Natural Cholesterol Treatments

Beat Cholesterol

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. While IP6 is well known for its cancer-fighting properties, Davis points to its use to lower blood cholesterol. Indeed, the U.S. National Institutes for Health (NIH) actually performed research that actually drew the same conclusion in 1999. IP6 is also known to actually reduce the presence of calcium deposits in arteries, another benefit which will delay or prevent the onset of heart disease. When you download the e-book you learn how to be in control of your cholesterol and live a longer and more fulfilling life. Youll also learn diet tips, discover supplements that can help you and even learn how to avoid toxins found in most water. However, the most important thing that youll get is a 30 day action plan. Continue reading...

Natural Cholesterol Guide Overview

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My Natural Cholesterol Guide Review

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Statins and atherosclerosis

Statins have been used for secondary prevention of CAD with good results. Simvastatin has been evaluated in several studies including the Scandanavian Simvastatin Survival Study (4S) (16), the Simvastatin Enalapril Coronary Atherosclerosis Trial (SCAT) (17), and the Multicentre Anti-Atheroma Study (MAAS) (18). In addition to lowering LDL cholesterol levels, simvastatin has been shown to cause angiographic improvement in the coronary vessels, as well as slowing the progression of diffuse and focal atherosclerosis. In addition, the drug is believed to induce positive vascular remodeling, thereby reducing the occurrence of restenosis (19). The 4S study included 4444 patients with documented or symptomatic CAD. This was the first study to unequivocally demonstrate a reduction in the total CAD mortality (34 reduction in treated group with a 51 reduction in of coronary revascularization rate). Risk reduction was evident in multiple subgroups such as women, diabetics, and elderly patients...

What Is The Best Way To Lower Cholesterol

The liver regulates the amount of cholesterol in the blood. The liver secretes cholesterol in the bile (which is stored in the gallbladder), which enters the gut. Therefore, there is a lot of cholesterol in the gut from the food we eat and the cholesterol made in the liver and then secreted into the gut. The most effective way to lower cholesterol is by both lowering the cholesterol made in the liver using a statin, and lowering the absorption of cholesterol from the gut into the bloodstream with ezetimibe.

Bile Acid Sequestrants

The bile acid sequestrants are contraindicated in patients with known hypersensitivity to the drugs. Bile acid sequestrants are also contraindicated in those with complete biliary obstruction. These drugs are used cautiously in patients with a history of liver or kidney disease. Bile acid sequestrants are used cautiously during pregnancy (Pregnancy Category C) and lactation (decreased absorption of vitamins may affect the infant). The bile acids sequestrants, particularly cholestyra-mine, can decrease the absorption of numerous drugs. For this reason, the bile acid sequestrants should be administered alone and other drugs given at least 1 hour before or 4 hours after administration of the bile acid sequestrants. There is an increased risk of bleeding when the bile acid sequestrants are administered with oral anticoagulants. The dosage of the anticoagulant is usually decreased. The bile acid sequestrants may bind with digoxin, thiazide diuretics, penicillin, propranolol, tetracyclines,...

Mevastatin and other Statins

Mevastatin Hydrolysed Form

Mevastatin (formerly compactin) (Figure 3.83) is produced by cultures of Penicillium citrinum and P. brevicompactum, and was shown to be a reversible competitive inhibitor of HMG-CoA reductase, dramatically lowering sterol biosynthesis in mammalian cell cultures and animals, and reducing total and low density lipoprotein cholesterol levels (see page 236). Mevastatin in its ring-opened form (Figure 3.84) mimics the half-reduced substrate mevaldate hemithioacetal during the two-stage reduction of HMG-CoA to mevalonate (see page 170), and the affinity of this agent towards HMG-CoA reductase is 10 000-fold more than the normal substrate. High blood cholesterol levels contribute to the incidence of coronary heart disease (see page 236), so mevastatin, or analogues, are of potential value in treating high risk coronary patients, and some agents are already in use. Although lowering of cholesterol levels reduces the risk of heart attacks, there is evidence that the beneficial effects of...

Effects of Inulin Type Fructans on Lipid Parameters in Genetically Modified Animals Prone to Develop Obesity or

Homozygous low-density lipoprotein receptor knock out mice (LDLR- -) is a recognized model of atherosclerosis.28 Indeed, these mice develop spontaneous hyperc-holesterolemia with elevated levels of LDL and IDL and arteriosclerosis due to a genetic defect-deficiency of functional LDL receptors which is analogous to the genetic defects in humans with familial hypocholesterolemia.29,30 After 3 weeks of treatment and throughout the study that lasted for 16 weeks, LDLR- - mice fed inulin (10 w w of the high molecular weight HP product in diet) had a significantly lower concentration of plasma cholesterol (30 ) but the same concentration of plasma TAGs compared to mice fed the standard diet.31 At the end of the protocol, the cholesterol content of VLDL, IDL, and LDL fractions of inulin-fed mice was lower (33, 40, 28 , respectively) than that of control mice. The concentration of cholesterol in HDL remained the same but the ratio HDL cholesterol over LDL cholesterol increased from 0.48 to...

Is High Cholesterol And Other Risk Factors Often Due To Lifestyle

People with a high cholesterol level are often overweight because they eat too much fat and other unhealthy food, drink too much alcohol, and do little if any regular exercise. Because of all these factors, they often have or develop diabetes. Therefore, they have not only high cholesterol as a risk factor, but also, obesity, inactivity, and diabetes. If they also smoke, they are at particularly high risk.

Clinical Spectrum Of

Atherothrombosis is a silent process that usually commences 20-30 yr prior a patient's presentation with a clinical syndrome (3,4). Hypercholesterolemia, hypertension, diabetes, smoking and other coronary risk factors damage the endothelium which initiates the atherosclerotic process (3,4,32), When the endothelium is dysfunctional, macrophages bind to endothelial adhesion molecules and can infiltrate the endothelial cell. Low density lipoprotein (LDL) molecules are able to penetrate into the vessel wall, the macrophages digest the LDL, becoming foam cells, which thereby create a lipid-filled atherosclerotic plaque (4,33). Oxidized LDL may also have a direct toxic affect on the endothelium and smooth muscle cells, which contribute to the instability of the atherosclerotic plaque.

The Nature Of Complications

Only recently have these ideas, developed so effectively by Dr. Reaven, become conventional wisdom. In fact, syndromes of insulin resistance are manifest by impaired responses to insulin in skeletal muscle, adipose tissue, and the liver, clusters of abnormality including dyslipidemia with high triglycerides, low HDL cholesterol, decreased LDL particle size, postprandial lipemia, increased susceptibility to oxidation of LDL, obesity, hypertension, impaired fibrinolysis, and perhaps of most importance to the patient at risk, accelerated coronary artery disease manifested by acute coronary syndromes. Some or all of these derangements are seen in patients with syndromes of insulin resistance even in the ab- -o sence of the derangements in intermediary metabolism typical of diabetes, including hyperglycemia. Thus, women with the polycystic ovarian syndrome who are insulin resistant have accelerated coronary disease as do normal subjects who are not diabetic but have elevated fasting...

Predispositions to atherosclerosis

Patients with a family history of atherosclerotic disease are at higher risk of developing significant atherosclerotic disease, and several genes have been associated with worse manifestations of atherosclerosis 18 . The genes which transmit a heritable trait of susceptibility to worse forms of atherosclerosis do not follow simple Mendelian patterns, and atherosclerotic susceptibility is likely the result of multiple genes. For example, progression of atherosclerotic lesions is associated with 'remodeling' of the microenvironment of the lesion, including degradation of the extracellular matrix, by the family of matrix metalloproteinases (MMPs). Abnormal polymorphisms in the genes for MMPs-3 and -9 have been identified, in patients suffering from more severe atherosclerosis. Similarly, a large number of genes control plasma levels of lipids, such as LDL cholesterol, HDL cholesterol, triglycerides and lipoprotein (a) (reviewed by 4 ) which, typically in conjunction with diet, can play...

HMG CoA Reductase Inhibitors and Plaque Stabilization

An emerging concept, which is relevant to the issue of triggering of acute coronary disease, is that of plaque stabilization (11,12). An atherosclerotic lesion, which is more resistant to rupture, will be less likely to do so when exposed to a trigger that can induce plaque disruption. Angiographic studies of aggressive lipid-lowering therapy identified a disproportionately dramatic reduction in cardiac events compared to tiny changes in the arteriographic appearance of the coronary arteries. Large clinical studies demonstrating the success of both primary (180) and secondary (181) coronary event prevention strategies, using b-hydroxy-b-methylglutaryl (HMG) CoA reductase inhibitors (statins), have supported the concept that these drugs have their beneficial effects on coronary events by altering the composition and milieu of the plaque rather than by reducing plaque bulk and coronary stenosis severity. There are a variety of mechanisms by which the most prominent effect of statins,...

