Atherogenic Small Low-density Lipoprotein Research Articles

Randomized nutrient bar supplementation improves exercise-associated changes in plasma metabolome in adolescents and adult family members at cardiometabolic risk.

Poor diets contribute to metabolic complications of obesity, insulin resistance and dyslipidemia. Metabolomic biomarkers may serve as early nutrition-sensitive health indicators. This family-based lifestyle change program compared metabolic outcomes in an intervention group (INT) that consumed 2 nutrient bars daily for 2-months and a control group (CONT). Overweight, predominantly minority and female adolescent (Teen)/parent adult caretaker (PAC) family units were recruited from a pediatric obesity clinic. CONT (8 Teen, 8 PAC) and INT (10 Teen, 10 PAC) groups randomized to nutrient bar supplementation attended weekly classes that included group nutrition counseling and supervised exercise. Pre-post physical and behavioral parameters, fasting traditional biomarkers, plasma sphingolipids and amino acid metabolites were measured. In the full cohort, a baseline sphingolipid ceramide principal component composite score correlated with adiponectin, triglycerides, triglyceride-rich very low density lipoproteins, and atherogenic small low density lipoprotein (LDL) sublasses. Inverse associations were seen between a sphingomyelin composite score and C-reactive protein, a dihydroceramide composite score and diastolic blood pressure, and the final principal component that included glutathionone with fasting insulin and the homeostatic model of insulin resistance. In CONT, plasma ceramides, sphinganine, sphingosine and amino acid metabolites increased, presumably due to increased physical activity. Nutrient bar supplementation (INT) blunted this rise and significantly decreased ureagenic, aromatic and gluconeogenic amino acid metabolites. Metabolomic changes were positively correlated with improvements in clinical biomarkers of dyslipidemia. Nutrient bar supplementation with increased physical activity in obese Teens and PAC elicits favorable metabolomic changes that correlate with improved dyslipidemia. The trial from which the analyses reported upon herein was part of a series of nutrient bar clinical trials registered at clinicaltrials.gov as NCT02239198.

Tobacco smoking, estrogen receptor α gene variation and small low density lipoprotein level

High levels of small low density lipoprotein (LDL) particles are a major risk factor for cardiovascular morbidity and mortality. Both estrogens and smoking, with known anti-estrogenic effects, alter the atherogenic lipid profile. We tested for a role of interaction between smoking and estrogen receptor alpha gene (ESR1) variation in association with plasma concentration of atherogenic small LDL particles and LDL particle size. We studied 1727 unrelated subjects, 854 women and 873 men, mean age 51 years (SD 10), from the population-based Framingham Heart Study. After covariate adjustment, women who smoked and had the common ESR1 c.454-397 TT genotype (in 30% of women, T was present on both chromosomes at position 397 prior to the start of exon 2) had >1.7-fold higher levels of small LDL particles than women with the alternative genotypes (P-value for smoking-genotype interaction was 0.001). Similar results were obtained for three other ESR1 variants including c.454-351A > G, in the same linkage disequilibrium block. A similar substantial gender-specific result was also evident with a fifth variant, in a separate linkage disequilibrium block, in exon 4 (P = 0.003). Women who smoked and had specific, common ESR1 genotypes had a substantially higher plasma concentration of atherogenic small LDL particles. Significant results revealed a dose-dependent effect of smoking and were evident in both pre- and postmenopausal women. The reported association has the potential to explain the risks associated with estrogen use in certain women and a recent report of association between an ESR1 haplotype comprised of c.454-397 T and c.454-351 A alleles with increased myocardial infarction and ischaemic heart disease, independent of the standard, established cardiovascular risk factors.

HDL-C and the diabetic patient: Target for therapeutic intervention?

A low level of high-density lipoprotein cholesterol (HDL-C) is a key feature of the metabolic syndrome and type 2 diabetes. HDL particles exert an anti-atherogenic effect, and low HDL-C levels are associated with increased cardiovascular disease risk. The profile of lipoprotein sub-classes may also be abnormal in patients with the metabolic syndrome or type 2 diabetes, with an excess of atherogenic small low-density lipoprotein (LDL) particles. Statins are first-line lipid-modifying drugs that, in addition to varying in their effects on LDL-C, differ in their effects on HDL-C. Rosuvastatin has been shown to be at least as effective at increasing HDL-C compared with atorvastatin, pravastatin or simvastatin. Selecting an agent that will increase HDL-C levels, as well as lowering LDL-C levels, may be particularly beneficial in the treatment of patients with the metabolic syndrome and type 2 diabetes.

Low-density lipoprotein particle size and coronary atherosclerosis in subjects belonging to hypertensive sibships

Dyslipidemia in hypertensive sibships may be characterized by atherogenic small low-density lipoprotein (LDL) particles. Whether LDL particle size is associated with the extent of coronary atherosclerosis in hypertensive sibships is unknown. Subjects (n = 792, mean age 62 years, 60% women) were ascertained through sibships containing at least two individuals with essential hypertension diagnosed before age 60 years. The LDL particle size was measured by polyacrylamide gel electrophoresis. Coronary artery calcium (CAC) was measured noninvasively by electron beam computed tomography, and CAC score was calculated using the method of Agatston et al. Sex-specific multiple regression models were used to assess independent predictors of LDL particle size and the association of LDL particle size with CAC. In all, 76% of women and 77% of men were hypertensive. In each sex, independent predictors of smaller LDL particle size were total cholesterol, triglycerides, and lower HDL cholesterol. In women, greater age was an additional predictor of smaller LDL particle size. After adjustment for age and statin use, LDL particle size was significantly associated with the amount of CAC in women but not in men. After further adjustment for HDL cholesterol, triglycerides, diabetes, smoking, and hypertension, LDL particle size was not independently associated with CAC in either sex. After adjustment for age and statin use, LDL particle size was found to be significantly related to CAC quantity in women but not in men belonging to hypertensive sibships. In women, LDL particle size may mediate some of the atherogenic effects of low-HDL cholesterol-high-triglyceride dyslipidemia, but does not appear to be independently associated with the extent of coronary atherosclerosis in either sex.