Cholesterol How To Decrease

Lower Cholesterol Ebook

Is it possible to lower your cholesterol without harmful drugs? Thats the claim made by the e-book Beat Cholesterol in 30 Days by Scott Davis. Through this e-book you can learn the all-natural secrets that he used to lower his cholesterol 100 points in less than a month. This program reveals to people some main factors that cause their hypercholesterolemia such as smoking, high blood pressure, diabetes, obesity, and family history of heart disease. The program also covers tips to prevent the recurrence of hypercholesterolemia such as eating a low-fat and low-salt diet, stopping smoking, losing extra pounds, and maintaining a healthy weight. Davis' ability to collect such an astounding array of oftentimes obscure information and arrange it in a way that is easy for people of all ages to follow and apply to their lives immediately is itself quite an achievement. Read more...

Natural Cholesterol Guide Summary

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Are all Statins the Same

Statins are of proven efficacy in secondary prevention in high-risk groups such as PAD patients. However, we do not know if all statins are equally effective. This question can only be answered by head to head comparison trials that incorporate clinical endpoints. Potential differences between statins can conveniently be considered in the context of So far, head to head comparisons clearly show that some statins are considerably more potent, in terms of LDL-C lowering, than others 10, 27 . However, potency must not be considered in the decision-making process at the expense of safety and event-based evidence. What is less clear is whether statins differ in properties that may not be exclusively due to variations in their LDL-C-lowering capacity, the so-called pleiotropic actions 8 .

Statins

Statins yield a significant decrease in mortality, recurrent MI, recurrent episodes of unstable angina, stroke, the need for revascularization, and hospitalization in patients with established atherosclerosis.43-45 Statins reduce inflammation and stabilize vulnerable plaques and have been shown to benefit The Medical Research Council (MRC) British Heart Foundation (BHF) Heart Protection Study examined statin use in 20 536 high-risk individuals (women and men) aged 40-80 years in the UK.46 These patients either had established vascular disease or diabetes or they were men with hypertension and aged over 60 years. They were randomized to 40 mg day of simvastatin or placebo and followed for five years. The study found that statin drugs protect a great variety of individuals who were at risk for CVD events. Statins cut the risk of events in patients with CHD and with CHD equivalents, including those with normal or low cholesterol. In the study, 33 had LDL below 116 mg dl or 3.0 mmol l, 25...

Atherogenesis and Lipid Metabolism

Central to the discussion of atherogenesis is the metabolism of the peripheral blood lipopro-teins. These are a complex macromolecule of lipid and protein in which the nonpolar lipid core is surrounded by a polar monolayer of phospholipids and heads of free cholesterol and apolipoproteins. This structure allows for the transport of the relatively insoluble lipids through the liquid plasma. The lipoproteins differ in their proportions of lipid content and proteins found on their surface. Lipid disorders alter the composition and structure of the lipoprotein. For example, as mentioned earlier, patients with high triglycerides produce LDL with a higher protein-to-lipid ratio, yielding a small dense LDL.

General Therapeutic Measures

Of smoking cessation programmes and antidepressant therapy, if necessary. Lipid-lowering drugs are especially indicated, with the use of HMG-CoA reductase inhibitors. Statins not only decrease cholesterol levels but also exert pleiotropic effects on the vascular wall limiting the inflammatory process within the plaques 1, 13 . Plaque regression with lipid-lowering therapy has been reported in both the aorta and carotids. An LDL cholesterol level less than 100 mg dl should be attained. The incidence of cardiac event may be minimized by appropriate control of heart rate and blood pressure. Diabetic patients should be adequately treated and monitored. Haemoglobin A1c should be less than 7 . Dietary supplementation of vitamin B12 and folic acid should be prescribed, especially in patients with hyperhomocysteinemia 25 . Exercise decreases LDL cholesterol and all patients should maintain a regular exercise regimen. Lastly, the use of anti-platelet drugs may reduce the risk of fatal and...

Reduction of the Risk of Vascular Events Associated with PAD

In a comparison of 318 PAD patients treated with statins versus 342 patients not on lipid-lowering drugs there were significant changes in the event rates after a mean follow-up of 39 months 1 . Sudden coronary death, fatal MI and new coronary events were all significantly reduced (p 0.0005, p 0.007 and p 0.0001, respectively).

Clinical Evaluation of Patients with Vascular Disease

The primary goal of the clinical evaluation of patients with vascular disease is to decide which tests will help the surgeon treat the patients' problem while at the same time minimizing patient discomfort. Investigation of patients with vascular disease differs from that of other surgical patients and depends mainly on the underlying disease process. For instance, patients with lower extremity occlusive vascular disease suffer not only from their index problem (claudication, ischemic rest pain, gangrenous ulcers) but also from some of the conditions that have predisposed them to vascular disease in the first place (diabetes, hypercholesterolemia, etc.). In addition, they are likely to require a number of medications for these predisposing conditions, some of which require consideration in diagnosing and treating vascular disease. It is also important to keep in mind that the presence of occlusive vascular disease in the lower limbs indicates the likely involvement of other vessels...

Of Lipidlowering Drugs that may Benefit PAD Patients

Statins exert pleiotropic effects, which may be independent of LDL-C lowering. These effects may appear even before a change in lipid level occurs 26, 35 . Statins increase nitric oxide (NO) production and improve endothelial function (e.g. increased flow-mediated dilatation). They have antioxidant properties and they inhibit the migration of macrophages and smooth muscle cell proliferation, leading to an antiproliferative effect and the stabilization of atherosclerotic plaques. Statins have anti-inflammatory effects including a reduction in the circulating levels of CRP, inflammatory and proinflammatory cytokines e.g. interleukin-6 (IL-6), IL-8 , adhesion molecules e.g. intercellular adhesion mol-ecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1) and other acute phase proteins. They reduce tissue factor expression and platelet activity, whereas fi-brinolysis can be enhanced. Statins improve microalbu-minuria, renal function, hypertension and arterial wall stiffness. A...

Methyldopa Side Effects

Labs Serum glucose elevated (157 mg dL) LDL lowered considerably in comparison to last visit triglycerides decreased, but not as markedly HDL increased AST and ALT mildly elevated elevated uric acid normal levels of 5-hydroxyindoleacetic acid (vs. carcinoid syndrome, which may also produce facial Hushing) constituent of NAD and NADP that is used in redox reactions. As a drug, it is used for its lipid-lowering properties (decreases VLDL, decreases LDL, and increases HDL cholesterol). Hepatitis, hyperglycemia, and exacerbation of peptic ulcer are other side effects.

Digestion and absorption

Digestion commences as soon as the food enters the mouth. Chewing helps to break up large particles of food, whilst also mixing food with saliva, which acts as a lubricant and contains the enzymes salivary amylase and lingual lipase. Lingual lipase has only a minor role in digestion of dietary triglycerides however, salivary amylase plays a major role in digestion of dietary starch. Most of the enzymatic activity of salivary amylase occurs in the stomach, where there is a much longer time for it to interact with the starch.

Foods Nutrients Vegetarianism and Coronary Heart Disease

It is likely that the reduction in CHD among vegetarians is, at least partly, due to a lower serum cholesterol concentration caused by a lower dietary intake of saturated fat and cholesterol. Unfortunately, none of the five prospective studies of mortality in vegetarians has complete information on serum cholesterol concentrations in all subjects, therefore, it is currently impossible to investigate whether the difference in CHD between vegetarians and non-vegetarians can be statistically explained by the difference in cholesterol levels. Some data are available, however, on the relationships of various foods to CHD within the cohort studies of vegetarians. Meat intake was strongly positively associated with CHD among male Seventh-Day Adventists in the two large prospective studies in California.49,77 There was also a positive, but weaker, association with meat intake among women in the earlier study,77 but not in the more recent study.49 Eggs, but not dairy products, were also...

Metabolic Degradation of Mineral Oil Adjuvants

To study the clearing of mineral oil he injected 14C-labeled hexadecane in an emulsion with unlabeled mannide monooleate im and sc in the thigh of the animals. One week after injection 85-98 of the radioactivity remained at the site of injection. After 1 mo 65-75 after 3 mo 55-65 and after 10 mo approx 30 of the labeled oil could still be found at the injection site. Thin-layer chromatography separation was undertaken to tell in which type of lipid the radioactivity was found. It was clearly shown that after 10 mo, the radioactivity at the injection site was still found in the hydrocarbon fraction. Samples from the major organs showed that there was an increasing level of radioactivity in the liver that peaked after 1 wk to 1 mo. After 10 mo, the level was back to normal. This was accompanied by a slightly later, but analogous rise-and-fall pattern in the radioactivity of the depot fat. No other organs achieved high levels of radioactivity. In the liver, the radioactivity after 1 mo...

