Effects of age, gender, and menopausal status on plasma low density lipoprotein cholesterol and apolipoprotein B levels in the Framingham Offspring Study.

Plasma low density lipoprotein (LDL) cholesterol, non-high density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) B, the major protein constituent of LDL, were measured in 1,533 men (mean age 49 +/- 10 years) and 1,597 women (mean age 49 +/- 10 years) participating in the 3rd examination cycle of the Framingham Offspring Study. Mean plasma levels of LDL cholesterol and apoB were higher in men than in women (136 versus 132 mg/dl, P < 0.0001; and 109 versus 95 mg/dl, P < 0.0001, respectively). Increased age was associated with higher plasma LDL cholesterol and apoB levels, especially in women. After adjustment for age and body mass index, LDL cholesterol and apoB levels were still significantly higher in postmenopausal than in premenopausal women, indicating a hormonal effect on LDL metabolism. The associations between coronary heart disease (CHD) and LDL cholesterol, non-HDL cholesterol, apoB, and other plasma lipid and lipoprotein parameters were examined by dividing participants in four groups, based on approximate quartiles for these parameters. Elevated LDL cholesterol levels were not significantly associated with CHD in men, but were in women. This result, at variance with that of several longitudinal studies, is likely due to the cross-sectional design of our analysis. Elevated non-HDL cholesterol and apoB levels were significantly associated with the presence of CHD, in both males and females. A plasma apoB value > or = 125 mg/dl may be associated with an increased risk for CHD. Low plasma levels of HDL cholesterol were also significantly associated with CHD. Plasma triglyceride levels, age and body mass index were strong determinants of LDL cholesterol, non-HDL cholesterol, and apoB levels in men and women. In women, postmenopausal status and elevated blood pressure were also significantly associated with elevated levels of these parameters.

Factors associated with low and elevated plasma high density lipoprotein cholesterol and apolipoprotein A-I levels in the Framingham Offspring Study.

A decreased high density lipoprotein (HDL) cholesterol level (< 35 mg/dl) has been shown to be a significant independent risk factor for coronary heart disease (CHD). Moreover, increased HDL cholesterol levels (> or = 60 mg/dl) are associated with a decreased CHD risk. Levels of HDL cholesterol and apoA-I, the major protein constituent of HDL, were measured in plasma from fasting participants in the Framingham Offspring Study (1,584 men and 1,639 women, mean age 49 +/- 10 years). In this population, an HDL cholesterol value < 35 mg/dl was observed in 18.2% of men and 3.8% of women, and these subjects had mean apoA-I levels of 104 and 106 mg/dl, respectively, and triglyceride levels of 234 and 261 mg/dl, respectively. CHD was observed in 14.2% of men and 14.5% of women in this category. An HDL cholesterol level > or = 60 mg/dl was observed in 11.7% of men and 39.3% of women, and these subjects had mean apoA-I levels of 182 and 185 mg/dl, respectively, and mean triglyceride levels of 81 and 75 mg/dl, respectively. CHD was noted in 2.7% of men and 1.9% of women in this category. HDL cholesterol levels were much more strongly related to triglycerides (r = -0.54 in men and -0.47 in women) than was apoA-I (r = -0.26 in men and -0.13 in women). The relationship between plasma HDL cholesterol and triglyceride levels was not linear. In both men and women, triglycerides, body mass index (BMI), and alcohol intake contributed significantly to HDL cholesterol and apoA-I variability.

Contribution of apoB-48 and apoB-100 triglyceride-rich lipoproteins (TRL) to postprandial increases in the plasma concentration of TRL triglycerides and retinyl esters.

After the ingestion of a fat-rich meal, there is a postprandial increase in the plasma concentration of both apolipoprotein B-48- and apoB-100-containing triglyceride-rich lipoproteins (apoB-48 and apoB-100 TRL). In order to determine the contribution of these lipoproteins to postprandial lipemia, the concentration of triglycerides (TG) and retinyl esters (RE) was measured in apoB-48 and apoB-100 TRL after an oral fat load. Six normolipidemic male subjects were fed heavy cream (1 g fat per kg body weight) containing vitamin A (3000 retinol equivalents). TRL were isolated by ultracentrifugation from plasma samples obtained at regular intervals after the meal, and apoB-100 TRL were separated from apoB-48 TRL by affinity chromatography using monoclonal antibodies. Postprandial increase in plasma TG concentration was due to an increase in TG in the TRL fraction, which in turn was predominantly (82 +/- 4%) due to an increase in TG in apoB-48 TRL. Contribution of apoB-100 TRL to postprandial increase in TRL TG was 3-27% in individual subjects. ApoB-100 TRL remained a significant carrier of total plasma triglyceride in the fed state, as reflected by similar apoB-100 and apoB-48 TRL TG concentrations at 2, 4, and 6 h after the fat meal. Retinyl esters were regularly detected in apoB-100 TRL. Seventy-five (+/- 9) percent of the increase in TRL-RE was due to RE in apoB-48 TRL and 25 +/- 9% was due to RE in apoB-100. These data suggest that RE in plasma are not always associated with apoB-48-containing lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)

The evolving law of adolescent health care.

