Adhésion au traitement de la maladie rénale chronique chez les québécois âgés de 18 ans ou plus

Introduction La progression de la maladie rénale chronique (MRC) augmente le risque des maladies cardiovasculaires. L’hypertension, le diabète et la dyslipidémie sont à la fois des facteurs de risque et des comorbidités de la MRC. Chez les individus souffrant de MRC, la persistance et l’observance du traitement de ces facteurs de risque, i.e. le traitement antihypertenseur (TAH), le traitement hypolipémiant (THL) et le traitement antidiabétique (TAD) contribuent à réduire le risque de mortalité et de morbidité cardiovasculaires. Néanmoins, la persistance et l’observance de ces traitements restent encore peu étudiées chez les individus ayant la MRC. Objectifs: Spécifiquement pour chacun des trois traitements (TAH, THL et TAD), une étude de cohorte a été menée dans le but : 1) d’estimer la persistance à prendre le traitement un an après le début du traitement; 2) d’estimer l’observance du traitement au cours de l’année suivant le début du traitement chez les persistants; 3) d’identifier les facteurs associés à la persistance; et 4) d’identifier les facteurs associés à l’observance. Méthodologie: Nous avons utilisé les banques de données administratives de la Régie de l’assurance maladie du Québec (RAMQ) pour mener trois études de cohorte chez les personnes âgées de 18 ans ou plus. Une étude a été conduite chez les individus qui ont commencé un TAH, l’autre conduite chez les patients ayant commencé un THL et la dernière menée chez les nouveaux utilisateurs de TAD. Les individus qui poursuivaient encore leur traitement un an après son début ont été considérés persistants. Parmi les persistants, les patients qui ont eu une proportion de jours couverts (PJC) ≥ 80 % ont été considérés observants. Les facteurs associés à la persistance et ceux associés à l’observance ont été identifiés à l’aide d’une régression de Poisson modifiée. Résultats: Parmi les 7 119 patients ayant débuté un TAH, 78,8 % ont été persistants et 87,7 % des persistants ont été observants. Les individus qui étaient plus susceptibles d’être persistants se trouvaient dans le groupe des utilisateurs de monothérapie d’inhibiteurs de l’enzyme de conversion de l’angiotensine (IECA) (Rapport de prévalences (RP) : 1,20; intervalle de confiance (IC) à 95 % : 1,13-1,27), d’antagonistes du récepteur de l’angiotensine II (ARA) (1,22; 1,14-1,31), de bloquants des canaux calciques (BCC) (1,20; 1,14-1,26), de bêta-bloquants (BB) (1,16; 1,10-1,23) et de multithérapie (1,31; 1,25-1,38) (référence : monothérapie de diurétiques (DIU)). Les individus qui étaient plus susceptibles d’être observants étaient les utilisateurs de monothérapie d’IECA (1,08; 1,03-1,04), de BB (1,10; 1,05-1,15), de BCC (1,10; 1,05-1,15) et de multithérapie. Des 14 607 individus ayant débuté un THL, 80,7 % ont persisté à le prendre; de ces derniers, 88,7 % étaient observants du THL. Les patients qui étaient plus susceptibles d’être persistants étaient ceux ayant un statut socio-économique (SSE) faible (1,03; 1,01-1,06) (référence : SSE élevé) et ceux dont le traitement initial avait été prescrit par un néphrologue (1,06; 1,04-1,09) (référence : omnipraticien). Les individus qui étaient plus susceptibles d’être observants étaient ceux âgés ≥ 66 ans (référence : 18-65) (1,04; 1,01-1,07), ceux ayant un SSE faible (1,08; 1,06-1,10) et ceux qui avaient pris plus de 12 médicaments différents (référence : <7) (1,03; 1.00-1,05). Sur un total de 6 671 individus ayant débuté un TAD, 76,9 % ont persisté à prendre le traitement. Parmi les persistants, 87,9 % étaient observants. Les individus ayant un SSE faible (1,04; 1,01-1,07) (référence : SSE élevé) ou une multithérapie (1,12; 1,08-1,16) (référence : monothérapie de metformine) étaient plus susceptibles d’être persistants, tout comme ceux ayant une comorbidité dont l’hypertension artérielle (1,04; 1,01-1,07), la dyslipidémie (1,06; 1,03-1,10), l’accident vasculaire cérébral (AVC) (1,05; 1,01-1,11) ou la maladie coronarienne (1,03; 1,01-1,06). Les individus plus susceptibles d’être observants étaient ceux ayant un SSE moyen (1,03; 1,01-1,07) ou une multithérapie (1,06; 1,03-1,09). Conclusion: Peu importe le traitement initié par les individus souffrant de MRC, environ 30% des patients ne seraient pas persistants un an après le début du traitement ou observants dans l’année suivant l’initiation. Certains facteurs sont associés de façon consistante à la persistance, par exemple l’AVC, la maladie coronarienne et le nombre de visites médicales, alors que l’âge et le SSE sont associés à l’observance peu importe que le traitement initial soit un TAH, un THL ou un TAD.

