Influence of the Mediterranean diet on carotid intima–media thickness in hypercholesterolaemic children: A 12-month intervention study

Background and aimsThe Mediterranean diet has been recognised as having a protective role on the cardiovascular system due to its low lipid and high antioxidant content. Lipid profile and oxidant status represent two important risk factors related to endothelial dysfunction, even at early stages of cardiovascular diseases. The aim of the study was to evaluate the influence of a 12-month Mediterranean diet on the variation of lipid profile and carotid intima–media thickness (cIMT) in pre-pubertal hypercholesterolaemic children.Methods and resultsWe performed a cross-sectional study comparing lipid profile and cIMT in a group of 68 pre-pubertal children (36 with hypercholesterolaemia and 32 controls). In addition, in the hypercholesterolaemic children a 12-month intervention programme with a Mediterranean diet was started to evaluate the variation of lipid profile and cIMT. At baseline, hypercholesterolaemic children showed a significantly higher cIMT (both right and left carotid artery) compared to controls (both p < 0.05). After 12 months of diet intervention, a significant reduction of total cholesterol, LDL-cholesterol and cIMT was documented (all p < 0.05). Furthermore, at the end of follow-up, delta body mass index-Standard Deviation score and delta LDL-cholesterol were significantly and independently related to the changes of cIMT (both p < 0.05).ConclusionThe Mediterranean diet represents a valid approach in the treatment of hypercholesterolaemia even during childhood.     

Elsibucol inhibits atherosclerosis following arterial injury: Multifunctional effects on cholesterol levels,oxidative stress and inflammation

Background: Elsibucol is a metabolically stable derivative of probucol with antioxidant, anti-inflammatory and antiproliferative properties. Here we investigated the effect of elsibucol on the development of atherosclerosis following arterial injury in hypercholesterolemic rabbits. Methods and results: New Zealand White rabbits were fed a high cholesterol diet that was supplemented or not with 0.5% elsibucol, 1% elsibucol or 1% probucol. An angioplasty of the iliac artery was performed after 3 weeks of diet. We found that treatment with elsibucol significantly decreases blood total cholesterol, LDLc and triglyceride levels. This is associated with a significant 46% reduction of neointimal hyperplasia following arterial injury. Interestingly, the effect of elsibucol on cholesterol levels and neointimal formation appears to be more pronounced than that of probucol. In vitro, elsibucol reduces vascular smooth muscle cell proliferation without affecting cell viability. In vivo, treatment with elsibucol is associated with a significant reduction of cellular proliferation (PCNA immunostaining), oxidative stress (nitrotyrosine immunostaining), VCAM-1 expression and macrophage infiltration in injured arteries. Despite its potent effect on neointimal hyperplasia, elsibucol does not prevent endothelial healing (Evans blue staining) following arterial injury. Conclusions: In hypercholesterolemic animals, elsibucol inhibits atherosclerosis and preserves endothelial healing following arterial injury. The mechanisms involved include lowering of blood cholesterol levels together with a reduction of oxidative stress and inflammation in injured arteries.     

Increased secretion of gelatinases A and B from the aortas of cholesterol fed rabbits: relationship to lesion severity

Basement membrane degrading metalloproteinases (gelatinases) have been implicated in the regulation of vascular smooth muscle cell migration and proliferation in culture and during neointima formation in vivo. We compared the expression and activation of gelatinases A and B in explants derived from the arch, mid and distal portions of thoracic aortas of normal rabbits and those given a 1% cholesterol-containing diet for 8 weeks. Neointimal/medial ratio was less than 0.01 in normal rabbits but was significantly increased by cholesterol feeding in the arch (1.08±0.26), mid (0.75±0.28) and distal (0.32±0.12) portions of the aorta (mean±S.E.M., n=6), and to a significantly (P<0.05) greater extent in the arch and mid than distal portions. Secretion of gelatinase B measured by densitometric scanning of zymograms was undetectable from normal aortas, but was significantly increased by cholesterol feeding in the arch (0.16±0.06), mid (0.26±0.08) and distal (0.11±0.05) portions (optical density units, n=6, each P<0.05 versus normal diet). The increase in gelatinase B expression was localised by in situ hybridisation to neointimal vascular smooth muscle cells, macrophages and endothelial cells. Secretion of pro-gelatinase A was detected from normal aortas; it was increased by cholesterol feeding from the arch (4.0 versus 2.8, P<0.05) and mid (3.6 versus 2.8, P<0.05) but not distal portions of the aorta (1.8 versus 1.2, n.s.). Similar results were obtained for active gelatinase A secretion from the arch (0.50 versus 0.28, P<0.05) and mid (0.47 versus 0.23, P<0.05) but not distal portions (0.19 versus 0.20, n.s.). Increases in pro- and active gelatinase A secretion therefore paralleled the severity of atheroma formation. The results imply that increased basement membrane turnover mediated by gelatinases occurs during cholesterol induced atherosclerosis formation.     