Preoperative Planning

The patient's medical status must be evaluated preopera-tively, and all documented preoperative measures to prevent peri-operative ischaemia need to be taken. Initiation of -blockers and platelet inhibitors is particularly important, as are smoking cessation and the implementation of preoperative optimal regulation of blood pressure and blood glucose. Also, the use of statins seems to be associated with reduced peri-operative mortality in major non-cardiac surgery, probably due to their anti-inflammatory, plaque-stabilizing effects 57, 65 .

Creactive Protein CRP

Physical activity may lower serum CRP levels in patients with PAD 1 . Statins reduce the event rate in PAD. 7, 18 . However, there is evidence that this benefit is limited to, or at least more obvious in, the presence of high inflammatory activity. In this context, it is interesting that statins lower the circulating levels of CRP 1 . It is not clearly established if there is a dose-response relationship between the extent of LDL-C lowering (and possibly the statin dose used) and the fall in CRP levels. In this context, it is interesting that ezetimibe (a selective cholesterol transport inhibitor) lowers CRP levels further when added to a statin 7 . Some fibrates (e.g. ciprofibrate and fenofibrate) can also lower the circulating levels of CRP 7 .

Other Markers of Inflammation

Platelet activation may play a significant role through the expression of CD40 ligand as a source of activation signals to endothelial cells. This, in turn, may modulate the inflammatory response. In this context, it is relevant that both statins and the antiplatelet agent clopidogrel may influence the CD40 activation process 13, 16 .

Guidelines For Exercise

The participants in this study were young white and black men and women (ages 1830) who completed treadmill testing and then were followed from 1985 to 2001. Glucose, lipids, and blood pressures were measured and physical activity was assessed by interview and self-reporting. Outcome measurements included hypercholesterolemia, metabolic syndrome, hypertension, and type-2 diabetes. 3. Hypercholesterolemia 11.7.

Studies Relating Very Low Meat Intake To Longevity

A group of 5000 non-vegetarians were identified using a method whereby investigators asked the vegetarians to identify friends and relatives of similar lifestyle and social class but who ate meat. These 11,000 subjects completed a food frequency questionnaire at baseline (1980-1984) with items on meat intake and were then enrolled in a 12-year follow-up. In a validation sub-study, conducted 2-4 years after baseline, it was found that the non-meat-eaters had significantly lower total cholesterol and LDL cholesterol levels. Thorogood et al.90 reported the relation between very low meat intake and all-cause mortality in this study population.

Weil Fed Absorptive State

Immediately after a meal, the blood glucose level rises and stimulates the release of insulin. The three major target tissues for insulin are liver, muscle, and adipose tissue (Figure 1-11-2). Insulin promotes glycogen synthesis in liver and muscle. After the glycogen stores are filled, the liver converts excess glucose to fatty acids and triglycerides. Insulin promotes triglyceride synthesis in adipose tissue and protein synthesis in muscle, as well as glucose entry into both tissues. After a meal, most of the energy needs of the liver are met by the oxidation of excess amino acids.

Association between high blood cholesterol and atherosclerosis

An early demonstration of the link between hy-percholesterolaemia and atherosclerosis took place in 1913 when Anitschkow in Russia observed that feeding pure cholesterol to rabbits produced elevated blood cholesterol levels as well as atherosclerosis in the aorta and coronary arteries. The causal relationship between high blood cholesterol levels and atherosclerosis is demonstrated unequivocally by the genetic disorder familial hypercholesterolaemia (FH). This disorder is an example of an inborn error of metabolism and is due to impaired production of the LDL receptor. There are two forms of FH a heterozygous form and a more severe homozygous form. FH heterozygotes inherit one mutant gene and number about one in 500 people in most ethnic groups. The cells of these individuals produce approximately half the normal number of LDL receptors. As a result, LDL is removed from the circulation at half the normal rate, the lipoprotein accumulates in blood to levels twofold above normal, and...

Endothelial dysfunction Vasomotor control

Hypercholesterolaemia and atherosclerosis profoundly impair endothelium-dependent arterial relaxation as demonstrated, for example, in the aortas of rabbits (Habib et al., 1986 Verbeuren et al., 1986), the iliac arteries of monkeys (Freiman et al., 1986) and the coronary arteries of pigs (Shimokawa & Vanhoutte, 1989) and humans (Ludmer et al., 1986 Bossaller et al., 1987 F rstermann et al., 1988a). Depletion of tetrahydrobiopterin, an essential cofactor for nitric oxide synthase, causes impaired nitric oxide generation (Schmidt et al., 1992). Stroes et al. (1997) speculated that decreased nitric oxide-dependent va-sodilation in hypercholesterolaemia could be related to a relative deficiency of tetrahydrobiopterin, resulting in impaired nitric oxide synthase activity. They then showed that tetrahydrobiopterin did indeed restore the disturbed nitric oxide-dependent vasodila-tion in patients with familial hypercholesterolaemia, at a stage when macrovascular disease had not yet occurred.

Lipid Differences Between Omnivores And Vegetarian Or Vegans

The dominance of unsaturated fat to saturated fat of the vegetarian diet lowers total cholesterol and LDL-C levels. The saturated fatty acids (SFA) lauric (C12 O), myristic (C14 O), and palmitic (C16 O) are very hypercho-lesterolemic. Palmitic acid is the dominant fatty acid synthesized in the human body from excess calories that are converted to fat.42 Thus, the elderly vegetarian on a plant protein diet does not synthesize large amounts of palmitic acid. The SFA, stearic acid (C18 O), has no effect on blood lipoproteins and is considered neutral, with moderate amounts of dietary carbohydrate.43 Of all the added dietary fats, the most hypercholesterolemic are palm-kernel, coconut, and palm oils, and butter. SFA raise LDL-C by decreasing LDL receptor synthesis and activity. All fatty acids will lower fasting triglycerides if they replace carbohydrates in the diet.44 The most significant way to lower LDL-C and raise HDL is to replace carbohydrate with linoleic acid (C18 2), the...

Discussion And Perspectives

Liver, a proportion of the newly absorbed chylomicron retinyl ester is taken up into extrahepatic tissues, especially tissues that express lipoprotein lipase and are active in the metabolism of chylomicron triglycerides. Additionally, some of the newly absorbed VA is oxidized in the intestine and absorbed as RA into the portal system (Ross, 2006). Newly absorbed VA and intestinally formed metabolites may have a metabolic fate different from that of retinol bound to retinol-binding protein. It was shown in studies of chylomicron metabolism that chylomicron-associated VA is taken up, in an apparently transient manner, by bone marrow (Hussain et al., 1989a,b). However, the implications of this uptake process for hematopoiesis and immune function have not been studied. It is also interesting that, among several large-scale community trials on the effect of VA on child mortality, the study showing the largest reduction in all-cause mortality, 54 (Rahmathullah et al., 1990), delivered VA as...

Activation of Fatty Acids

Omega-3 fatty acids in the diet are correlated with a decreased risk of cardiovascular disease. These appear to replace some of the arachidonic acid (an omega-6 fatty acid) in platelet membranes and may lower the production of thromboxane and the tendency of the platelets to aggregate. A diet high in omega-3 fatty acids has also been associated with a decrease in serum triglycerides. Omega-3 fatty acids are found in cold-water fish, such as salmon, tuna, and herring, as well as in some nuts (walnuts) and seeds (flax seed).

Absorption And Deposition Of Dietary Vitamin A By The Skin

Following ingestion of a meal rich in vitamin A, the skin and other organs in the body encounter a changing profile of blood-borne vitamin A. In humans, retinyl esters (mostly retinyl palmitate) in chylomicrons may predominate in the blood for 3-6 h following ingestion of a retinol-rich meal. Smaller amounts of retinyl esters may be found in VLDL (Lemieux et al., 1998). The clearance of chylomicrons from the bloodstream is preceded by chylomicron catabolism in the blood, which involves removal of triglycerides from chylomicrons catalyzed by blood-borne lipoprotein lipases producing smaller lipoprotein particles called chylomicron remnants (Goodman and Blaner, 1984). Most retinyl esters in chylomicron remnants are efficiently removed from circulation, primarily by the liver. However, up to 30 of chylomicron retinyl esters are cleared from the circulation by extra-hepatic tissues (Vogel et al., 1999). It is unclear whether the skin plays any significant role in the clearance of...

