Plasma Cholesterol Levels In Patients Research Articles

Changes in plasma cholesterol level and risk factors of death in patients with sepsis

To analyze the characteristics of change in plasma cholesterol level in patients with sepsis, and to explore its relationship with prognosis and its clinical significance. A retrospective analysis was conducted. 568 patients with sepsis admitted to Department of Critical Care Medicine of Beijing Friendship Hospital Affiliated to Capital Medical University from August 2013 to August 2015 were enrolled, and 475 patients without sepsis hospitalized in the same period served as the control. The basic clinical data of the two groups were collected, and the results of blood fat and biochemical parameters were compared. The patients with sepsis were divided into death group and survival group, and risk factors influencing the prognosis of patients with sepsis were analyzed with multivariate logistic model regression analysis. Compared with non-sepsis patients, the levels of plasma total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) in the patients with sepsis were significantly lower [TC (mmol/L): 2.5±1.2 vs. 3.4±1.4, t = 4.274, P = 0.021; HDL-C (mmol/L): 1.6±0.9 vs. 2.5±0.8, t = 3.413, P = 0.018], and that of low density lipoprotein cholesterol (LDL-C) showed no statistically significant difference (mmol/L: 1.9±0.9 vs. 2.1±0.9, t = 0.749, P = 0.614). In the patients with sepsis, the patients in death group (n = 227) were older than those of the survival group (n = 341, years: 74.3±15.5 vs. 65.5±17.5, t = 4.037, P = 0.012), serum creatinine (SCr) was higher than that of survival group (μmol/L: 251.0±115.6 vs. 167.4±108.7, t = 3.254, P = 0.023), the levels of plasma TC, HDL-C and LDL-C were significantly lower than those of survival group [TC (mmol/L): 2.2±1.6 vs. 2.9±1.1, t = 3.057, P = 0.023; HDL-C (mmol/L): 1.4±0.8 vs. 1.9±0.8, t = 4.692, P = 0.016; LDL-C (mmol/L): 1.7±0.7 vs. 2.0±0.8, t = 2.541, P = 0.038]; there was no significant difference in the proportion of male, body mass index (BMI), based disease, intensive care unit (ICU) hospitalization time, the severity of the disease and other biochemical indexes between two groups. With single factor analysis with indicators of statistical significance as a covariate into binary logistic regression equation, the results show that age was the risk factor of death in patients with sepsis [odds ratio (OR) = 1.024, 95% confidence interval (95%CI) = 1.010-1.048, P = 0.009], and TC was the protective factor on the prognosis of patients with sepsis (OR = 0.747, 95%CI = 0.682-0.811, P = 0.013). Plasma cholesterol levels in patients with sepsis were significantly lowered, and the levels in death group was significantly lower than that in the survival group. TC may be used as a clinical indicator to assess the outcome of patients with sepsis.

Recent developments in modulating atherogenic lipoproteins.

Randomized clinical trials have assessed the effects of several classes of drugs on plasma cholesterol levels in patients with coronary artery disease. Agents including niacin, fibrates and statins significantly lower LDL-cholesterol, but tolerance issues and undesirable side-effects are common. Residual risk may also be present in patients with persistently low HDL-cholesterol despite a reduction in LDL-cholesterol. Recent trials of drugs that increase circulating HDL-cholesterol have also been disappointing. Ongoing efforts target the development of new pharmacotherapies to reduce circulating levels of atherogenic lipoproteins. The goal of this review is to discuss recent advances in the treatment of coronary artery disease and other vascular diseases characterized by an increase in circulating atherogenic lipoproteins. These include the development of inhibitors of ATP citrate lyase and proprotein convertase subtilisin/kexin type 9. We also discuss recent developments in HDL therapy, including the clinical assessment of cholesteryl ester transfer protein inhibitors and apolipoprotein E mimetic peptides. Several new classes of drug are undergoing clinical evaluation that show promise for atherogenic lipoprotein reduction in patients who are statin intolerant.