Meta-analysis of the cholesterol-lowering effect of ezetimibe added to ongoing statin therapy

ABSTRACT

Objective: To review and analyse the evidence for the cholesterol-lowering effect of ezetimibe in adult patients with hypercholesterolaemia who are not at low-density lipoprotein cholesterol (LDL?C) goal on statin monotherapy.

Research design: Systematic review and meta-analysis.

Methods: MEDLINE and EMBASE were searched to identify ezetimibe randomised controlled trials (RCTs) published between January 1993 and December 2005. The meta-analysis combined data from RCTs, with a minimum treatment duration of 6 weeks, that compared treatment with ezetimibe 10?mg/day or placebo added to current statin therapy.

The difference between treatments was analysed for four co-primary outcomes: mean percentage change from baseline in total cholesterol (TC), LDL?C, and high-density lipoprotein cholesterol (HDL?C), and number of patients achieving LDL?C treatment goal. Meta-analysis results are presented for a modified version of the inverse variance random effects model.

Results: Five RCTs involving a total of 5039 patients were included in the meta-analysis. The weighted mean difference (WMD) between treatments significantly favoured the ezetimibe/statin combination over placebo/statin for TC (–16.1% (–17.3, –14.8); p < 0.0001), LDL?C (–23.6% (–25.6, –21.7); p < 0.0001) and HDL?C (1.7% (0.9, 2.5); p < 0.0001). The relative risk of reaching the LDL?C treatment goal was significantly higher for patients on ezetimibe/statin relative to those on placebo/statin (3.4 (2.0, 5.6); p < 0.0001). In pre-defined sub-group analyses of studies in patients with coronary heart disease, the WMD between treatments remained significantly in favour of ezetimibe/statin (?p < 0.0001) for TC and LDL?C but was no longer significant for HDL?C. Elevations in creatine kinase, alanine aminotransferase or aspartate aminotransferase that were considered as an adverse effect did not differ significantly between treatments.

Conclusions: The meta-analysis we performed included only five studies and was restricted to analysis of the changes in cholesterol levels relative to baseline. However, the results suggest that ezetimibe co-administered with ongoing statin therapy provides significant additional lipid-lowering in patients not at LDL?C goal on statin therapy alone, allowing more patients to reach their LDL?C goal.     

Beneficial effects of atorvastatin on myocardial regions with initially low vasodilatory capacity at various stages of coronary artery disease

Purpose The aim of this study was to analyse non-invasively the regional effect of therapy with an HMG-CoA reductase inhibitor on myocardial blood flow in patients with coronary artery disease (CAD) with special reference to segments with initially substantially impaired vasodilation.Methods The study included 26 patients with untreated hypercholesterolaemia. Coronary angiography revealed CAD in nine patients with stenosis >50% and wall irregularities or minimal stenosis <30% in 17 patients. Before and 4.6±1.8 months after atorvastatin therapy, ¹³N-ammonia positron emission tomography (PET) studies were performed at rest and under pharmacological stress. Minimum coronary vascular resistance (MCR) and coronary flow reserve (CFR) were determined. Segments were divided into those with normal or near-normal (MBF during adenosine 2.0 ml/min/g) and those with abnormal (MBF<2.0 ml/min/g) vasodilator flow response. In CAD patients, 156 segments were analysed, 85 of which had abnormal MBF; in the non-obstructive group, 59 of 297 segments had abnormal MBF.Results LDL cholesterol decreased after atorvastatin therapy from 186±43 mg/dl to 101±26 mg/dl (p<0.001). In normal segments no significant changes in MBF, CFR and MCR were found. However, initially abnormal segments showed significant improvements in MCR (15%, p<0.0001) and MBF during adenosine (30%, p<0.0001) after therapy.Conclusion The improvement in regional coronary vasodilator function after atorvastatin in patients with coronary atherosclerosis may be caused, at least in part, by increased flow-mediated (endothelium-dependent) dilation of the total arteriolar and arterial vascular system. These data further support the concept of non-invasive management of stable CAD by statin therapy and life-style modification guided by PET.P. Wielepp and D. Baller contributed equally to the study     