This article provides an outline of the legal principles applicable to the health care of adolescents. Over the past 20 years, states have expanded the ability of minors to seek medical treatment without parental consent. Minor treatment statutes, the mature minor rule, and specific types of health care (including contraception and abortion) are discussed. Recent trends permitting some older adolescents to refuse serious treatment are analyzed.

Delay in diagnosis of breast cancer. A professional liability risk.

This article notes that liability claims of failure to diagnose breast cancer are increasing in number and severity, at least in part because women understand that early diagnosis improves survival. Legal cases are presented that illustrate particular liability risks, and risk management recommendations are made.

DNA polymorphisms of the apolipoprotein B gene in patients with premature coronary artery disease.

Elevated plasma levels of low density cholesterol and their major apolipoprotein (apo B) are associated with an increased risk of coronary artery disease (CAD). We have examined allele frequencies of restriction fragment length polymorphisms (RFLP) of the apo B gene in 111 male Caucasians with premature CAD (mean age 49 +/- 7 years) and in 122 elderly Caucasian males (mean age, 73 +/- 5 years), free of clinical cardiovascular disease. The rare allele (R1) of the EcoR1 RFLP in exon 29, resulting in an amino acid change (Glu----Lys4154) was seen more frequently in CAD than in controls (0.270 vs 0.207, P less than 0.05). The R1 RFLP and the MspI insertion polymorphisms (MI) within the 3' hypervariable region (HVR) were observed together in 87% and are likely in linkage disequilibrium. The MI RFLP were slightly more frequent in CAD than control (0.239 vs. 0.211, P = 0.08). A second MspI RFLP in exon 26 results in an amino acid change (Arg----Glu3611); the rare allele M2 was seen more frequently in patients than in controls (0.150 vs. 0.057, P less than 0.005). No significant differences in allele frequencies were observed for the Xba1 RFLP in exon 26 (0.500 vs. 0.529, P = ns) or for the PvuII RFLP near the 5' end (P2) (0.105 vs. 0.088, P = ns). No statistically significant differences in lipid, lipoprotein cholesterol or apolipoproteins A-I and B were observed in patients or in controls. Two of the RFLPs examined (R1 and M2) result in changes in amino acid sequence and their allele frequencies are increased in CAD cases when compared with controls. Genetic variability within the apo B gene may thus contribute to cardiovascular risk. The physiological effects of individual mutations within apo B remain to be determined. It is unlikely, however that the single site polymorphisms examined in this study, will impart further information about CAD risk than conventional lipid parameters.

Measurement of very low density and low density lipoprotein apolipoprotein (Apo) B-100 and high density lipoprotein Apo A-I production in human subjects using deuterated leucine. Effect of fasting and feeding.

Six normolipidemic male subjects, after an 8-h overnight fast, were given a bolus injection and then a 15-h constant intravenous infusion of [D3]L-leucine. Subjects were studied in the fasted state and on a second occasion in the fed state (small, physiological meals were given every hour for 15 h). Apolipoproteins were isolated by preparative gradient gel electrophoresis from plasma lipoproteins separated by sequential ultracentrifugation. Incorporation of [D3]L-leucine into apolipoproteins was monitored by negative ionization, gas chromatography-mass spectrometry. Production rates were determined by multiplying plasma apolipoprotein pool sizes by fractional production rates (calculated as the rate of isotopic enrichment [IE] of each protein as a fraction of IE achieved by VLDL (d less than 1.006 g/ml) apo B-100 at plateau. VLDL apo B-100 production was greater, and LDL (1.019 less than d less than 1.063 g/ml) apo B-100 production was less in the fed compared with the fasted state (9.9 +/- 1.7 vs. 6.4 +/- 1.7 mg/kg per d, P less than 0.01, and 8.9 +/- 1.2 vs. 13.1 +/- 1.2 mg/kg per d, P less than 0.05, respectively). No mean change was observed in high density lipoprotein apo A-I production. We conclude that: (a) this stable isotope, endogenous-labeling technique, for the first time allows for the in vivo measurement of apolipoprotein production in the fasted and fed state; and (b) since LDL apo B-100 production was greater than VLDL apo B-100 production in the fasted state, this study provides in vivo evidence that LDL apo B-100 can be produced independently of VLDL apo B-100 in normolipidemic subjects.

HIV seropositivity. Legal issues for patient and nurse-midwife.