Influence of pharmacotherapy complexity on compliance with the therapeutic objectives for HIV+ patients on antiretroviral treatment concomitant with therapy for dyslipidemia: INCOFAR Project

Objectives: To analyze the relationship between pharmacotherapeutical complexity and compliance of therapeutic objectives in HIV+ patients on antiretroviral treatment and concomitant dyslipidemia therapy. Materials and methods: A retrospective observational study including HIV patients on stable antiretroviral treatment during the past 6 months, and dyslipidemia treatment between January and December, 2013. The complexity index was calculated with the tool developed by McDonald et al. Other variables analyzed were: age, gender, risk factor of HIV, smoking, alcoholism and drugs, psychiatric disorders, adherence to antiretroviral treatment and lipid lowering drugs, and clinical parameters (HIV viral load, CD4 count, plasma levels of total cholesterol, LDL, HDL, and triglycerides). In order to determine the predictive factors associated with the compliance of therapeutic objectives, univariate analysis was conducted through logistical regression, followed by a multivariate analysis. Results: The study included 89 patients; 56.8% of them met the therapeutic objectives for dyslipidemia. The complexity index was significantly higher (p = 0.02) in those patients who did not reach the objective values (median 51.8 vs. 38.9). Adherence to lipid lowering treatment was significantly associated with compliance of the therapeutic objectives established for dyslipidemia treatment. A 67.0% of patients met the objectives for their antiretroviral treatment; however, the complexity index was not significantly higher (p = 0.06) in those patients who did not meet said objectives. Conclusions: Pharmacotherapeutical complexity represents a key factor in terms of achieving health objectives in HIV+ patients on treatment for dyslipidemia.

Effects of simvastatin in abdominal sepsis in rats

Statins are widely recognized as hypolipemic drugs, but some studies have observed anti-inflammatory and immunomodulatory effects, known as pleiotropic. The aims of this work was to study possible anti-inflammatory effects of simvastatin in abdominal sepsis. Serum pro-inflammatory cytokines and leukocytes count were determined in an experimental model of abdominal sepsis, using cecal ligation and puncture (CLP) in rats. Methods: Twenty eigth Wistar rats weighing 285±12g were randomly divided in: CLP/Sinvastatin rats (n=7), treated with 10 mg/Kg of oral simvastatin 18 and 2 hs berofe CLP; CLP/Saline group rats (n=7), treated with oral saline; group Sham/Simvastatin (n=7), treated with simvastatin, and group Sham/Saline (n=7), treated with saline. Serum TNF-α, IL-1β and IL-6 by ELISA and total leukocytes, neutrophils, lymphocytes, and eosinophils were determined 24 hs after CLP. ANOVA and Tukey test were used considering significant p<0.05. Results: It was demonstrated that serum TNF-α, IL-1β and IL-6 were respectively 364,8±42pg/mL; 46,3±18pg/mL and 28,4±13pg/mL in CLP/Sinvastatin rats, significantly lower (p<0.05) than in group CLP/Saline (778,5±86pg/ml; 176,9±46pg/ ml; 133,6±21 pg/ml, respectively). The same results were observed in total leukocytes and neutrophils counts. Conclusion: These results clearly demonstrate that simvastatin is an effective agent that reduces cytokines levels and leukocyte count in sepsis, independently of its well-known lipid-lowering effects. Thus, HMG-CoA reductase inhibitors like simvastatin have important anti-inflammatory effects in abdominal sepsis in rats