Emerging antiplatelet and lipid lowering therapies

Antiplatelet therapy is used widely with proven benefit for the primary prevention of cardiovascular disease as well as for the prevention of further ischemic cardiovascular events in patients with proven coronary artery disease (CAD) and in those with a history of acute coronary syndrome (ACS). The limitations of conventional antiplatelet therapy with aspirin, clopidogrel, or prasugrel, as well as the fact that rates of recurrent ischemic events still remain high with use of these agents, underscore the need to investigate alternative molecules that may be effective in further reducing the occurrence of events without increasing the risk of bleeding. The armamentarium of antiplatelet therapy has been further enriched by ticagrelor, cangrelor, vorapaxar, prasugrel and atopaxar. Ticagrelor was approved in 2011 by the European Medicines Agency swiftly followed by the US Food and Drug Administration. Reversible antiplatelet agents acting as P2Y12 antagonists similar to ticagrelor are cangrelor, and elinogrel. A new class of oral protease-activated receptor-1 (PAR-1) inhibitors, vorapaxar and atopaxar has also been proposed as effective antiplatelets but their clinical benefit is still under debate. The P2Y12 antagonists prasugrel and ticagrelor prevent adverse cardiac outcomes albeit their absolute benefit is very small. The beneficial effect of prasugrel and ticagrelor comes at a cost of an increased risk of bleeding. Furthermore, new adverse effects have also become evident with the new P2Y12 antagonists and these include dyspnea (for all of the reversible P2Y12 antagonists: ticagrelor, cangrelor, and elinogrel) and ventricular pauses for ticagrelor. In addition, the newer P2Y12 antagonists have a peculiar pharmacodynamic profile with a fast onset and offset. Two of these agents, cangrelor and elinogrel, are available as intravenous formulations, which may provide additional benefits in patients who undergo coronary artery bypass graft (CABG) surgery. Trials with the PAR-1 inhibitors have also shown trends toward reductions in cardiac events, but not without the possibility of increased bleeding. Physicians must carefully assess patient-specific factors such as risk of thrombosis, concomitant disease states, age, drug adherence, and aspirin dose, and plan for those patients who will be undergoing CABG when selecting antiplatelet therapy in order to optimally balance bleeding and thrombosis risk. In addition to adequate anti-platelet therapy the treatment of blood lipids is important for the primary and secondary prevention of cardiovascular disease. Elevated low-density lipoprotein cholesterol is an important risk factor for cardiovascular and cerebrovascular events. HMG-CoA reductase inhibitors, or statins, are very effective in lowering cholesterol levels, and in reducing mortality and cardiovascular events in patients with and without cardiovascular disease. The evidence cumulated with the studies conducted with statin has led to the recent recommendations that all patients with known vascular disease, or who are at high risk for vascular disease, should be considered candidates for statin therapy. Nonstatin therapies (either as monotherapy or in addition to statins) to reduce LDL cholesterol by mechanisms that do not involve inhibition of HMG-CoA reductase are likely to be useful for patients in need of LDL reduction; particularly those who either cannot take statins or respond only partially or not at all to statins alone. These therapies include cholesterol absorption inhibitors, Acyl-CoA cholesterol acyl transferase inhibitors, farnesoid X receptor antagonists, sterolregulating binding protein cleavage activating protein, and microsomal triglyceride transfer protein. Recent studies with the PCSK9 have shown that these drugs significantly reduce total and LDL cholesterol in patients with familial hypercholesterolaemia and that are effective in further reducing plasma cholesterol levels in patients receiving statins. Therefore, therapeutic options are becoming available for patients who cannot tolerate full dose statin therapy or for those few patients who are intolerant to statin therapy.