The ability of the legal system to respond to the challenges of HIV positivity and AIDS has been somewhat limited. Nevertheless, there have been state and federal initiatives which have affected nurse-midwifery practice to a degree unrecognized by many in practice. Areas of particular relevance to practice have been identified and discussed in a practical way.

Plasma apolipoprotein changes in the triglyceride-rich lipoprotein fraction of human subjects fed a fat-rich meal.

Twenty two subjects (9 males, 13 females) were fed a fat-rich meal (1 g of fat/kg body weight). Triglyceride-rich lipoproteins (TRL) were isolated by ultracentrifugation (d less than 1.006 g/ml) from blood drawn 0, 3, 6, 9, and 12 hr after the meal. Plasma triglyceride increased then decreased postprandially, while plasma apoA-I and apoB concentrations decreased. TRL triglyceride, TRL total protein, and TRL apoB concentrations all increased then decreased after the fat-rich meal. Postprandial rise in plasma triglyceride was significantly correlated with fasting plasma triglyceride levels (r = 0.66, P less than 0.001); postprandial rise in TRL triglyceride was significantly correlated with fasting TRL triglyceride levels (r = 0.58, P less than 0.01); postprandial rise in TRL apoB was not, however, significantly correlated with fasting TRL apoB levels (r = 0.37, N.S.). TRL apolipoproteins were separated by polyacrylamide gradient (4-22.5%) gel electrophoresis and protein bands were scanned in two dimensions with a laser densitometer. Relative postprandial changes in the concentration of the TRL apolipoproteins were determined. TRL apoB-100, apoB-48, apoE, and apoC increased then decreased postprandially. The increase in TRL apoB-100 after the fat-rich meal was confirmed in 8 subjects by direct measurement of apoB-100 with a monoclonal antibody ELISA assay. ApoA-I concentration in TRL was unchanged. Albumin in the TRL fraction was significantly increased 12 hr after the meal. Subjects with a greater magnitude of postprandial triglyceridemia had a greater increase in TRL triglyceride and TRL apoB, but their TRL apoB-100/apoB-48 ratios were not different from subjects with less pronounced triglyceridemia. Assuming that plasma TRL containing apoB-100 are predominantly derived from the liver, our data suggest that triglyceride-rich lipoproteins from both the liver and intestine make a significant contribution to postprandial triglyceridemia.

Postprandial plasma lipoprotein changes in human subjects of different ages.

Plasma lipoprotein changes were monitored for 12 hr after a fat-rich meal (1 g of fat/kg body weight) in 22 subjects (9 males, 13 females, 22-79 yr old). Plasma triglyceride, measured hourly, peaked once in some subjects, but twice or three times in others. The magnitude of postprandial triglyceridemia varied considerably between subjects (range: 650-4082 mg.hr/dl). Males tended to have greater postprandial triglyceridemia than females, and elderly subjects had significantly (P less than 0.05) greater postprandial triglyceridemia than younger subjects. Total plasma cholesterol, measured every three hr, increased significantly (6.0 +/- 2.1%) in 7 subjects, decreased significantly (7.1 +/- 1.2%) in 10 subjects, and remained unchanged in the remainder. Single spin ultracentrifugation and dextran sulfate precipitation procedures were used to quantitate triglyceride and cholesterol in triglyceride-rich lipoproteins (TRL, d less than 1.006 g/ml), low density lipoproteins (LDL), and high density lipoproteins (HDL). Plasma TRL and HDL triglyceride increased after the fat meal, while LDL triglyceride decreased at 3 hr but increased at 9 and 12 hr. TRL cholesterol increased postprandially, while LDL and HDL cholesterol decreased. Phospholipid (PL), free (FC) and esterified (EC) cholesterol measurements were carried out on the plasma and lipoprotein fractions of 8 subjects. Plasma PL increased significantly at 3, 6, and 9 hr after the fat-rich meal, due to increases in TRL and HDL PL. TRL CE increased postprandially, but a greater decrease in LDL and HDL CE caused plasma CE to be decreased. Plasma FC increased, predominantly due to an increase in TRL FC. Plasma concentrations of apolipoprotein A-I and apolipoprotein B both decreased after the fat-rich meal. The magnitude of postprandial triglyceridemia was inversely correlated with HDL cholesterol levels (r = -0.502, P less than 0.05) and positively correlated with age (r = -0.449, P less than 0.05), fasting levels of plasma triglyceride (r = 0.636, P less than 0.01), plasma apoB (r = 0.510, P less than 0.05), TRL triglyceride (r = 0.564, P less than 0.01), TRL cholesterol (r = 0.480, P less than 0.05) and LDL triglyceride (r = 0.566, P less than 0.01). Change in postprandial cholesterolemia was inversely correlated with fasting levels of HDL cholesterol (r = -0.451, P less than 0.05) and plasma apoA-I (r = -0.436, P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)