What Are Risk Factors

A person with a risk factor is more likely to get coronary heart disease compared to someone who does not have that risk factor. But just because a person has a risk factor, for example, being a smoker or having high cholesterol, does not mean that he will definitely get coronary heart disease. This explains why some people, albeit only a tiny minority, live to a good age, even if they smoke or have high cholesterol. Also, people without risk factors still get angina and die from a heart attack.

What Makes a Condition a Risk Factor

It has been known for 100 years that people who died from a heart attack had fat (cholesterol) in their arteries. Over the last 50 years, it has been confirmed that people with a lot of cholesterol in their blood are more likely to get angina and have a heart attack. The high cholesterol level is partly due to diet but

Phytoestrogens in the Human Diet

Genistein has been promoted as a possible preventive treatment or therapy for several diseases and conditions. There are claims that it reduces hot flashes associated with menopause, that it can prevent or delay the onset of osteoporosis in post-menopausal women, and that it can lower blood cholesterol levels. In each instance the potential effectiveness of genistein would be attributable to its acting as an estrogen replacement in older women, in whom the level of estradiol is naturally low. Genistein may also be effective in the treatment of certain breast cancers that require estrogen in order to grow. In this case it is theorized that the genistein, with weak estrogen activity, acts to reduce cancer growth by competing with the more potent estradiol for the estrogen receptor.

Specific saturated and trans fatty acids and CHD risk

Different specific saturated fatty acids may have different effects on CHD risk. In particular, there is a growing interest in stearic acid as a substitute for TFA to give texture and solidity to foods. Metabolic studies show that lauric acid most markedly increases total and LDL cholesterol, whereas stearic acid somewhat lowers total and LDL cholesterol when it replaces carbohydrates (Fig. 1.2) (Mensink et al., 2003). However, lauric acid also has the strongest HDL raising effect, whereas stearic acid raises HDL cholesterol less than other saturated or cis-unsaturated fatty acids. The net effect is that lauric and stearic acid have less unfavourable effects on the total to HDL cholesterol ratio than myristic and palmitic acids. However, consequences of these differences for CHD risk are unclear. Saturated fatty acids tend to occur together in diets due to shared food sources, there are therefore hardly any epidemiological data for specific saturated fatty acids. Only one published...

Implications controlling fat intake

During the past several decades, reduction in fat intake has been the main focus of dietary recommendations to decrease the risk of chronic diseases, including coronary heart disease. However, several lines of evidence indicate that the quality of dietary fat has a more important role in reducing risk than the total amount of dietary fat. Metabolic studies have clearly established that replacing saturated and trans fatty acids with cis-unsaturated fatty acids has the most favourable effect on plasma total and LDL cholesterol levels, and that reducing the total amount of fat can reduce HDL cholesterol and increase fasting TG levels. Results from epidemiological studies and controlled clinical trials show that replacing saturated and trans fatty acids with c s-unsaturated fatty acids is more effective in lowering risk of CHD than reducing total fat consumption. There is still no consensus on whether the total amount of dietary fat increases body weight in the long term and in this way...

Beneficial And Adverse Effects Of Screening

A study examining potential adverse psychological effects of screening for cardiovascular risk factors showed that a minority (about 20 ) of those screened to be at high risk reacted with some degree of anxiety and confusion (7). Another study, also examining adverse psychological effects of screening, found a mild degree of worry in people labelled as having high cholesterol levels when compared to those labelled as normals. However, the level of

Lipoprotein Metabolism

Chylomicrons are assembled in the enterocytes of the small intestine after ingestion of dietary fat (triglyceride) and cholesterol. In the lymph and the blood, chylomicrons acquire several apolipoproteins, including apo C-II, apo C-III, and apo E. In the capillary beds of adipose tissue and muscle, chylomicrons interact with the enzyme lipoprotein lipase (LPL), which is activated by apo C-II, and the chylomicron core triglyceride is hydrolyzed. The lipolytic products, free fatty acids, can be taken up by fat cells where they are converted back into triglyceride, or by muscle cells, where they can be used for energy. Apo C-III can inhibit lipolysis, and the balance of apo C-II and apo C-III determines, in part, the efficiency with which LPL hydrolyzes chylomicron triglyceride. The product of this lipolytic process is the chylomicron remnant, which has only about 25 of the original chylomicron triglyceride remaining. Importantly, the chylomicron remnants are relatively enriched in...

Altered membrane proteins cause many diseases

Some of the most common human genetic diseases show their primary phenotype as altered membrane receptor and transport proteins. About one person in 500 is born with familial hypercholesterolemia (FH), in which levels of cholesterol in the blood are several times higher than normal. The excess cholesterol can accumulate on the inner walls of blood vessels, leading to complete blockage if a blood clot forms. If a clot forms in a major vessel serving the heart, the heart becomes starved of oxygen, and a heart attack results. If a

Specific Lipid Monitoring Recommendations for Patients With Schizophrenia

However, when dietary measures have failed to normalize serum lipids, results from the landmark statin trials should make it abundantly clear that simple pharmacological interventions in those with low HDL, high LDL, or elevated triglycerides or TC may yield substantial reductions in cardiovascular morbidity and mortality. Nonetheless, undertreatment of hyper-lipidemia is an ongoing problem for many patients, even those without major mental illness who have established CHD (Smith 2000). Although mental health practitioners may not choose to institute lipid agents themselves, patients with established CHD or CHD-equivalent disorders (e.g., DM, severe atherosclerotic vascular disease) should be started on low-dose aspirin therapy (81 mg day, or one baby aspirin) this simple intervention has been proven to reduce important vascular events by 25 -33 (Braunstein et al. 2001). On the other hand, some psychiatrists may feel comfortable initiating treatment of hyperlipidemia under the...

Human genetic diseases have several patterns of inheritance

Familial hypercholes-terolemia is caused by an abnormal autosomal dominant allele. In this case, the presence of only one mutant allele is enough to produce the clinical phenotype. In people who are heterozygous for familial hypercholesterolemia, having half the normal number of functional receptors for low-density lipoprotein on the surface of liver cells is simply not enough to clear cholesterol from the blood. In autosomal dominance, direct transmission from an affected parent to offspring is the rule.

New Technologies Promise to Expedite the Discovery of New Pharmaceuticals

TIt is difficult to summarize all the ways in which genomics and proteomics might affect the development of pharmaceutical agents, but a few examples illustrate the potential. Hypertension, congestive heart failure, hypercholesterolemia, and obesity are treated by pharmaceutical drugs that alter human physiology. Therapies are arrived at by identifying an enzyme or receptor involved in the process and discovering an inhibitor that interferes with its action. Proteomics will play an increasing role in identifying such potential drug targets. For example, the most potent vasoconstrictor known is the peptide hormone urotensin II. First discovered in fish spinal fluid, urotensin II is a small cyclic peptide, with 11 amino acid residues in humans and 12 or 13 in some other organisms. The vasoconstriction it induces can cause or exacerbate hypertension, congestive heart failure, and coronary artery disease. Some of the methods described in Section 9.3 for elucidating

One approach to treatment is to modify the phenotype

As we described earlier, people with familial hypercholesterolemia accumulate dangerous levels of cholesterol in their blood. These people are not only unable to metabolize dietary cholesterol, but also synthesize a lot of it. One effective treatment for people with this disease is the drug mevinolin, which blocks the patient's own cholesterol synthesis. Patients who receive this drug need only worry about cholesterol in their diet, and not about the cholesterol their cells are making.

Rna Interference And microRNA

In recent years, RNA interference (RNAi) has surged into the spotlight of pharmacy, genomics, and system biology. Dozens of RNAi-based drugs are entering FDA trials, and as of this writing, at least three companies are based exclusively on RNAi technology. The massive excitement surrounding RNAi stems from its vast potential for therapeutic and genomic applications. Currently, promising RNAi-based therapies include treatments for HIV, Huntington's disease, macular degeneration, hypercholesterolemia, and even prion diseases such as bovine spongiform encepha-lopathy (BSE mad cow disease), and potential new therapies are being announced nearly daily.

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Disease Treatment RNAi can specifically knock down genes responsible for human diseases, providing a novel means of therapeutics. Chemically modified siRNAs targeting the apoB gene were injected through the tail of mice and reduced their total level of cholesterol 65 . shRNAs were transfected into mice to investigate the therapeutical treatment of dominant polyglutamine expansion diseases, which include Huntington's disease 72 . These experiments in mice demonstrated the therapeutic potential of RNAi for the treatment of human hypercholesterolaemia and Huntington's disease. HIV-1 RNAs were inhibited by siRNAs and shRNAs in human cell lines 28 , showing that HIV virus is amenable to RNAi treatment. In addition to silencing efficacy and specificity, the concentration and temporal changes of the siRNA and the target mRNA should be accessible for efficient transfection. The RNAi kinetics can be modeled by differential equations.

