Search

Patients with malignant disease may need hormonal therapy as primary or adjuvant treatment or for palliation. Oestrogens usually decrease serum levels of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), increase high density lipoprotein cholesterol (HDL-C) concentration, but induce an elevation in serum triglyceride (TG) levels. Progestogens in the short-term decrease TC, LDL-C and HDL-C concentrations, and increase TG levels. In long-term treatment, progestogens usually have a small impact on lipid profile. Tamoxifen induces a decrease in TC and LDL-C levels, an increase in TG concentration, whereas either an increase, decrease or no change has been reported for HDL-C levels. Aromatase inhibitors induce an elevation, reduction or no change in lipid variables. These results depend mainly on the trial design, i.e. whether patients received prior treatment with tamoxifen or not and the duration of therapy. Gonadorelin analogues increase all lipid variables, but LDL-C alterations are usually non-significant. Anti-androgens usually decrease TC, LDL-C and HDL-C levels, whereas TG alterations vary. Information regarding the effects on lipid profile of somatostatin analogues is available almost exclusively in patients with acromegaly. In these patients somatostatin analogues usually induce no change or a decrease in TC and LDL-C levels, whereas they increase HDL-C and decrease TG serum concentrations. Oncologists should consider the lifestyle changes, and if needed hypolipidemic treatment, used to lower cardiovascular risk in non-cancer patients. Tamoxifen may rarely cause serious TG-related side effects, like acute pancreatitis. © 2008 Elsevier Ltd. All rights reserved. 35 2 175 184

The focus of this review is on the role of apolipoprotein C-II (apoC-II) in lipoprotein metabolism and the potential effects on the risk of cardiovascular disease (CVD). We searched PubMed/Scopus for articles regarding apoC-II and its role in lipoprotein metabolism and the risk of CVD. Apolipoprotein C-II is a constituent of chylomicrons, very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein (HDL). Apolipoprotein C-II contains 3 amphipathic alpha-helices. The lipid-binding domain of apoC-II is located in the N-terminal, whereas the C-terminal helix of apoC-II is responsible for the interaction with lipoprotein lipase (LPL). At intermediate concentrations (approximately 4 mg/dL) and in normolipidemic subjects, apoC-II activates LPL. In contrast, both an excess and a deficiency of apoC-II are associated with reduced LPL activity and hypertriglyceridemia. Furthermore, excess apoC-II has been associated with increased triglyceride-rich particles and alterations in HDL particle distribution, factors that may increase the risk of CVD. However, there is not enough current evidence to clarify whether increased apoC-II causes hypertriglyceridemia or is an epiphenomenon reflecting hypertriglyceridemia. A number of pharmaceutical interventions, including statins, fibrates, ezetimibe, nicotinic acid, and orlistat, have been shown to reduce the increased apoC-II concentrations. An excess of apoC-II is associated with increased triglyceride-rich particles and alterations in HDL particle distribution. However, prospective trials are needed to assess if apoC-II is a CVD marker or a risk factor in high-risk patients. Metabolism

Objective: Mixed dyslipidemia, oxidative stress and inflammation are related to a high risk for cardiovascular events. The aim of this open-label randomized study was to compare the effects of high-dose rosuvastatin, low-dose rosuvastatin plus fenofibrate and low-dose rosuvastatin plus omega 3 fatty acids on inflammation and oxidative stress indices in patients with mixed dyslipidemia. Methods: Ninety patients with mixed dyslipidemia participated in the study. Patients were randomly allocated to receive rosuvastatin 40 mg (n = 30, group R), rosuvastatin 10 mg plus fenofibrate 200 mg (n = 30, group RF) or rosuvastatin 10 mg plus omega 3 fatty acids 2 g daily (n = 30, group R Omega). Plasma and high-density lipoprotein (HDL)-associated lipoprotein-associated phospholipase A2 (LpPLA2) activities, high-sensitivity C reactive protein (hsCRP), plasma isoprostane and paraoxonase (PON1) activities were measured at baseline and after 3 months of treatment. Results: Serum concentrations of non-HDL cholesterol and low-density lipoprotein cholesterol (LDL-C) were significantly reduced in all study groups. However, these changes were more pronounced in the rosuvastatin monotherapy group. In all treatment groups a significant reduction in total plasma LpPLA2 activity was observed (by 41, 38 and 30% for groups R, RF and RW, respectively). This decrease was greater in the R and RF groups compared with the RW combination (p < 0.05). HDL-LpPLA2 activity was increased more in the RF group (+43%) compared with the R and RW groups (+ 18% and + 35%, respectively; p < 0.05 for both comparisons). In all treatment groups there was a nonsignificant reduction in plasma 8-iso-PGF2 alpha levels. A 53% reduction of hsCRP levels was observed in the R group, while in the RF and RW groups the reduction was 28 and 23%, respectively (p < 0.05 and p < 0.01 for the comparisons of group R with groups RF and RW, respectively). No significant changes were observed in PON activities in all treatment groups. Conclusion: The greater non-HDL-C- and LDL-C-lowering efficiency of rosuvastatin monotherapy along with its more potent effect on LpPLA2 activity and hsCRP levels indicate that this regimen is a better treatment option for patients with mixed dyslipidemia. Expert Opinion on Pharmacotherapy