Triglyceride Triacylglycerol Synthesis

Triglycerides Triglycerides, the storage form of fatty acids, are formed by attaching three fatty acids (as fatty acyl CoA) to glycerol. Triglyceride formation from fatty acids and glycerol 3-phosphate occurs primarily in liver and adipose tissue. Liver sends triglycerides to adipose tissue packaged as very low-density lipoproteins (VLDL reviewed later in this chapter). A small amount of triglyceride may be stored in the liver. Accumulation of significant triglyceride in tissues other than adipose tissue usually indicates a pathologic state.

Treatment of Hyperlipidemia

In a meta-analysis of the available epidemiolog-ical studies (450,000 patients), no association was observed between cholesterol level and overall stroke rate. However, meaningful interpretation of these data was confounded by the fact that although a higher cholesterol level was associated with an increased risk of ischemic stroke, this was offset by an increased risk of hemorrhagic stroke in patients with lower cholesterol levels. A subsequent systematic review of randomized trials indicated that statin In the U.K., there is conflicting advice regarding statin therapy. The National Service Framework for Coronary Heart Disease recommends statin therapy (cholesterol to be reduced to

Why change what you eat

What you eat has an effect on your general health and well-being. Many people think that they already have a healthy diet but, on average, people in the UK eat too much fat and too many calories. This can result in high cholesterol levels and weight problems and lead to many heart attacks each year. Heart disease by reducing cholesterol levels, blood pressure, weight.

Diseasespecific Guidelines

Coronary Heart Disease (CHD) is the major cause of death in industrialized and emerging nations and is the most common and serious form of cardiovascular disease. Elevated blood lipids and related disorders of lipoprotein metabolism are implicated in the progression of atherosclerosis and subsequent obstruction of coronary blood vessels and development of atherosclerotic heart disease. Atherosclerosis is infrequently hereditary in origin and there is an extensive body of epidemiologic, laboratory, and clinical evidence of an association between diet and the incidence of CHD. Recent clinical trials provide evidence that reducing serum cholesterol levels through diet, drugs, or both decreases the incidence of CHD. Although much attention has been focused on the effect of dietary fat and cholesterol on blood lipids, diet may influence other steps in the pathogenic sequence leading to atherosclerosis or to a cardiac event. For example, dietary factors may influence the propensity toward...

Cerebral Arteriosclerotic Vascular Disease

Patients with diabetes who have cerebral vascular arteriosclerotic disease should be on ACE inhibitors, statins, and platelet antagonists. Stroke is the third leading cause of death in this country, with more than 160,000 deaths occurring each year, and diabetic patients are at significantly increased risk. Triglycerides have also been shown to inhibit the progression of early carotid arteriosclerotic vascular disease, and the Losartan Intervention For Endpoint Reduction in Hypertension study (45) has demonstrated that losartan (Cozaar) can be effective in reducing stroke in hypertensive diabetic patients.

Efficacy Of Lowcarbohydrate Diets On Fasting Lipids

A principal concern about low-carbohydrate approaches is that the high-fat content of the diet may adversely affect serum lipids and increase the risk for cardiovascular disease. As discussed in a review by Volek et al. (31), preliminary findings challenge this argument. In studies that compared low-carbohydrate and low-fat diets over the course of 6 to 12 mo, there were no differences in total cholesterol or low-density lipoprotein (LDL) cholesterol concentrations between groups (8-12,21). One study reported that the low-carbohydrate diet was less effective than the low-fat diet in reducing total cholesterol and LDL cholesterol at 1 yr (13). Only one study reported a small, transient increase in total cholesterol and LDL cholesterol during the third month of a 1-yr treatment (8). Furthermore, compared with the conventional group, those in the low-carbohydrate group experienced greater improvements in high-density lipoprotein (HDL) cholesterol (8,12) and triglycerides (8-10,12). Only...

Risk Factors for Abdominal Aortic Aneurysm

Factors associated with an increased risk of aneurysmal development in the infrarenal aorta include increasing age, male sex, ethnic origin, family history, smoking, hypercholesterolemia, hypertension, and prior vascular disease. Studies suggest that of these, male sex and smoking are the most important, increasing the chances of AAA development by 4.5 and 5.5 times, respectively. A positive family history (first-degree relative affected) alone doubles the risk of AAA presentation and is more likely if the affected relative is a female. Interestingly,

Posterior Duodenal Ulcer

Icteric dry mucous membranes xanthelasma (due to hypercholesterolemia) scratch marks and excoriations over skin mild firm hepatomegaly splenomegaly no evidence of ascites. Direct hyperbilirubinemia serum alkaline phosphatase markedly elevated mild elevation of serum transaminases markedly raised anti-mitochondrial antibody titers hypercholesterolemia lipoprotein X present. Cholestyramine resin to control pruritus immunosuppressants consider liver transplantation.

Ultrasound For The Transdermal Extraction Of Analytes

The idea has been taken up by Langer and colleagues (Mitragotri et al., 2000b) who placed a chamber on the backs of anesthetized Sprague Dawley rats and filled it with 1 sodium lauryl sulfate solution. A 0.02 MHz transducer was then immersed in the solution and switched on for a few minutes to produce a pulsed 7 W cm-2 beam. Subsequently, a vacuum was applied to the sonicated sites for 15 minutes in order to extract the analytes. The treatment led to a 100fold elevation in glucose permeability, which persisted for at least 3 hours. Other ultrasonically extracted analytes were albumin, calcium, urea, triglycerides, lactate, and dextran. Crucially, transdermally extracted fluid had a composition similar to that of interstitial fluid. The efficacy of low-frequency ultrasound surfactant combination was proven in other rat studies that employed similar though not identical protocols (Kost et al., 2000 Mitragotri et al., 2000a). In particular, these studies demonstrated that the...

Metabolic events in the intestine Esterification of retinol

Within enterocytes retinol becomes bound in a 1 1 molar ratio to CRBP-II, which is present exclusively and abundantly in these cells. CRBP-II binds all-trans and 13- cis retinol with high affinity it also binds retinaldehyde, but not retinoic acid. The protein-bound retinol is esterified with saturated long-chain fatty acids, preferentially palmitic acid. The esterifica-tion uses a different pool of fatty acids and hence different enzymes than are used for the synthesis of triglycerides. Two microsomal enzymes are involved in the esterification of retinol, namely acyl coenzyme A retinol acyltransferase (ARAT) and lecithin retinol acyltransferase (LRAT). The substrates for the ARAT-catalysed reaction are free retinol and acyl-CoAs retinol bound to CRBP-II is not a substrate for ARAT. LRAT is an unusual enzyme in that it utilizes a membrane phospholipid, phosphatidylcholine (lecithin), as an endogenous donor of fatty acids for esterifica-tion. The enzyme activity shows positional...

Medications Monotherapy

Thiazide diuretics will increase glucose intolerance, hypokalemia, hypomagnesemia, and total cholesterol and triglycerides (but relatively neutral for high-density lipoprotein HDL levels). Thiazide diuretics act as vasodilators, with data confirming their ability to reduce left ventricular hypertrophy. The P-blockers without intrinsic sympathomimetic activity except third-generation P-blockers (carvedilol), will tend to increase triglycerides and glucose intolerance,

Protocol Considerations

Early studies using inbred mice required the use of a modified diet to generate a hyperlipidemic state, with subsequent development of atherosclerotic lesions. The most common modification was to have mice consume a diet highly enriched in saturated fat, cholesterol, and cholate (10). This diet is often referred to as the Paigen diet, after the investigator who popularized it. However, in the era in which genetically modified mice are available, such pronounced dietary manipulations are not needed. The apoE- - mouse develops hypercholesterolemia and atherosclerosis when maintained on a normal diet. However, many studies have been performed on these mice during feeding of a diet that is primarily enriched with saturated fat and cholesterol to a level present in the diet of western industrial nations. This diet contains 40 of calories from fat (21 by weight) and is colloquially referred to as the western diet. It has been demonstrated that feeding this diet accelerates the development...

Increase in Fatty Acids

An increase in fatty acids may be associated with an increased loading of triglycerides (grease and animal fat) and the death of large numbers of bacteria. To reduce the quantity of fatty acids produced in an anaerobic digester, triglycerides (fats, oils, and grease) should be removed upstream of the digester and treated aerobically with an appropriate bioaugmentation product to ensure adequate degradation of fats, oils, and grease before transferring these wastes to the anaerobic digester.