Plant sterols for adults with hypercholesterolemia treated with or without medication (statins)

Hypercholesterolemia is the most common coronary risk factor among the Spanish population; 37.4% of the Spanish adult population have cholesterol levels between 190 and 240 mg/dl. Foods enriched with plant sterols (PS) can effectively reduce plasma cholesterol in patients with high levels. However, its effectiveness and safety in adults with moderate hypercholesterolemia who are on medication (statins) or not has been less studied. The aim of this review is to establish the possible role of plant sterols in the control of hypercholesterolemia, as well as how safe they are for people with moderate hypercholesterolemia treated with statins. The main studies were looked at, regardless of design, language or publication date which studied the connection between “plant sterols” and “hypercholesterolemia”, using Pubmed/Medline, SCOPUS and Google Scholar databases. The studies brought together in this review show that an intake of between 2 and 3g/day of plant sterols effectively reduces plasma cholesterol levels in patients with hypercholesterolemia. Both clinical studies and available meta-analyses do not indicate any problems related to the drug-nutrient interaction associated with the use of plant sterol-enriched foods. In patients with moderate hypercholesterolemia where the use of statins is not justified a healthy diet, exercise and foods high in PS can provide the best therapeutic approach.

Ezetimibe ameliorates intestinal chylomicron overproduction and improves glucose tolerance in a diet-induced hamster model of insulin resistance

Ezetimibe is a cholesterol uptake inhibitor that targets the Niemann-Pick C1-like 1 cholesterol transporter. Ezetimibe treatment has been shown to cause significant decreases in plasma cholesterol levels in patients with hypercholesterolemia and familial hypercholesterolemia. A recent study in humans has shown that ezetimibe can decrease the release of atherogenic postprandial intestinal lipoproteins. In the present study, we evaluated the mechanisms by which ezetimibe treatment can lower postprandial apoB48-containing chylomicron particles, using a hyperlipidemic and insulin-resistant hamster model fed a diet rich in fructose and fat (the FF diet) and fructose, fat, and cholesterol (the FFC diet). Male Syrian Golden hamsters were fed either chow or the FF or FFC diet ± ezetimibe for 2 wk. After 2 wk, chylomicron production was assessed following intravenous triton infusion. Tissues were then collected and analyzed for protein and mRNA content. FFC-fed hamsters treated with ezetimibe showed improved glucose tolerance, decreased fasting insulin levels, and markedly reduced circulating levels of TG and cholesterol in both the LDL and VLDL fractions. Examination of triglyceride (TG)-rich lipoprotein (TRL) fractions showed that ezetimibe treatment reduced postprandial cholesterol content in TRL lipoproteins as well as reducing apoB48 content. Although ezetimibe did not decrease TRL-TG levels in FFC hamsters, ezetimibe treatment in FF hamsters resulted in decreases in TRL-TG. Jejunal apoB48 protein expression was lower in ezetimibe-treated hamsters. Reductions in jejunal protein levels of scavenger receptor type B-1 (SRB-1) and fatty acid transport protein 4 were also observed. In addition, ezetimibe-treated hamsters showed significantly lower jejunal mRNA expression of a number of genes involved in lipid synthesis and transport, including srebp-1c, sr-b1, ppar-γ, and abcg1. These data suggest that treatment with ezetimibe not only inhibits cholesterol uptake, but may also alter intestinal function to promote improved handling of dietary lipids and reduced chylomicron production. These, in turn, promote decreases in fasting and postprandial lipid levels and improvements in glucose homeostasis.

インスリン非依存型糖尿病 (NIDDM) 患者の血清コレステロール値に及ぼす卵摂取の影響について

インスリン非依存型糖尿病 (NIDDM) 患者の血清コレステロール値に及ぼす卵摂取の影響について

Hypocholesterolemia is associated negatively with hemolysate lipid peroxidation in sickle cell anemia patients

The oxidative stress levels in plasma and hemolysate and cholesterol levels in plasma of sickle cell anemia patients, carriers and controls were evaluated. A total of 40 cases-17 patients, 13 carriers and 10 controls-were involved in the study. Plasma and hemolysate malondialdehyde (MDA) were detected via thiobarbituric acid reaction with a fluorimetric detector by high-performance liquid chromatography system. Plasma cholesterol was determined by enzymatic colorimetric method. Mean MDA levels of SCA patients were higher than those of the carriers' and healthy children's both in plasma and in hemolysate (P<0.005). The mean plasma and hemolysate MDA levels were 25.3±1.6nmol/l and 86.7±19.3nmol/l in patients, 19.1±0.8nmol/l and 54.1±10.8nmol/l in carriers and 19.6±0.8nmol/l and 56.8±9.3nmol/l in healthy children. Mean plasma total cholesterol levels were 92.1±19.1mg/dl in patients, 116.2±23.3mg/dl in carriers and 126.6±16.4mg/dl in controls (P<0.005). There was a significant negative correlation of -0.520 between hemolysate MDA and plasma cholesterol levels in patients (P<0.05). The degree of correlation increased up to -0.782 (P=0.008) in the patients with HbSS phenotype. This negative correlation between MDA and cholesterol may imply a potential association between oxidative stress and hypocholesterolemia in sickle cell anemia.