In this article we discuss the available data on the effects of combined therapy of ezetimibe with agents affecting lipid metabolism other than statins. We consider studies evaluating the effects of combined therapy of ezetimibe with bile acid sequestrants, fenofibrate, niacin, n-3 fatty acids, plant sterols, orlistat, metformin, acarbose and glitazones. Combination of ezetimibe with bile acid sequestrants (especially colesevelam) was shown to have additional effects on lipid parameters in patients with hyperlipidemia. Combination of ezetimibe with fenofibrate may be a good approach to improve the overall lipid profile of patients with mixed hyperlipidemia. The addition of ezetimibe to niacin-based therapy can be useful for high-risk patients with dyslipidemia who are not achieving their assigned treatment goals. For patients who cannot tolerate statins there are useful combinations of ezetimibe with other drugs affecting lipid metabolism. These combinations improve many metabolic parameters, but more trials should be carried out to reach more robust conclusions about their effects on cardiovascular disease prevention. Expert Rev Cardiovasc Ther

Atherosclerosis Supplements

BACKGROUND AND AIMS: Visfatin is associated with atherosclerosis-related diseases. We assessed in non-diabetic individuals the association of plasma visfatin levels with cardiovascular disease (CVD) risk and the atherosclerosis-related metabolic variables. METHODS AND RESULTS: When study population (n = 179, age 49 +/- 11 years) was divided according to visfatin tertiles, the 10-year CVD Framingham risk scores were significantly increased in the top visfatin tertile. We observed a positive association between visfatin tertiles with waist circumference and blood pressure, as well as with total cholesterol and triglyceride levels, but not with apolipoprotein C-III, fibrinogen or pre-beta1 high density lipoprotein (HDL). The percentage of large HDL subclasses was significantly lower and the percentage of small HDL subclasses over the HDL-C concentration was significantly higher in the top visfatin tertile compared with the other tertiles. The atherogenic small dense low density lipoprotein subclasses (sdLDL-C) were significantly increased in the top visfatin tertile compared with the lower tertiles. High sensitivity C-reactive protein (hsCRP) concentration was significantly increased in the top visfatin tertile compared with the lower tertiles. Although age and sex distribution did not differ between visfatin tertiles, the simultaneous adjustment for these parameters attenuated the significance of the differences observed in sdLDL-C and hsCRP levels. Similarly, after adjustment for hsCRP or waist circumference, only triglycerides and blood pressure levels, as well as the distribution of HDL subclasses, remained significantly different between visfatin tertiles. CONCLUSIONS: Our results support a role for visfatin in the detection of subjects with many metabolic abnormalities, which result in increased CVD risk. Nutr Metab Cardiovasc Dis

Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to steatohepatitis, advanced fibrosis and inflammatory changes. Ezetimibe inhibits cholesterol absorption from the intestinal lumen into enterocytes. The molecular target of ezetimibe is the sterol transporter Niemann-Pick C1-like 1 protein (NPC1L1). Human NPC1L1 is abundantly expressed in the liver and may facilitate the hepatic accumulation of cholesterol. Ezetimibe exerts beneficial effects on several metabolic variables. Ezetimibe treatment attenuates hepatic steatosis and is beneficial in terms of NAFLD biochemical markers. The combination of ezetimibe with other interventions may also be beneficial in NAFLD patients. Our group investigated the ezetimibe-orlistat combination treatment in overweight and obese patients with hypercholesterolemia, with beneficial effects on NAFLD biochemical markers. These results are promising for patients with NAFLD, who usually have increased cardiovascular disease risk and need a multifactorial treatment. However, it should be mentioned that most results are from animal studies and, although modest elevation of liver function tests may raise the suspicion of NAFLD, none of these tests are sensitive to establish the diagnosis of NAFLD with great accuracy. World J Hepatol

The objective of the present study was to evaluate the effects of acute infection with Leptospira interrogans on lipids, lipoproteins and associated enzymes. Fasting serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoproteins (apo) A-I (TM), B, E, C-II, C-III and lipoprotein (a) [Lp(a)] were determined in patients with Leptospirosis on diagnosis and 4 months after recovery as well as in age- and sex-matched controls. Activities of cholesteryl-ester transfer protein (CETP) and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) as well as paraoxonase 1 (PON1) hydrolysing activity and levels of cytokines were determined. LDL subclass analysis was performed with Lipoprint LDL System. Eleven patients (10 men, mean age 49.5 +/- A 8.4 years) and 11 controls were included. TC, HDL-C, LDL-C, apoA-I, apoB and Lp(a) levels were lower at baseline, whereas TG and apoE levels were elevated compared with 4 months later. At baseline, higher levels of cytokines and cholesterol concentration of small dense LDL particles (sdLDL-C) were noticed, whereas LDL particle size was lower compared with follow-up. Activities of plasma Lp-PLA(2) and HDL-associated Lp-PLA(2) were lower at baseline compared with post treatment values, whereas PON1 activity was similar at baseline and 4 months later. 4 months after recovery, the levels of all lipid parameters evaluated did not differ compared with controls, except for HDL-C which remained lower. PON1 activity both at baseline and 4 months later was lower in patients compared with controls. Leptospirosis is associated with atherogenic changes of lipids, lipoproteins and associated enzymes. Lipids

Consumption of foods and supplements enriched with plant sterols/stanols (PS) may help reduce low-density lipoprotein cholesterol (LDL-C) levels. In this review, we consider the effects of PS beyond LDL-C lowering. Plant sterols/stanols exert beneficial effects on other lipid variables, such as apolipoprotein (apo) B/apoAI ratio and, in some studies, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Plant sterols/stanols may also affect inflammatory markers, coagulation parameters, as well as platelet and endothelial function. Evidence also exists about a beneficial effect on oxidative stress, but this does not seem to be of greater degree than that expected from the LDL-C lowering. Many of these effects have been demonstrated in vitro and animal models. Some in vitro effects cannot be seen in vivo or in humans at usual doses. The epidemiological studies that evaluated the association of plasma PS concentration with cardiovascular disease (CVD) risk do not provide a definitive answer. Long-term randomized placebo-controlled studies are required to clarify the effects of supplementation with PS on CVD risk and progression of atherosclerosis. J Cardiovasc Pharmacol Ther

Atherosclerosis Supplements

Atherosclerosis Supplements

Atherosclerosis Supplements

Non-alcoholic fatty liver disease (NAFLD) includes simple steatosis, a benign condition, and non-alcoholic steatohepatitis, a condition that beyond TG accumulation also includes necroinflammation and fibrosis. An association between NAFLD and cardiovascular disease (CVD) has been recently suggested. NAFLD patients usually have an increased CVD risk profile. NAFLD is also associated with metabolic syndrome (MetS) and is considered as the hepatic component of MetS by some authors. Currently, the only established treatment of NAFLD is gradual weight loss. However, multifactorial treatment of NAFLD risk factors may be needed to reduce the increased CVD risk of NALFD patients. Drug combinations that include antiobesity drugs (such as orlistat and sibutramine) and target CVD risk factors may be a good approach to NAFLD patients. Our group has investigated the orlistat-fenofibrate combination treatment in obese patients with MetS and the orlistat-ezetimibe and sibutramine-antihypertensive combination treatment in obese patients with hyperlipidaemia with promising results in CVD risk factor reduction and improvement of liver function tests. Small studies give promising results but double-blind, randomized trials examining the effects of such multifactorial treatment in hard CVD endpoints in NAFLD patients are missing. World J Hepatol

