Biomedical subjects

L G Holl

Publications and source records attributed to L G Holl.

3 recordsLinked to original sources

PubMed1996

A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction.

OBJECTIVE: To test whether a predominance of small, dense low-density lipoprotein (LDL) particles and elevated triglyceride levels are independent risk factors for myocardial infarction (MI). DESIGN: Nested case-control study with prospectively collected samples. SETTING: Prospective cohort study. PARTICIPANTS: Blood samples were collected at baseline (85% nonfasting samples) from 14916 men aged 40 to 84 years in the Physicians' Health Study. MAIN OUTCOME MEASUREMENTS: Myocardial infarction diagnosed during 7 years of follow-up. RESULTS: Cases (n=266) had a significantly smaller LDL diameter (mean [SD], 25.6 [0.9] nm) than did controls (n=308) matched on age and smoking (mean [SD], 25.9 [8] nm; P<.001). Cases also had higher median triglyceride levels (1.90 vs 1.49 mmol/L [168 vs 132 mg/dL]; P<.001). The LDL diameter had a high inverse correlation with triglyceride level (r=-0.71), and a high direct correlation with high-density lipoprotein cholesterol (HDL-C) level (r=0.60). We observed a significant multiplicative interaction between triglyceride and total cholesterol (TC) levels (P=.01). After simultaneous adjustment for lipids and a variety of coronary risk factors, LDL particle diameter was no longer a statistically significant risk indicator, with a relative risk (RR) of 1.09 (95% confidence interval [CI], 0.85-1.40) per 0.8-nm decrease. However, triglyceride level remained significant with an RR of 1.40 (95% CI, 1.10-1.77) per 1.13 mmol/L (100-mg/dL) increase. The association between triglyceride level and MI risk appeared linear across the distribution; men in the highest quintile had a risk about 2.5 times that of those in the lowest quintile. The TC level, but not HDL-C level, also remained significant, with an RR of 1.80 (95% CI, 1.44-2.26) per 1.03-mmol/L (40-mg/dL) increase. CONCLUSIONS: These findings indicate that nonfasting triglyceride levels appear to be a strong and independent predictor of future risk of MI, particularly when the total cholesterol level is also elevated. In contrast, LDL particle diameter is associated with risk of MI, but not after adjustment for triglyceride level. Increased triglyceride level, small LDL particle diameter, and decreased HDL-C levels appear to reflect underlying metabolic perturbations with adverse consequences for risk of MI; elevated triglyceride levels may help identify high-risk individuals.

Adult↗

PubMed1993

Lipoprotein subclasses in genetic studies: the Berkeley data set.

In conjunction with a study examining the inheritance of LDL subclass patterns in a healthy population, measurements of lipids, lipoproteins, and lipoprotein subclasses were performed in 301 individuals in 27 kindreds. Questionnaires were used to obtain information on use of medications, hormones, cigarettes, and alcohol. Laboratory data from this study (the Berkeley data set) include measurements of LDL and HDL size subclasses by nondenaturing gradient gel electrophoresis, and measurement of apolipoprotein A-I by radial immunodiffusion.

Adult↗

PubMed1992

Variations in oxidative susceptibility among six low density lipoprotein subfractions of differing density and particle size.

Oxidative modification of low density lipoproteins (LDL) has been implicated in the sequence of events leading to fatty streak formation in the arterial intima. Increased oxidative modifications of dense versus buoyant LDL particles could contribute to increased atherosclerosis associated with lipoprotein profiles enriched in small, dense LDL. In the present studies, we compared rates of copper-induced oxidative changes for six LDL subfractions ranging in density from 1.023 to 1.053 g/ml and mean particle diameter from 282 +/- 10 to 245 +/- 3. Rates of formation of thiobarbituric acid-reactive substances (TBARS), as indicated by the time required for half-maximal TBARS formation (T1/2max), decreased with increasing density and decreasing particle diameter to a minimum in fraction 5 (d = 1.046 g/ml, diameter = 250 +/- 5) (P = 0.007). In parallel studies using unfractionated LDL (d = 1.019-1.063 g/ml), T1/2max values were inversely correlated with the predominant LDL species diameter as determined by 2-16% gradient gel electrophoresis (P less than 0.05), consistent with the involvement of subclass composition in determining oxidative behavior. In separate experiments, subfraction differences in oxidation rates as assessed by TBARS formation were verified by the finding of similarly dispartate changes in fluorescence intensity and anionic electrophoretic mobility. T1/2max values were not related to LDL contents of alpha-tocopherol, beta-carotene, protein, triglycerides or phospholipids, but were significantly correlated with unesterified cholesterol content (r = 0.46; P less than 0.001) and were inversely associated with cholesteryl ester content (r = 0.28; P less than 0.05). The positive association of T1/2max with unesterified cholesterol suggests that this constituent may impart resistance to oxidative modification, possibly by altering properties of the surface monolayer where it resides.

Adult↗