Hypercholesterolemia: Sullivan D

Sullivan D, Anonymous00139. · Department of Biochemistry, Royal Prince Alfred Hospital, NSW 2050, Australia. · Heart Lung Circ. · Pubmed #17188936 No free full text.

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Emery J, Barlow-Stewart K, Metcalfe SA, Sullivan D. · Discipline of General Practice, University of Western Australia. · Aust Fam Physician. · Pubmed #17925900 links to  free full text

Abstract: BACKGROUND: Advances in our understanding of the genetics of common chronic disease is beginning to impact on clinical practice and preventive health care. OBJECTIVE: This article discusses the potential for genetic medicine to inform disease prevention strategies. It describes two examples already affecting clinical general practice: familial hypercholesterolaemia and hereditary haemochromatosis. These represent important inherited conditions that, if diagnosed early, can be simply treated and their complications avoided. DISCUSSION: General practitioners can play an important role in the early diagnosis of these conditions and subsequent screening of at risk relatives. These conditions highlight the potential for genetic medicine to be applied to support tailored disease prevention in general practice.

Clifton PM, Noakes M, Sullivan D, Erichsen N, Ross D, Annison G, Fassoulakis A, Cehun M, Nestel P. · CSIRO Health Sciences and Nutrition, Adelaide, South Australia, Australia. · Eur J Clin Nutr. · Pubmed #14985690 No free full text.

Abstract: OBJECTIVE: To measure the relative effects of each of four phytosterol ester-enriched low-fat foods (bread, breakfast cereal, milk and yoghurt) on serum lipids, plasma phytosterols and carotenoids. DESIGN:: Three research centres undertook a randomised, incomplete crossover, single-blind study consisting of four treatment periods of 3 weeks each, one of which was a control period. Each sterol-enriched test food provided 1.6 g/day of phytosterols as sterol esters. SETTING: General Community. SUBJECTS: In all 58, free-living men and women with mean age (s.d.) 54 (8) y, moderately elevated plasma total cholesterol 6.2 (0.7) mmol/l and body mass index 26.2 (3.0) kg/m(2). MAIN OUTCOME MEASURES: Serum lipids, plasma phytosterols and carotenoids. RESULTS: Serum total and LDL cholesterol levels were significantly lowered by consumption of phytosterol-enriched foods: milk (8.7 and 15.9%) and yoghurt (5.6 and 8.6%). Serum LDL cholesterol levels fell significantly by 6.5% with bread and 5.4% with cereal. They were both significantly less efficacious than sterol-enriched milk (P<0.001). Plasma sitosterol increased by 17-23% and campesterol by 48-52% with phytosterol-enriched milk and bread. Lipid-adjusted beta-carotene was lowered by 5-10% by sterols in bread and milk, respectively. CONCLUSIONS: This is the first study to demonstrate that cholesterol-lowering effects of plant sterol esters may differ according to the food matrix. Plant sterols in low-fat milk was almost three times more effective than in bread and cereal. Despite phytosterol-enriched cereal products resulting in lower serum cholesterol reductions compared to sterol-enriched milk, the detection of similar changes in plasma phytosterols demonstrated that such products still delivered and released phytosterols to the gut.

Howes JB, Sullivan D, Lai N, Nestel P, Pomeroy S, West L, Eden JA, Howes LG. · Department of Obstetrics and Gynaecology, St George Hospital, University of New South Wales, NSW, 2217, Kogarah, Australia. · Atherosclerosis. · Pubmed #10996349 No free full text.

Abstract: The effects of dietary isoflavone supplementation using a purified extract of red clover containing approximately biochanin A 26 mg, formononetin 16 mg, daidzein 0.5 mg and genistein 1 mg per tablet at doses of one or two tablets per day were compared to placebo in a three-period, randomised, double blind, ascending dose study in 66 post menopausal women with plasma cholesterol levels between 5.0 and 9.0 mmol/l. Each treatment period lasted 4 weeks and a further nine women received placebo for the full 12-week period. All women consumed a low isoflavone diet for 2 weeks preceding the commencement of the study and for the 12-week study period. Urinary isoflavone excretion was very low in subjects receiving placebo but increased in a dose-dependent manner during therapy with one and two of isoflavone tablets. Dietary supplementation with isoflavones did not significantly alter total plasma cholesterol, LDL cholesterol, HDL cholesterol or plasma triglyceride levels. However, inverse correlations were found between urinary genistein excretion and plasma triglyceride levels and between urinary O-DMA excretion (an isoflavone metabolite) and plasma triglyceride levels in subjects receiving one isoflavone tablet, suggesting a weak relationship between isoflavone intake and plasma triglycerides which may be influenced by individual differences in isoflavone absorption or metabolism. The results suggest that isoflavone phytoestrogens from red clover in the proportions and quantities studied do not significantly alter plasma lipids in post menopausal women with moderately elevated plasma cholesterol levels.