Residual effects of lovastatin and simvastatin on urinary mevalonate excretions in patients with familial hypercholesterolemia

3-Hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitors are widely used to decrease plasma cholesterol levels in patients with heterozygous familial hypercholesterolemia (FH) who are at increased risk of premature coronary artery disease. Tissue-culture and animal studies have indicated that administration of HMG CoA reductase inhibitors (eg, lovastatin, simvastatin, etc) induces a compensatory increase in the activity of HMG CoA reductase, both by increasing its synthesis and decreasing catabolism. To determine in human subjects whether cessation of therapy with this class of drugs leads to induction of HMG CoA reductase activity and above-normal rates of cholesterol biosynthesis, we measured urinary concentrations of mevalonic acid (an indicator of cholesterol biosynthesis) after the cessation of therapy with lovastatin and simvastatin (80 mg/day) in patients with heterozygous FH. Plasma concentrations of LDL increased promptly on discontinuation of reductase inhibitor therapy but did not increase above pretreatment levels at any point after drug discontinuation. Similarly, the 24-hour urinary excretion of mevalonic acid was reduced during treatment with lovastatin or simvastatin and increased promptly on discontinuation of drug but did not increase to levels exceeding those found at baseline when the patients were receiving dietary therapy only. We conclude that cessation of treatment with HMG CoA reductase inhibitors in patients with FH does not result in a rebound increase in cholesterol biosynthesis and that no rebound overshoot occurs in plasma concentrations of low-density-lipoprotein cholesterol. (J Lab Clin Med 2003;141:250-6)

Ezetimibe: a selective inhibitor of cholesterol absorption

Ezetimibe is a novel selective cholesterol absorption inhibitor that effectively blocks intestinal absorption of dietary and biliary cholesterol. Ezetimibe undergoes glucuronidation to a single metabolite and is localized in the intestinal wall, where it prevents cholesterol absorption. Enterohepatic recirculation of ezetimibe and the glucoronide ensures repeated delivery to the site of action and limits peripheral exposure. Ezetimibe does not affect the absorption of fat-soluble vitamins or triglycerides. Results from pre-clinical studies in various animal models have shown the lipid-lowering and anti-atherosclerotic properties of ezetimibe as a single agent, and a synergistic effect when combined with a statin. In cholesterol-fed rhesus monkeys, ezetimibe reduced both plasma cholesterol (ED50 = 0·0005 mg.kg−1.day−1) and low-density lipoprotein cholesterol levels in a dose-dependent manner. In apo F knockout mice, ezetimibe reduced serum cholesterol more than 50% and decreased carotid (97%) and aortic (47–87%) atherosclerosis. Ezetimibe inhibited the rise of plasma cholesterol in cholesterol-fed dogs (ED50 = 0·007 mg.kg−1.day−1). Co-administration of ezetimibe and lovastatin in chow-fed dogs synergistically reduced plasma cholesterol to levels lower than those achieved with either agent alone (⁠ \(P{<}0{\cdot}05\) ⁠). These results suggest that ezetimibe combined with a statin may similarly reduce plasma cholesterol levels in patients with hypercholesterolaemia.

High dose of simvastatin normalizes postprandial remnant-like particle response in patients with heterozygous familial hypercholesterolemia.

