Treatment effects on serum lipoprotein lipids, apolipoproteins and low density lipoprotein particle size and relationships of lipoprotein variables to progression of coronary artery disease in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT).

OBJECTIVES: To investigate the mechanisms by which bezafibrate retarded the progression of coronary lesions in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT), we examined the relationships of on-trial lipoproteins and lipoprotein subfractions to the angiographic outcome measurements. BACKGROUND: BECAIT, the first double-blind, placebo-controlled, randomized serial angiographic trial of a fibrate compound, showed that progression of focal coronary atherosclerosis in young survivors of myocardial infarction could be retarded by bezafibrate treatment. METHODS: A total of 92 dyslipoproteinemic men who had survived a first myocardial infarction before the age of 45 years were randomly assigned to treatment for 5 years with bezafibrate (200 mg three times daily) or placebo; 81 patients underwent baseline and at least one post-treatment coronary angiography. RESULTS: In addition to the decrease in very low density lipoprotein (VLDL) cholesterol (-53%) and triglyceride (-46%) and plasma apolipoprotein (apo) B (-9%) levels, bezafibrate treatment resulted in a significant increase in high density lipoprotein-3 (HDL3) cholesterol (+9%) level and a shift in the low density lipoprotein (LDL) subclass distribution toward larger particle species (peak particle diameter +032 nm). The on-trial HDL3 cholesterol and plasma apo B concentrations were found to be independent predictors of the changes in mean minimum lumen diameter (r=-0.23, p < 0.05), and percent (%) stenosis (r = 0.30, p < 0.01), respectively. Decreases in small dense LDL and/or VLDL lipid concentrations were unrelated to disease progression. CONCLUSIONS: Our results suggest that the effect of bezafibrate on progression of focal coronary atherosclerosis could be at least partly attributed to a rise in HDL3 cholesterol and a decrease in the total number of apo B-containing lipoproteins.

Smaller, denser LDL particles are not a risk factor for cardiovascular disease in healthy nonagenarian women of the Cremona Population Study.

We evaluated LDL particle size and its relation with other established risk factors for cardiovascular disease in a group of healthy nonagenarian ( > or = 90 years) women participating in the Cremona Population Study. A group of younger healthy postmenopausal women (45-75 years) was used as control group. Nonagenarian women had significantly lower body mass index, systolic and diastolic blood pressure, and fasting insulin concentrations. Plasma total, LDL and HDL cholesterol, apo AI and apo B concentrations, and LpAI and LpAI:AII particles were significantly lower in the nonagenarian group as well. LDL particle size (262.7+/-0.9 vs. 270.1+/-1.1 A) was also lower in the nonagenarian group. The presence of the E4 isoform of apo E in the nonagenarian group resulted in significantly higher levels of plasma apo AI and LpAI:AII particles, and a trend toward larger LDL particles, and a lower diastolic blood pressure. In conclusion, smaller and denser LDL particles might not represent an important risk factor for cardiovascular disease in healthy nonagenarian women of the Cremona Population Study, characterised by a reduced number of LDL particles and other protective factors, like low systolic and diastolic blood pressure, body mass index, and plasma insulin levels.

Hypobetalipoproteinemia associated with apo B-48.4, a truncated protein only 14 amino acids longer than apo B-48.

Familial hypobetalipoproteinemia is an autosomal codominant trait that can be caused by mutations in the apo B gene. Here we report a novel apo B gene mutation causing hypobetalipoproteinemia, that is associated with the synthesis of a truncated apo B protein in a young healthy male subject and his mother. The mutation is an A deletion at position 6627 of the apo B cDNA leading to a truncated protein of 2166 amino acids (apo B-48.4). This truncated apo B was detected mainly in VLDL, LDL and in trace amounts in HDL, but not in the lipoprotein deficient plasma fraction. Affected family members present with elevated levels of HDL-cholesterol, mainly due to an increase in HDL2 particles. Postprandial triglycerides and retinyl esters in the d < 1.006 g/ml lipoprotein in the proband showed a normal response to an oral fat load compared to a group of eight matched healthy controls. In summary this novel mutation is associated with hypobetalipoproteinemia with a normal fat absorption as expected for a protein with a length similar to that of apo B-48.

