Hyperlipidemias: Latin America

Alcocer L. · México City General Hospital and National Autonomous University of México, México City, Mexico. · Am J Ther. · Pubmed #14624280 No free full text.

Abstract: Classically, the statins are the first choice drugs when treating dyslipidemias, especially in patients with hypercholesterolemia alone or accompanied by hypertriglyceridemia. The recent evidence of the effectiveness, safety and impact comes from hard endpoints, as demonstrated in 6 trials which included more than 40,000 subjects. The statins are being recommended for the treatment of a large number of patients with overt coronary heart disease, regardless of serum cholesterol levels, in patients with acute phases of coronary syndromes, and in patients without apparent coronary heart disease with moderate risk and average serum cholesterol and LDL cholesterol levels. These drugs are also being prescribed to patients with high-risk medical conditions that are "equivalent to coronary heart disease," like diabetes, lower limb atherosclerosis, or vascular cerebral disease, independent of the basal serum cholesterol levels or LDL cholesterol ranging from normal to high. Despite all the evidence collected as to the efficacy and safety of these drugs, the statins are not sufficiently used in daily practice, probably due to the ignorance of new concepts and the doubts related to the safety that may be cleared by careful analysis of 6 major studies with these drugs.

Zanlungo S, Nervi F. · Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago Chile. · Eur Rev Med Pharmacol Sci. · Pubmed #12911117 No free full text.

Abstract: Arteriosclerosis and cholesterol cholelithiasis are characterized by abnormal regulation of cholesterol trafficking and solubilization, and subsequent development of the arteriosclerotic plaque in the artery walls and gallstone formation in the gallbladder, respectively. Cholesterol metabolism is controlled by many complex polygenetic - environmental interactions that contribute to the regulation of serum lipoprotein cholesterol levels and biliary cholesterol and bile acids secretion, which constitute the only pathway for sterol elimination from the organism. Much of our understanding of cholesterol metabolism has arisen from studies of the pathways controlling cholesterol synthesis and the uptake and degradation of LDL and HDL lipoproteins. Recently, two new members of the ABC transporter family (ABCG5 and ABCG8 heterodimers) have been discovered in the apical pole of the enterocyte and in the canalicular membrane of hepatocytes. Experiments in genetically engineered mice have demonstrated that ABCG5/G8 represent the physiological canalicular transporter of biliary cholesterol and the intestinal secretory mechanism of absorbed dietary plant sterols. Interestingly, mutation of ABCG5 and or ABCG8 genes in man causes sitosterolemia, a rare genetic disease characterized by massive absorption of plant sterols and premature arteriosclerosis. The potential pharmacological manipulation of biliary cholesterol secretion represents another important therapeutic target to treat hypercholesterolemia, if this manipulation is simultaneously accompanied by measures aimed to avoid gallbladder cholesterol crystallization. The best theoretical drug should decrease serum lipoprotein cholesterol levels, increase biliary cholesterol secretion and fecal elimination and favoring at the same time gallbladder emptying to prevent gallstone formation.

Forti N, Salazar LA, Diament J, Giannini SD, Hirata MH, Hirata RD. · Faculdade de Medicina, USP, Faculdad de Medicina Universidad de La Fontera, Temuco, Chile. · Arq Bras Cardiol. · Pubmed #12792722 links to  free full text

This publication has no abstract.

Lerman Garber I. · Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. · Rev Invest Clin. · Pubmed #12587422 No free full text.

This publication has no abstract.

Velásquez E. · Unidad de Endocrinología, Facultad de Medicina, Hospital Universitario de Los Andes, Mérida, Venezuela. · Invest Clin. · Pubmed #12229282 No free full text.

Abstract: In addition to neuroendocrine abnormalities, women with polycystic ovary syndrome have insulin resistance and beta-cell dysfunction associated with a high frequency of metabolic syndrome components, such as glucose intolerance, type 2 diabetes mellitus (DM-2), dyslipidemia and a higher risk for endothelial dysfunction, haemostatic abnormalities, hypertension and cardiovascular disease. Obesity, a common finding in this disorder, plays an important role in the development of metabolic and cardiovascular disorders. Early identification of patients and prompt initiation of insulin sensitizing therapy by pharmacological agents or changes in life style such diet and exercise might improve the metabolic and endocrine abnormalities and reduce the risk of DM-2 and cardiovascular disease in these patients.

Alvarez-Martínez H, Pérez-Campos E. · Hospital Regional Presidente Juárez, ISSSTE, Oaxaca, Oax. · Rev Gastroenterol Mex. · Pubmed #12214335 No free full text.

Abstract: Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that occurs in patients with no significant alcohol consumption; it is not histologically different from alcoholic hepatitis because it presents macrovesicular steatosis, hepatocellular necrosis, mixed inflammatory infiltrate, and various stages of fibrosis in addition Mallory bodies in some patients. Some authors have even described NASH as a benign disease; however, it is presently considered a potentially serious disease that may evolve into liver cirrhosis and probably, liver cancer. It is more often related to female sex, obesity, and dyslipidemia, although it may be present in other population groups and associated with other factors. Its origin may be multifactorial, including insulin resistance, protein glycation, oxidative stress, and others. The disease may be asymptomatic and found in routine physical exams when the patient shows increased aminotransferases with no other explanation. At present the only specific diagnosis procedure is liver biopsy. The sole available current treatment is body weight control, normalizing glucose and lipid blood levels, as well as the administration of some medication, as illustrated in the subsequent article.

