Adjustment For Triglycerides Research Articles

Genome-wide scan for quantitative trait loci influencing LDL size and plasma triglyceride in familial hypertriglyceridemia

Small, dense LDLs and hypertriglyceridemia, two highly correlated and genetically influenced risk factors, are known to predict for risk of coronary heart disease. The objective of this study was to perform a whole-genome scan for linkage to LDL size and triglyceride (TG) levels in 26 kindreds with familial hypertriglyceridemia (FHTG). LDL size was estimated using gradient gel electrophoresis, and genotyping was performed for 355 autosomal markers with an average heterozygosity of 76% and an average spacing of 10.2 centimorgans (cMs). Using variance components linkage analysis, one possible linkage was found for LDL size [logarithm of odds (LOD) = 2.1] on chromosome 6, peak at 140 cM distal to marker F13A1 (closest marker D6S2436). With adjustment for TG and/or HDL cholesterol, the LOD scores were reduced, but remained in exactly the same location. For TG, LOD scores of 2.56 and 2.44 were observed at two locations on chromosome 15, with peaks at 29 and 61 cM distal to marker D15S822 (closest markers D15S643 and D15S211, respectively). These peaks were retained with adjustment for LDL size and/or HDL cholesterol. These findings, if confirmed, suggest that LDL particle size and plasma TG levels could be caused by two different genetic loci in FHTG.

Fasting and Postprandial Plasma Concentrations of Acylation‐Stimulation Protein (ASP) in Lean and Obese Pima Indians Compared to Caucasians

ASP stimulates the clearance of free fatty acids (FFA) from the circulation and the synthesis of triglycerides (TG) in adipose tissue. We tested whether fasting and post-prandial plasma ASP concentrations are increased in Pima Indians, a population with a very high prevalence of obesity, but a remarkably low prevalence of dyslipidemia. Plasma concentrations of ASP, TG, FFA, total cholesterol (CHOL), and insulin (INS) were measured in 15 Pima Indians (P) and 15 Caucasians (C) closely matched for age, sex, and body weight [7 lean and 8 obese subjects, body mass index (BMI) cut-off 30 kg/m2], before and for 4 hours after a standard mixed meal (20% of daily caloric requirements, 41% carbohydrate, 44% fat, 15% protein). Fasting ASP was positively related to percent body fat (dual energy X-ray absorptiometry; r=0.49, p<0.01) and to TG and FFA, independently of percent body fat (partial r = 0.42 and 0.46, respectively, both p<0.05). There were no differences in fasting TG, FFA, CHOL, INS, or ASP between lean C and lean P. In contrast, obese P had lower TG, lower CHOL, higher INS and, on average, 27% lower ASP compared to obese C. The ethnic difference in ASP remained after adjustment for TG, FFA, and percent body fat. ASP decreased in response to the meal in all four groups with no differences between groups. There was a significant inverse correlation between preprandial ASP and the change in FFA 60 minutes after the meal (r=-0.56, p<0.001). Pima Indians do not have higher plasma ASP concentrations than Caucasians. Whether other alterations in the ASP-pathway, such as increased sensitivity of adipocytes to ASP, contribute to the high prevalence of obesity and low prevalence of dyslipidemia in Pima Indians, remains to be elucidated.

Epidemiologic aspects of lipid abnormalities

Existing cholesterol guidelines aimed at preventing cardiovascular disease emphasize the role of total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol in lipid management decisions, with a subsidiary role for high-density lipoprotein (HDL) cholesterol in guiding treatment and little role for triglycerides. In this article, epidemiologic evidence is reviewed relating to the independent value of lipid factors in prediction of cardiovascular disease risk, including TC, LDL cholesterol, HDL cholesterol, very-low-density lipoprotein (VLDL) cholesterol and triglycerides, LDL particle size (“pattern B”), and the TC/HDL-cholesterol ratio. Several observations are highlighted. Triglycerides appear to be an independent risk factor in specific populations. Postprandial triglycerides may be superior to fasting triglycerides as a predictor of risk. LDL particle size does not have independent predictive value after adjustment for triglycerides. Particular emphasis is placed on the observation that the single most predictive lipid factor is the TC/HDL-cholesterol ratio, which implicitly incorporates information on both LDL and triglycerides in the numerator. This is the best predictor both of outcome and of treatment benefit, and its predictive value appears to be maintained into older age. It is concluded that increasing emphasis should be placed on the TC/HDL cholesterol ratio in epidemiologic analyses and in monitoring patients on therapy for dyslipidemia.

Serum concentrations of vitamins A and E in impaired glucose tolerance

Serum concentrations of vitamins A and E were measured in 32 subjects with impaired glucose tolerance (IGT) and 148 subjects with normal glucose tolerance using reversed-phase high-performance liquid chromatography. Fasting glucose, insulin and lipid concentrations were also measured. Serum vitamin A concentrations were higher in subjects with IGT 2.5 (1.1–3.4) vs. 2.1 (1.4–3.2) μmol/l [median (2.5–97.5 percentiles)] ( P=0.002), the difference remaining significant after adjustment for triglycerides ( P=0.028). There was a univariate association between vitamin A levels and insulin resistance ( r=0.164; P=0.02) and in multivariate logistic regression analysis the relative risk of subjects with high vitamin A concentrations having IGT was 3.8 ( P=0.002). There were no differences in serum vitamin E concentrations between the groups. These data suggest that higher vitamin A concentrations found in non-insulin-dependent diabetes pre-date the onset of diabetes. Further studies are required to confirm this finding and to investigate the possibility of a role for vitamin A in the aetiology of diabetes and IGT.

Segregation analysis for high density lipoprotein in the berkeley data

Transmission models for high density lipoprotein (HDL) were evaluated in the Berkeley data set through segregation analyses using S.A.G.E. These preliminary analyses indicate that among the models fitted, an additive model with non-Mendelian transmission probabilities provides a good fit for HDL, suggesting the possibility of a significant environmental component in the transmission of HDL. After adjustment for triglyceride, however, Mendelian models for a major gene seem to provide as good a fit as non-Mendelian models but the results do not permit distinction between a dominant model and an additive model.