Drugs on the Near and Distant Horizons

The results of four phase III trials of rimonabant for the treatment of obesity have been presented. These reports are posted on the Sanofi website (82) only one exists in the form of a peer-reviewed publication at the time of this writing (82,83). The summary of these trials, therefore, comes primarily from these Sanofi press releases. The first trial to be announced was called the Rio-Lipids trial. This was a 1-yr trial that randomized 1018 obese subjects equally to placebo, 5 mg d rimonabant, or 20 mg d rimonabant. The subjects in this trial had untreated dyslipidemia, a BMI between 27 and 40, and a mean weight of 96 kg. Weight loss was 2 in the placebo group and 8.5 in the 20-mg rimonabant group. In the 20 mg d rimonabant group, waist circumference was reduced 9 cm, triglycerides were reduced by 15 , and HDL cholesterol was increased by 23 , compared with 3.5 cm, 3 ,and 12 respectively in the placebo group. In the 20 mg d group the LDL particle size increased, adiponectin...

Protein Differences Between Omnivores And Vegetarians Or Vegans

Additional advantages from the decrease or elimination of animal protein for the elderly can be seen in the lower serum lipid levels of vegetarians or vegans. The type of dietary protein, animal or plant, is the primary factor in the effect of proteins on serum cholesterol levels. Thus, the amino acid composition of the protein is a controlling factor for serum cholesterol levels.19 Sixteen references in this cited paper indicate that the lysine arginine ratio in proteins explains the effect of proteins on the level of serum cholesterol and, in turn, atherogenesis.19 Figure 11.1 shows the relationship between animal and vegetable protein on serum cholesterol levels. Soy protein from the soybean is a plant protein source that has been successfully used in long-term studies to decrease the level of serum cholesterol in hypercholesterolemic subjects. A high saturated fat intake however, can mask the soy protein effect.20 As the level of cholesterol in serum is decreased, the plasma...

The answer is d Fauci 14e pp 21162118 Gynecomastia is

The answer is c. (Fauci, 14 e, p 1976. Tierney, 39 e, p 1070.) Patients may use anabolic steroids to improve athletic performance. The risks associated with use of these agents include mood swings, aggressiveness, paranoid delusions, psychosis, gynecomastia, infertility, testicular atrophy, hepatic tumors, peliosis hepatis, hypertension, and decreased HDL cholesterol levels. Patients with prolactinomas (pituitary tumors) generally present with galactorrhea, reduced libido, erectile dysfunction, amenorrhea, infertility, and visual field defects. Chronic cocaine use may

Aortofemoral Graft Infection

A 66-year-old man, an ex-smoker with hypertension and hypercholesterolemia, had undergone a Dacron bifurcated aortic graft and bilateral ureteric stents for an inflammatory aortic aneurysm with ureteric obstruction at another hospital 4 years previously. The left limb of the graft had been anastomosed to the common femoral artery and the right limb to the common iliac bifurcation. Postoperatively he had suffered a mild groin wound infection, which had healed with antibiotics. At follow-up he complained of left calf and thigh claudication. On examination, he appeared generally well with a midline abdominal scar and a left vertical groin scar. He had good right femoral pulse but an absent left femoral pulse.

Initiation of Atherosclerosis and Role of Endothelial Dysfunction

Initiation Atherosclerosis

To explain the process of developing atherosclerosis, several theories have been proposed. For example, the plaque cluster could result from the monoclonal proliferation of modified SMC originating from a single progenitor (monoclonal theory) 2 . Another theory considers the role of a small accumulation of SMC, which acts as a primordial stage of stem cells prone to playing a role in the development of atherosclerosis (intimal cell hypothesis) 49 . Although some isolated cases are perhaps relevant, none of these theories is able to completely explain all the aspects of ongoing atherosclerosis. This suggests that the eventual onset of atherosclerosis is also determined by superimposed extrinsic factors such as increased cholesterol levels, smoking, etc.

The Effect Of A Vegetarian Diet On Performance

Nineteen long-term (mean of 46 years) vegetarian and 12 non-vegetarian, healthy, physically active elderly women (mean age of 71 years) were compared on a variety of hematological, anthropometric, and metabolic factors.30 Although the vegetarian subjects had significantly lower blood glucose and cholesterol levels, no differences between groups were found for submaximal and maximal cardiorespiratory and electrocardio-graphic parameters measured during graded treadmill testing. The authors Animal product intake was measured and related to VO2max in a group of 80 women who varied widely in age, body mass, maximal aerobic power, and meat intake (1.1 to 31.6 meat exchanges per day).33 Maximal aerobic power was not related to meat intake, an animal product index, or dietary cholesterol. Multiple regression analysis, using models to control for age and body composition, failed to alter these findings.

Ehlersdanlos Syndrome

Diet, exercise and cholesterol-lowering drugs (althought HMG-GoA reductase inhibitors are ineffective in homozygous FH patients due to complete lack of LDL. receptors). Consider portocaval anastamosis or liver transplantation. Familial hypercholesterolemia is also called type II hyperlipoproteinemia it is an autosomal-dominant defect in LDL receptor with a gene frequency of 1 500. Homozygotes may have an LDL count eight times that of normal.

Chronic Critical Limb Ischemia

An 85-year-old male with a history of diabetes, hypertension, hypercholesterolemia, coronary artery bypass, and active tobacco use presented with a gangrenous right first toe. The patient stated that he had no history of trauma to the area, and complained of rest pain in the foot. The patient had been in otherwise good health since his coronary artery bypass 12 years ago. On physical examination, the patient was in no physical distress. The patient had a well-healed median sternotomy scar. Auscultation of the heart revealed a regular rate without any murmurs. He was obese. Abdominal examination revealed no palpable masses. The patient had bilateral femoral and popliteal pulses but no pedal pulses. The patient had bilateral, well-healed scars from the greater saphenous vein harvest sites. The right gangrenous toe was dry without any evidence of infection.

Very LowDensity Lipoprotein VLDL Low Density Lipoprotein LDL

Very-low-density lipoproteins (VLDLs) are plasma proteins composed primarily of triglycerides and small amounts of cholesterol. The VLDLs transport triglycerides from the liver to the peripheral tissue. The breakdown of VLDLs is a major source of low-density lipoproteins (LDLs), which are cholesterol-rich plasma proteins. Increased levels of very-low-density lipoprotein is accompanied by increased levels of low-density lipoproteins. Very-low-density lipoproteins are associated with atherosclerosis, but not to the same degree as low-density lipoproteins.

Chylomicrons VLDL and Idl Vldl Remnants

Vldl Idl Triglycerides Chart

Lipoprotein (LPLase) is required for the metabolism of both chylomicrons and VLDL. This enzyme is induced by insulin and transported to the luminal surface of capillary endothelium where it is in direct contact with the blood. Lipoprotein lipase hydrolyzes the fatty acids from triglycerides carried by chylomicrons and VLDL and is activated by apoC-II. In capillaries of adipose tissue (and muscle), apoC-II activates lipoprotein lipase, the fatty acids released enter the tissue for storage, and the glycerol is retrieved by the liver, which has glycerol kinase. The chylomicron remnant is picked up by hepatocytes through the apoE receptor thus, dietary cholesterol, as well as any remaining triglyceride, is released in the hepatocyte. The receptor may recycle to the surface, the LDL is degraded, and cholesterol is released into the ceU. Expression of the gene for LDL receptors (apoB-100 receptor) is regulated by the cholesterol level within the cell. High cholesterol decreases expression...

Species of Plants Reported to Be Used Traditionally to Treat

Reduces blood glucose (Ivorra et al., 1989) Used to treat diabetes (Lust, 1986) Reduces blood glucose level in blood of alloxan-treated rats (Lemus et al., 1999) Contains triterpenes with hypoglycemic activity (Reher et al., 1991) Contains triterpenes with hypoglycemic activity (Reher et al., 1991) Reduces blood glucose (Handa et al., 1989) Extracts reduce blood glucose, cholesterol and triglycerides in patients with type 2 diabetes that did not respond to conventional treatments (Herrera-Arellano et al., 2004) Used to treat diabetes (Winkelman,

Species of Plants Reported to Be Used Traditionally to Treat Diabetes

Contains berberine (Soffar et al., 2001), which reduces levels of fasting blood glucose, triglycerides, and total cholesterol (Leng et al., 2004) and decreases glucose absorption (Pan et al., 2003) Berberine administration to impaired glucose tolerance rats reduces levels of fasting blood glucose, triglycerides and total cholesterol (Leng et al., 2004)

Magnetic Resonance Spectroscopy Quantification of Ectopic

Schick et al. (118) were the first to identify two compartments of triglycerides in muscle that have resonant frequencies separated by 0.02 ppm. The two compartments were identified to represent the lipid located inside (IMCL) and outside (EMCL) the muscle cell. IMCL droplets are spherical with a relatively homogenous distribution, and as such, are independent of muscle orientation relative to the magnetic field (115-117,119). On the other hand, EMCL lies outside the muscle fiber, and appears in plate-like structures (115-117,120) that have a highly variable distribution throughout the muscle. Due to the varying orientations and patterns of EMCL, misalignment of the muscle fibers relative to the magnetic field will cause the EMCL line to broaden, and potentially overlap the IMCL resonance peak (117). Further, Boesch et al. demonstrated that IMCL, and not EMCL, signals scale linearly with voxel size, water, and creatine signals, which are used to quantify and scale the IMCL spectra...