Cubeddu LX, Hoffmann IS. · Nova Southeastern University, HPD, Florida, USA, and Center for the Detection and Treatment of Silent Cardiovascular Risk Factors (SIL-DETECT), Central University of Venezuela, Caracas, Venezuela. · J Hum Hypertens. · Pubmed #11986895 links to  free full text

Abstract: Reduced insulin-mediated glucose disposal, indicative of insulin resistance, has been demonstrated in lean male hypertensives both with the hyperinsulinaemic euglycaemic clamp and the insulin suppression test. In lean hypertensives, insulin resistance was not accompanied by increases in fasting plasma insulin and glucose levels; but with modest hyperglycaemia and hyperinsulinaemia after a glucose load. Population studies (no stratification) reveal that: (1) insulin sensitivities vary widely in normotensives and hypertensives, (2) there are hypertensives and normotensives with similar degrees of insulin resistance, (3) not all hypertensives are insulin resistant, and (4) insulin resistance does not contribute to the blood pressure level of the hypertensive population. In large cross-sectional studies, the clustering of obesity, dyslipidaemia and type 2 diabetes is largely responsible for the observed associations between insulin or insulin resistance and hypertension. Recent studies indicate a role of glucose in blood pressure control. Glucose has been shown to elevate blood pressure in the presence of endothelial dysfunction and glucose values in the upper-normal range have been shown to be associated with increased cardiovascular mortality. Since endothelial dysfunction is present in hypertensives, dyslipidaemic, obese and in glucose intolerant individuals, lowering of high-normal glucose levels becomes a new, additional therapeutic target in the management of these patients. Hyperglycaemia together with endothelial dysfunction may account for the increased incidence of hypertension in obesity and diabetes mellitus. Because of the strong association between insulin resistance, hyperglycaemia and endothelial dysfunction, and the clustering of risk factors in these subjects, we propose the lowering of high normal glucose levels as part of the therapeutic strategy to prevent cardiovascular and metabolic disease.

Bassan R. · Hospital Pró-Cardíaco, Rio de Janeiro, Brazil. · Arq Bras Cardiol. · Pubmed #10347915 No free full text.

This publication has no abstract.

Ghattas AE, Pimenta J. · Hospital do Servidor Público Estadual, São Paulo, SP, Brasil. · Arq Bras Cardiol. · Pubmed #18066453 links to  free full text

Abstract: BACKGROUND: Statins are widely used because they reduce cardiac events. Although they are indicated for daily use, some doctorsgive prescriptions for every other day, mainly with the purpose of reducing costs. OBJECTIVE: To evaluate the efficacy of atorvastatin, when not administered everyday, on LDL-cholesterol (LDL-C) levels, and also to evaluate cost reduction. METHODS: A total of 100 patients with hypercholesterolemia in primary (PP) and secondary prevention (SP) were assessed. After a 12-week diet period, atorvastatin was initiated at a dose of 10 mg per day. After six weeks, LDL-C was determined, and if the levels were <80 or <104 mg/dL for SP and PP, respectively, two atorvastatin doses were subtracted per week. If LDL-C remained <80 or <104 mg/dL, a further reduction to three times a week was allowed, and the last determination was performed after six more weeks. The percentage variation in costs was the parameter to evaluate the saving. RESULTS: In 47 out of the 52 patients of this group, a reduction by 32% in LDL-C was observed, and daily atorvastatin was maintained. Forty one patients remained throughout the study and had their weekly dosage reduced. In 25 patients the medication was administered three times a week, and in 16, five times a week, with reductions of 42.4% and 46.1% in LDL-C, respectively. As regards costs, one of the groups had their monthly expense reduced from R$ 106.65 to R$ 74.65, and the other group from R$ 106.65 to R$ 53.33. CONCLUSION: The results suggest that atorvastatin may be administered on a non-daily basis. A cost reduction between 30% and 50% was also observed.

Reyna-Villasmil N, Bermúdez-Pirela V, Mengual-Moreno E, Arias N, Cano-Ponce C, Leal-Gonzalez E, Souki A, Inglett GE, Israili ZH, Hernández-Hernández R, Valasco M, Arraiz N. · Center for Metabolic and Endocrine Research, The University of Zulia, Maracaibo, Venezuela. · Am J Ther. · Pubmed #17414591 No free full text.

Abstract: OBJECTIVE: To investigate the effect of bread formulated with 6 g of beta-glucan (oat soluble fiber) on serum lipids in overweight normotensive subjects with mild to moderate hypercholesterolemia. DESIGN: Thirty-eight male subjects [mean age 59.8 +/- 0.6 yr, mean body mass index (BMI) 28.3 +/- 0.6 kg/m(2)] who were eligible for the study ate an isocaloric diet for a 1-week period. They were then divided into 2 groups: group A (n = 19), who were maintained on American Heart Association (AHA) Step II diet, including whole wheat bread, and group B (n = 19), who were maintained on AHA Step II diet containing high levels of monounsaturated fatty acids plus bread containing 6 g of beta-glucan (Nutrim-OB) for 8 weeks. Plasma lipids and glucose were measured at baseline and after weeks 8 in all subjects. All subjects were advised to walk for 60 minutes every day. RESULTS: There was a significant increase (upward arrow 27.8%) in plasma high density lipoprotein (HDL) cholesterol in the beta-glucan group (group A) from 39.4 +/- 2.0 to 49.5 +/- 2.1 mg/dL (P < 0.001), but there was no change in group B. There was a significant reduction in total cholesterol in the 2 groups to approximately the same extent: group A, from 232.8 +/- 2.7 mg/dL to 202.7 +/- 6.7 mg/dL; P < 0.001; and group B, from 231.8 +/- 4.3 mg/dL to 194.2 +/- 4.3 mg dL; P < 0.001. Plasma low density lipoprotein (LDL) cholesterol also decreased significantly in the two groups: group A, from 160.3 +/- 2.8 mg/dL to 133.2 +/- 5.4 mg/dL; P < 0.001; group B, from 167.9 +/- 4.3 mg/dL to 120.9 +/- 4.3 mg/dL; P < 0.001; however, the beta-glucan fortified diet was significantly more effective (downward arrow 27.3% vs. downward arrow 16.8%; P < 0.04). There was a small and insignificant reduction in plasma very LDL (VLDL) cholesterol and triglycerides in the two groups. Similarly, non-HDL cholesterol levels were also decreased, with beta-glucan diet producing significantly higher effect (downward arrow 24.5% vs. downward arrow 16.1%; P < 0.04). The beta-glucan diet also produced higher reduction in total cholesterol/HDL cholesterol ratio (downward arrow 33.3% vs. downward arrow 8.4%; P < 0.003) and LDL cholesterol/HDL cholesterol ratio (downward arrow 42.1% vs. downward arrow 13.3%; P < 0.001) than the diet without beta-glucan. The beta-glucan diet also decreased fasting plasma glucose (P < 0.4), whereas the other diet had no effect. Interestingly, both diets reduced body weight and BMI significantly, with beta-glucan diet having a greater effect. CONCLUSIONS: Six grams of beta-glucan from oats added to the AHA Step II diet and moderate physical activity improved lipid profile and caused a decrease in weight and, thus, reduced the risk of cardiovascular events in overweight male individuals with mild to moderate hypercholesterolemia. The diet with added beta-glucan was well accepted and tolerated.

