/L [0.005-0.041]), and higher apolipoprotein B (3.2% [1.3-5.1]; 0.027 g/L [0.011-0.043]). By contrast, for every C allele inherited, mean triglyceride concentration was 16.0% (95% CI 12.9-18.7), or 0.25 mmol/L (0.20-0.29), higher (p=4.4x10(-24)). The odds ratio for coronary heart disease was 1.18 (95% CI 1.11-1.26; p=2.6x10(-7)) per C allele, which was concordant with the hazard ratio of 1.10 (95% CI 1.08-1.12) per 16% higher triglyceride concentration recorded in prospective studies. -1131T>C was significantly associated with higher VLDL particle concentration (mean difference per C allele 12.2 nmol/L [95% CI 7.7-16.7]; p=9.3x10(-8)) and smaller HDL particle size (0.14 nm [0.08-0.20]; p=7.0x10(-5)), factors that could mediate the effects of triglyceride. INTERPRETATION: These data are consistent with a causal association between triglyceride-mediated pathways and coronary heart disease

Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies.

BACKGROUND: Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality. METHODS: We assessed the -1131T>C (rs662799) promoter polymorphism of the apolipoprotein A5 (APOA5) gene in relation to triglyceride concentration, several other risk factors, and risk of coronary heart disease. We compared disease risk for genetically-raised triglyceride concentration (20,842 patients with coronary heart disease, 35,206 controls) with that recorded for equivalent differences in circulating triglyceride concentration in prospective studies (302 430 participants with no history of cardiovascular disease; 12,785 incident cases of coronary heart disease during 2.79 million person-years at risk). We analysed -1131T>C in 1795 people without a history of cardiovascular disease who had information about lipoprotein concentration and diameter obtained by nuclear magnetic resonance spectroscopy. FINDINGS: The minor allele frequency of -1131T>C was 8% (95% CI 7-9). -1131T>C was not significantly associated with several non-lipid risk factors or LDL cholesterol, and it was modestly associated with lower HDL cholesterol (mean difference per C allele 3.5% [95% CI 2.6-4.6]; 0.053 mmol/L [0.039-0.068]), lower apolipoprotein AI (1.3% [0.3-2.3]; 0.023 g/L [0.005-0.041]), and higher apolipoprotein B (3.2% [1.3-5.1]; 0.027 g/L [0.011-0.043]). By contrast, for every C allele inherited, mean triglyceride concentration was 16.0% (95% CI 12.9-18.7), or 0.25 mmol/L (0.20-0.29), higher (p=4.4x10(-24)). The odds ratio for coronary heart disease was 1.18 (95% CI 1.11-1.26; p=2.6x10(-7)) per C allele, which was concordant with the hazard ratio of 1.10 (95% CI 1.08-1.12) per 16% higher triglyceride concentration recorded in prospective studies. -1131T>C was significantly associated with higher VLDL particle concentration (mean difference per C allele 12.2 nmol/L [95% CI 7.7-16.7]; p=9.3x10(-8)) and smaller HDL particle size (0.14 nm [0.08-0.20]; p=7.0x10(-5)), factors that could mediate the effects of triglyceride. INTERPRETATION: These data are consistent with a causal association between triglyceride-mediated pathways and coronary heart disease