Formation of Vldl Hdl and LDL

In the liver, the constituent lipids of chylomicron remnants are repackaged into HDL and VLDL particles (mainly the latter), which are released into the circulation. There is no direct synthesis of LDL in the liver. VLDL contain high concentrations of triglycerides and moderate concentrations of cholesteryl esters and phospholipids. The triglycerides are removed

Principle Paracrine Secretion Involved In Inhibition Of Gastric Secretions

The answer is d. (Guyton, pp 756-758.) Long-chain fatty acids are extruded from enterocytes in the form of chylomicrons into the lymphatic system. Triglycerides are hydrolyzed to monoglycerides and taken into mucosal cells. If the fatty acids are short chains (less than 10 to 12 carbon atoms), they are extruded in the form of free fatty acids into the portal blood. Chylomicrons represent triglycerides and esters of cholesterol that 181. The answer is b. (Berne, 4 e, pp 666-672.) Medium-chain triglycerides (MCTs) are readily absorbed from the small intestine and can be used as a source of calories in patients with a wide variety of GI diseases resulting in malabsorption. MCTs are fatty acids of 6 to 12 carbon chain lengths that are present in small amounts in the normal diet. They are hydrolyzed by lipases more rapidly than long-chain fatty acids and are much more water-soluble than long-chain triglycerides. MCTs are not utilized for resynthesis of triglycerides and therefore are...

Microscopic Testing of Feces

Microscopic testing for fats is performed to identify the amount of fat present in feces. Using a microscopic exam, the laboratory professional is able to determine the number and size of fat droplets present in feces, as well as the type of fats present. The types of fats in feces include triglycerides, fatty acids, and fatty acid salts. The presence of fat in the stool is called steatorrhea, a possible sign or symptom of serious malabsorption syndromes and diseases such as celiac sprue and cystic fibrosis. Triglycerides 1-5 Fatty acids 5-15

Multiple Riskfactor Reduction

The Heart Outcomes Prevention Evaluation (HOPE) trial, which was a nonhypertensive trial, showed the superiority of 10 mg of the ACE inhibitor, ramipril with statistically significant reductions in myocardial infarction, stroke, and overall cardiovascular mortality and morbidity, independent of blood-pressure effect and medications that were concomitantly used, including aspirin, statins, and other antihypertensive drugs. This data was especially impressive in the diabetic subgroup, where there was a 22 reduction in combined cardiovascular events that was statistically significant. Additionally, the HOPE trial demonstrated a 24 reduction in total mortality, a 24 reduction in overt The HPS (16) involved almost 6000 patients with diabetes. This represented more patients than all other studies with statins and diabetic patients combined. Of the close to 2000 patients with diabetes and known coronary disease, tremendous benefit was derived by simvastatin therapy at any level of LDL. The...

Coronary heart disease

This condition is responsible for the majority of cardiovascular deaths. Although incidence is decreasing, CHD remains the leading cause of death in men and women in developed countries. It thus dominates statistics for cardiovascular mortality and has an impact on total mortality. A number of CHD risk factors have been uncovered by epidemiological studies. Among the established risk factors with probable causal effect are cigarette smoking, HTN, diabetes mellitus, increased LDL cholesterol, and decreased HDL cholesterol. Atherosclerotic narrowing of major epicardial coronary arteries is the usual basis of CHD. Thrombosis in narrowed vessels plays a critical role in major events, such as acute myocardial infarction or sudden death. The biological state of the atherosclerotic plaque and the endothelial lining of the coronary vessels plays an important role in the risk of these major CHD events. There is a progressive positive relation between higher levels of LDL cholesterol, the...

Fruits And Vegetables A Population Studies

Reductase, the rate-limiting enzyme in cholesterol synthesis. Cholesterol synthesis is suppressed and LDL receptor activity is augmented by the carotenoids te-carotene and lycopene, similar to that seen with the drug fluvastatin. When lycopene supplements (60 mg day) were given to men for a 3-month period, a 14 reduction in their LDL cholesterol levels occurred.44 Therefore, lycopene may be useful for decreasing the risk of coronary heart disease. The regular use of red wine is suggested for lowering the risk of heart disease. Two possible mechanisms explain this effect. First, alcohol raises HDL cholesterol levels.58 Second, wine inhibits the formation of blood clots. Since purple grape juice and dealcoholized red wine inhibit platelet aggregation, it is clearly not an effect of alcohol, but appears to be related to the flavonoid pigments in the grape juice or wine.59,60 Dealcoholized red wines and red grape juice inhibit platelet aggregation by blocking thromboxane B2 synthesis in...

Overview Of The Nuclear Receptor Superfamily

Severely impaired cholesterol and bile acid metabolism when fed with a cholesterol-enriched diet. Indeed, these mutant mice fail to induce CYP7A and consequently suffer from a dramatic accumulation of cholesteryl esters in the liver with no increase in bile acid production (Peet et al., 1998). However, it is now clear that the human CYP7A is not responsive to LXR and might even be repressed by LXRa activation (Chen et al., 2002 Goodwin et al., 2003). This difference between mouse and human is of interest as it might explain at least in part both the higher capability of mouse to face high-cholesterol diet and its increased resistance to the development of atherosclerosis. In summary, LXR is a major transcription factor, which acts as a sensor of cholesterol levels via its interaction with oxysterols and, in turn, drives the disposal of the excess of cholesterol. It also acts at the level of individual cells, by increasing the ABC transporter molecules responsible for cholesterol...

Digestion absorption and transport of dietary fat

The plasma lipoproteins are a family of globular proteins, each of which consists of a core of neutral lipid (predominantly triglyceride or cholesteryl ester) surrounded by a coat of phospholipid and protein. These particles can be divided into four broad categories (1) chylomicrons, which primarily transport dietary triglyceride and cholesterol (2) very-low-density lipoproteins (VLDL), which primarily transport triglycerides that have been synthesized in the liver Absorption of the fat-soluble vitamins takes place mainly in the proximal jejunum and depends on the proper functioning of the digestion and absorption of dietary fat. The fat content of a typical Western diet is composed mainly of triglycerides accompanied by smaller amounts of phospholipids and sterols. The efficiency of absorption of fat-soluble vitamins parallels that of fat absorption and is affected by the nature of the lipid component of the diet. The stomach is the major site for emulsification of dietary fat. The...

Diet and medical problems Diabetes

Whereas dietary fat helps to modulate the absorption of glucose, saturated fat and cholesterol should be limited in the diet. Saturated fat in the diet stimulates low-density lipoprotein (LDL) cholesterol production, and people with diabetes are more sensitive than the general population to dietary cholesterol. Less than 10 of calories should come from saturated fats, and dietary cholesterol should be less than 300 mg day. Some individuals may benefit from lowering intake further (7 saturated fat, 200 mg day cholesterol) (evidence level A). Intake of trans fatty acids should be minimized (evidence level B).

Bypass to the Popliteal Artery

A 62-year-old overweight postal worker presented with complaints of cramps in his right calf. He stated that this reproducible pain occurred each time he walked 50 yards and resolved upon sitting down. He denied tissue loss or rest pain. His past medical history was significant for hypertension, hypercholesterolemia and tobacco use, as well as coronary revascularization.

Recent Recommendations on Vitamins and Chronic Disease Prevention

American Heart Association (176) Vitamin or mineral substitutes are not a substitute for a balanced, nutritious diet that limits excess calories, saturated fat, trans fat, and dietary cholesterol. Scientific evidence does not suggest that consuming antioxidant vitamins can eliminate the need to reduce blood pressure, lower blood cholesterol level, or stop smoking.