Isolation and identification of two galangin metabolites from rat urine and determination of their in vitro hypolipidemic activity

Purpose: To investigate the lipid-lowering activity of two metabolites of galangin, namely, galangin-3-Oβ-D-glucuronic acid (GG-1) and galangin-7-O-β-D-glucuronic acid (GG-2). Methods: Female Sprague-Dawley rats were orally administered with galangin. The two metabolites of galangin were isolated from urine sample and purified using Sephadex LH-20 and semi-preparative high performance liquid chromatography (HPLC). The structures of the metabolites were identified by analyzing spectroscopic data. Hypolipidemic activity was evaluated in HepG2 cells. The down- or upregulation of lipogenic genes was detected using real-time quantitative polymerase chain reaction (qPCR). Results: Both metabolites of galangin showed hypolipidemic activity. These activities are closely associated with the down-regulation of lipogenic genes such as SREBP-1a, SREBP-1c, and SREBP-2 transcription factors, and the downstream genes such as FAS, ACC, and HMGR were revealed by realtime qPCR data. Conclusion: The results show that both metabolites possess better lipid-lowering activities than galangin. These hypolipidemic activities are closely associated with inhibiting key genes or proteins that regulated the biosynthesis of both cholesterol and triglycerides.

Hábitos de consumo de alimentos enriquecidos com fitoesteróis

O interesse crescente pelos alimentos enriquecidos com esteróis vegetais deve-se ao fato de que estes diminuem as concentrações sanguíneas de colesterol sem efeitos adversos colaterais. Neste contexto, o enriquecimento de alimentos com esteróis vegetais poderá constituir uma ajuda importante na proteção da população contra a aterosclerose e doenças cardiovasculares. As informações sobre o comportamento alimentar são praticamente inexistentes em Portugal, pelo que se torna indispensável perceber a importância dos produtos funcionais nos hábitos de consumo. O presente trabalho pretendeu avaliar os hábitos de consumo de uma população de Viseu relativamente aos leites fermentados com baixo teor de gordura enriquecidos com esteróis vegetais e margarinas enriquecidas com fitoesteróis. Para cada produto foram feitos 577 inquéritos a indivíduos escolhidos aleatoriamente numa população que efetuava as suas compras semanais em vários hipermercados da cidade de Viseu. Inquiriu-se sobre vários parâmetros respeitantes a leites fermentados com baixo teor de gordura enriquecidos com esteróis vegetais e margarinas enriquecidas com fitoesteróis. Os resultados preliminares obtidos mostraram que, para a maioria dos inquiridos a compra dos alimentos era condicionada pelo seu custo elevado. Os indivíduos que afirmaram consumir os produtos eram maioritariamente mulheres com idade entre os 40≤65 anos. Relativamente aos parâmetros avaliados não se observam diferenças estatisticamente significativas entre ambos os sexos. Estes inquiridos ingeriam maioritariamente o alimento 1vez/dia (leites fermentados, margarina (fatia/dia)) fazendo esta escolha por apresentarem colesterol elevado ou por lhes atribuírem efeitos preventivos para a doença. Para além disso quer os que estavam sob terapêutica antidislipidémica quer os que não estavam declararam observar efeitos positivos na hipercolesterolemia. Parece evidente que são as preocupações com a saúde que influenciam a aquisição dos leites fermentados com baixo teor de gordura e margarinas enriquecidos com fitoesteróis. As declarações feitas sobre os níveis de colesterol, ingestão declarada e efeitos observados parecem sugerir uma ingestão com quantidade e frequência suficiente. Também a faixa etária que mais consome parece estar de acordo com as recomendações. A elevada taxa de não consumidores encontrada no estudo e que alega não necessidade e descrença de efeitos mesmo quando tal não acontece pode atribuir-se à escassez de informação nos rótulos e/ou custo acrescido do produto. Esclarecer sobre a importância da inclusão destes produtos na dieta sozinhos ou como coadjuvantes de terapêutica instituída poderá ser uma forma de conseguir o equilíbrio na gestão da hipercolesterolemia.