Increased J774 macrophage cytotoxicity of late postprandial triglyceride-rich lipoproteins from normolipidemic young men expressing an apolipoprotein epsilon 4 allele.

It has been demonstrated that normolipidemic young men with apolipoprotein E4/3 phenotype have a prolonged postprandial clearance of triglyceride-rich lipoproteins following a high-fat diet. In the present study, we isolated fasting and postprandial (3 and 8 h) lipoprotein fraction from normolipidemic young men with E3/3 and E4/3 phenotypes and examined the in vitro cytotoxicity of these lipoproteins towards J774 macrophages. 8 h E4/3 very low density lipoprotein (VLDL) were significantly more cytotoxic than either 8 h E3/3 VLDL or fasting and 3 h E4/3 VLDL (lactate dehydrogenase (LDH) released: 161 +/- 21, 107 +/- 9, 88 +/- 16 and 101 +/- 12 I.U./l, respectively). Fasting E4/3 intermediate density lipoprotein (IDL) were also significantly more cytotoxic than either fasting E3/3 IDL or 3 h and 8 h E4/3 IDL (LDH released: 105 +/- 23, 60 +/- 9, 37 +/- 5 and 53 +/- 16 I.U./l, respectively), whereas either fasting or postprandial low density lipoprotein (LDL) and high density lipoprotein (HDL) samples did not show any difference in cytotoxicity between the two groups studied. 8 h E4/3 VLDL samples incubated with J774 macrophages had a lower esterified cholesterol (40 +/- 3 versus 52 +/- 3 micrograms), and higher triglyceride (783 +/- 133 versus 418 +/- 64 micrograms) and free fatty acid (FFA) (2.0 +/- 0.4 versus 0.9 +/- 0.1 microgram) content than fasting E4/3 VLDL. The increased macrophage cytotoxicity of late postprandial triglyceride-rich lipoproteins seems to be related to the FFA content of E4/3 VLDL.

Influence of breast- and formula-feeding on plasma cholesterol precursor sterols throughout the first year of life.

We evaluated endogenous cholesterol synthesis and plasma lipid profile longitudinally from birth to 1 year old in infants who were exclusively breast-fed (n = 19) or formula-fed (n = 19) for the first 4 months of life. At 1 and 4 months of age, breast-fed infants had higher plasma total and low-density lipoprotein cholesterol and apolipoprotein B levels than formula-fed infants, whereas plasma mevalonate and lanosterol levels were not different between the two study groups.

Twenty-four-hour ambulatory blood pressure monitoring and antihypertensive treatment: focus on ACE inhibitors.

The use of ambulatory blood pressure monitoring in clinical studies offers some advantages in comparison to the clinic blood pressure measurement. In fact, this approach does not induce any alerting reaction and provides 24-h blood pressure values that are more reproducible and not affected by the placebo effect. This allows a better evaluation of blood pressure under antihypertensive treatment and an optimization of the number of patients to be studied in pharmacologic trials. In a recent double-blind, parallel-group study, ambulatory blood pressure monitoring was used to investigate the antihypertensive efficacy of a new angiotensin-converting enzyme inhibitor, trandolapril, in 62 mild and moderate hypertensive patients. After a washout period, patients received trandolapril, 2 mg o.d., or placebo for 6 weeks, followed by a second washout period. Clinic and 24-h blood pressures were assessed at the end of each period. In comparing the pre- and post-treatment period, trandolapril significantly reduced clinic and 24-h systolic and diastolic blood pressures. The fall was evident throughout the 24 h and was statistically significant also in the last 4 h of blood pressure monitoring. The placebo group did not show any significant blood pressure change. Thus, trandolapril, 2 mg once daily, is effective in reducing blood pressure. Its efficacy over 24 h is better documented by 24-h blood pressure monitoring than by isolated clinic blood pressure measurement.