7 Matching Annotations
  1. Mar 2017
    1. Findings In a meta-regression analysis of 49 clinical trials with 312 175 participants, each 1-mmol/L (38.7-mg/dL) reduction in LDL-C level was associated with a relative risk (RR) of major vascular events of 0.77 (95% CI, 0.71-0.84; P < .001) for statins and 0.75 (95% CI, 0.66-0.86; P = .002) for established nonstatin interventions that act primarily via upregulation of LDL receptor expression.Meaning These data suggest statins and nonstatin therapies that act through upregulation of LDL receptor expression are associated with similar cardiovascular risk reduction per decrease in LDL-C. The clinical value of adding specific nonstatin interventions to lower LDL-C to background statin therapy should be confirmed in appropriately powered clinical trials.
    1. In addition, the vast majority of animal studies have shown that oral administration of PS reduces the progression atherosclerosis. However, it has been recently suggested that an increase in PS plasma concentrations may increase CV risk. Evidence to support this hypothesis come mainly from observations in sitosterolemic patients who hyperabsorb PS and cholesterol and display very high levels of PS, which may be associated with a premature atherosclerosis. Some epidemiological studies in non-sitosterolemic subjects have shown a positive correlation between PS plasma levels and coronary heart disease. However, these are observational studies and some of them present major methodological bias. In addition, recent studies with a larger number of subjects have indicated, either an absence or a negative relationship between PS and the incidence of CV disease.
    1. One way exercise can protect against atherosclerosis (and therefore heart disease) is by increasing shear stress on the arterial walls, which causes the endothelium to become less permeable (less accepting of oxidized LDL particles) and produce more nitric oxide (a potent inhibitor of LDL oxidation). You can think of exercise, then, not just as training for your muscles, but also for your arterial walls. It’s enough of an inflammatory stressor to induce an adaptive response. Of course, too much shear stress can be too inflammatory and might actually cause atherosclerosis to progress.
    1. The most effective approach has been minimizing fat stores located inside the abdominal cavity (visceral body fat) in addition to minimizing total body fat.[46] Visceral fat, which is more metabolically active than subcutaneous fat, has been found to produce many enzymatic signals, e.g. resistin, which increase insulin resistance and circulating VLDL particle concentrations, thus both increasing LDL particle concentrations and accelerating the development of diabetes mellitus.
    1. In summary, reducing dietary saturated fat is associated with an increase in LDL-receptor abundance of magnitude similar to the decrease in serum LDL-cholesterol. Thus, an important mechanism by which reductions in dietary saturated fatty acids decrease LDL-cholesterol in humans is through an increase in LDL-receptor number.
    1. Polyunsaturated fats protect against cardiovascular disease by providing more membrane fluidity than monounsaturated fats, but they are more vulnerable to lipid peroxidation (rancidity). The large scale KANWU study found that increasing monounsaturated fat and decreasing saturated fat intake could improve insulin sensitivity, but only when the overall fat intake of the diet was low.[1] However, some monounsaturated fatty acids (in the same way as saturated fats) may promote insulin resistance, whereas polyunsaturated fatty acids may be protective against insulin resistance.[2][3] Studies have shown that substituting dietary monounsaturated fat for saturated fat is associated with increased daily physical activity and resting energy expenditure. More physical activity was associated with a higher-oleic acid diet than one of a palmitic acid diet. From the study, it is shown that more monounsaturated fats lead to less anger and irritability.[4]
    1. In line with data in humans [8], feeding of dietary monounsaturated fat to nonhuman primates reduced LDL without lowering HDL, and in comparison to saturated and polyunsaturated fat, provided the lowest LDL to HDL ratio [9•]. On the other hand, replacement of some of the saturated fat with monounsaturated fat was associated with an even greater enrichment of LDL particles with cholesteryl oleate, a change in LDL particle composition that has been shown to confer atherogenicity [9•]. However, caution is needed in applying the results from animal experiments to humans.