Familial hypercholesterolemia (FH) and disturbances in postprandial lipoprotein metabolism are both associated with premature atherosclerosis. The effect of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors on plasma cholesterol levels in patients with FH is well established; however, it is not known whether postprandial lipoproteins are also influenced. In this case-controlled intervention study, we investigated the effects of high-dose simvastatin on postprandial lipoproteins. We used a new method to analyze remnant lipoproteins based on the immunoseparation principle (remnant-like particle cholesterol [RLP-C] assay) and the well-established measurement of retinyl ester (RE) analysis in plasma and in the Svedberg flotation unit (Sf)<1000 fraction. Seven heterozygous FH patients and 7 control subjects matched for sex, age, body mass index, triglycerides, and apolipoprotein E genotype were enrolled in the study. An oral vitamin A (RE) fat-loading test was performed at baseline in both groups and after 3 months of high-dose simvastatin (80 mg/d) treatment in the FH patients. Before treatment, FH patients had significantly higher fasting and postprandial concentrations of lipoprotein remnants (plasma RLP-C 42+/-19 mg/dL and area under the RLP-C curve 415+/-82 mg. L(-1). h(-1), respectively) than did control subjects (7+/-3 mg/dL and 101+/-35 mg. L( -1). h(-1), respectively; P<0.05), suggesting a delayed clearance of chylomicron remnant particles in the FH patients. Treatment with simvastatin significantly reduced fasting and postprandial remnant lipoprotein cholesterol concentrations (13+/-3 mg/dL and 136+/-53 mg. L(-1). h(-1), respectively; P<0.05 for both). Postprandial RE in the Sf<1000 fraction, not total RE in plasma, was also significantly higher in FH patients than in control subjects (24+/-10 versus 6.3+/-5.9 mg. L( -1). h(-1), P<0.05), but treatment with simvastatin did not result in improvement of the postprandial RE response, either in the Sf<1000 fraction or in plasma. It is concluded that heterozygous FH patients have increased fasting and postprandial remnant lipoprotein concentrations. Treatment with simvastatin significantly reduced the fasting and postprandial RLP-C concentrations but did not result in improved postprandial RE response.

A Multicenter, Placebo-Controlled, Dose-Ranging Study of Atorvastatin.

BACKGROUND: Coronary heart disease (CHD) is the number one cause of death in Western societies. Elevated levels of plasma low-density lipoprotein (LDL) cholesterol and triglycerides (TG) increase the risk for CHD. 3-Hydroxy-3-methylglutaryl conenzyme A (HMG-CoA) reductase inhibitors effectively reduce plasma cholesterol levels in patients with hypercholesterolemia. This study assesses the safety and dose-related effects of atorvastatin calcium on lipoprotein fractions in patients with LDL cholesterol levels between 160 mg/dL (4.1 mM) and 250 mg/dL (6.5 mM) or less and TG levels of 400 mg/dL (4.5 mM) or less. METHODS AND RESULTS: Sixty-five patients were enrolled in a 6-week, randomized, placebo-controlled, parallel-group study. Patients received placebo or atorvastatin 10, 20, 40, 60, or 80 mg once daily. Adjusted mean decreases in LDL cholesterol for patients receiving atorvastatin 10, 20, 40, 60, and 80 mg were 37%, 42%, 50%, 52%, and 59%, respectively, compared with a mean increase of 0.3% for patients receiving placebo; the differences between each of the atorvastatin dose groups and placebo were statistically significant (P =.0001). Total cholesterol, triglycerides, and apolipoprotein B were significantly reduced in atorvastatin groups (P =.0001). Adverse events were similar in the placebo and atorvastatin treatment groups. No patient had a serious adverse event or withdrew because of an adverse event during this study. CONCLUSIONS: Atorvastatin effectively lowered plasma LDL cholesterol, triglycerides, and apoB levels in a dose-related manner. Atorvastatin was well tolerated in hyperlipidemic patients over a 6-week period.

Increased LDL receptor mRNA expression in colon cancer is correlated with a rise in plasma cholesterol levels after curative surgery.