Isaza C, Henao J, Ramirez E, Cuesta F, Cacabelos R. · Laboratory of Medical Genetics, Pereira Technological University Medical School, Pereira, Colombia. · Methods Find Exp Clin Pharmacol. · Pubmed #16082424 No free full text.

Abstract: Different polymorphisms of the ADRB2 gene encoding the beta-adrenergic receptor (ADRB2) are associated with changes in a variety of responses of the sympathetic nervous system (SNS). In this study, we have investigated the distribution of frequencies of ADRB2-related allelic variants (Arg16Gly, Gln27Glu, Thr164Ile) in the Colombian population, as well as the influence of the Gln27Glu polymorphism as a risk factor for the development of dyslipidemia following propranolol administration. Genotyping was performed in unrelated Colombian volunteers, using PCR-RFLP methods. To examine the association between the Gln27Glu polymorphism of the ADRB2 gene and dyslipidemia induced by propranolol, we recruited 19 healthy individuals who were homozygous for either the Gln27 (wild-type, N = 11) or the Glu27 (homozygous mutant, N = 8) genotype. Electrocardiography (ECG), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), serum lipid levels (T-CHO, HDL-CHO, TG), and fibrinogen were determined before and after propranolol administration. The distribution of genotypes was as follows: Arg16Arg 46%, Arg16Gly 47.4%, Gly16Gly 6.6%, Gln27Gln 44.7%, Gln27Glu 48.2%, and Glu27Glu 7.1%, with allelic frequencies of 69.7% for Arg16, 30.3% for Gly16, 68.8% for Gln27, and 31.2% for Glu27. The Thr164Ile polymorphism was found only in one subject, who was heterozygous for the isoleucine variant. Significant changes in physiological parameters (HR, SBP, DBP) have been found in association with ADRB2 variants in both native and mutant subgroups after propranolol intake. HDL-CHO levels diminished (p = 0.005) in native homozygous individuals (Gln27Gln), whereas TG levels were found increased (p = 0.012) in the mutant homozygous individuals (Glu27Glu). T-CHO levels and serum fibrinogen levels remained unaltered in both subgroups. The evidence that subjects homozygous for Gln27 in the ADRB2 gene show a significant reduction of HDL-CHO levels, as well as the increased TG levels in subjects homozygous for Glu27 after propranolol administration, suggest that the Gln27Glu polymorphism represents a risk factor for dyslipidemia induced by propranolol. These results may contribute to a better understanding of the mechanisms underlying dyslipidemia induced by ADRB2 antagonists.

Castaño G, Fernández L, Mas R, Illnait J, Gámez R, Mendoza S, Mesa M, Fernández J. · Surgical Medical Research Center, Havana City, Cuba. · Drugs R D. · Pubmed #16050054 No free full text.