Man with Coronary Heart Disease but a Normal Exercise Test Result

An example of a false negative test result would be of a 65-year-old man who has typical angina and an almost full house of cardiovascular risk factors (he smokes, he is very overweight, he has a high cholesterol level, and he has high blood pressure and diabetes). When he does the exercise test, there are no ECG changes and he does not get angina. This test is almost certainly wrong and misleading. The fact that he has angina means that

Estimation Of Parameters

The entire process of statistical design and analysis can be described briefly as follows. The target of a scientist's investigation is a population with certain characteristic of interest for example, a man's systolic blood pressure or his cholesterol level, or whether a leukemia patient responds to an investigative drug. A numerical characteristic of a target population is called a parameter for example, the population mean m (average SBP) or the population proportion p (a drug's response rate). Generally, it would be too time consuming or too costly to obtain the totality of population information in order to learn about the parameter(s) of interest. For example, there are millions of men to survey in a target population, and the value of the information may not justify the high cost. Sometimes the population does not even exist. For example, in the case of an investigative drug for leukemia, we are interested in future patients as well as present patients. To deal with the...

Atherosclerosis dyslipidemia and peripheral arterial disease

Compared to patients with CAD, patients with peripheral, carotid, and aortic atherosclerosis receive less attention to lipid risk factors (9,10). In one study of 299 patients with symptomatic PAD documented by angiography, only 27 had any lipid profiles done, and of these only 9 were receiving treatment for hypercholesterolemia (9). Physician recognition and management of hypercholesterolemia in patients with peripheral and carotid atherosclerosis undergoing vascular surgery was evaluated in 80 patients retrospectively (10). Of the 66 screened patients found to be hypercholesterolemic, only 24 received in-hospi-tal management and only 13 received intervention at discharge. This underscores the need for education and greater awareness of surgeons and physicians involved in the management of patients with PAD.

Intervention trials in atherosclerosis

Recent advances have emphasized the importance of lipid lowering in the prevention of atherosclerosis and the management of its clinical manifestations. Stabilization and even reversal of the underlying atherosclerotic process can occur with lipid-lowering therapies. Multiple trials over the past decades have clearly shown that lowering elevated cholesterol levels reduces the progression of coronary atherosclerosis and lowers the incidence of acute coronary events. Extrapolating from these data, effective lipid reduction likely results in beneficial effects on the atherosclerotic process at other sites such as the carotid and femoral arteries, thereby reducing the need for invasive therapies. Helsinki Heart Study (15) have all demonstrated the benefit of lipid lowering using various hypolipidemic agents for prevention of initial cardiac events. Secondary prevention trials have unequivocally shown that lipid lowering therapy not only reduces acute coronary events and other clinical...

Other Drugs Used In Patients With Angina

Statins are used in patients with angina, even those who have a normal cholesterol level, because they make the fatty plaques stable and less likely to rupture. They are also useful in patients with unstable angina for the same reason. Statins in big doses slow the progression, and in some patients reverse, coronary heart disease. The target LDL-cholesterol level in patients with angina or unstable angina or previous heart attack is less than 2.0 mmol l. Statins also reduce the inflammation in arteries.

Metabolic downregulation

The only studies to date using PET radiotracers have employed 18F-Fluouro deoxyglucose (FDG). FDG is taken up by metabolically active cells as a glucose analog, but cannot be metabolized. Uptake is particularly high in anaerobic cells, such as most tumors and macrophages 49 . Yun and colleagues observed vascular FDG uptake in approximately 50 of 137 consecutive cancer patients undergoing PET 95 . This uptake was associated with risk factors for atherosclerosis 94 . Age and hypercholesterolemia had the strongest associations. Rudd et al., studied 8 patients with symptomatic carotid atherosclerosis with CT PET image fusion 75 . They found uptake of FDG within the plaque in all patients. They also performed autoradiography of the removed plaques from 3 patients that underwent end-arterectomy. Tritiated deoxyglucose (an analogue of FDG) accumulation was localized to macrophage-rich areas of the plaque.

Fibrates and atherosclerosis

Outcome studies employing the statins have conclusively shown that reduction of LDL translates into reduced clinical cardiovascular events. However, in patients with normal LDL or after LDL levels have been normalized, TG and HDL levels assume an important role in the progression of atherosclerosis. The importance of HDL-cholesterol as an inverse These studies suggest the importance of TG-rich lipoprotein reduction and HDL raising for the retardation of atherosclerosis in mild to moderate lesions, and a role for fibric acid derivatives in secondary prevention. Analysis of data from Cholesterol Lowering Atherosclerosis Study (CLAS), the Program on the Surgical Control of Hyperlipidemias (POSCH), and MARS studies also provide evidence for the importance of TG rich lipoprotein in progression of CAD.

Cholesterol and other sterols

And cause serious pathological consequences in the body, such as artherosclerosis. Recently, the analysis of oxidation products of cholesterol (and other lipids) has gained interest due to their putative pathophysiological role 113 . There is also growing interest toward various plant sterols (phytosterols) as their intake significantly reduces plasma cholesterol levels 114 .

Why Do People Get Angina After Angioplasty

Around 10 of patients treated with angioplasty may get angina again within a year if the artery that has been treated narrows again. We now use drug eluting stents which leak drugs into the wall of the heart artery. These drugs reduce the chances of the artery narrowing again (restenosis). These relatively new drug eluting stents, when used with other drugs to lower cholesterol, and to reduce the risk of blood clotting, have reduced the restenosis rate to around 5 .

Lipid lowering in peripheral arterial disease

The Saint Thomas's Trial was the first randomized controlled trial evaluating the effect of lipid lowering therapy on the course of femoral atherosclerosis in hyperlipidemic patients with intermittent claudication (40). The patients were randomized to receive diet, cholestyramine, nicotinic acid, or clofibrate depending upon their lipoprotein phenotype. Total cholesterol (TC) decreased by 25 , LDL cholesterol by 28 , and TG by 45 following therapeutic intervention. Femoral atherosclerosis was studied by arteriography. In patients receiving lipid-lowering therapy, progression of atherosclerosis was reduced by 60 compared to the placebo group. The rate of increase in the cross-sectional area of the plaque in the treated group was one-third that of the placebo group. Change in edge irregularity was 2.5-fold greater in the placebo group, whereas twice as many arterial segments showed improvement in the therapy group. The Probucol Quantitative Regression Swedish Trial (43) (PQRST) was a...

Overcoming the Manifestations of Syndrome X

Dietary recommendations to reduce CHD have until quite recently been based upon the principle that hypercholesterolemia (more specifically, an elevated LDL cholesterol level) is the only CHD risk factor that needs to be addressed. The result has been almost total emphasis on the use of low-fat-high-carbohydrate (CHO) diets. More to the point, advice to replace saturated fat (SF) with CHO in order to lower LDL cholesterol concentrations continues to be given, regardless of how insulin resistant the individual. Unfortunately, this dietary approach will make all of the manifestations of syndrome X worse. The greater the CHO content in an isocaloric diet, the more insulin must be secreted in order to maintain glucose homeostasis. This poses no danger to insulin-sensitive individuals, but low-SF high-CHO diets will significantly increase the already high day-long plasma insulin concentrations in patients with syndrome X. As a consequence, fasting plasma TG concentrations will increase, as...

The Insulin Resistance Syndrome

Insulin resistance and hyperinsulinemia are frequently associated with a cluster of clinical and biochemical abnormalities that have been described with increasing detail and given a variety of names including deadly quartet, syndrome X, insulin resistance syndrome, metabolic syndrome, and cardiovascular dysmeta-bolic syndrome (9-13). Many prefer to call it insulin resistance syndrome because insulin resistance and the resulting hyperinsulinemia appear to be the underlying abnormalities from which the other features of the syndrome are derived (see Chap. 7). The hallmarks of insulin resistance syndrome are obesity, particularly central or intra-abdominal obesity, glucose intolerance, or type 2 diabetes mellitus, hypertension, a dyslipidemia characterized by elevated triglycerides, low HDL cholesterol and small dense LDL cholesterol, a hypercoagulable state

Relationship Between Obesity And Type 2 Diabetes Mellitus

Dyslipidemia Hypertriglyceridemia and Low HDL Cholesterol Monkeys, like humans, frequently develop dys-lipidemia in middle age, including hypertrig-lyceridemia and reduced HDL cholesterol levels (92), and this dyslipidemia is highly associated with the presence of obesity, with or without diabetes. Pharmaceutical agents which alter dyslipidemia in humans do so in monkeys as well (93,94).