Glucose Intolerance and Insulin Resistance

People with diabetes (both non-insulin-dependent and insulin-dependent) or with impaired glucose tolerance have a higher risk of CHD than people with normal glucose tolerance.34 Some of this association is due to the coexistence of glucose intolerance with low HDL cholesterol, high blood

MI Studies Addressing Dyslipidemia and Diabetes Dietary Intervention Study in Children

The Dietary Intervention Study in Children (DISC) was a multicenter, randomized controlled trial sponsored by the National Heart, Lung, and Blood Institute to assess the efficacy of dietary counseling to decrease elevated serum lipids (LDL-C). Children with elevated LDL-C entered the initial clinical trial when they were 8 to 10 yr of age (34). As the intervention cohort moved into adolescence, the investigators elected to add an MI-based intervention to renew adherence to the prescribed diet among the original intervention group (there was no control group for this phase). The counselors were primarily masters-level health educators and dietitians who received 18 h of MI training. Each study participant received one in-person MI session and one follow-up session that was conducted either in person or by telephone. Twenty-four-hour recall data from the first 127 youths to complete the two-session protocol indicated that the proportion of calories from fat and dietary cholesterol was...

Nuts Seeds And Oils

While 73 to 95 of the calories in nuts come from fat, they are low in saturated fat. On average, nuts contain about 60 of their calories from monounsaturated fat, which facilitates a reduction in blood total- and LDL cholesterol levels, without lowering the HDL cholesterol levels. A number of clinical trials have demonstrated the effectiveness of diets that contain either almonds, pecans, peanuts, hazelnuts, macadamia nuts, pistachios, or walnuts to significantly lower blood cholesterol levels.122-129 Human feeding trials that incorporated these nuts into the diet produced significant reductions in LDL cholesterol levels ranging from an 8 decrease with macadamia nuts to a 16 decrease with walnuts. Except for the studies with almonds and pistachios, all of the clinical trials involved normocho-lesterolemic subjects. Only in the case of the pistachio study did HDL cholesterol levels increase (up 12 ).129 In an analysis of the nut-feeding studies, Kris-Etherton reports that the...

Laboratory Evaluation of the Obese Patient

Although one could make a case for obtaining a large number of biochemical tests in the evaluation of an obese patient, a more limited initial screen seems warranted. A fasting sample of blood for glucose total, LDL, and HDL cholesterol and triglyceride levels is clearly indicated. These tests, along with an appropriate history, will provide the information necessary for cardiovascular risk stratification and can be used to rule out diabetes or impaired fasting glucose (25,57). Some have advocated obtaining a glycosylated hemoglobin (HbA1C) level to screen for diabetes. Although this test should be useful in the diagnosis of diabetes, the assay method has not been standardized and at this time there is no widely accepted diagnostic criteria for diabetes based on an HbA1C level. In addition, some have advocated obtaining a fasting insulin level to determine whether insulin resistance is present. Unfortunately, here again, methods for assaying insulin have not been standardized and...

Vertebrobasilar Ischemia Embolic Mechanism

A 51-year-old male experienced over a period of 6 months a major stroke and several transient ischemic attacks (TIAs) of vertebrobasilar distribution. The original episode consisted of loss of balance, loss of coordination, and loss of the left visual field while driving a bus, which resulted in a road accident. Since then, he had experienced four additional episodes of aphasia and paraparesis lasting for 4-5 h. A diagnosis of vertebral artery dissection was made at the local hospital and he was placed on Coumadin. Concomitant diagnoses were hypertension, non-insulin-dependent diabetes, and hypercholesterolemia. In spite of adequate international normalized ratio (INR) levels, his symptoms continued and he was referred to us.

Evaluation Of The Severity Of Mr

Obviously, patients should not undergo valve surgery unless there is severe regurgitation. Non-invasive imaging can provide all the information needed to gauge the severity of MR left and right ventricular function, the cause and severity of MR, the presence of pulmonary hypertension and associated valve lesions as tricuspid regurgitation and aortic valve disease Cardiac catheterisation with exercise hemodynamics and angiography is only indicated when there is discrepancy between clinical and non-invasive findings. Although ventriculography has its own limitations11, it provides an additional method to assess chamber dilation and function and to estimate MR severity. Right heart catheterisation is only indicated when there is uncertainty about MR severity and pulmonary hypertension. Coronary angiography is indicated in patients with risk factors for coronary artery disease including age, hypercholesterolemia, and hypertension.

Diabetes And Carbohydrates

Although carbohydrates, like monounsaturates, do not have significant effects on cholesterol, they can have significant effects on lipoprotein metabolism. This is because high-carbohydrate diets stimulate the synthesis of very low-density lipoprotein (VLDL) and triglycerides and subsequently can raise serum triglyceride levels. This usually effects HDL in a reciprocal fashion, with decreased levels of HDL. Removal of fats from the diet and replacement with carbohydrates reduces LDL levels despite the lowering effects of HDL. Dietary cholesterol intake should be

Selective estrogen receptor modulators

Raloxifene therapy results in decreased serum total and low-density lipoprotein (LDL) cholesterol without any beneficial effects on serum total high-density lipoprotein (HDL) cholesterol or triglycerides.41,42 The side effects of raloxifene are vaginitis and hot flushes.43 Investigators in the Multiple Outcomes of Raloxifene (MORE) trial of more than 7000 postmenopausal, osteoporotic women over three years showed a decreased breast cancer risk in those already at low risk for the disease.44 The study results were analyzed separately for women presenting with pre-existing fracture. While treatment effectiveness was similar in both groups, the absolute risk of fractures in the group with

Risk factors for atherosclerosis

Conditional risk factors are those where the existence of a cause-and-effect relationship and the magnitude of the relationship are less clear. These risk factors include elevated triglycerides, lipoprotein (a), small LDL particles, homocysteine, fibrinogen, plasminogen activator inhibitor, and C reactive protein.

Prevention of coronary heart disease in women

Case 1 a 62-year-old woman comes to you as a new patient. She has no complaints but needs preventive care. She smokes one pack of cigarettes per day and is on no medications. She does no regular physical exercise and has a desk job. She has no chronic medical problems. Her blood pressure is 150 90 mmHg, and she has a body mass index (BMI) of 38 kg m2 and a waist-to-hip ratio of 1.2. There are no other physical exam abnormalities. You order fasting screening labs, which show total cholesterol of 265 mg dl (6.9 mmol l), low-density lipoprotein (LDL) 180 mg dl (4.7 mmol l), high-density lipoprotein (HDL) 25mg dl (0.65mmol l), triglycerides 300mg dl (3.4mmol l), and glucose 180 mg dl. She is taking atenolol, aspirin, and atorvastatin. Her blood pressure is 160 100mmHg, pulse is 90bpm, BMI is 35kg m2, and the reminder of her examination is unremarkable. In hospital, her cholesterol was 330 mg dl (8.5mmol l), LDL190mg dl (4.9mmol l), HDL40 mg dl (1.0mmol l), triglycerides 500 mg dl (5.6...

Regular physical activity

Moderate levels of physical activity have significant effects on a woman's health. Burning approximately 150 kilocalories per day or 1000 kilocalories per week leads to a reduction in the risk of coronary heart disease by 50 and of hypertension, diabetes, and colon cancer by 30 .2 After adjusting for covariates such as age, smoking, alcohol use, history of hypertension, and history of high cholesterol, women who are regularly physically active are 50 less likely to develop type II diabetes (relative risk 0.54) than women who are not regularly active.8 Vasomotor and psychosomatic symptoms associated with menopause are also reduced with moderate amounts of activity.6,9 Examples of moderate levels of physical activity are depicted in Table 2.2.

Diabetes complications

Dyslipidemia in women is a powerful contributing factor to the macrovas-cular complications of diabetes, in particular the increasing cardiovascular morbidity and mortality. Subset analysis has shown that goal low-density lipoprotein (LDL) cholesterol of less than 100 mg dl and triglycerides less than 200 mg dl impact cardiovascular events in women with diabetes. In addition to diet and exercise, lipid-lowering medications such as the 3-hydroxy-3-methylglutaryl ceenzyme A (HMG CoA) reductase inhibitors (to lower LDL) or fibric acid derivatives (to lower triglycerides) maybe necessary to achieve target lipid levels.