Cost-effectiveness of cholesterol-lowering therapy with pravastatin in patients with previous acute coronary syndromes aged 65 to 74 years compared with younger patients: Results from the LIPID study

Background We compared cost-effectiveness of pravastatin in a placebo-controlled trial in 5500 younger (31-64 years) and 3514 older patients (65-74 years) with previous acute coronary syndromes. Methods Hospitalizations and long-term medication within the 6 years of the trial were estimated in all patients. Drug dosage, nursing home, and ambulatory care costs were estimated from substudies. Incremental costs per life saved of pravastatin relative to placebo were estimated from treatment effects and resource use. Results Over 6 years, pravastatin reduced all-cause mortality by 4.3% in the older patients and by 2.3% in the younger patients. Older patients assigned pravastatin had marginally lower cost of pravastatin and other medication over 6 years (A$4442 vs A$4637), but greater cost offsets (A$2061 vs. A$897) from lower rates of hospitalizations. The incremental cost per life saved with pravastatin was A$55500 in the old and A$167200 in the young. Assuming no treatment effect beyond the study period, the life expectancy to age 82 years of additional survivors was 9.1 years in the older and. 17.3 years in the younger. Estimated additional life-years saved from pravastatin therapy were 0.39 years for older and 0.40 years for younger patients. Incremental costs per life-year saved were A$7581 in the older and A$1.4944 in the younger, if discounted at 5% per annum. Conclusions Pravastatin therapy was more cost-effective among older than younger patients, because of their higher baseline risk and greater cost offsets, despite their shorter life expectancy.

Cholesterol-lowering management of stroke : inconsistencies of evidence and practice

Cholesterol-lowering treatment by statins is an important and costly issue; however, its role in stroke has not been well documented. The aim of the present study was to review literature and current practice regarding cholesterol-lowering treatment for stroke patients. A literature review was conducted on lipids in stroke and their management with both statins and diet, including the cost-effectiveness of medical nutrition therapy. Qualifying criteria and prescription procedures of the Pharmaceutical Benefits Scheme (PBS) were also reviewed. Data on lipid levels and statin prescriptions were analysed for 468 patients admitted to a stroke unit. The literature shows that management with both medication and diet can be effective, especially when combined; however, 60% of patients with an ischaemic event had fasting total cholesterol measures ≥4 mmol/L (n = 231), with only 52% prescribed statins on discharge (n = 120). Hypercholesterolaemia is an underdiagnosed and undertreated risk factor within the stroke population. It appears that the PBS has not kept pace with advances in the evidence in terms of statin use in the stroke population, and review is needed. The present review should address the qualifying criteria for the stroke population and recommendations on referral to dietitians for dietary advice. Cholesterol-lowering treatment for both stroke patients and the wider population is an area that needs awareness raising and review by the PBS, medical practitioners and dietitians. The role of dietary and pharmacological treatments needs to be clearly defined, including adjunct therapy, and the cost-effectiveness of medical nutrition therapy realised.

Synthesis and characterization of novel cationic lipid and cholesterol-coated gold nanoparticles and their interactions with dipalmitoylphosphatidylcholine membranes

Novel gold nanoparticles bearing cationic single-chain, double-chain, and cholesterol based amphiphilic units have been synthesized. These nanoparticles represent size-stable entities in which various cationic lipids have been immobilized through their thiol group onto the gold nanoparticle core. The resulting colloids have been characterized by UV-vis, (1)H NMR, FT-IR spectroscopy, and transmission electron microscopy. The average size of the resultant nanoparticles could be controlled by the relative bulkiness of the capping agent. Thus, the average diameters of the nanoparticles formed from the cationic single-chain, double-chain, and cholesterol based thiolate-coated materials were 5.9,2.9, and 2.04 nm, respectively. We also examined the interaction of these cationic gold nanoparticles with vesicular membranes generated from dipalmitoylphosphatidylcholine (DPPC) lipid suspensions. Nanoparticle doped DPPC vesicular suspensions displayed a characteristic surface plasmon band in their UV-vis spectra. Inclusion of nanoparticles in vesicular suspensions led to increases in the aggregate diameters, as evidenced from dynamic light scattering. Differential scanning calorimetric examination indicated that incorporation of single-chain, double-chain, and cholesteryl-linked cationic nanoparticles exert variable effects on the DPPC melting transitions. While increased doping of single-chain nanoparticles in DPPC resulted in the phases that melt at higher temperatures, inclusion of an incremental amount of double-chain nanoparticles caused the lowering of the melting temperature of DPPC. On the other hand, the cationic cholesteryl nanoparticle interacted with DPPC in membranes in a manner somewhat analogous to that of cholesterol itself and caused broadening of the DPPC melting transition.