Approach To Treatment

130 80 mmHg is now accepted for most patients. It is also clear that patients with diabetes respond well to lipid-lowering therapy with HMG CoA reductase inhibitors (statins) and fibric acid derivatives, often showing better reductions in cardiovascular events and death rates than patients without diabetes. Detailed approaches to treatment of diabetes and reduction in cardiovascular risk are presented in subsequent chapters and will not be discussed here.

Regional Adiposity And Metabolic Aberrations

Female cynomolgus monkeys with high central fat have higher glucose and insulin concentrations in an intravenous glucose tolerance test than females with relatively low central fat. They also have higher blood pressure and total plasma cholesterol concentrations, and lower HDL cholesterol concentrations compared to low central fat females (50). In women, central obesity has been linked with a metabolic syndrome consisting of impaired glucose tolerance, raised serum triglycerides and low levels of HDL cholesterol (51).

Third Category Prevention

We do as yet not have a clear understanding of what can plausibly count as treatment and what cannot. That poses problems of a primarily conceptual nature and highlights several other semantic fields whose boundaries are also not very clearly defined, such as those of health and disease. But even before approaching these questions, one encounters another problem with a clear-cut distinction in the dualistic scheme of treatment and enhancement It does not seem to do justice to strategies of prevention. Vaccination provides us with a particularly clear example of preventive medicine, but practices of prescribing and taking statins to reduce the likelihood of stroke and myocardial infarction, and other such preventive strategies could be cited as well. Nobody doubts that vaccination, and similar preventive measures of the said kind, are a sensible and legitimate part of medicine and medical research. On the other hand, they cannot properly be labeled treatments, not even anticipated...

Lipidgene interactions diet and health

Acids, then to dietary cholesterol and finally the metabolic syndrome. We shall then focus on the mechanisms of regulation of gene expression by fat, a process that involves, for a large part, nuclear receptors. This extensively studied gene family of transcription factors provides a heuristic paradigm of regulation of gene expression. Finally, we will suggest what can be deduced currently from these studies in terms of 'optimal' dietary fat and possible ways toward a better knowledge of diet-genetic background interactions.

Genetic influences on lipid metabolism

Two major genetic defects are known to dramatically affect lipoprotein metabolism. The most famous is the defect in apoB,E-receptor that induces familial hypercholesterolaemia and elevated LDL levels (Brown and Goldstein, 1974). The second one is the defect in MTP that almost completely abolishes triglyceride-rich lipoprotein (TRL) production by the liver and small intestine resulting in abetalipoproteinaemia (Gregg and Wetterau, 1994). Such marked

Treatment knowledge

The so-called best medical treatment plan is based on the control of vascular risk factors and the application of antiplatelet anticoagulation drugs, statins (HMG-CoA reductase inhibitors) and an-giotensin-converting enzyme inhibitors. Maximal medical treatment can be defined as receiving daily doses of > 81 mg acetylsalicylic acid, 500 mg ticlopi-dine, 75 mg clopidogrel, or comparable doses of marcumar warfarin or heparin 80 . A more aggressive treatment regimen like angioplasty should be considered in cases where maximal medical therapy fails to prevent massive ischemic stroke. Medical therapy failure is not clearly defined, but should be assumed when recurrent cerebral symptoms occur under maximal medical treatment 80 .

ADP Antagonists Ticlopidine and Clopidogrel

In summary, combination therapy with a reduced-dose fibrinolytic and a GP IIb IIIa inhibitor does offer improvements in infarct-related artery patency, but these have not translated into mortality benefits. It may be that, between rescue angioplasty and improved overall medical therapy (e.g., angiotensin converting enzyme ACE inhibitors and statins), small differences in patency do not have a large impact on survival. Nonetheless, the reductions in nonfatal ischemic events seen with combination therapy are clinically important. Moreover, combination therapy offers a more attractive transi

ApoB and lipoprotein metabolism

Several common mutations have been found in the human apoB gene. Owing to the protein's dual role as a transport protein and a peripheral recognition signal for LDL clearance, these mutations have been shown to result either in reduced VLDL secretion or in hypercholesterolaemia (LDL accumulation). Several studies have investigated the influence of some of the apoB polymorphisms on responses to change from high-fat to low-fat diets (or the opposite). Three polymorphisms have been mostly associated with diet-induced LDL cholesterol changes a XbaI restriction site located in exon 26, an EcoRI site in exon 29 and a MspI site. Lopez-Miranda et al. (1997) reported that subjects with the homozygous absence of the XbaI site have a greater postprandial response (retinyl palmitate and apoB48 levels) to a fat-rich meal than the subjects with the presence of the XbaI site. More recently, it has been shown that a high-fat diet also induced a larger increase in plasma LDL cholesterol in subjects...

Should the Patient Fast before a Cholesterol Blood Test

Although the total and HDL cholesterol levels are not significantly raised after a meal, the important LDL cholesterol and triglyceride levels are. Therefore, patients are usually asked to fast for 12 hours (but they can drink as much water as they like) before a blood test for cholesterol. Most patients find it most convenient to have their blood test in the morning. Ifthe cholesterol level is high in a fasting patient, it cannot be due to a recent meal. Cholesterol levels can vary a little in the same person from day to day.

Impact On Cardiovascular Disease The Dcct And Ukpds Studies

Clinical atherosclerosis results largely from acute embolic or thrombotic events that arise from long-term changes in the arterial wall. The pathogenesis of the arterial wall changes in relation to the metabolic abnormalities that attend poorly controlled diabetes are not well known in humans. Epidemiological studies indicate that both hyperglycemia and hyperinsulinemia increase the risk of atherosclerosis and of the acute clinical complications of that condition. The high triglyceride and low HDL cholesterol concentrations that frequently attend hyperglycemia may contribute as well. Animal studies suggest that good blood glucose control can mitigate the effects of diabetes on the arterial wall. Cross-sectionally, worsening glycemia is associated with thickening of the intima and media layers of the common carotid arteries. Intervention studies to test the impact of improved glycemic control on this or other measures of atherosclerosis are lacking. However, there is mounting evidence...

Lipoprotein lipase and lipoprotein metabolism

LPL activity can be somewhat reduced in subjects bearing the p.291S or the p.9N allele and these variants are associated with higher fasting triglycerides and lower HDL cholesterol levels (Gerdes et al., 1997 Senti et al., 2000). In heterozygote carriers of the p.291S variant, postprandial levels of large VLDL apoB48, triglycerides and retinyl palmitate were higher than in non-carriers (Mero et al., 1999). Regarding long-term dietary interventions, it has been reported that homologous carriers of the HindIII site had a significantly smaller

Blood cells vascular injury and thrombosis

Platelets produce NO, which is increased by the dietary supplementation of L-arginine to hypercholesterolemic rabbits. This effect is associated with reduced platelet aggregation (45). Platelet activation is increased in patients with CAD (46). Hypercholesterolemia primes human platelets for recruitment to lesion-prone sites via endothelial von Willebrand factor (vWF), platelet GPlba, and platelet p-selectin before lesions are detectable (47).

Fatty Acids and Lipid Metabolism

NEFAs may also promote a complex dyslipidemia characterized by increased VLDL-triglyceride rich particles, reduced levels of HDL-cholesterol, and an increased number of small dense LDL-cholesterol particles. Potential mechanisms by which NEFAs may contribute to these complex disturbance of lipid metabolism include increasing hepatic apoprotein B production and VLDL synthesis, with an increase in the number of VLDL-triglyceride rich particles (4). HDL-cholesterol concentrations fall in part as cholesterol is transferred from HDL to VLDL by the activity of cholesterol-ester transfer protein (CETP). As triglycerides are hydrolyzed from the greater number of VLDL-particles by endothelial lipoprotein lipase, large numbers of small, dense LDL particles are produced (18).

So Should I Stop Taking Vitamin E

A high cholesterol level is even more dangerous in people who have any other risk factor. So a person with high cholesterol and any one or more of the following risk factors is very much more likely to get blocked arteries and have a higher risk of heart attack and stroke than someone who only has high cholesterol. The more risk factors a person has, the greater the chances of that person developing coronary heart disease and its consequences. People with high cholesterol and any one of these cardiovascular risk factors will probably need medications to lower their cholesterol. Exercise helps people lose weight, and people who exercise regularly usually control their diet, too. Exercise increases the good, protective HDL cholesterol. WHAT MEDICATION IS USED TO LOWER CHOLESTEROL The most commonly used and the most effective drugs are statins (they all end in -statin). There are five different types that all act in a similar way, although some are more powerful than others. They...