Abstract: BACKGROUND: Policosanol is a mixture of higher aliphatic primary alcohols purified from sugar-cane wax. The mixture has cholesterol-lowering efficacy, its specific effects being to reduce serum total (TC) and low-density lipoprotein cholesterol (LDL-C), and to increase high-density lipoprotein cholesterol (HDL-C). The effects of policosanol on triglycerides (TG) are modest and inconsistent. Omega-3 fatty acids (FA) from fish oil protect against coronary disease, mainly through antiarrhythmic and antiplatelet effects. Omega-3 FA also have lipid-modifying effects, mostly relating to TG reduction. Thus, potential benefits could be expected from combined therapy with omega-3 FA and policosanol. OBJECTIVE: To investigate whether combined therapy with omega-3 FA + policosanol offers benefits compared with omega-3 FA + placebo with respect to the lipid profile of patients with type II hypercholesterolaemia. METHODS: This randomised, double-blind study was conducted in 90 patients with type II hypercholesterolaemia. After 5 weeks on a cholesterol-lowering diet, patients were randomised to omega-3 FA + placebo, omega-3 FA + policosanol 5 mg/day or omega-3 FA + policosanol 10 mg/day for 8 weeks. Omega-3 FA was supplied as 1g capsules (two per day); placebo and policosanol were provided in tablet form. Physical signs and laboratory markers were assessed at baseline and after 4 and 8 weeks on therapy. Drug compliance and adverse experiences (AEs) were assessed at weeks 4 and 8. The primary efficacy variable was LDL-C reduction; other lipid profile markers were secondary variables. RESULTS: After 8 weeks, omega-3 FA + policosanol 5 and 10 mg/day, but not omega-3 FA + placebo, significantly reduced LDL-C by 21.1% and 24.4%, respectively (both p < 0.0001). Omega-3 FA + policosanol 5 mg/day also significantly lowered TC (12.7%; p < 0.01) and TG (13.6%; p < 0.05), and significantly increased HDL-C (+14.4%; p < 0.001). Omega-3 FA + policosanol 10 mg/day significantly decreased TC (15.3%; p < 0.001) and TG (14.7%; p < 0.01), and significantly increased HDL-C (+15.5%; p < 0.0001). Omega-3 FA + placebo significantly reduced TG (14.2%; p < 0.05) but had no significant effect on other lipid profile variables. The proportion of randomised patients in the omega-3 FA + policosanol 5 or 10 mg/day groups that achieved LDL-C targets or reductions 15% was significantly greater than in the omega-3 FA + placebo group (p < 0.001). Combined therapy with omega-3 FA + policosanol 5 or 10 mg/day resulted in significantly greater changes in LDL-C, TC and HDL-C than treatment with omega-3 FA + placebo, but did not modify the TG response compared with the omega-3 FA + placebo group. Four patients (two in the omega-3 FA + placebo group and two in the omega-3 FA + policosanol 10 mg/day group) withdrew from the study; none of these withdrawals was due to AEs. Two patients reported mild AEs, namely nausea/headache (one in the omega-3 FA + placebo group) and heartburn (one in the omega-3 FA + policosanol 5 mg/day group). CONCLUSIONS: Policosanol 5 or 10 mg/day administered concomitantly with omega-3 FA 1 g/day improved LDL-C, TC and HDL-C, maintained the reduction in TG attributable to omega-3 FA monotherapy, and was well tolerated. Treatment with omega-3 FA + policosanol could be useful for regulating lipid profile in patients with type II hypercholesterolaemia, but further studies involving larger sample sizes are needed before definitive conclusions can be drawn.

Macin SM, Perna ER, Farías EF, Franciosi V, Cialzeta JR, Brizuela M, Medina F, Tajer C, Doval H, Badaracco R. · Coronary Intensive Care Unit, Instituto de Cardiología Juana F. Cabral, Corrientes, Argentina. · Am Heart J. · Pubmed #15864233 No free full text.

Abstract: BACKGROUND: C-reactive protein (CRP) levels are associated with cardiovascular risk. We assessed the hypothesis that atorvastatin might have anti-inflammatory effects in acute coronary syndromes (ACS) as shown by CRP reduction. METHODS: This study was a prospective, randomized, double-blind, placebo-controlled study of 90 consecutive patients admitted within 48 hours of onset of ACS with CRP levels > or =1.4 mg/dL. Patients were assigned to atorvastatin 40 mg daily or placebo over 30 days. C-reactive protein levels, lipid profiles, serum fibrinogen, white cell count, and erythrocyte sedimentation rate were measured at entry, hospital discharge, and 1 month later. RESULTS: Baseline clinical characteristics did not differ between atorvastatin and placebo groups (mean age 59.3 +/- 13.4 vs 61.1 +/- 11.5, P = ns); myocardial infarction 52.3% versus 67.4% ( P = ns). In both groups, median baseline CRP levels were comparable (5.97 +/- 6.2 vs 4.64 +/- 4.2 mg/dL, P = ns). C-reactive protein levels were lower in the atorvastatin group versus control group at discharge (1.68 +/- 1.65 vs 4.12 +/- 4.18 mg/dL) and at 30 days (0.50 +/- 0.71 vs 2.91 +/- 2.68 mg/dL, both P < .0001). C-reactive protein levels significantly decreased from baseline to discharge and 1 month later in placebo and atorvastatin groups (both P < .0001); however, the reduction was greater in the atorvastatin group (62% vs 11% at discharge [P < .0001]; 84% vs 30% at 1 month [P < .0001]). In addition, atorvastatin was associated with a reduction in total and low-density lipoprotein cholesterol and erythrocyte sedimentation rate at discharge and at 30 days (P < .0001 for all comparisons). No correlation was found between changes in CRP and cholesterol levels. CONCLUSIONS: C-reactive protein levels in ACS were rapidly reduced with atorvastatin. These data provide evidence that statins have fast and early anti-inflammatory effects in addition to lipid-lowering effects in ACS.

Paulós CP, Nygren CE, Celedón C, Cárcamo CA. · Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile. · Ann Pharmacother. · Pubmed #15827075 No free full text.

Abstract: BACKGROUND: Inappropriate use of medications is a significant problem in health care today. A possible solution to this problem may be achieved through better control of patients' drug therapy. OBJECTIVE: To design a pharmaceutical care program for dyslipidemic patients within a community pharmacy setting that provides education in the areas of medication compliance and lifestyle modifications, while emphasizing the importance of achieving cholesterol goals to ensure improvement in quality of life. METHODS: Patients at an outpatient pharmacy volunteered to be surveyed for 16 weeks. Although both the intervention and control groups were surveyed, the randomly selected intervention group was interviewed more frequently and more comprehensively. Cholesterol, triglycerides, glucose, weight, risk factors, drug-related problems (DRPs), and quality of life were measured via a survey at the onset of the study and continually measured until the study's conclusion. RESULTS: In the intervention group, 26 DRPs were detected, of which 24 were resolved; in the control group, 26 DRPs were detected, of which 5 were resolved. When comparing initial and final blood cholesterol levels in the intervention group, the mean decrease was 27.0 +/- 41.1 mg/dL (p = 0.0266); in the control group, the average blood cholesterol level decreased by a mean of 1.4 +/- 37.2 mg/dL (p = 0.6624). In the intervention group, the triglyceride level decreased an average of 50.5 +/- 80.3 mg/dL (p = 0.0169), while the control group experienced a mean triglyceride level increase of 29.6 +/- 118.5 mg/dL (p = 0.1435). As a result of the intervention, the quality of life in the intervention group was improved. CONCLUSIONS: Short-term pharmaceutical care plans developed in a retail pharmacy within the proper setting may contribute to improved blood lipid values, cardiovascular disease risk factors, and patients' quality of life.

