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Biomedical subjects

Maud N Vissers

Publications and source records attributed to Maud N Vissers.

9 recordsLinked to original sources

Low plasma adiponectin exacerbates the risk of premature coronary artery disease in familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is characterized by increased risk for premature coronary artery disease (CAD). This risk is exacerbated in the presence of abdominal obesity and insulin resistance. Low adiponectin is part of the clustering of metabolic abnormalities associated with abdominal obesity and insulin resistance. The present study, therefore, aims to examine the relationship between plasma adiponectin and age at CAD diagnosis in FH patients. Plasma adiponectin was measured by ELISA in 568 non-diabetic FH individuals of French-Canadian origin. CAD was defined according to strict clinical criteria. Prior to analyses, patients were grouped according to age and gender-specific tertiles of plasma adiponectin levels. Multivariate Cox proportional hazards regression was used to estimate the association between plasma adiponectin levels and age at diagnosis of CAD. Overall, FH patients in the lowest tertile of plasma adiponectin exhibited CAD at a significantly younger age (hazard ratio=1.73, confidence interval 95%: [1.19-2.53]; p=0.004). These results suggest that low plasma adiponectin is associated with an increased risk of premature CAD over and above the already exaggerated risk seen in FH patients.

Adiponectin↗

Plasma levels of plant sterols and the risk of coronary artery disease: the prospective EPIC-Norfolk Population Study.

Some studies have suggested that a modest increase of plant sterol levels is a risk factor for coronary artery disease (CAD). We studied the relationship between plant sterol levels and CAD risk in a prospective nested case-control study consisting of 373 cases and 758 controls. Sitosterol and campesterol concentrations did not differ between cases and controls [sitosterol, 0.21 vs. 0.21 mg/dl (P = 0.1); campesterol, 0.31 vs. 0.32 mg/dl (P = 0.5)]. The sitosterol-to-cholesterol ratio was significantly lower in cases than in controls (1.19 vs. 1.29 microg/mg; P = 0.008), whereas the campesterol-to-cholesterol ratio did not differ significantly (1.78 vs. 1.88 microg/mg; P = 0.1). Plant sterol concentrations correlated positively with cholesterol levels and inversely with body mass index and triglyceride and lathosterol concentrations. Among individuals in the highest tertile of the sitosterol concentration, the unadjusted odds ratio (OR) for future CAD was 0.75 [95% confidence interval (CI) = 0.56-1.01]. After adjustment for traditional risk factors, the OR was 0.79 (95% CI = 0.56-1.13). For the campesterol concentration, the unadjusted OR was 0.95 (95% CI = 0.71-1.29) and the adjusted OR was 0.97 (95% CI = 0.68-1.39). In this large prospective study, higher levels of plant sterols, at least in the physiological range, do not appear to be adversely related to CAD in apparently healthy individuals.

Aged↗

Oxidized low-density lipoprotein in children with familial hypercholesterolemia and unaffected siblings: effect of pravastatin.

OBJECTIVES: To assess the role of oxidized phospholipids (OxPLs) in children with familial hypercholesterolemia (FH) and the effect of pravastatin. BACKGROUND: Oxidized phospholipids are a major component of oxidized low-density lipoprotein (OxLDL) and are bound to lipoprotein (a) [Lp(a)]. The significance of OxPL markers in children is unknown. METHODS: Children with FH were randomized to placebo (n = 88) or pravastatin (n = 90) after instruction on American Heart Association step II diet. Unaffected siblings (n = 78) served as controls. The OxPL content on apolipoprotein B-100 (apoB) detected by antibody E06 (OxPL/apoB ratio), immunoglobulin (Ig)G and IgM immune complexes per apoB (IC/apoB) and on all apoB particles (total apoB-IC = IC/apoB multiplied by plasma apoB levels), autoantibodies to malondialdehyde (MDA)-low-density lipoprotein (LDL), Lp(a), and apoB levels were measured at baseline and after two years of treatment. RESULTS: Compared with unaffected siblings, children with FH had significantly lower levels of OxPL/apoB but higher levels of IgG and IgM total apoB-IC and IgM MDA-LDL autoantibodies. From baseline to two-year follow-up, compared with placebo pravastatin treatment resulted in a greater mean percentage change in apoB (-18.7% vs. 0.3%; p = 0.001), total IgG apoB-IC (-31.9% vs. -12.2%; p < 0.001), and total IgM apoB-IC (-25.5% vs. 13.2%; p = 0.001). Interestingly, pravastatin also resulted in higher OxPL/apoB (48.7% vs. 29.3%; p = 0.028) and Lp(a) levels (21.9% vs. 10.7%; p = 0.044). CONCLUSIONS: Compared with unaffected siblings, children with FH are characterized by elevated levels of apoB-IC and IgM MDA-LDL autoantibodies. Compared with placebo, pravastatin led to a greater reduction in apoB-IC but also to a greater increase in OxPL/apoB and Lp(a), which may represent a novel mechanism of mobilization and clearance of OxPL.

