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

Milk and dairy products: good or bad for human health? An assessment of the totality of scientific evidence

Background: There is scepticism about health effects of dairy products in the public, which is reflected in an increasing intake of plant-based drinks, for example, from soy, rice, almond, or oat. Objective: This review aimed to assess the scientific evidence mainly from meta-analyses of observational studies and randomised controlled trials, on dairy intake and risk of obesity, type 2 diabetes, cardiovascular disease, osteoporosis, cancer, and all-cause mortality. Results: The most recent evidence suggested that intake of milk and dairy products was associated with reduced risk of childhood obesity. In adults, intake of dairy products was shown to improve body composition and facilitate weight loss during energy restriction. In addition, intake of milk and dairy products was associated with a neutral or reduced risk of type 2 diabetes and a reduced risk of cardiovascular disease, particularly stroke. Furthermore, the evidence suggested a beneficial effect of milk and dairy intake on bone mineral density but no association with risk of bone fracture. Among cancers, milk and dairy intake was inversely associated with colorectal cancer, bladder cancer, gastric cancer, and breast cancer, and not associated with risk of pancreatic cancer, ovarian cancer, or lung cancer,while the evidence for prostate cancer risk was inconsistent.Finally,consumption of milk and dairy products was not associated with all-cause mortality. Calcium-fortified plant-based drinks have been included as an alternative to dairy products in the nutrition recommendations in several countries. However, nutritionally, cow’s milk and plant-based drinks are completely different foods,and an evidence-based conclusion on the health value of the plant-based drinks requires more studies in humans. Conclusion: The totality of available scientific evidence supports that intake of milk and dairy products contribute to meet nutrient recommendations, and may protect against the most prevalent chronic diseases, whereas very few adverse effects have been reported

Gemfibrozil reduces small low-density lipoprotein more in normolipemic subjects classified as low-density lipoprotein pattern B compared with pattern A.

We tested the hypothesis that gemfibrozil has a differential effect on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclass distributions and postprandial lipemia that is different in subjects classified as having LDL subclass pattern A or LDL pattern B who do not have a classic lipid disorder. Forty-three normolipemic subjects were randomized to gemfibrozil (1,200 mg/day) or placebo for 12 weeks. Lipids and lipoproteins were determined by enzymatic methods. The mass concentrations of lipoproteins in plasma were determined by analytic ultracentrifugation and included the Sf intervals: 20 to 400 (very LDL), 12 to 20 (intermediate-density lipoprotein), 0 to 12 (LDL), and HDL2 mass (F1.20 3.5 to 9.0) and HDL 3 mass (F1.20 0 to 3.5). Postprandial measurements of triglycerides and lipoprotein(a) were taken after the patients consumed a 500 kcal/M2 test meal. Treatment with gemfibrozil, compared with placebo, significantly reduced fasting plasma triglycerides (difference from placebo ± SE; -50.2 ± 20.6 mg/dl, p = 0.02), total cholesterol (-16.4 ± 7.5 mg/dl, p = 0.04), apolipoprotein B (-16.1 ± 5.5 mg/dl, p = 0.006), very LDL mass of Sf 20 to 400 (-50.8 ± 24.1 mg/dl, p = 0.02), Sf 20 to 60 (-17.5 ± 8.5 mg/dl, p = 0.05), S f 60 to 100 (-16.2 ± 8.1 mg/dl, p = 0.05), and increased peak SF (0.48 ± 0.27 Svedberg, p = 0.08). Gemfibrozil reduced the postprandial triglyceride level significantly at 3 (p = 0.04) and 4 (p = 0.05) hours after the test meal. A significantly different subclass response to gemfibrozil was observed in those with LDL pattern A versus B. Those with LDL pattern B had a significantly greater reduction in the small LDL mass S f 0 to 7 (p = 0.04), specifically regions Sf 0 to 3 (p = 0.009) and Sf 3 to 5 (p = 0.009). In conclusion, normolipemic subjects with either predominantly dense or buoyant LDL respond differently to gemfibrozil as determined by the changes in LDL subclass distribution. Thus, treatment with gemfibrozil may have additional antiatherogenic effects in those with LDL pattern B by decreasing small dense LDL that is not apparent in those with pattern

Effects on lipoprotein subclasses of combined expression of human hepatic lipase and human apoB in transgenic rabbits

Objective—The effects of combined expression of human hepatic lipase (HL) and human apolipoprotein B (apoB) on low-density lipoprotein (LDL) subclasses were examined in rabbits, a species naturally deficient in HL activity. Methods and Results—In apoB-transgenic rabbit plasma, 80% of the protein was found in the 1.006- to 1.050-g/mL fraction. Gradient gel electrophoresis (GGE) of this fraction revealed two distinct species, designated large and small LDL. A denser fraction (d 1.050 to 1.063 g/mL) contained small LDL as well as another discrete LDL subspecies, designated very small LDL. Expression of HL resulted in reductions in protein concentrations in the 1.006- to 1.050-g/mL density-gradient subfractions containing large (6.5 4.1 versus 32.6 12.0 mg/dL, P 0.005) and small LDL (59.6 17.4 versus 204.3 50.3 mg/dL, P 0.002). A concomitant small but not significant increase in protein concentration in the denser LDL fraction (48.0 28.2 versus 44.6 18.2 mg/dL) was due primarily to an increase in very small LDL (25.9 3.1 versus 9.6 5.4% of total LDL GGE densitometric area, P 0.002). Conclusion—These findings support a direct role for HL in regulating total plasma LDL concentrations as well as in the production of smaller, denser LDL from larger, more buoyant precursors

Plasma clearance of human low-density lipoprotein in human apolipoprotein B trangenic mice is related to particle diameter

To test for intrinsic differences in metabolic properties of low-density lipoprotein (LDL) as a function of particle size, we examined the kinetic behavior of 6 human LDL fractions ranging in size from 251 to 265 A injected intravenously into human apolipoprotein (apo) B transgenic mice. A multicompartmental model was formulated and fitted to the data by standard nonlinear regression using the Simulation, Analysis and Modeling (SAAM II) program. Smaller sized LDL particles (251 to 257 Å) demonstrated a significantly slower fractional catabolic rate (FCR) (0.050 ± 0.045 h-1) compared with particles of larger size (262 to 265 Å) (0.134 ± -0.015 h-1, P < .03), and there was a significant correlation between FCR and the peak LDL diameter of the injected fractions (R2 = .71, P < .034). The sum of the equilibration parameters, k(2,1) and k(1,2), for smaller LDL (0.255 h-1 and 0.105 h -1, respectively) was significantly smaller than that for larger LDL (0.277 h-1 and 0.248 h-1, respectively; P < .01), indicative of slower intravascular-extravascular exchange for smaller LDL. Therefore in this mouse model, smaller LDL particles are cleared more slowly from plasma than larger LDL and are exchanged more slowly with the extravascular space. This might be due to compositional or structural features of smaller LDL that lead to retarded clearance