Melo NR, Latrilha MC, Santos RD, Pompei LM, Maranhão RC. · Department of Gynecology, University of São Paulo Medical School Hospital, São Paulo, Brazil. · Maturitas. · Pubmed #15780526 No free full text.

Abstract: OBJECTIVE: To evaluate the effects of transdermal estradiol and medroxyprogesterone acetate (MPA) treatment on the removal from the plasma of a cholesterol-rich microemulsion (LDE) that roughly resembles low-density lipoprotein (LDL) structure and that binds to LDL receptors. METHODS: Ten healthy post-menopausal women were studied before and after 3-month treatment with transdermal estradiol in the following dosages administered every 3.5 days: 25, 50, 50, 100, 100, 50, 50 and 25 microg. From the 15th to the 21st day and from the 22nd to the 28th day of estrogen treatment, respectively, 10 and 5 mg q.d. MPA per oral were associated to the transdermal estrogen. The emulsion labeled with 14C-cholesteryl oleate was injected after 12 h fasting and its fractional catabolic rate (FCR) was calculated from the plasma decaying curves of the isotope. RESULTS: Treatment reduced LDL-cholesterol levels by 8% only (149.0 +/- 36.0 mg/dl, 138.0 +/- 27.0 mg/dl; P = 0.046), but the FCR of LDE expressed in medians (25%; 75%) increased from 0.0054 (0.003; 0.052) h(-1) to 0.021 (0.009; 0.10) h(-1), P = 0.002. CONCLUSION: The association used in this study so as to mimic the increasing-decreasing pattern of the hormonal ovarian production reduced modestly LDL-cholesterol levels but pronouncedly increased the lipoprotein removal as tested by LDE FCR.

Castaño G, Mas R, Gámez R, Fernández J, Illnait J, Fernández L, Mendoza S, Mesa M, Gutiérrez JA, López E. · Center for Natural Products, National Center for Scientific Research, Havana City, Cuba. · Int J Clin Pharmacol Res. · Pubmed #15689053 No free full text.

Abstract: Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. It is safe and well tolerated, even in populations with high consumption of concomitant drugs. These data suggest that adverse events (AE) due to drug-to-drug interactions (DDI) with policosanol are not relevant. Experimental data indicate that potential DDI between policosanol and drugs metabolized through the cytochrome P450 hepatic system are not expected, but pharmacodynamic DDI cannot be excluded. Several clinical studies have shown that policosanol decreased arterial pressure compared with placebo, and a pharmacological interaction with beta-blockers was experimentally proven. Therefore, clinical DDI between policosanol and beta-blockers can be expected. This study investigated whether policosanol reinforces the antihypertensive effects of beta-blockers and/or whether this combination impairs some safety indicators or induces specific AE in older patients. After 5 weeks on a diet-only baseline period, 205 older hypercholesterolemic patients taking beta-blockers were randomized to policosanol 5 mg/day or placebo for 3 years. After 1 year on therapy, policosanol significantly reduced (p < 0.00001 versus placebo) low-density lipoprotein-cholesterol (LDL-C) (20.9%), total cholesterol (TC) (19.3%) and triglycerides (TG) (25.7%), whereas it increased (p < 0.01 and p < 0.001 versus placebo) high-density lipoprotein-cholesterol (HDL-C) levels (4.1%). Treatment effects did not to wear off during the 3-year follow-up. At study completion, policosanol lowered (p < 0.00001 versus placebo) LDL-C (34.3%), TC (23.2%) and TG (21.2%) and raised (p < 0.00001 versus placebo) HDL-C (12.3%). Thirty-one patients (15.1%) discontinued the study, 22 in the placebo group (20.6%) and nine in the policosanol group (9.2%). Of these, 20 patients (16 in the placebo group and four in the policosanol group) withdrew from the study due to AE. The frequency of serious adverse events (SAE), mostly vascular, in policosanol patients (3/98, 3.1%) was lower than in the placebo group (15/107, 14.0%). No impairment of safety indicators was observed. Nevertheless, reductions in systolic and diastolic blood pressure were observed in policosanol patients compared with those in the placebo group. The frequency of policosanol patients reporting mild or moderate AE (18/98, 18.4%) was also lower than in the placebo group (30/107, 28.0%). In conclusion, policosanol was well tolerated in elderly patients taking beta-block- ers and did not increase AE. Additional reduction of blood pressure and a lower frequency of SAE were observed in policosanol patients compared with those taking placebo. The cholesterol-lowering efficacy of policosanol was that expected. These results provide support that policosanol therapy added to hypercholesterolemic elderly individuals taking beta-blockers could provide additional benefits in lowering blood pressure; SAE were not more frequent in the policosanol group than in the placebo group and there was no increase in AE.

Herrera-Arellano A, Aguilar-Santamaría L, García-Hernández B, Nicasio-Torres P, Tortoriello J. · Centro de Investigación Biomédica del Sur, Instituto Mexicano del Seguro Social, Xochitepec, Morelos, México. · Phytomedicine. · Pubmed #15636168 No free full text.