Lipid transfer proteins

A lipotransfer protein, the cholesterol ester transfer protein (CETP) promotes the exchange of cholesterol from HDL particles to triglyceride-rich particles (TRL) and of triacylglycerol from TRL to HDL. Since HDL can be roughly considered as responsible for transferring to the liver endogenously synthesized cholesterol, the CETP activity would modify the ratio between LDL cholesterol and HDL cholesterol. For example, in a recent study undertaken in a population from diverse origins, an association was demonstrated between the g. 629> C allele and a 30 decrease in CETP mass (Thompson et al., 2003). In another study, such a decrease in mass has been shown to result in changes in the size of HDL particles with a marked increase in the large alpha-1 HDL particles and decrease in the small pre-beta-1 particles, features that have been clearly associated with lower risk for coronary heart disease (Asztalos et al., 2000,

Caveolae and Caveolin1

Into account the heterogeneity and functional differences between distinct cell types. In a parallel argument, cells in which caveolin expression has been lost or ablated in culture will respond differently, reflecting the alteration of steady-state equilibria between caveolae domains, lipid rafts, and phospholipids regions of the plasma membrane and intracellular membranes. Thus, some signaling or trafficking pathways normally regulated by caveolin may show little impact of caveolin disruption due to compensatory activation of secondary pathways localized to lipid rafts or even phospholipids domains. A number of ligands that initiate signaling in caveolae can be internalized by clathrin-mediated endocytosis, although in cav-eolin-expressing cells the rapid caveolae-mediated endocytic pathway dominates under normal physiologic conditions. This also holds true for membrane components. Overexpression of caveolin-1 changed the uptake of specific glycosphingo-lipids and shifted GM1 from...

Genetic influences on the metabolic syndrome

Although the metabolic syndrome per se is not central to the focus of this review, we must give brief consideration to this major public health concern. The prevalence of the metabolic syndrome as defined by the NCEP-ATP III report is about 23 in the American population and rises to about 43 of elderly people in the USA, while higher prevalence rates can be observed in various ethnic groups around the world (Ford et al., 2002). This syndrome associates obesity, excessive blood pressure, high plasma glucose with disturbances of lipid homeostasis (high plasma triglycerides and low HDL cholesterol). The main feature of the metabolic syndrome is an association between dysfunction of energy storage (adipocyte physiology) and insulin resistance in a dramatic vicious circle (Miranda et al., 2005). Insulin resistance results in a decreased translocation of the GLUT4 glucose transporter to the plasma membrane of adipocytes. This would induce a relative glucose deprivation, thus contributing to...

Mechanisms of Differential Exposure Misclassification

The timing of exposure ascertainment relative to the onset of disease has been examined as well to indicate the likely magnitude of distortion. A series of studies in the 1970s and early 1980s had suggested that low levels of serum cholesterol were related to development of a number of types of cancer, with cholesterol assessed prior to the onset of disease (Kritchevsky & Kritchevsky, 1992). Nonetheless, there was great concern with the possibility that even cancer in its early, preclinical stage may have affected the serum cholesterol levels. Under this scenario, low levels of cholesterol followed within a limited period, say 6 to 12 months, by the diagnosis of cancer, may have been low due to the developing cancer itself. The approach taken to assess this problem has been to examine risk stratified by time since the measurement in longitudinal studies, in order to determine whether the pattern of association with disease differs across time. It would be more plausible that...

Introductionepidemiology

The association between obesity and type 2 (non-insulin-dependent) diabetes mellitus has been recognized for several decades. It has now been shown that obesity is also associated with cardiovascular disease (CVD) and stroke. Population-based follow-up studies have revealed this concealed link, bringing the importance of obesity as an independent risk factor for cardiovascular morbidity and mortality to the forefront. However, at first, it was assumed that only severe obesity was as powerful a risk indicator of CVD and stroke as other, established risk factors such as hypercholesterolaemia and high blood pressure.

Effects of Inulin Type Fructans on Lipid Parameters in Healthy Experimental Animals Fed a Standard Diet

Only two publications reported no statistically significant effect on serum TAGs in rats fed a diet containing 5 6 or 10 inulin17-18 even though the former study still reported a significant decrease (31 ) in the serum TAGs in rats fed a 20 inulin diet.17 In the same rats, a statistically significant reduction in serum total cholesterol is reported in 4 studies (18, 11, 15, and 21 in, respectively,13-1417-18) but not in the others.11121516 Moreover, in Levrat et al. the effect on serum cholesterol is dose-dependent at 11, 18, and 26 for doses of 5, 10, and 20 inulin, respectively.11 In the studies in which such parameters have been quantified, the hypocholesterolemic effect concerns esterified cholesterol only14 or both esterified and free cholesterol.18 Moreover, one publication12 reports an increase (1.9-fold) in the ratio HDL cholesterol over LDL cholesterol and two publications report a decrease in serum PLPs (D15 and D17 in, respectively,14 and15). Liver TAGs have only been...

Does Stress On Its Own Increase The Risk For Heart Disease

Stress is thought to be an independent cardiovascular risk factor. This means that people who are stressed, even if they do not have any other risk factor, are more likely to develop heart disease than those people who are not stressed. It has taken many years for stress to be identified as an independent risk factor, because it is difficult to measure and the effects of stress acting alone were difficult to separate from the other well-established risk factors. Stressed people may have high blood pressure, may smoke, may eat fatty food and be inactive and overweight, and therefore have high cholesterol and high blood sugar, or come from a family affected by heart disease at a young age.

The Liver Produces Urea

The liver plays an important role in cholesterol homeostasis. Liver cholesterol is derived from both de novo synthesis and the lipoproteins taken up by the liver. Hepatic cholesterol can be used in the formation of bile acids, biliary cholesterol secretion, the synthesis of VLDLs, and the synthesis of liver membranes. Because the absorption of biliary cholesterol and bile acids by the GI tract is incomplete, this method of eliminating cholesterol from the body is essential and efficient. However, patients with high plasma cholesterol levels might be given additional drugs, such as statins, to lower their plasma cholesterol levels. Statins act by inhibiting enzymes that play an essential role in cholesterol synthesis. VLDLs secreted by the liver provide cholesterol to organs that need it for the synthesis of steroid hormones (e.g., the adrenal glands, ovaries, and testes).

Chapter Objectives

Bile acid sequestrants Discuss therapeutic life changes and how they affect cholesterol levels. are the two lipids in the blood. Elevation of one or both of these lipids is seen in hyperlipidemia. Serum cholesterol levels above 240 mg dL and triglyceride levels above 150 mg dL are associated with atherosclerosis. Atherosclerosis is a disorder in which lipid deposits accumulate on the lining of the blood vessels, eventually producing degenerative changes and obstruction of blood flow. Atherosclerosis is considered to be a major contributor in the development of heart disease. plaque formation. Elevation of the LDL increases the risk for heart disease. High-density lipoproteins (HDL) take cholesterol from the peripheral cells and bring it to the liver, where it is metabolized and excreted. The higher the HDL, the lower the risk for development of atherosclerosis. Therefore, it is desirable to see an increase in the HDL (the good lipoprotein) because of the protective nature of its...

Effect of Inulin Type Fructans on Lipid Parameters in Normolipidemic Subjects

In a rigorously designed study with adequate statistical power (doubleblind randomized cross over design in 66 young healthy women) reported by Pedersen et al., inulin (14 g d in a low-fat spread for 4 weeks) had no effect on blood lipids.34 Although HDL cholesterol and the LDL HDL

HMGCoA Reductase Inhibitors

Another group of antihyperlipidemic drugs are called HMG-CoA reductase inhibitors. HMG-CoA (3-hydroxy-3-methyglutaryl coenzyme A) reductase is an enzyme that is a catalyst (a substance that accelerates a chemical reaction without itself undergoing a change) in the manufacture of cholesterol. These drugs appear to have one of two activities, namely, inhibiting the manufacture of cholesterol or promoting the breakdown of cholesterol. This drug activity lowers the blood levels of cholesterol and serum triglycerides and increases blood levels of HDLs. Examples of these drugs are fluvastatin (Lescol), lovastatin (Mevacor), and simvastatin (Zocor).

Preadministration Assessment

In many individuals, hyperlipidemia has no symptoms and the disorder is not discovered until laboratory tests reveal elevated cholesterol and triglyceride levels, elevated LDL levels, and decreased HDL levels. Often, these drugs are initially prescribed on an outpatient basis, but initial administration may occur in the hospitalized patient. Serum cholesterol levels (ie, a lipid profile) and liver functions tests are obtained before the drugs are administered.