Change in cardiovascular risk factors in France, 1985–1997

The change in the main cardiovascular risk factors in France was assessed using the MONICA population surveys conducted in the Urban Community of Lille, Bas-Rhin and Haute-Garonne. Trends in obesity, tobacco smoking, hypertension, hypercholesterolaemia and self-reported diabetes were established for the first (1985-1988) and the last (1995-1997) survey. The results indicate that the prevalence of overweight and obesity remained stable in both genders; tobacco smoking decreased in men but increased in women. Prevalence of hypertension decreased, and preventive measures improved in both genders. Prevalence of hypercholesterolaemia remained stable, and preventive measures improved only in men. Prevalence of self-reported diabetes increased solely in women, and preventive measures improved in both genders. However, in 1995-1997 still 40% of the treated hypertensive and 30% of the treated hypercholesterolaemic subjects were not adequately controlled. We conclude that prevalence and prevention of the main cardiovascular risk factors have evolved favourably in France, but the management of hypercholesterolaemia and hypertension can still be improved.     

Influence of dietary intervention on growth in children with hypercholesterolaemia

Aim: To determine whether a moderately reduced fat diet affects longitudinal growth in children with hypercholesterolaemia with a mean duration of 7.42 ± 1.93 y. Methods: Subjects with hypercholesterolaemia, total cholesterol above 5.18 mmol/L and LDL-cholesterol above 3.49 mmol/L (n = 144; 69 males and 75 females) from 2 to 13 y of age were studied. Patients were seen in our outpatient department for regular health check-ups. Weight and height were measured every year. At the same time, cholesterol, triglycerides, LDL-C, HDL-C, A-apoprotein and B-apoprotein levels were analysed. Furthermore, degrees of compliance at 1 mo, 6 mo and each year after starting the dietary treatment were determined. Results: No significant change in height or weight was found after fat restriction. In contrast, significant reductions in total cholesterol, LDL cholesterol and B-apoprotein levels of 19%, 24% and 14%, respectively, were detected. Finally, no significant differences were seen in HDL-cholesterol, A-apoprotein or triglycerides.

Conclusions: These data support the hypothesis that growth is not influenced by moderate fat restriction in healthy children who otherwise have normal nutrition.     

Physician response to screening for hypercholesterolaemia in a coronary care unit

Abstract Hypercholesterolaemia is a known risk factor for coronary artery disease. This study describes a retrospective analysis of 176 patients admitted to the Coronary Care Unit (CCU) in a six month period with an admission fasting serum cholesterol of greater than 5.5 millimoles per litre (mmols/L). The patient records were examined at least six months after hospital discharge to determine what action, if any, was instituted in response to their hypercholesterolaemia. One hundred and thirty-four (76%) patients had a discharge diagnosis of myocardial ischaemia or infarction. Of the 176 patients, 73 were referred to a dietitian, 31 were given dietary advice by a medical officer, 13 were commenced on lipid-lowering drugs with nine continuing lipid-lowering drugs and only 13 patients were referred to this hospital's lipid clinic. Sixty-nine (39%) received no response to their hypercholesterolaemia. It is likely that our experience is not unique and greater attention to CCU measured lipid results and risk factor modification should be instituted by physicians. (Aust NZ J Med 1991; 21: 401–404.)