Abstract: Cecropia obtusifolia and Marrubium vulgare have been widely used in Mexican traditional medicine for the control of type 2 diabetes. In order to evaluate the clinical effect produced by the aqueous extract from these species on type 2 non-controlled diabetes mellitus, a total of 43 outpatients were included. Based on the European NIDDM (policy group) criteria, only patients with poor response to the conventional treatment were selected. All patients maintained their medical treatment and also received a prepared infusion of the dry leaves of the plant treatment for 21 days. In a double-blind manner, the patients were randomly grouped as follows: 22 patients were treated with C. obtusifolia and 21 with M. vulgare. The fasting blood glucose values were reduced by 15.25% on patients treated with C. obtusifolia, while cholesterol and triglycerides were decreased by 14.62% and 42.0%, respectively (ANOVA p< 0.02). In the case of patients treated with M. vulgare, the plasma glucose level was reduced by 0.64% and cholesterol and triglycerides by 4.16% and 5.78%, respectively. When the results were compared between groups, significant differences in glucose and cholesterol diminution were found. The obtained results showed that the infusion prepared with the leaves of C. obtusifolia (containing 2.99+/-0.14mg of chlorogenic acid/g of dried plant) produced beneficial effects on carbohydrate and lipid metabolisms when it was administered as an adjunct on patients with type 2 diabetes with poor response to conventional medical treatment.

Zdrenghea D, Gligor E, Ossian V, Pop D. · Division of Cardiology, Rehabilitation Hospital, University of Medicine Cluj-Napoca, Romania. · Rom J Intern Med. · Pubmed #15529604 No free full text.

Abstract: Statins are highly effective in lowering TC and LDL-C but the increasing of HDL-C is modest and the cost of long-term treatment is too high. On the other hand it is known that the association of H2 receptor blockers increases the plasmatic level of statins, and moderate alcohol consumption increases HDL-C. The purpose of the study was to compare the effect of statins alone and in association with either H2 receptor blockers or alcohol upon serum lipids in dyslipidemic patients. Three groups of dyslipidemic patients were studied, each of them consisting of 20 patients. The group A was treated with simvastatin 20 mg/day, the group B with simvastatin 20 mg/day + ranitidine 150 mg/day and the group C with simvastatin 20 mg/day + 30 g alcohol/day. Before and after two weeks treatment TC, LDL-C, HDL-C and TG were determined in each patient. For the group A patients the studied lipid fractions were modified into the limits described by the literature; for the group B patients, the decreasing of LDL-C was significantly, higher than for A group; for the group C patients, the incresing of HDL-C was significantly, higher than for A group, after two week alcohol consumption. In conclusions, the association of H2 receptor blockers increases the effect of statins upon dyslipidemia and the association of statins with moderate alcohol consumption increases the effect of statins upon HDL-C but the clinical implication has to be established.

Faludi AA, Aldrighi JM, Bertolami MC, Saleh MH, Silva RA, Nakamura Y, Pereira IR, Abdalla DS, Ramires JA, Sousa JE. · Dante Pazzanese Institute of Cardiology, São Paulo, Brazil. · Atherosclerosis. · Pubmed #15488870 No free full text.

Abstract: This double blind randomized placebo controlled study assessed the effects of atorvastatin, estradiol and norethisterone, isolated and in combination, on the lipid profile and on vascular reactivity, in post-menopausal women with hypercholesterolemia and arterial hypertension. Ninety-four women aged 50-65 were selected. All have received dietary counseling (4 weeks), placebo (4 weeks), and drug therapy (12 weeks): 17-beta estradiol 2mg/day (E) (n=17); E + norethisterone acetate 1mg/day (P) (n=18); Atorvastatin 10mg/day (A) (n=20); E + A (n=21) and E + P + A (n=18). All treatment modalities have significantly reduced total cholesterol (TC) (E=8.8%, E + P=10.1%, A=27.9%, A + E=29.4% and E + P + A=35.7%) and LDL-cholesterol (LDL-c) levels (E + P + A=46.6%, E + A=45.9%, A=40.2%, E=20.3%, and E + P=12.1%). As concerns HDL-cholesterol (HDL-c), Groups E and E + A had increases of 15.5% and 13.1%, respectively. The addition of a progesterone compound reduced its concentration (Group E + P=-9.1%, and Group E + P + A=-9.5%). By random, approximately half of the patients in each group were designated to the endothelial function evaluation (brachial artery ultrasound). We observed that in Group A (n=10), in Group E (n=10) and with the association (Group E + A) (n=7), there was a significant increase in the flow-mediated vasodilatation as compared to basal measurements. The addition of a progestin has annulled these benefits. CONCLUSIONS: Atorvastatin has promoted more beneficial effects on TC and LDL-c, whereas estradiol was responsible for an increase in HDL-c. The addition of a progesterone derivative abolished these benefits. Atorvastatin, estradiol or both together improved endothelial function, an effect suppressed by the addition of norethisterone.

Zaffari D, Losekann A, Santos AF, Manfroi WC, Bittar AE, Keitel E, Souza VB, Costa M, Prates VC, Kroth L, Braun ML. · Postprogram in Cardiology and Cardiovascular Sciences, Federal University of Rio Grande do Sul, and Nephrology Outpatient and Renal Transplantation Ward and Division of Nutrition and Dietetics, Complexo Hospitalar Santa Casa de Porto Alegre, Brazil. · Transplant Proc. · Pubmed #15194305 No free full text.