Systemic Corticosteroids

Corticosteroids are potent modulators of the immune system but have low specificity and serious side effects. Their well-known and serious side effects, including osteopaenia, weight gain, hyperglycaemia, hypercholesterolaemia, hypertension, and skin fragility, can occur with modest doses administered over relatively short periods. Despite this they are widely used in solid organ transplantation, where their combination with other immunosuppressive agents enables the use of lower doses of the individual agents with a corresponding reduction in the side effects. However, even when used in combination, the side effects from systemic administration of

Epidemiology

Coronary artery disease (CAD) has been recognized as the leading cause of death since the late 1940s. Hypertension, hypercholesterolemia, cigarette smoking, and diabetes mellitus were identified as key contributors to atherosclerosis and the development of cardiovascular risk. These risk factors are also related to cere-brovascular and peripheral vascular disease (Table 1.2).

Hyperlipidemia

An estimated 50 of American adults have total blood cholesterol levels of 200mg dL and higher, and about 20 of American adults have levels of 240mg dL or higher. Levels of 240mg dL or higher are considered high risk and levels from 200 to 239 mg dL are considered borderline high risk. Evidence linking lipids to atherosclerosis has grown, suggesting that lowering serum cholesterol, whether through diet and lifestyle modification alone or in combination with cholesterol-lowering pharmacother-apy, decreases the incidence of vascular events. For example a 1 mg dL increase in high-density lipoprotein (HDL) cholesterol concentration is associated with a 2 to 3 decrease in CAD and a 4 to 5 decrease in cardiovascular mortality. Data from the Multiple Risk Factor Intervention Trial (MRFIT) demonstrate a strong, graded, positive correlation between serum cholesterol and cardiovascular mortality rate (Neaton and Wentworth, 1992). Elevations in lipoprotein (a) Lp(a) constitute a more recently...

Diabetes

Diabetes mellitus magnifies the risk of cardiovascular morbidity and mortality. Diabetics have a two- to fourfold increase in the risk of CAD. Diabetics, particularly those with non-insulin-dependent diabetes mellitus (NIDDM) are at high risk of vascular disease because of high levels of triglycerides, LDL, and very low-density lipoprotein (VLDL) particles. Patients with NIDDM tend to produce small, dense LDL particles that are more vulnerable to oxidation. Other mechanisms for the adverse effects of diabetes that promote vascular disease include glycation of arterial wall proteins, enhancement of LDL oxidation, microvascular disease of the vasa vasorum, change in cellular function, promotion of thrombogenesis, and the development of renal disease and hypertension (Beckman et al., 2002).

Question

Postoperative outcome in patients undergoing major vascular surgery has been improved in those taking beta-blockers and statins. Medical therapy may reduce the need for additional preoperative testing for coronary artery disease as the incidence of perioperative cardiac mortality is reduced to less than 1 percent, and may even reduce the indications for preoperative coronary revascularization. D. Beta-blockers and statins are independently associated with an improved postoperative outcome.

Lipoproteins

Very low-density lipoproteins are not as large as chylomicrons and are slightly more dense. They carry triglycerides and other fats synthesized in the liver. The IDLs are formed when some of the triglyceride is removed from VLDL. Under normal circumstances it is removed so rapidly from plasma that its concentration is quite low. Alterations of LDL metabolism may create species of LDL particles with higher protein-lipid concentrations. Increased levels of these types of particles (termed small, dense LDL) are associated with increased risk of atherosclerotic disease and with elevated triglycerides (TGs) and low levels of HDL cholesterol. The mechanism linking these particles and hypertriglyc-eridemia relates to the production of chylomicrons and VLDL that are particularly rich in TGs. Catabolism of these TG-saturated VLDL particles produce LDL particles that have higher than normal TG content. These TG-rich LDLs are susceptible to further lipolysis by hepatic lipase, producing a...

Lipid Metabolism

Very low-density lipoprotein exchanges triglycerides for cholesterol esters from HDL. Like chylomicrons, lipoprotein lipase catalyzes the hydrolysis of triglyceride in VLDL to fatty acids that are used by muscle or stored as fat in adipose tissue. This hydrolysis step reduces VLDL to IDL. Intermediate-density lipoprotein can be taken up by the LDL receptor or be reduced to LDL by hepatic lipase. Intermediate-

Commentary

Q1 A This high frequency of cardiac complications is related to the high prevalence of coronary artery disease 54 percent of patients undergoing major vascular surgery have advanced or severe coronary artery disease and only 8 percent of patients have normal coronary arteries 2 . Perioperative cardiac complications are equally caused by prolonged myocardial ischemia or by coronary artery plaque rupture with subsequent thrombus formation and coronary artery occlusion 1, 3 . Q1 B, C, D Prolonged perioperative myocardial ischemia usually occurs from either increased myocardial oxygen demand or reduced supply, or from a combination of the two. There are several perioperative factors that can increase myocardial oxygen demand including tachycardia and hypertension resulting from surgical stress, postoperative pain, interruption of beta-blocker use, or the use sympathomimetic drugs. Decreased oxygen supply, on the other hand, can occur as a result of hypotension,...

Response to Injury

The response-to-injury hypothesis initially proposed that endothelial denudation was the first step in atherosclerosis. More recent data suggest that endothelial dysfunction rather denudation is the primary problem. According to this model, atherogenesis is a response to injury of the vascular endothelium. At its mildest, atherosclerosis may represent a repara-tive process that leads to thrombus formation and smooth muscle cell proliferation at the site of endothelial injury. The production of the endothelial injury may be from hypertension, cytotoxic molecules, or blood flow changes. Atherosclerosis develops at sites exposed to unusual shear stress, such as in the abdominal aortic bifurcation. Hypercholesterolemia, hyperhomo-cystinemia, and smoking may all contribute to endothelial injury.

Prevention

Additionally, large epidemiological studies have demonstrated that lower cholesterol levels are associated with a lower overall risk of morbidity and mortality due to CAD (Martin et al., 1986). Numerous clinical trials support these epidemiological data, and show that cholesterol lowering therapies lead to a significant reduction in morbidity and mortality associated with CAD. Additionally, these benefits extend to a population presenting with peripheral arterial disease as well. The benefits of statin therapy to decrease risk is seen as early as the first year of treatment and extend not only to prevention of cardiovascular disease but also to the quality of life. In this era of evidence-based medicine, it would be difficult not to treat patients identified at risk with statin therapy based on these data. Recommended treatment guidelines are given in Table 1.5. medication Low HDL cholesterol (

Controversy

The importance of treating patients to lower the cholesterol levels and to lessen the risk of developing atherosclerosis is well accepted. However, the question remains whether there is a threshold below which cholesterol reduction may translate into clinical benefit. On average drug therapy with simvastatin loweres LDL cholesterol levels by 35 and reduces heart risk by 34 (Pedersen et al., 1998). The goal of this study was to reduce total cholesterol below 200. However, many patients achieved reductions greater than this and were associated with continuing but progressively smaller reductions in heart attack risk. This subgroup analysis estimated a 1 reduction in LDL, reducing the risk of major coronary events by 1.7 . However, at what point this benefit can

Prevention of PAD

In the Program on the Surgical Control of Hyperlipid-emias (POSCH) 9 the effect of cholesterol-lowering induced by partial ileal by-pass in patients (n 838) with a previous MI and hyperlipidaemia was assessed. The incidence of new cases of claudication was significantly lower relative risk (RR) 0.66, 95 confidence interval (CI) 0.20-0.90 p 0.009 in the intervention group when compared with the control (nonintervention) group 4 years after the closure of the trial.

Hyperlipidaemia

Raised serum total cholesterol, low serum high-density lipoprotein cholesterol and raised serum triglycerides are recognised risk factors that lead to PAD. Therefore, lowering plasma lipid levels with drugs such as statins benefits patients at risk of cardiovascular events. The current recommendation of treating only total cholesterol over 5 mmol l has been challenged by evidence that statins may have a direct beneficial effect on atherosclerosis (Shearman, 2002). Results from studies currently underway are needed to evaluate this in greater detail, in particular the cost-effectiveness of more widespread use of these drugs (Leng et al., 2001).

Concluding Comments

Although statins can improve both clinical outcomes and symptoms in PAD, it is possible that further benefit can be obtained if LDL-C levels are lowered beyond the older targets for high-risk patients from 96-100 mg dl (2.5-2.6 mmol l) to 70-77 mg dl (1.8-2.0 mmol l) . However, we do not know if these new LDL-C targets provide further symptomatic improvement or a more effective prevention of events in PAD. These issues need to be resolved by appropriately designed trials.