OBJECTIVE: We present the available data on the effects of combined therapy of fenofibrate with drugs affecting lipid metabolism other than statins. METHODS: We consider studies evaluating the effects of combined therapy of fenofibrate with bile acid sequestrants (BAS), ezetimibe, niacin, n-3 fatty acids, plant sterols, orlistat, rimonabant, metformin and glitazones. RESULTS: Combination of BAS (especially colesevelam) with fenofibrate had additional effects on metabolic parameters in patients with mixed hyperlipidemia. Combination of ezetimibe with fenofibrate may be a useful approach to improve the overall lipid profile of patients with mixed hyperlipidemia. There is a further reduction in triglyceride levels when n-3 fatty acids are administered with fenofibrate in patients with severe hypertriglyceridemia. Combined fenofibrate and orlistat treatment further improves metabolic parameters in overweight/obese patients with metabolic syndrome. The fenofibrate/thiazolidinedione combination is an alternative for diabetic patients intolerant to statins, though differences exist between pioglitazone and rosiglitazone. CONCLUSIONS: For patients who cannot tolerate statins there are useful combinations of fenofibrate with other drugs affecting lipid metabolism. These combinations improve several metabolic parameters, but more trials should be carried out to reach more robust conclusions about their effects on cardiovascular events. Curr Pharm Des

Visfatin is highly expressed in adipose tissue (mainly by the stromal cells), but it is also ubiquitously present in most tissues. Visfatin, which plays a role in nicotinamide adenine dinucleotide (NAD) biosynthesis, has been implicated in inflammatory states. Controversial results exist about the expression, circulating levels and the role of visfatin in atherosclerosis-related diseases. Most studies showed increased levels of visfatin in diabetes mellitus, obesity, hypertension, renal and cardiovascular disease. However, other studies reported lower levels of visfatin in these diseases. The discrepancies in clinical studies may be attributed to the multifactorial regulation of visfatin. There is evidence that visfatin expression and circulating levels are influenced by fat area and distribution, inflammatory state, renal function, iron metabolism, hormones as well as several other factors. Furthermore, discrepancies and lack of correlation between commercially available visfatin assays have been reported. More research is needed to better understand the factors that control its synthesis/release and to evaluate the role of visfatin in atherosclerosis-related disease. Large studies with homogeneous populations will probably be needed to answer these questions. Whether visfatin will eventually become a therapeutic target remains to be established. Curr Vasc Pharmacol

Objective: Experimental studies have shown that the pre beta-1 subclass of high-density lipoprotein particles (pre beta-1 HDL) may play an important role in the reverse cholesterol transport pathway as the initial acceptors of cellular cholesterol. The aim of the present study was the direct comparison of pre beta-1 HDL values in individuals with various types of primary dyslipidemias. Methods: Four hundred and eighty-six unrelated individuals were included in the study. According to their lipid values study participants were subdivided into four groups: control group (n = 206), type IIA dyslipidemia group (n = 148), type IIB dyslipidemia group (n = 49) and type IV dyslipidemia group (n = 83). Results: All dyslipidemic patients displayed higher concentrations of pre beta-1 HDL compared to control individuals. However, patients with dyslipidemias characterized by an abnormal catabolism of triglyceride-rich lipoproteins (such as dyslipidemias of type IIB and IV) tend to have higher pre beta-1 HDL values compared to patients with hypercholesterolemia, and this increase is proportional to the degree of hypertriglyceridemia. In addition, patients with metabolic syndrome exhibited significantly higher levels of pre beta-1 HDL compared to individuals that do not fulfill the criteria for the diagnosis of this syndrome. Multiple regression analysis revealed that serum triglyceride concentrations and body mass index (BMI) values were the most important determinants of pre beta-1 HDL levels in our population. Conclusion: All dyslipidemic patients exhibit increased pre beta-1 HDL concentrations as compared to normolipidemic individuals. Whether this increase represents a defensive mechanism against atherosclerosis or it is indicative of impaired maturation of HDL particles and thus of a defective reverse cholesterol transport mechanism remains to be established. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Atherosclerosis