Raitakari OT, McCredie RJ, Witting P, Griffiths KA, Letters J, Sullivan D, Stocker R, Celermajer DS. · Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia. · Free Radic Biol Med. · Pubmed #10832071 No free full text.

Abstract: Oxidative modification of low-density lipoprotein (LDL) may cause arterial endothelial dysfunction in hyperlipidemic subjects. Antioxidants can protect LDL from oxidation and therefore improve endothelial function. Dietary supplementation with coenzyme Q (CoQ(10)) raises its level within LDL, which may subsequently become more resistant to oxidation. Therefore, the aim of this study was to assess whether oral supplementation of CoQ(10) (50 mg three times daily) is effective in reducing ex vivo LDL oxidizability and in improving vascular endothelial function. Twelve nonsmoking healthy adults with hypercholesterolemia (age 34+/-10 years, nine women and three men, total cholesterol 7.4+/-1.1 mmol/l) and endothelial dysfunction (below population mean) at baseline were randomized to receive CoQ(10) or matching placebo in a double-blind crossover study (active/placebo phase 4 weeks, washout 4 weeks). Flow-mediated (FMD, endothelium-dependent) and nitrate-mediated (NMD, smooth muscle-dependent) arterial dilatation were measured by high-resolution ultrasound. CoQ(10) treatment increased plasma CoQ(10) levels from 1.1 +/-0.5 to 5.0+/-2.8 micromol/l (p =.009) but had no significant effect on FMD (4.3+/-2.4 to 5.1+/-3.6 %, p =.99), NMD (21.6+/-6.1 to 20.7+/-7.8 %, p = .38) or serum LDL-cholesterol levels (p = .51). Four subjects were selected randomly for detailed analysis of LDL oxidizability using aqueous peroxyl radicals as the oxidant. In this subgroup, CoQ(10) supplementation significantly increased the time for CoQ(10)H(2) depletion upon oxidant exposure of LDL by 41+/-19 min (p = .04) and decreased the extent of lipid hydroperoxide accumulation after 2 hours by 50+/-37 micromol/l (p =.04). We conclude that dietary supplementation with CoQ(10) decreases ex-vivo LDL oxidizability but has no significant effect on arterial endothelial function in patients with moderate hypercholesterolemia.

Wlodarczyk J, Sullivan D, Smith M. · John Wlodarczyk Consulting Services, New Lambton, NSW, Australia. · Am J Cardiol. · Pubmed #19064019 No free full text.

Abstract: The benefit from statin therapy is proportional to the low-density lipoprotein (LDL) cholesterol reduction. However, adverse events appear to be related to dose rather than LDL cholesterol reduction. Although serious side effects are rare, any comparison of statins requires scrutiny of the relation between therapeutic effect and risk of side effects. This report sought to determine whether the additional LDL cholesterol lowering with rosuvastatin over atorvastatin could be obtained without increased risk of short-term adverse events. Twenty-five studies (approximately 20,000 patients) were identified that provided 28 comparisons of 1:1 dose ratios, 20 comparisons of 1:2 dose ratios, and 6 comparisons of 1:4 dose ratios. Treatment difference in benefit (percentage of LDL cholesterol reduction) and risk (odds ratios for myalgia, increased alanine aminotransferase >3 times the upper limit of normal, creatine kinase >10 times the upper limit of normal, and percentage of change in glomerular filtration rate, as well as deaths, serious adverse events, and withdrawals caused by adverse events) were estimated using meta-analysis and presented in benefit-risk planes. Rosuvastatin was more efficacious than the same dose of atorvastatin (1:1 dose ratio) or a 2 times higher dose (1:2 dose ratio) of atorvastatin. There was no significant difference between rosuvastatin and a 4 times higher dose of atorvastatin (1:4 dose ratio). There were no significant differences between rosuvastatin and atorvastatin at any dose ratio for adverse events. Percentages of change in GFR improved significantly with both treatments. In conclusion, at 1:1 and 1:2 dose ratios, significant additional decreases in LDL cholesterol were obtained using rosuvastatin compared with atorvastatin at a similar risk of the adverse events presented.