Anticholesteremic Agents↗

Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels.

OBJECTIVE: To examine the effect of plant stanols on lipids and endothelial function in pre-pubertal children with familial hypercholesterolemia (FH). STUDY DESIGN: Children with FH (n=42), aged 7-12 years, were enrolled in a double-blind crossover trial, in which they consumed 500 mL of a low-fat yogurt enriched with 2.0 g of plant stanols and 500 mL of a low-fat placebo yogurt for 4 weeks, separated by a 6-week washout period. Lipid profiles and endothelial function were assessed after both consumption periods. Endothelial function was measured as flow-mediated dilation (FMD) of the brachial artery. RESULTS: This daily intake of 2.0 g of stanols significantly decreased the levels of total cholesterol (TC) by 7.5% and low-density lipoprotein cholesterol (LDL-C) by 9.2% as compared with placebo. High-density lipoprotein cholesterol and triglyceride levels remained unaltered. The reduction of LDL-C levels did not improve FMD, which was 10.5%+/-5.1% after plant stanol consumption and 10.6%+/-5.0% after placebo consumption, respectively (P=.852). CONCLUSION: This study demonstrates that plant stanols reduce LDL-C levels in children with FH without improving endothelial function.

Anticholesteremic Agents↗

Premature cardiovascular disease in young women with heterozygous familial hypercholesterolemia.

Heterozygous familial hypercholesterolemia is associated with elevated low-density lipoprotein cholesterol levels and the development of premature cardiovascular disease. Despite this general statement, data regarding the incidence of cardiovascular disease in young women with familial hypercholesterolemia are lacking. In this review, information of age-specific incidence, risk factors and therapeutic avenues in women with heterozygous familial hypercholesterolemia are discussed.

Adult↗

Inhibition of cholesterol absorption by the combination of dietary plant sterols and ezetimibe: effects on plasma lipid levels.

Consumption of plant sterols and treatment with ezetimibe both reduce cholesterol absorption in the intestine. However, the mechanism of action differs between the two treatments, and the consequences of combination treatment are unknown. Therefore, we performed a double-blind, placebo-controlled, crossover study for the plant sterol component with open-label ezetimibe treatment. Forty mildly hypercholesterolemic subjects were randomized to the following treatments for 4 weeks each: 10 mg/day ezetimibe combined with 25 g/day control spread; 10 mg/day ezetimibe combined with 25 g/day spread containing 2.0 g of plant sterols; 25 g/day spread containing 2.0 g of plant sterols; and placebo treatment consisting of 25 g/day control spread. Combination treatment of plant sterols and ezetimibe reduced low density lipoprotein cholesterol (LDL-C) by 1.06 mmol/l (25.2%; P < 0.001) compared with 0.23 mmol/l (4.7%; P = 0.006) with plant sterols and 0.94 mmol/l (22.2%; P < 0.001) with ezetimibe monotherapy. LDL-C reduction conferred by the combination treatment did not differ significantly from ezetimibe monotherapy (-0.12 mmol/l or -3.5%; P = 0.13). Additionally, the plasma lathosterol-to-cholesterol ratio increased with all treatments. Sitosterol and campesterol ratios increased after plant sterol treatment and decreased upon ezetimibe and combination therapy. Our results indicate that the combination of plant sterols and ezetimibe has no therapeutic benefit over ezetimibe monotherapy in subjects with mild hypercholesterolemia.

Absorption↗

Lipid-lowering medications.