Atherosclerosis Supplements

Patients with rheumatoid arthritis (RA) appear to have increased plasma levels of leptin and adiponectin. These adipokines may be implicated in the pathophysiology of RA. Tumour necrosis factor alpha (Tau NF-alpha) is a potential modulator of adipokines. The effects of long-term anti-TNF treatment on plasma levels of leptin and adiponectin are not clear. The aim of this study was to assess the effects of 6-month anti-TNF treatment (infliximab) on leptin and adiponectin plasma levels in RA patients. Thirty women with RA were included in the study. Patients with diabetes mellitus, any endocrine disorder or receiving any hypolipidemic or antidiabetic medication were not included. Thirty healthy age- and body mass index-matched women served as controls. Plasma levels of leptin and adiponectin were measured with enzyme immunoassay methods prior to and after the 6-month treatment with infliximab. Mean age and disease duration of patients were 51.8 +/- 14.4 and 12.2 +/- 6.7 years, respectively. Body weight did not change significantly over the 6-month period. Plasma levels of leptin and adiponectin were higher in patients than controls and did not change significantly after 6-month treatment. Interestingly, in the tertile of patients with the highest baseline adiponectin concentrations, adiponectin levels were significantly reduced (P < 0.05). Infliximab treatment did not change plasma levels of leptin and adiponectin after 6-month treatment in the whole study population. However, a reduction of adiponectin levels was observed in patients with higher baseline adiponectin levels. Fundamental & Clinical Pharmacology

Although the raising effect of rosuvastatin on high-density lipoprotein cholesterol is well-established, there is a paucity of data regarding the effect of this statin on the high-density lipoprotein subfraction phenotype. A total of 150 participants without evidence of cardiovascular disease were randomized to therapeutic lifestyle modification (nonstatin-treated group) or to therapeutic lifestyle modification plus rosuvastatin at 10 mg/d (RSV10 group) or 20 mg/d (RSV20 group). We assessed the effect of rosuvastatin on the cholesterol mass of high-density lipoprotein subfractions at baseline as well as after 12 weeks post-treatment. Rosuvastatin treatment close-dependently increased the high-density lipoprotein cholesterol (3.4% vs 5.3% in the RSV10 and RSV20 groups, respectively, P = .02). A dose-related rosuvastatin-induced increase in the cholesterol concentration of large high-density lipoprotein particles was also noted (by 11.4% in RSV10 group vs 22.0% in the RSV20 group, P = .01). Rosuvastatin treatment increases the high-density lipoprotein cholesterol by increasing the cholesterol mass only of the larger high-density lipoprotein particles in a dose-dependent manner. Journal of Cardiovascular Pharmacology and Therapeutics

Patients with malignant disease may need hormonal therapy as primary or adjuvant treatment or for palliation. Oestrogens usually decrease serum levels of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), increase high density lipoprotein cholesterol (HDL-C) concentration, but induce an elevation in serum triglyceride (TG) levels. Progestogens in the short-term decrease TC, LDL-C and HDL-C concentrations, and increase TG levels. In long-term treatment, progestogens usually have a small impact on lipid profile. Tamoxifen induces a decrease in TC and LDL-C levels, an increase in TG concentration, whereas either an increase, decrease or no change has been reported for HDL-C levels. Aromatase inhibitors induce an elevation, reduction or no change in lipid variables. These results depend mainly on the trial design, i.e. whether patients received prior treatment with tamoxifen or not and the duration of therapy. Gonadorelin analogues increase all lipid variables, but LDL-C alterations are usually non-significant. Anti-androgens usually decrease TC, LDL-C and HDL-C levels, whereas TG alterations vary. Information regarding the effects on lipid profile of somatostatin analogues is available almost exclusively in patients with acromegaly. In these patients somatostatin analogues usually induce no change or a decrease in TC and LDL-C levels, whereas they increase HDL-C and decrease TG serum concentrations. Oncologists should consider the lifestyle changes, and if needed hypolipidemic treatment, used to lower cardiovascular risk in non-cancer patients. Tamoxifen may rarely cause serious TG-related side effects, like acute pancreatitis. Cancer Treat Rev