Abstract: In renal transplant patients dietary therapy alone does not always provide satisfactory results to control hyperlipidemia. To assess the effectiveness of diet, 151 renal transplant patients were selected for a prospective clinical study using pre- and posttest groups. During 8 weeks these patients received a diet with 25% energy intake from lipids, less than 10% from saturated fats, and less than 500 mg of cholesterol per day. Total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were measured (pre- versus postdiet). The degree of compliance with the diet was measured by a 24-hour food recall record. Patients who had 90% compatibility between the questionnaire and the prescribed diet were considered compliant. The diet was considered effective in the patients who achieved a reduction of cholesterolemia to less than 200 mg/dL after 8 weeks of treatment. Ultimately 108 patients completed the study, with a significant reduction in total serum cholesterol from 262.37 mg/dL pretest to 252.85 mg/dL posttest (P =.010); LDL cholesterol from 174.29 mg/dL pretest to 166.60 mg/dL posttest (P =.036), of body weight from 68.98 kg pretest to 67.78 kg posttest (P =.01) and of body mass index from 25.86 kg/m(2) pretest to 25.41 kg/m(2) posttest (P =.01). Cholesterol variation was 3.63% as compared to prediet levels. Only 22 patients (20.4%) achieved cholesterol levels below 200 mg/dL. In conclusion, although diets decrease cholesterolemia, they alone are not effective to control hyperlipidemia in most renal transplant patients.

Bricarello LP, Kasinski N, Bertolami MC, Faludi A, Pinto LA, Relvas WG, Izar MC, Ihara SS, Tufik S, Fonseca FA. · Cardiology Division, Federal University of São Paulo, Rua Pedro de Toledo 458, São Paulo, Brazil. · Nutrition. · Pubmed #14962687 No free full text.

Abstract: OBJECTIVE: This study assessed whether the consumption of soy milk could add significantly to the lipid profile and lipid peroxidation in comparison with non-fat milk. METHODS: A double-blind, randomized, crossover study was conducted on 60 outpatients with primary hypercholesterolemia following a lipid-lowering diet for at least 6 wk. Lipid profile was obtained at baseline and at 6 and 12 wk, with the patients randomly assigned to receive initially 1 L/d of soy milk or non-fat cow milk for 6 wk. Lipid peroxidation was estimated by plasma thiobarbituric reactive substances. Apolipoprotein E genotypes were examined by polymerase chain reaction restriction fragment length polymorphism. RESULTS: The soy milk diet was associated with low-density lipoprotein cholesterol reduction (baseline = 157 +/- 5 mg/dL; soy milk = 148 +/- 4 mg/dL; non-fat cow milk = 158 +/- 4 mg/dL; P < 0.05, soy milk versus other treatments) and with high-density lipoprotein cholesterol increase (baseline = 58 +/- 2 mg/dL; soy milk = 62 +/- 2 mg/dL; non-fat cow milk = 57 +/- 2 mg/dL; P < 0.05, soy milk versus other treatments). In addition, plasma thiobarbituric reactive substances were reduced by the soy milk diet (baseline = 1.82 +/- 0.12 nM/L; soy milk = 1.49 +/- 0.09 nM/L; non-fat cow milk = 1.91 +/- 0.11 nM/mL; P < 0.05, soy milk versus non-fat cow milk). Changes in lipid profile were not influenced by APOE genotypes. CONCLUSIONS: These results indicate that soy milk as part of a lipid-lowering diet has beneficial effects in improving lipid profile and reducing lipid peroxidation.

Sposito AC, Gonbert S, Bruckert E, Atassi M, Beucler I, Amsellem S, Khallouf O, Benlian P, Turpin G. · Dyslipoproteinemia and Atherosclerosis Research Unit (U.551), National Institute for Health and Medical Research, Paris, France. · Arterioscler Thromb Vasc Biol. · Pubmed #14512370 links to  free full text

Abstract: OBJECTIVE: The combination of LDL apheresis with high doses of a potent hepatic hydroxymethylglutaryl coenzyme A reductase inhibitor, such as atorvastatin, has been the best therapy available for the prevention of cardiovascular disease in patients with homozygous familial hypercholesterolemia (HFH). However, some concerns have been made about the effect of atorvastatin on HDL cholesterol levels in these patients. METHODS AND RESULTS: HDL cholesterol levels were determined bimonthly over the course of 2 years of treatment with high-dose atorvastatin in genotypically defined HFH patients either receptor-defective (n=6) or receptor-negative (n=6) under long-term treatment with LDL apheresis. We additionally stratified the atorvastatin effect on HDL cholesterol according to the genotype as an indicator of residual in vivo LDL receptor activity. Our findings indicate that (1) an early and transitory reduction of plasma HDL cholesterol levels occurs during the first 4 weeks of atorvastatin treatment; (2) the degree of the transient HDL reduction is higher in receptor-negative than in receptor-defective patients (-21+/-11 versus -10+/-4%; P=0.01); and (3) after long-term treatment, HDL cholesterol concentration remains higher in receptor-defective than receptor-negative patients (P=0.026). CONCLUSIONS: The present study reveals that HDL cholesterol reduction after high-dose atorvastatin is an early and transient event in HFH patients which magnitude depends on the presence of a residual LDL-R activity.

Cuevas AM, Irribarra VL, Castillo OA, Yañez MD, Germain AM. · Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica, Santiago, Chile. · Eur J Clin Nutr. · Pubmed #12879082 No free full text.