Limiting fat intake

In the average American diet, approximately 36 of calories come from fat. To reduce the risk of heart disease, the fat content of the diet should be limited to 30 or less. Some have taken this much lower (see Pritikin and Ornish diets, pp. 29). To control cholesterol levels and heart disease risk, reduction in saturated fat intake is generally recommended. Modifying the type of fat in the diet to replace saturated fats with polyunsaturated fat will reduce the risk of coronary artery disease.1 Considering both heart disease and cancer risk, less than 10 of the total calories per day should come from each category of fat (saturated, monounsaturated, polyunsaturated). Providers should recommend use of low-fat dairy products, limited amounts of lean meats, and avoidance of added fats. For cooking, high monounsaturated oils (olive, canola) are preferable.

Lipid Profile

Lipids are fat substances that provide energy to the body are necessary for the production of steroid hormones and bile acids and have a role in creating cell membranes. Two dominant lipids are cholesterol and triglyceride. Cholesterol and triglycerides are transported in the bloodstream by lipoproteins, which are complex molecules consisting of plasma proteins and lipids. Lipoproteins are categorized as high-density lipoproteins (HDL), cholesterol-rich plasma proteins very-low-density lipoproteins (VLDL), A lipid profile includes measuring plasma levels of cholesterol, triglycerides, HDLs, LDLs, and VLDLs. The purpose of the lipid profile is to detect disorders of lipid metabolism and to assess the risk of atherosclerosis, arteriosclerotic heart disease (ASHD), and peripheral vascular disease. Table 2-3 identifies each lipid test and related diagnostic applications.

Heart disease

C.B. is a 58-year-old woman who presents for hospital follow-up. She is now four weeks after her first heart attack and still stunned that this happened to her. At hospital discharge, she declined cholesterol-lowering medication, saying she really doesn't want more drugs. She asks what she can do with her diet to reduce her risk of another heart attack. Soy protein intake has been found consistently to induce modest reduction of serum cholesterol. The US FDA and the American Heart Association now agree that 25 g per day of soy protein, in conjunction with a low-fat diet, may reduce the risk of heart disease. Fenugreek, a legume used as a supplement, has also shown cholesterol-lowering effects in preliminary studies.17

Diagnosing Diabetes

IGT is not defined by clinical signs and symptoms but strictly by plasma glucose levels alone. This state has also been referred to as chemical diabetes, borderline diabetes, or prediabetes. Although these patients do not yet have the microvascular complications of diabetes mellitus they are at risk for, and begin to develop, macrovascular complications caused by arteriosclerotic deposition secondary to the hyperglycemic state and are at significant risk for developing diabetes, especially when associated with concomitant risk factors of hypertension, body mass index (BMI) greater than 25 kg m2, sedentary lifestyle, dyslipidemia (especially increased small, dense low-density lipo-proteins LDL and increased triglycerides), history of gestational diabetes, polycystic ovaries and associated ethnicity (African American, Latin American, Native American, and Pacific Islanders) (13).

Dyslipidemia

Abnormal lipid profiles are well recognized in patients with atherosclerosis. The relationship between cholesterol level and CAD risk is continuous, with no obvious safe cut-off point. Patients with PAD are likely to be identical. A number of studies investigated cholesterol in PAD and found it to be a significant, though weak, risk factor for claudication, and above the age of 55 years to correlate with ABI. Reduced HDL is associated with increased PAD severity,6 with strong inverse relationships between HDL cholesterol and PAD that persist after adjustment for other risk factors. Furthermore, elevated serum triglyceride levels have been reported in both cross section and longitudinal studies. It has been suggested that the link between increased triglyceride level in patients with PAD and the development of the disease might be explained by the increase in low-density lipoprotein (LDL) providing the enhanced vascular risk. More recently, the Heart Protection Study (HPS) demonstrated...

Creatinine

Future studies should determine whether correcting or preventing impaired renal function will result in a decreased risk of vascular events. In this context, there is evidence that treatment with statins and antihypertensive drugs results in improved renal function or a delay in renal disease progression 6, 7 .

Block

A 62-year-old woman with hypertension, diabetes, hypercholesterolemia, and a long smoking history comes to the emergency department with altered mental status. She is started on supplemental oxygen, and an intravenous catheter is inserted. Oxygen saturation is 95 on 3 L nasal cannula, pulse is 102 beats min, temperature is 96-2 F, and the blood pressure is 78 42 mmHg. The chest has scattered rhonchi. but the patienl is unable to cooperate enough to take a deep breath.

Atherosclerosis

The causal relationship between high blood cholesterol levels and atherosclerosis is well established (Levine et al., 1995). Hypercholesterolaemia may be thought of as any plasma cholesterol level above 160 mg 100 mL. Cholesterol-lowering therapy is effective in both the primary prevention of coronary artery disease and the secondary prevention of subsequent cardiac events in patients with established coronary disease.

Oral contraceptives

Other potential adverse effects of OCP use include metabolic changes similar to pregnancy, including elevations in thyroid binding proteins and thyroxin, elevations in total cholesterol and triglycerides (in combination pills), decreased glucose tolerance, and the development of biliary diseases, including cholelithiasis, cholecystitis, and cholestatic jaundice.

Relapses

Relapse with this particular combination therapy when compared with standard antimicrobial therapy alone.79 There are anecdotal reports of successful therapy using metronidazole followed by oral Lactobacillus,80 vancomycin in combination with rifampin or cholestyramine,81-83 tapering or pulse doses of vancomycin,84 rectal instillation of stool or mixed broth cultures,85 and intravenous immune globulin.86,87 None of these therapies appear to be uniformly effective, and their use is empirical for any particular patient. With increasingly worrisome antibiotic-resistant enteric organisms (e.g., vancomycin-resistant enterococci), clearly the need is increasing for chemotherapeutic or immunologic agents (other than antimicrobials) that block the dramatic effects of the toxin(s),88 such as antitoxic antibody, pharmacologic blockers such as phospholipase A2 or cyclooxygenase inhibitors, or platelet-activating factor antagonists.89

Future Perspectives

Because estrogen monotherapy has been linked to increases in the risk of endometrial cancer (202), progestins have usually been included to reduce this risk (203). The role of progesterone in combination with estrogen in cardioprotection is currently controversial. A number of previous investigations have proposed that progestins counteract the beneficial antiatherogenic effects of estrogen by its negative influence on serum lipids, particularly HDL cholesterol (204). However, these findings have recently been challenged (205), and as mentioned previously, estrogen-induced beneficial effects on serum lipoproteins accounts for less than 50 of the total cardioprotective effects of this hormone. Recent studies have demonstrated that those postmenopausal women, using both estrogen and progesterone replacement, exhibited a significantly lower incidence of cardiovascular deaths than those using estrogen monotherapy (206). These observations support a beneficial role for progesterone in...

Smoking

Smoking by women causes 1.5 times as many deaths from CHD as from lung cancer.9 Active or passive exposure to nicotine and its by-products impairs endothelial function. Exposure to nicotine increases clotting proteins (fibrinogen), enhances the reactivity of platelets (making thrombosis more likely), and increases the viscosity of the blood. Smoking also decreases the advantageous HDL cholesterol.11 Nicotine exposure injures the endothelium and destabilizes previously established atherosclerotic plaques by promoting plaque rupture and the development of superimposed coronary thrombosis. The process ofplaque ruptures and superimposed thrombosis is the sequence of events now accepted to be at the root of most MIs.

Conclusions

19 Lemaitre, R.N., Psaty, B.M., Heckbert, S. R., et al. Therapy with hydroxymethyl-glutaryl coenzyme A reductase inhibitors (statins) and associated risk of incident cardiovascular events in older adults - evidence from the cardiovascular health study. Arch. Intern. Med. 2002 162 1395-400. 20 Downs, J. R., Clearfield, M., Weis, S., et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels results of AFCAPS TexCAPS. J. Am. Med. Assoc. 1998 279 1615-22. 21 Sacks, F. M., Pfeffer, M. A., Moye, L. A., et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels cholesterol and recurrent events trial investigators. N. Engl. J. Med. 1996 335 1001-9. 23 LaRosa, J. C., He, J. and Vupputuri, S. Effect of statins on the risk of coronary disease a meta-analysis of randomized controlled trials. J. Am. Med. Assoc. 1999 282 2340-46. 24 Yeung, A. C. and Tsao, P. Statin therapy...

Jo Ann Rosenfeld

Case M.M. is a 54-year-old obese woman who has not seen a physician in two years. She has a history of hypertension and high cholesterol. She works full time as an accountant for a medium-sized firm and has spent all her spare time for the past two years caring for her mother, who died two years after being incapacitated by a stroke. She has two married daughters who live across the country. She wants to control her hypertension so she doesn't end up like her mother and as a burden to her children.

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