Freeze-Dried Strawberries Lower Serum Cholesterol and Lipid Peroxidation in Adults with Abdominal Adiposity and Elevated Serum Lipids

Dietary flavonoid intake, especially berry flavonoids, has been associated with reduced risks of cardiovascular disease (CVD) in large prospective cohorts. Few clinical studies have examined the effects of dietary berries on CVD risk factors. We examined the hypothesis that freeze-dried strawberries (FDS) improve lipid and lipoprotein profiles and lower biomarkers of inflammation and lipid oxidation in adults with abdominal adiposity and elevated serum lipids. In a randomized dose-response controlled trial, 60 volunteers [5 men and 55 women; aged 49 ± 10 y; BMI: 36 ± 5 kg/m2 (means ± SDs)] were assigned to consume 1 of the following 4 beverages for 12 wk: 1) low-dose FDS (LD-FDS; 25 g/d); 2) low-dose control (LD-C); 3) high-dose FDS (HD-FDS; 50 g/d); and 4) high-dose control (HD-C). Control beverages were matched for calories and total fiber. Blood draws, anthropometrics, blood pressure, and dietary data were collected at screening (0 wk) and after 12-wk intervention. Dose-response analyses revealed significantly greater decreases in serum total and LDL cholesterol and nuclear magnetic resonance (NMR)–derived small LDL particle concentration in HD-FDS [33 ± 6 mg/dL, 28 ± 7 mg/dL, and 301 ± 78 nmol/L, respectively (means ± SEMs)] vs. LD-FDS (−3 ± 11 mg/dL, −3 ± 9 mg/dL, and −28 ± 124 nmol/L, respectively) over 12 wk (0–12 wk; all P < 0.05). Compared with controls, only the decreases in total and LDL cholesterol in HD-FDS remained significant vs. HD-C (0.7 ± 12 and 1.4 ± 9 mg/dL, respectively) over 12 wk (0–12 wk; all P < 0.05). Both doses of strawberries showed a similar decrease in serum malondialdehyde at 12 wk (LD-FDS: 1.3 ± 0.2 μmol/L; HD-FDS: 1.2 ± 0.1 μmol/L) vs. controls (LD-C: 2.1 ± 0.2 μmol/L; HD-C: 2.3 ± 0.2 μmol/L) (P < 0.05). In general, strawberry intervention did not affect any measures of adiposity, blood pressure, glycemia, and serum concentrations of HDL cholesterol and triglycerides, C-reactive protein, and adhesion molecules. Thus, HD-FDS exerted greater effects in lowering serum total and LDL cholesterol and NMR-derived small LDL particles vs. LD-FDS in the 12-wk study. These findings warrant additional investigation in larger trials. This trial was registered at clinicaltrials.gov as NCT01883401.

Dietary fat manipulation has a greater impact on postprandial lipid metabolism than the apolipoprotein E (epsilon) genotype: insights from the SATgenε study

Scope: Our aim was to determine the effects of chronic dietary fat manipulation on postprandial lipaemia according to apolipoprotein (APO)E genotype. Methods and results:Men (mean age 53 (SD 9) years), prospectively recruited for the APOE genotype (n = 12 E3/E3, n = 11 E3/E4), were assigned to a low fat (LF), high fat, high-saturated fat (HSF), and HSF diet with 3.45 g/day docosahexaenoic acid (HSF-DHA), each for an 8-week period in the same order. At the end of each dietary period, a postprandial assessment was performed using a test meal with a macronutrient profile representative of that dietary intervention. A variable postprandial plasma triacylglycerol (TAG) response according to APOE genotype was evident, with a greater sensitivity to the TAG-lowering effects of DHA in APOE4 carriers (p ≤ 0.005). There was a lack of an independent genotype effect on any of the lipid measures. In the groups combined, dietary fat manipulation had a significant impact on lipids in plasma and Svedberg flotation rate (Sf) 60–400 TAG-rich lipoprotein fraction, with lower responses following the HSF-DHA than HSF intervention (p < 0.05). Conclusion: Although a modest impact of APOE genotype was observed on the plasma TAG profile, dietary fat manipulation emerged as a greater modulator of the postprandial lipid response in normolipidaemic men.