Abstract: BACKGROUND: Postmenopausia and hypercholesterolemia are related to endothelial dysfunction, a pathogenic event in atherosclerosis. Soy protein reduces plasma cholesterol, but there is scanty information about its effect on endothelial function. OBJECTIVE: To evaluate the effect of isolated soy protein compared to caseinate on plasma lipoproteins and endothelial function in postmenopausal hypercholesterolemic women. DESIGN: Randomized, double-blind, cross-over trial. SETTING: Outpatient clinic of the Catholic University of Chile. SUBJECTS: Eighteen healthy, postmenopausal women with hypercholesterolemia were recruited, included and completed the protocol. INTERVENTIONS: During the trial, all patients followed a low fat/low cholesterol diet and were randomly assigned to receive isolated soy protein or matching caseinate for 4 weeks, and then the alternative treatment until week 8. At pre-study and at the end of the first and second period, plasma lipoprotein levels and endothelial function (flow-mediated dilatation (FMD) of the brachial artery) were evaluated. RESULTS: Plasma total and low density lipoprotein (LDL)-cholesterol concentration were significantly lower with the low fat/low cholesterol diet compared to pre-study, either with caseinate or soy protein. No significant differences in plasma lipid concentration between caseinate or soy protein interventions were observed. FMD did not change with the caseinate. In contrast, when soy protein was administered, FMD was significantly higher compared to pre-study (9.4+/-1.8% vs 5.3+/-1.2%; P<0.05) and compared to caseinate intervention (9.4+/-1.8% vs 4.9+/-1.5%; P<0.033). CONCLUSIONS: These results suggest that in postmenopausal hypercholesterolemic women, soy protein improves endothelial function, regardless of changes in plasma lipoproteins.

Castaño G, Menéndez R, Más R, Amor A, Fernández JL, González RL, Lezcay M, Alvarez E. · Medical Surgical Research Center, Havana City, Cuba. · Int J Clin Pharmacol Res. · Pubmed #12837046 No free full text.

Abstract: In this pilot, randomized, double-blind study, we compared the effects of policosanol and lovastatin on lipid profile and lipid peroxidation in patients with dyslipidemia and type 2 diabetes mellitus. After 4 weeks on a cholesterol-lowering diet, 36 patients were randomized to policosanol (10 mg/day) or lovastatin (20 mg/day) tablets o.i.d. for 8 weeks. Policosanol significantly (p < 0.001) lowered serum low-density lipoprotein-cholesterol (LDL-C) (29.9%), total cholesterol (21.1%), triglycerides (13.6%) and the LDL-C/high-density lipoprotein-cholesterol (HDL-C) (36.7%) and total cholesterol/HDL-C (28.9%) ratios and significantly (p < 0.01) increased HDL-C (12.5%). Lovastatin significantly (p < 0.001) lowered LDL-C (25%), total cholesterol (18%), triglycerides (10.9%) and the LDL-C/HDL-C (30.4%) and total cholesterol/HDL-C ratios (23.9%) and significantly (p < 0.01) raised HDL-C (8.3%). Policosanol was more effective (p < 0.05) than lovastatin in reducing both ratios and in increasing (p < 0.05) HDL-C. Policosanol, but not lovastatin, significantly raised the lag time (20.9%) of Cu+2-induced LDL peroxidation and total plasma antioxidant activity (24.2%) (p < 0.05). Both policosanol and lovastatin significantly decreased the propagation rate (41.9% and 41.6% respectively, p < 0.001), maximal diene production (8.3% and 5.7%) and plasma levels of thiobarbituric acid reactive substances (9.7% and 11.5%, p < 0.001). Both treatments were well tolerated. Only one patient in the lovastatin group withdrew from the trial due to adverse events. In conclusion, policosanol and lovastatin administered short term to patients with dyslipidemia secondary to type 2 diabetes were effective in lowering cholesterol and in inhibiting the extent of lipid peroxidation. Policosanol (10 mg/day) was slightly more effective than lovastatin (20 mg/day) in reducing the LDL-C/HDL-C and total cholesterol/HDL-C ratios, in increasing HDL-C levels and in preventing LDL oxidation. Nevertheless, since this was a pilot study, further clinical studies performed in larger sample sizes of diabetic patients are needed for definitive conclusions.

Pereira EC, Bertolami MC, Faludi AA, Salem M, Bersch D, Abdalla DS. · Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Av. Prof. Lineu Prates, 580, Cidade Universitária-Butantã, 05508-900 São Paulo, Brazil. · Free Radic Res. · Pubmed #12797474 No free full text.

Abstract: Hypercholesterolemia is linked to endothelial dysfunction and enhancement of the endogenous inhibitor of NO synthase. The statins have lipid-lowering and pleiotropic properties, which could exert protective effects on the endothelium in hypercholesterolemia. The association of L-arginine with simvastatin could promote a further improvement on endothelial function in this condition. Thus, we investigated whether simvastatin, with or without supplementation with L-arginine, could improve endothelium-dependent vasodilation. In this study, 25 hypercholesterolemic subjects were treated according to the following protocol: washout period of 1 month; simvastatin (20 mg/day) for 2 months; simvastatin (20 mg/day) + L-arginine (7 g/day) for 2 months. From these patients, 10 were chosen at random for evaluation of vascular function by high resolution ultrasonography of the brachial artery. In subjects treated with simvastatin plus L-arginine, an increase of L-arginine levels (68%) and L-arginine/asymmetric dimethylarginine (ADMA) ratio (67%) were observed. Simvastatin reduced the plasma concentrations of NO metabolites nitrite + nitrate (NOx: 34%), S-nitrosothiols (RSNO: 42%), total cholesterol (25%), low density lipoprotein (LDL)-cholesterol (36%) and the LDL-cholesterol/high density lipoprotein (HDL-cholesterol ratio (34%). Simvastatin, associated or not to L-arginine, did not affect ADMA levels and endothelium-dependent vasodilation. Our data showed that simvastatin reduced the plasma concentrations of NOx and RSNO without affecting either the levels of ADMA or endothelium-dependent vasodilation in hypercholesterolemia.