Person:

Campos, Hannia

Apolipoprotein (apo) E and apoC-III concentrations in VLDL and LDL are associated with coronary heart disease. We studied the relationship between apoE and apoC-III and the abnormal concentrations and distribution of apoB lipoproteins in 10 hypercholesterolemic and 13 hypertriglyceridemic patients compared with 12 normolipidemic subjects (mean age, 45 years). Sixteen distinct types of apoB lipoprotein particles were separated by first using anti-apoE and anti-apoC-III immunoaffinity chromatography in sequence and then ultracentrifugation [light VLDL, dense VLDL, IDL, and LDL, with apoE with or without apoC-III (E(+)C-III(+), E(+)C-III(-)) or without apoE with or without apoC-III (E(-)C-III(+), E(-)C-III(-))]. The concentrations of VLDL particles with apoC-III (E(+)C-III(+), E(-)C-III(+)) were increased in the hypertriglyceridemic group compared with the hypercholesterolemic and normolipidemic groups. These particles were the most triglyceride rich of the particle types, and their triglyceride content was twice as high in hypertriglyceridemics compared with the other two groups. Hypertriglyceridemics had a similar concentration of total E(-)C-III(-) particles compared with normolipidemics, but the E(-)C-III(-) particles were distributed more to VLDL and IDL than to LDL. Hypercholesterolemics, in contrast, were distinguished from the normolipidemic group by 2-fold higher concentrations of apoB lipoproteins without apoE or apoC-III (E(-)C-III(-)), mainly LDL, which had high cholesterol content. Nonetheless, both normolipidemics and hypercholesterolemics had apoC-III-containing VLDL, which comprised 68% and 43% of their total VLDL particles. E(+)C-III(-) particles were a minor type, comprising <10% of particles in all lipoproteins and patient groups. Therefore, VLDL particles with apoC-III may play a central role in identifying the high risk of coronary heart disease in hypertriglyceridemia, but their substantial prevalence in normolipidemics may be of clinical significance as well.

Background

Plasma apolipoprotein (apo) C-III strongly predicts myocardial infarction (MI) and directly activates atherogenic processes invascularcells.Geneticvariationintheinsulinresponseelementofthe APOC3 promoter is associated with an increased risk of MI.

Objective

The objective was to determine whether the APOC3 promoter variation affects plasma apo C-III concentrations and MI only when insulin sensitivity is normal.

Design

TheAPOC3*222haplotype,definedbytheminorallelesofthe single nucleotide polymorphisms 3238C→G, –455T→C, and –482C→T, was studied in 1703 matched nonfatal case-control pairs with MI in the Central Valley of Costa Rica. We used fasting hyper-glycemia and abdominal obesity as surrogates for insulin sensitivity.

Results

The APOC3222 haplotype was associated with higher apo C-III concentrations only in those with the lowest waist circumference or fasting glucose concentration. The association between the APOC3222 haplotype and nonfatal MI, previously reported in this population, was strongly influenced by fasting hyperglycemia and abdominal obesity. The odds ratios for MI for the APOC3*222 haplotype were 1.72 (95% CI: 1.16, 2.54) and 1.84 (1.31, 2.59) in subjects in the lowest quintiles of abdominal obesity and fasting hyperglycemia, respectively, and were 0.75 (0.54, 1.05) and 1.16 (0.85, 1.59) in subjects in the highest quintiles, respectively (P for interaction <0.05).

Conclusion

The results support the concept that mutations in the APOC3 promoter inhibit the down-regulation of APOC3 expression by insulin. This cardioprotective system becomes dysfunctional in abdominal obesity and hyperglycemia.

Background

The effect of daily prenatal and postnatal vitamin supplementation on concentrations of breast milk nutrients is not well characterized in HIV-infected women.

Objective

We examined the impact of vitamin supplementation during pregnancy and lactation on breast milk concentrations of retinol, carotenoids, and tocopherols during the first year post-partum among 626 HIV-infected Tanzanian women.

Design

We conducted a randomized, double-blind, placebo controlled trial. Women were assigned to one of four daily oral supplements: vitamin A + β-carotene (VA+BC); multivitamins (B, C, E (MV)); MV+VA+BC; or placebo. Concentrations of breast milk nutrients were determined by HPLC at birth and every 3 mo thereafter.

Results

Supplementation with VA+BC increased concentrations of retinol, β-carotene, and α-carotene at delivery by 4799, 1791, and 84 nmol/L, respectively, compared to no VA+BC (all p<0.0001). MV supplementation did not increase concentrations of α-tocopherol or δ-tocopherol at delivery but significantly decreased concentrations of breast milk γ-tocopherol and retinol. Although concentrations of all nutrients decreased significantly by 3 months postpartum, retinol, α-carotene, and β-carotene concentrations were significantly higher among those receiving VA+BC at 3, 6, and 12 mo compared to no VA+BC. Alpha tocopherol was significantly higher, while γ-tocopherol concentrations were significantly lower, among women receiving MV compared to no MV at 3, 6, and 12 mo post-partum.

Conclusions

Sustained supplementation of HIV-infected breastfeeding mothers with MV could be a safe and effective intervention to improve vitamin E concentrations in breast milk. VA+BC supplementation increases concentrations of breast milk retinol but it is not recommended in HIV-infected mothers due to the elevated risk of vertical transmission.