Impact of probiotics, prebiotics and synbiotics on lipid metabolism in humans

Public health strategies for reducing the risk of coronary heart disease have focused on lowering plasma lipids, particularly cholesterol levels, with recent studies also highlighting triacylglycerol (TAG) as an important modifiable risk factor. One approach is to supplement the diet with probiotics, prebiotics or synbiotics. Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Putative health benefits include improved resistance to gastrointestinal infections, reduction in lipid levels and stimulation of the immune system. Prebiotics are selectively fermented dietary components that are aimed at improving host health through selective fermentation by the gut microbiota, such as bifidobacteria and lactobacilli. Animal studies have shown prebiotics to markedly reduce circulating TAG and to a lesser extent cholesterol concentrations, with favourable but inconsistent findings with respect to changes in lipid levels in human studies. Here we provide an overview of the effects, and possible mechanisms, of probiotics, prebiotics and synbiotics (combination of a probiotic and prebiotic) on circulating lipeamia in humans.

Cholesterol-Lowering Properties of Whole Cowpea Seed and Its Protein Isolate in Hamsters

Hypercholesterolemic hamsters were fed for 4 wk on diets rich in saturated fatty acids and cholesterol, differing only in protein source (20%): casein (control group, HC), whole cowpea seed (HWS), and cowpea protein isolate (HPI). Hamsters fed on HWS and HPI presented significant reductions in plasma total cholesterol and non-HDL cholesterol. HPI and HC presented similar protein digestibility, which were significantly higher than that of HWS. Animals fed on HWS presented significantly higher levels of bile acids and cholesterol in feces than did the animals fed on casein or HPI diets. Histological analyses of the liver showed that HC diet resulted in steatosis widely distributed throughout the hepatic lobule, while HWS and HPI diets promoted reductions in liver steatosis. The effectiveness of HWS for modulating lipid metabolism was greater than that of HPI, as measured by plasma cholesterol reduction and liver steatosis.

Interaction of hypercaloric diet and physical exercise on lipid profile, oxidative stress and antioxidant defenses

The present study examined the interaction of hypercaloric diet (HD) and physical exercise on lipid profile and oxidative stress in serum and liver of rats. Male Wistar rats (60-days-old) were fed with a control (C) and hypercaloric diet (H). Each of the two dietary groups (C and H) was divided into three subgroups (n = 8), sedentary (CS and HS), exercised 2 days a week (CE2 and HE2) and exercised 5 days a week (CE5 and HE5). The swimming was selected as a model for exercise performance. After 8-weeks exercised rats showed decreased lactate dehydrogenase serum activities, demonstrating the effectiveness of the swimming as an aerobic-training protocol. Exercise 5-days a week reduced the body weight gain. Triacylglycerol (TG) and very low-density lipoprotein (VLDL-C) were increased in HD-fed rats. HE5 and CE5 rats had decreased TG, VLDL-C and cholesterol. HE2 rats had enhanced high-density lipoprotein (HDL-C) in serum. No alterations were observed in lipid hydroperoxide (LH), while total antioxidant substances (TAS) were increased in serum of exercised rats. HD-fed rats had hepatic TG accumulation. Superoxide dismutase activities were increased and catalase was decreased in liver of exercised rats. The interaction of HD and physical exercise reduced TAS and enhanced LH levels in hepatic tissue. In conclusion, this study confirmed the beneficial effect of physical exercise as a dyslipidemic-lowering component. Interaction of HD and physical exercise had discrepant effects on serum and liver oxidative stress. The interaction of HID and physical exercise reduced the oxidative stress in serum. HD and physical exercise interaction had pro-oxidant effect on hepatic tissue, suggesting that more studies should be done before using physical exercise as an adjunct therapy to reduce the adverse effects of HD. (c) 2006 Elsevier Ltd. All rights reserved.