It is currently under debate whether the low serum cholesterol levels that are frequently observed in cancer patients represent a risk factor for/or, rather, are a consequence of the tumour. We postulate that malignant tumours are directly involved in an increased catabolism of cholesterol-rich low-density lipoprotein (LDL) particles. In a prospective study of 25 patients with colorectal carcinoma, we measured intraindividual shifts in serum cholesterol levels after surgery, and the expression of LDL-receptor mRNA in surgically removed specimens. A significant rise in plasma cholesterol levels was observed in patients 3 and 12 months after curative surgery, but not after non-curative surgery. In human colon carcinoma tissues LDL receptor mRNA expression, as determined by competitive reverse-transcriptase-polymerase-chain reaction, was found to be significantly increased when compared to tissues from the tumour-free margin (median values, 1.2 x 10(6) vs. 2.0 x 10(5) molecules/micrograms total cellular RNA, respectively, n = 17). The extent of LDL-receptor mRNA expression positively correlated to the percentage rise of plasma cholesterol levels 3 months (n = 7, r = 0.8763) and 12 months (n = 6, r = 0.9181) after curative surgery. This finding provides in vivo evidence that the tumour tissue itself contributes to decreased plasma cholesterol levels in patients suffering from colorectal carcinomas. It supports the hypothesis that low cholesterol levels in cancer patients are a consequence, and not the cause, of the malignancy.

Cholesterol content of peripheral blood lymphocytes: relationship to plasma cholesterol level in patients with different types of hyperlipidemia

Cholesterol content of peripheral blood lymphocytes: relationship to plasma cholesterol level in patients with different types of hyperlipidemia

Effect of simvastatin treatment on the dyslipoproteinemia in capd patients

HMG-CoA reductase inhibitors have been proven effective in decreasing the plasma cholesterol levels in patients affected with various forms of hypercholesterolemia, familial dysbetalipoproteinemia, familial combined hyperlipidemia and in nephrotic and diabetic dyslipidemia. The purpose of this study was to monitor and evaluate the efficiency and safety of the therapy with simvastatin, an HMG-CoA reductase inhibitor, in a group of patients treated by continuous ambulatory peritoneal dialysis (CAPD) with severe hypercholesterolemia. Monitoring of the changes occurring in the various lipids and apolipoproteins in these patients included the measurements of the plasma lipids and apolipoproteins A-I, A-II, B, C-II, A-IV and Lp(a). Lipoproteins were separated by gel filtration, on a Superose 6HR column, before and after 24 weeks of treatment. The patterns were compared to those observed in a group of primary hyperlipidemic patients treated with Lovastatin, a compound of the same class. The drug was well tolerated by the CAPD patients and no adverse reaction was observed. In addition to the decrease of the total and LDL cholesterol, similar to that reported in other groups of patients, we further observed a decrease of the apo E concentration in both the CAPD and the hyperlipidemic patients. This decrease was especially pronounced in the HDL E fraction and could involve an upregulation of the apo B-E and/or apo E receptor. These results should provide information about the mechanism of action of this drug in patients with end-stage renal disease.

Synvinolin: lowers plasma cholesterol levels in patients with polygenic or familial hypercholesterolaemia

Synvinolin: lowers plasma cholesterol levels in patients with polygenic or familial hypercholesterolaemia

Diet and Probucol in Lowering Cholesterol Concentrations

Probucol [4,4-(isopropylidendithio bis)(2,6-di-t-butylphenol)], as as an adjunct to diet, was evaluated for its effect on lowering the plasma cholesterol level in patients with familial hypercholesterolemia (type II). The trial had a double-blind, placebo-controlled, crossover design. About half of the 30 patients responded to a low-cholesterol modified-fat diet with a decrease in the plasma cholesterol level of approximately 13%. When probucol was added to the diet of the responders, their plasma cholesterol level was lowered a further 13%. Patients who did not respond to the diet did show reduced plasma cholesterol concentrations when receiving probucol plus the diet. Analysis of the cholesterol content of the various lipoprotein fractions showed that the low-density lipoproteins accounted for most of the total plasma cholesterol level decrease. There was, as expected, no effect on plasma triglyceride concentrations. Neither the 7-dehydrocholesterol nor the desmosterol level was increased in the plasma of patients treated with probucol for three months. Probucol is useful as an adjunct to diet in lowering plasma cholesterol levels in patients with familial hypercholesterolemia. The drug was well tolerated by all patients.