Effect of Inulin Type Fructans on Lipid Parameters in Slightly Hyperlipidemic Subjects

In a randomized crossover trial in subjects with modest hyperlipidemia, Davidson et al. showed significantly lower total (8.7 ) and LDL cholesterol (14.4 ) concentrations during inulin compared with placebo phases, but the authors reported no effects on HDL cholesterol or serum TAGs concentrations.38 3. In a double-blind randomized parallel study conducted in 54 middle-aged subjects with moderately raised blood lipid concentrations over a longer period than any of the previous human studies (i.e., 8 weeks compared to 3-4 weeks), inulin (10 g d in a powdered form added to beverages, soups, cereal, etc.) had no significant effect on total LDL or HDL cholesterol or apolipoproteins B and A. However, after intervention, serum TAGs levels were significantly lower in the inulin treated group (19 ) than in the control group.39

Promoting an Optimal Response to Therapy

Bile acid sequestrants may interfere with the digestion of fats and prevent the absorption of the fat-soluble vitamins (vitamins A, D, E, and K) and folic acid. When the bile acid sequestrants are used for long-term therapy, vitamins A and D may be given in a water-soluble form or administered parenterally. If bleeding tendencies occur as the result of vitamin K deficiency, parenteral vitamin K is administered for immediate treatment, and oral vitamin K is given for prevention of a deficiency in the future.

Educating the Patient and Family

The nurse stresses the importance of following the diet recommended by the primary health care provider because drug therapy alone will not significantly lower cholesterol and triglyceride levels. The nurse provides a copy of the recommended diet and reviews the contents of the diet with the patient and family. If necessary, the Using Diet and Drugs to Control High Blood Cholesterol Levels Emphasizes that drug therapy alone will not significantly lower blood cholesterol levels. nurse refers the patient or family member to a teaching dietitian, a dietary teaching session, or a lecture provided by a hospital or community agency (see Patient and Family Teaching Checklist Using Diet and Drugs to Control High Blood Cholesterol Levels). The nurse develops a teaching plan to include the following information BILE ACID SEQUESTRANTS Cholestyramine powder The prescribed dose must be mixed in 4 to 6 fluid ounces of water or noncar-bonated beverage and shaken vigorously. The powder can also be...

Critical Thinking Exercises

A patient in the medical clinic is taking cholestyramine (Questran) for hyperlipidemia. The primary health care provider has prescribed TLC for the patient. The patient is on a low-fat diet and walks daily for exercise. His major complaint at this visit is constipation, which is very bothersome to him. Discuss how you would approach this situation with the patient. What information would you give the patient concerning his constipation 2. Discuss the important points to include in a teaching plan for a patient who is prescribed atorvastatin (Lipitor).

Cardiovascular Disease

The Framingham Study showed in 2005 men and 2521 women that the 28-year age-adjusted rates (per 100) of CHD was 26.3 for a mean BMI of 21.6kg m2 and 42.2 for a mean BMI of 31 in men, and 19.5 for a BMI of 20.4 and 28.8 for a BMI of 32.3 in women, respectively (82). The 28-year age-adjusted relative risks and their 95 confidence intervals for the highest quintile compared to the lowest were 1.9 (1.4-2.5) for CHD and 1.8 (1.4-2.4) for CHD excluding angina pectoris for men and 1.7 (1.3-2.3) and 1.6 (1.2-2.3) for women, respectively. The Gothenburg study, in a 12-year incidence period, showed in a multivariate analysis, that the WHR was the strongest predictor (84) of myocardial infarction in 1462 women. In 1990, the Nurses Health Study, during an 8-year observation, clearly showed in a population of 121700 females that obesity is a determinant of CHD after control for cigarette smoking, which is essential to assess the true effect of obesity, even mild-to-moderate overweight increased...

The Blood Lipid Profile Is Influenced by Exercise Training

Because exercise acutely and chronically enhances fat metabolism and cellular metabolic capacities for (3-oxidation of free fatty acids, it is not surprising that regular activity increases both muscle and adipose tissue lipoprotein lipase activity. Changes in lipoprotein li-pase activity, in concert with increased lecithin-cholesterol acyltransferase activity and apo A-I synthesis, enhance the levels of circulating HDLs.

Exercise Has a Role in Preventing and Recovering From Several Cardiovascular Diseases

Changes in the ratio of HDL to total cholesterol that take place with regular physical activity reduce the risk of atherogenesis and coronary artery disease in active people, as compared with those who are sedentary. A lack of exercise is now established as a risk factor for coronary heart disease similar in magnitude to hypercholesterolemia, hypertension, and smoking. A reduced risk grows out of the changes in lipid profiles noted above, reduced insulin requirements and increased insulin sensitivity, and reduced cardiac (-adrenergic responsiveness and increased vagal tone. When coronary ischemia does occur, increased vagal tone may reduce the risk of fibrillation.

Factors Related To Increased Gallstone Formation In The Obese

Dietary Cholesterol Surprisingly, there is little evidence that cholesterol intake or serum total cholesterol is related to risk for formation of cholesterol gallstones. It has been suggested that since obese people have higher bile saturation indices than the non-obese, perhaps because of increased hepatic secretion of cholesterol into the bile, that dietary cholesterol may make little additional difference for these individuals (3,14).

Intracellular Compartments and Ab Generation Involvement of Lipid Rafts

AP formation. (B) In an alternative model, the P-cleavage of APP should occur outside lipid rafts, as APP is mainly distributed in non-raft domains (a). In this model, the amy-loid-P is physiologically produced, but under mild cholesterol reduction (b) raft disorganization occurs and this process facilitates the close contact between APP and BACE1, leading to P-cleavage and a higher production of AP. Under strong cholesterol depletion (c), although BACE1 can more easily encounter APP, its activity is repressed because of raft disruption, and consequently AP production is inhibited.

Long Term Effects ofET1 on Blood Vessels in Experimental Hypertension

ET-1 stimulates cell migration and VEGF production (39,40), which could imply its involvement in angiogenesis. ET-1 antagonists block angiogenesis and tumor progression (41). However, ETa ETb antagonism has improved survival after myocardial infarction, which may relate to improved perfusion resulting from triggering of an angiogenic response (42). In a model of hindlimb ischemia the ET system is activated and ET antagonists increase neovascularization (43). Capillary density in the left ventricular myocardium is decreased in DOCA-salt rats (44). This rarefaction may be prevented by use of an ETa receptor blocker, which suggests that ET-1 has detrimental effects on the microcirculation, whereas ETa receptor blockers favor angiogenesis. The role of ET-1 in angiogenesis post-ischemia or on tumor growth remains therefore undefined. A recent study examined the role of ET-1 in the development of coronary vasa vasorum in experimental hypercholesterolemia in pigs using microscopic-computed...

Is Stress More Dangerous To Women Than

Although the well-established risk factors appear to be more dangerous to women than to men, it is not clear whether stress and work pressures, are also more powerful risk factors in women. If so, this would not necessarily mean that women are weak and can't withstand the pressure. Stress may also be one of the risk factors, along with diabetes, high cholesterol, and smoking, that pose a greater danger to women than men. The reasons for these risk factors being more dangerous to women are not known. Work and domestic pressures in both men and women are complex and difficult to measure and distinguish from other risk factors (see Chapter 11).

Effects of Diabetes on LDL Oxidation

LDL from diabetic patients is more atherogenic and more likely to be bound (by affinity chromatography on Ricinus communis agglutinin-agarose). Bound LDL has lower sialic acid content and higher fructosyl lysine level, and induces cholesterol accumulation in cultured cells and has lower neutral lipids. Desialylated LDL has a low neutral carbohydrate level, decreased content of major lipids, small size, high density, increased electronegative charge, less phospholipids, and unesterified cholesterol on their surface, with resultant altered tertiary Apo B structure with more exposure of proteoglycans-binding regions and high affinity binding of small dense LDL to arterial proteoglycans. Secretary phospholipase A2 (PLA2) in arterial tissue or plasma reduces phospholipid content in the surface monolayer LDL leading to the formation of small, dense LDL with an enhanced tendency to interact with proteoglycans. The circulating level of secretary phospholipase A2-IIA is an...

The Contribution of Cholesterol and Sphingolipids in APP Processing

Furthermore, the possibility that cholesterol and sphingolipids depletion enhances APP a-cleavage in different ways cannot be excluded. Previous reports have shown that cholesterol depletion causes a decrease in b-cleavage activity and an increase in a-cleavage activity of APP 102 . In contrast, under conditions in which cholesterol levels are unchanged and lipid raft dysfunction is caused by sphingo-lipid depletion, the a-cleavage of APP is enhanced without affecting the b-cleavage activity of APP or the APP level in lipid rafts. These findings could suggest that sphingolipid depletion may enhance a-cleavage of APP without shifting the intracellular trafficking of APP from the Ab generation site (lipid rafts) to the Ab nongeneration site (outside rafts).