In the last decades, there has been an important progression in the development and assessment of various cholesterol-lowering agents. Until recently, in children under age 10, the focus of treatment has been on dietary and lifestyle adjustments. For children older than 10 years, bile acid-binding resins were also recommended if LDL-C levels remained high after dietary adjustment. However, the lipid-lowering effect of bile acid-binding resins is modest at best and long-term compliance is often poor. In contrast, HMG-CoA reductase inhibitors (statins) are currently widely used in adults and are considered the first choice in the treatment of hypercholesterolemia. In the last few years, several randomized trials have shown that statins are also effective in reducing LDL cholesterol levels in children and seem safe at least in the short term. Another novel development is the cholesterol-lowering agent, ezetimibe, which inhibits cholesterol absorption in the intestine. Although efficacy and safety data in children are still lacking, ezetimibe has a good safety profile in adults, either as monotherapy or in combination with a statin. Lastly, two other classes of lipid-lowering drugs include fibrates and nicotinic acid, but most agree that the side effect profile precludes their use in children except in extreme circumstances. Overall, therapeutic options to lower cholesterol levels in children are expanding.

Adult↗

Supplementation of plasma with olive oil phenols and extracts: influence on LDL oxidation.

Phenols present in olive oil may contribute to the health effects of the Mediterranean lifestyle. Olive oil antioxidants increase the resistance of low-density lipoproteins (LDL) against oxidation in vitro, but human intervention studies have failed to demonstrate similar consistent effects. To better mimic the in vivo situation, plasma was incubated with either individual olive oil phenols or olive oil extracts with different phenolic compositions, and LDL was subsequently isolated and challenged for its resistance to oxidation. The results show that the ortho-dihydroxy phenols (hydroxytyrosol and oleuropein-aglycone) are more efficient than their mono-hydroxy counterparts (tyrosol and ligstroside-aglycone) in increasing the resistance of LDL to oxidation. However, the concentration of antioxidants required to inhibit LDL oxidation when added to whole plasma was substantially higher as compared to previous data where antioxidants are directly added to isolated LDL. In conclusion, this study supports the hypothesis that extra virgin olive oil phenols protect LDL in plasma against oxidation. The explanation that in vitro studies show protective effects in contrast to the lack of effect in the majority of human studies may be that the dose of the phenols and thus their plasma concentration in humans was too low to influence ex vivo LDL oxidizability. Further studies are required to gain a better understanding of the potential health benefits that extra virgin olive oil may provide.

Diet↗

Olive oil phenols are absorbed in humans.

Animal and in vitro studies suggest that olive oil phenols are effective antioxidants. The most abundant phenols in olive oil are the nonpolar oleuropein- and ligstroside-aglycones and the polar hydroxytyrosol and tyrosol. The aim of this study was to gain more insight into the metabolism of those phenols in humans. We measured their absorption in eight healthy ileostomy subjects. We also measured urinary excretion in the ileostomy subjects and in 12 volunteers with a colon. Subjects consumed three different supplements containing 100 mg of olive oil phenols on separate days in random order. Ileostomy subjects consumed a supplement with mainly nonpolar phenols, one with mainly polar phenols and one with the parent compound oleuropein-glycoside. Subjects with a colon consumed a supplement without phenols (placebo) instead of the supplement with oleuropein-glycoside. Ileostomy effluent and urine were collected for 24 h after supplement intake. Tyrosol and hydroxytyrosol concentrations were low (< 4 mol/100 mol of intake) in the ileostomy effluent, and no aglycones were detected. We estimated that the apparent absorption of phenols was at least 55-66% of the ingested dose. Absorption was confirmed by the excretion of tyrosol and hydroxytyrosol in urine. In ileostomy subjects, 12 mol/100 mol and in subjects with a colon, 6 mol/100 mol of the phenols from the nonpolar supplement were recovered in urine as tyrosol or hydroxytyrosol. In both subject groups, 5--6 mol/100 mol of the phenols was recovered from the polar supplement. When ileostomy subjects were given oleuropein-glycoside, 16 mol/100 mol was recovered in 24-h urine, mainly in the form of hydroxytyrosol. Thus, humans absorb a large part of ingested olive oil phenols and absorbed olive oil phenols are extensively modified in the body.

Absorption↗