Lipid Lowering After Revascularization

Long-term follow-up data from BARI, EAST, and CABRI indicate that after PCI, progression of coronary disease in diabetics is accelerated compared to nondia-betics both at the treated site and in untreated sites (26-28). Although cholesterol lowering did not prove efficacious in reducing post-PCI restenosis in the Lova-statin restenosis trial (71), multiple beneficial effects of cholesterol-lowering therapy have been documented in this population with coronary disease including improved endothelial function and reduced cardiac events (72). More specific to the diabetic patient, in the 4S study, lowering cholesterol resulted in reduced cardiac events (11), inducing a reduction in 5-year mortality that was greater in diabetics than in nondiabetics (43 vs. 29 decrease) (73). A greater benefit in diabetics treated with HMG COA reductase inhibitors was also observed in the CARE and LIPID trials (74,75). In diabetics undergoing stent implantation, use of statins was associated with reduced...

Carbohydrate metabolism

The possibility that a diet with a high complex CHO intake might improve glucose metabolic control and lipid profile was of great interest. However, it soon became a concern that these diets could have negative effects on diabetic patients since they could raise the plasma levels of triglycerides and lower HDL cholesterol plasma levels (NIH, 1987). Although the findings were initially thought to be transitory, they were confirmed by several subsequent studies (Garg et al., 1992 Parillo et al., 1992 Blades and Garg, 1995). This led to the belief that CHO intake could favour the appearance of features of insulin resistance syndrome, owing to an increase in CHO intake, which would necessitate higher levels of hormone to maintain glucose homeostasis. Furthermore, recently studies have produced variable results with no consistent detrimental effects of high-CHO diets on insulin sensitivity. Thus, Gerhard et al. (2004) have shown, an ad libitum, low-fat, high-fibre, high-complex CHO diet...

Biomarkers in medicine

Expensive and invasive than other forms of testing facilitating a more efficient use of medical resources while improving health care. This becomes clear when we look at the use of diagnostic tests in the clinic. The measurement of cholesterol, for example, is so inexpensive and noninvasive that many people are tested twice a year in their entire life. This results in early detection of a problem and early treatment reducing the risk of disease resulting from high cholesterol.

What About The Birth Control Pill Is It Safe In Women With Cardiovascular Risk Factors

Yes, the Pill is safe in women who do not have any risk factors and so is almost always safe in young women. But in women who have risk factors, for example, women who smoke, are fat, have high cholesterol, are diabetic, or have high blood pressure, the Pill may not be safe because it adds to the risk of heart attacks. A woman with more than one risk factor should probably not take the Pill and may need another form of contraception.

Lipoproteins and CaveolineNOS Interaction

Fig. 11.4 Reversible lipoprotein-dependent regulation of caveolin-eNOS interaction. High levels of native LDL stimulate caveolin transcription and thereby promote the interaction of eNOS with the increased caveolin pool (left). The resulting inhibition of eNOS activity can be reversed by statins that, by inhibiting the endogenous synthesis of cholesterol in endothelial cells (as well as indirectly by reducing circulatory LDL-choles-terol), negatively impact on caveolin expres Fig. 11.4 Reversible lipoprotein-dependent regulation of caveolin-eNOS interaction. High levels of native LDL stimulate caveolin transcription and thereby promote the interaction of eNOS with the increased caveolin pool (left). The resulting inhibition of eNOS activity can be reversed by statins that, by inhibiting the endogenous synthesis of cholesterol in endothelial cells (as well as indirectly by reducing circulatory LDL-choles-terol), negatively impact on caveolin expres Whether such processes of native and...

So What Can And Should Women Do To Reduce Their Chances Of Getting A Heart Problem

Get their cholesterol checked if they are post-menopausal or if they have a family history or another risk factor. The target total cholesterol is 5 mmol l and the LDL cholesterol (the bad cholesterol that causes the problem in the arteries) should be less than 3.0 mmol l. The LDL cholesterol should be less than 2.0 mmol l, and the total cholesterol to HDL cholesterol ratio should be > 6.0, in patients with arterial disease, high blood pressure, and diabetes.

Lipid Lowering Agents

Studies of cholesterol-lowering agents for primary prevention of coronary heart disease that included women were underpowered to detect absolute decreases in mortality however, the Air Force Texas Coronary Atherosclerosis Prevention Study (AFCAPS TexCAPS) revealed that after an average of 5.2 yr follow-up, the risk of a first major acute coronary event was reduced in both men and women with a decrease in relative risk of 46 in women (53). Fig. 6. Hormone replacement therapy and coronary artery disease. In women treated with estrogen or a combination of estrogen and medroxyprogestin (MPA), there was a reduction in LDL cholesterol and an increase in HDL cholesterol however, this improvement in lipid profile did not translate into a regression of coronary artery disease at angiography, nor did it lead to a significant reduction in clinical events. LDL, low-density lipoprotein cholesterol HDL, high-density lipoprotein cholesterol MI, myocardial infarction (60). Fig. 6. Hormone replacement...

Baseline Clinical and Angiographic Characteristics

Gender differences in patients with coronary heart disease undergoing surgical (Table 1) (84-88) or percutaneous (Table 2) (89-93) revascularization procedures have been extremely consistent in virtually all published reports. Women who undergo revascularization procedures are older and have a higher prevalence of hypertension, diabetes, and hypercholesterolemia than men. Fewer women have had a prior myocardial infarction, and the prevalence of left ventricular dysfunction is lower in women than in men. In addition, women have a higher incidence of comorbid disease, and fewer women are considered to be ideal candidates for surgical revascularization in comparison with men.

Other Factors Involved in HDL Metabolism

PPARs enhance cholesterol efflux and stimulate critical steps of the reverse cholesterol transport pathway (reviewed in ref. 507). PUFA and activating PPAR increase hepatic cholesterol uptake. PPARy induces expression of SR B1 in rat hepatocytes, liver EC, and Kuppfer cells (508). PPARa activation in human macrophages and foam cells results in an enhanced availability of free cholesterol for efflux through the ABCA1 pathway by reducing cholesterol esterification rates and AC ATI activity (509).

Acipimox and Nicotinic Acid

Acipimox (5-methylpyrazine carboxylic acid-4-oxide) is a newer, well-tolerated derivative of nicotinic acid (NA) which shows lipid-lowering properties in patients with types II and IV hyperlipidemia 425 . The fall in plasma TAG is associated with a decrease in total and LDL cholesterol and an increase in HDL cholesterol 426-429 . NA has long been used in the treatment of dyslipidemia, producing a very desirable modification of multiple cardiovascular risk factors, increasing HDL, TAG, and lipoprotein(a), which results in a reduction in mortality 430 . NA is an effective therapeutic agent. However, it has to be administered at high doses and has a characteristic side-effect profile defined by intense, but transient, prosta-glandin-mediated cutaneous vasodilation (flushing) that affects patient compliance 431, 432 . Despite their long history of clinical use, the precise mechanism of action of acipimox and NA was unknown until recently, although inhibition of adipocyte lipolysis via the...

Glimepiride and Phosphoinositolglycans

Interestingly, hydrophilic PIG-P and lipophilic glimepiride, albeit differing completely in structure, have in common part of the signaling pathway that crosstalks to the insulin signal transduction cascade and thereby negatively regulates HSL activity and lipolysis in adipocytes 480 . The available data support the following model for their molecular mode of action. PIG(-P) bind as agonists antagonists to the receptor, p115, a transmembrane protein that is anchored at the cell surface within DIGs 484 . Upon binding, PIG(-P) displace endogenous GPI proteins from binding to p115 by competition with their GPI head-groups and thereby reduce their concentration at DIGs 485 . In contrast, glimepiride is not recognized by a proteinaceous receptor of the adipocyte plasma membrane but spontaneously inserts into DIGs via direct hydrophobic interactions in non-saturatable fashion with GPI lipids thereby altering the structural organization of DIGs 486, 487 . Both events induce the...

The Acetate Pathway Fatty Acids And Polyketides

Polyketides, metabolites built primarily from combinations of acetate units, are described. The biosynthesis of saturated and unsaturated fatty acids is covered, together with prostaglandins, thromboxanes, and leukotrienes. Cyclization of polyketides to give aromatic structures is then rationalized in terms of aldol and Claisen reactions. More complex structures formed via pathways involving alkylation reactions, phenolic oxidative coupling, oxidative cleavage of aromatic rings, and employing starter groups other than acetate are developed. The use of extender groups other than malonate gives rise to macrolides and polyethers, whilst further cyclization of polyketide structures may be achieved through Diels-Alder reactions. The application of genetic engineering to modify products from the acetate pathway is discussed. Monograph topics giving more detailed information on medicinal agents include fixed oils and fats, evening primrose oil, echinacea, prostaglandins and isoprostanes,...

Proximity Measurement Using HomoFRET

Gpi Anchor Plant

Using this technique in the steady-state measurement, Varma and Mayor 76 demonstrated the presence of lipid-dependent protein clusters on the surface of living cells. Since the extent of depolarization (or loss of anisotropy) resulting from FRET is dependent on distance (limited by R0 74 ), increasing depolarization would be seen with increasing concentration. Using this assay, Varma and Mayor showed that fluorophore-tagged Folate Receptor (FR-GPI a model GPI-AP) is organized in clusters maintained by cholesterol levels in the membrane, whereas the same FR ecto-domain - when linked to two different transmembrane domains -showed random organization. Cholesterol depletion led to a disruption of the clusters formed by FR-GPI. Later, Sharma and coworkers showed that GFP anchored to cell membranes via a GPI-anchor (GFP-GPI) and mYFP-GPI (mYFP is monomeric version of YFP 77 ) were also organized in cholesterol-dependent sub-reso-

Measures Of Subclinical Atherosclerosis

Testosterone Levels

Numerous studies have shown that carotid intima-media wall thickness predicts coronary atherosclerosis and the incidence of clinical cardiovascular disease (116). Lower total testosterone levels were associated with greater carotid atherosclerosis in 297 elderly Dutch men independent of body mass index, WHR, hypertension, diabetes, cigarette smoking, and serum cholesterol levels in one recent report (117). A similar inverse association between testosterone and carotid artery wall thickness was observed in men with and without prevalent cardiovascular disease. in the lowest tertile (< 9.8 nmol L) had 2.5-fold greater age-adjusted risk (95 confidence interval, 1.1, 5.0) of severe aortic atherosclerosis compared with men with the highest testosterone levels (> 12.6 nmol L). Men with bioavailable testosterone levels in the lowest tertile (< 5.6 nmol L) had a fivefold greater age-adjusted risk (95 confidence interval, 1.4-10.0) of severe aortic atherosclerosis compared with those...

True Bacteria Useful to Humans

Bacillus Thuringiensis Spray

Beneficial bacteria, such as Lactobacillus acidophilus (a common organism in healthy digestive tracts), aid in digestion, reduce the risk of cancer, and may even reduce cholesterol levels. Acidophilus bacteria also have been widely used, along with antibiotics, to control or eliminate human female yeast infections. Researchers at the University of Minnesota are working on developing strains of intestinal bacteria that have an external layer of sticky polysaccharides that make them resistant to being eliminated by less desirable bacteria in the digestive tract.

Roseann Cutroni MS RD

Vascular changes predictive of CVD. such as fatty-streaks of the intima. are evident in childhood. Children and adolescents with high cholesterol lev els are more likely than the general population to have hyperlidemia as adults.2 Identification and risk management should therefore begin in childhood.1 Figure 29-1 Risk assessment. Defined as a history of premature (before age 55 years) cardiovascular disease in a parent or grandparent. With permission from National Cholesterol Education Program. Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Dept. of Health and Human Services (US), National Institutes of Health 1991 Sept NIH Publication No. 91-2732. p. 7. Figure 29-1 Risk assessment. Defined as a history of premature (before age 55 years) cardiovascular disease in a parent or grandparent. With permission from National Cholesterol Education Program. Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Dept. of Health...

Pharmacological Therapeutical Management of IBDs During Pregnancy

In addition to the above-mentioned drugs, many studies show that the quality of life of pregnant patients may be incredibly improved by aspecific symptomatic drugs active on more frequently reported symptoms, such as abdominal pain, nausea and diarrhoea 34 . Among these drugs, metoclopramide (Plasil) may be used as an antiemetic without risk of foetal damage. On the contrary, given the small quantity of available data, loperamide, an antihemor-rhoidal drug frequently used by patients with IBD, must be taken cautiously and exclusively by patients where probable benefits are higher than the risks. An alternative to loperamide, kaolin with pectin or cholestyramine may be used, the latter being suggested especially in ileal localisation of CD or in patients with gravidic cholestasis.

Effects on risk factors in humans

The effect of dietary fats on the risk of coronary heart disease (CHD) has traditionally been estimated by their effects on serum total cholesterol (Keys et al. , 1965). However, as described above, there is now abundant evidence that effects on different types of lipoprotein cholesterol are important. In particular, specific effects of fatty acids of LDL and HDL cholesterol should be considered. The Mensink et al. (2003) meta-analysis provides predictive equations for the effects of SAFAs, MUFAs, PUFAs and TFAs on blood lipids and lipoproteins. Figure 1.2 shows what happens with total, LDL and HDL cholesterol if 1 of energy as carbohydrates in the diet is replaced by 1 of a particular fatty acid. The figure depicts effects of the different specific SAFAs, and it must be noted that these effects were derived from a smaller set of studies than the effect of all SAFAs together as a class. Nevertheless, palmitic acid is the most abundant dietary SAFA, and the effects of SAFAs together...

The History and Physical Examination

In the setting of chest pain, the physician's impression of the symptoms as definitely, probably, probably not, or not angina, along with key historical features of prior MI, sex of the patient, age, and number of risk factors (diabetes, smoking, hypercholesterolemia, and hypertension), help establish the likelihood of coronary artery disease (1).

Digestion And Absorption

Mixed Micelle Water Transport Absorption

On to the ileum where they are absorbed and recirculated in the portal blood to the liver, from whence they are re-secreted in the bile. This is also true for some cholesterol that is a constituent of bile. The recirculation of bile constituents in this way is referred to as the entero-hepatic circulation. It may be interrupted by resins (given by mouth) that bind cholesterol and bile salts and prevent their reabsorption, leading the liver to synthesize new bile salts from cholesterol. This is therefore a mechanism for depleting the body of cholesterol and may be useful in the treatment of high cholesterol levels. The absorption of cholesterol is slower and less complete than that of the other lipids, about half of the absorbed sterol being lost during desquamation of cells. Most of the absorbed portion is esterified either by reversal of cholesteryl esterase or via acyl-CoA cholesterol acyltransferase (Section 7.5.6). The latter enzyme is induced by high concentrations of dietary...

Chaperone Complexes Involved in Cholesterol Transport in Specialized Tissues

The intestine has a major role in the overall regulation of systemic cholesterol levels. We have identified a third chaperone complex that is involved in the net uptake and transport of cholesterol in the intestine 80 . Annexin II and caveolin-1 form a chaperone complex with cyp40 and cypA that binds cholesterol in the intestine. Ablation of annexin II or caveolin-1 in the zebrafish disrupted cholesterol uptake. Further, the drug ezetimibe decreased cholesterol levels in the circulation by disrupting intestinal cholesterol transport. Ezetimibe also disrupted this novel annexin II-caveolin-cholesterol chaperone complex. However, the interaction of annexin II with caveolin-1 in this intestinal complex is quite different from the two chaperone complexes described previously. Annexin II and caveolin-1 appear to form a heterodimeric band which is stable to heat, SDS and reducing agents, and was also immunoreactive against both annexin II and caveolin-1 and resolved as a complex at 55-58...

Uh Endocytosis and Exocytosis

Concentration Outside Cell

Receptor-mediated endocytosis is the method by which cholesterol is taken up by most mammalian cells. Water-insoluble cholesterol and triglycerides are packaged by liver cells into lipoprotein particles, which are then secreted into the bloodstream to provide body tissues with lipids. One type of these particles, called low-density lipoproteins, or LDLs, must be taken up by the liver for recycling. This uptake also occurs via receptor-mediated endocytosis. This process begins with the binding of LDLs to specific receptor proteins on the cell surface. Once engulfed by endocytosis, the LDL particle is freed from the receptors. The receptors segregate to a region of the vesicle that buds off to form a new vesicle, which is recycled to the plasma membrane. The freed LDL particle remains in the original vesicle, which fuses with a lysosome in which the LDL is digested and the cholesterol made available for cell use. Persons with the inherited disease familial hypercholesterolemia (-emia,...

Digestion And Absorption Of Lipids

Docosahexaenoic Acid Molecule

Dietary cholesterol is presented as a free sterol or as a sterol ester (cholesterol ester). The hydrolysis of cholesterol ester is catalyzed by the pancreatic enzyme car-boxylester hydrolase, also called cholesterol esterase (see Fig. 27.24). The digestion of cholesterol ester is important because cholesterol can be absorbed only as the free sterol.

Can We Get Rid Of Coronary Heart Disease

Once fat has been deposited inside an artery it cannot be removed completely. Modern treatments, such as the cholesterol-lowering drugs called statins, combined with a low-fat diet and vigorous daily exercise, may help reduce the amount of fat inside the artery. Statins (which can now be bought, like aspirin, over the counter) reduce the cholesterol level, reduce the inflammation in the arteries, and convert a lump of soft, inflammed fat which is likely to crack (an unstable fatty plaque) into a stable plaque. So even though there maybe fat in an artery, it can be changed into a relatively harmless type of fat. This reduces the risk of heart attacks and can improve symptoms of angina. We now give statins to everyone who has had a heart attack and has coronary or any other form of vascular disease.

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Lower Your Cholesterol In Just 33 Days

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