Lowering Your Cholesterol Naturally

Lower Cholesterol in 30 Days

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. Once Davis realized that this all-natural cholesterol lowering program worked for him, he sought out other people who also had high cholesterol and put it to the test. He found that his method worked for over 93% of the people who tried it. Because of this success, he decided to make the program available to the public in the form of an e-book. Davis believes so much in the results of this test that he is offering a no-risk guarantee when you buy his e-book. If for any reason you arent satisfied in the first 60 days you can get your money back. At the very worst, even if you dont learn anything new from this e-book you will get your money back. Continue reading...

Natural Cholesterol Guide Overview

Rating:

4.8 stars out of 19 votes

Contents: EBook
Author: Scott Davis
Official Website: blueheronhealthnews.com
Price: $39.00

Access Now

My Natural Cholesterol Guide Review

Highly Recommended

The author has done a thorough research even about the obscure and minor details related to the subject area. And also facts weren’t just dumped, but presented in an interesting manner.

Purchasing this e-book was one of the best decisions I have made, since it is worth every penny I invested on it. I highly recommend this to everyone out there.

Cholesterol Reduction

Flavonoids are known to reduce cholesterol. A 30-day study of induced hyperlipidaemia in rats found that baicalein, quercetin, rutin and naringin reduced cholesterol, with baicalein being the most potent. Baicalein was also the most effective flavonoid in reducing triglyceride levels (De Oliveira et al 2002). In another in vivo study, rats were fed a cholesterol-laden diet and half were also given 5. baicalensis radix extract (Regulska-llow et al 2004). The treatment rats displayed a significant reduction in plasma triglycerides and total cholesterol as compared with control animals.

Hypertension And Cholesterol Lowering

CoQ10 has been studied both as stand-alone and adjunctive treatment in hypertension. According to a review of 8 studies, supplemental CoQ10 results in a mean decrease in systolic blood pressure of 16 mmHg and in diastolic blood pressure of 10 mmHg (Rosenfeldt et al 2003). The effect on blood pressure has been reported within 10 weeks of treatment at doses usually starting at 100 mg daily. One small 10-week open study of 26 subjects with essential hypertension study found that an oral dose of 50 mg taken twice daily also reduced total serum cholesterol levels with a modest increase in serum HDL-cholesterol (Digiesi et al 1994).

Reduces Serum Cholesterol Levels

A 2000 meta-analysis of 13 clinical trials concluded that garlic is superior to placebo in reducing total cholesterol levels, exerting a modest effect (Stevinson et al 2001). The mechanism of action involves inhibition of cholesterol synthesis by deactivating HMG-CoA reductase via enhanced phosphorylation, but not changing theamount of the enzyme, according to in vitro research (Liu & Yeh 2002). The compounds containing an allyl-d sulfide or a I lyl-su If hyd ryl group are most likely responsible for the inhibition of cholesterol synthesis by garlic and that this inhibition is likely to be mediated at sterol 4-alpha-methyl oxidase (Singh & Porter 2006). Clinical evidence also suggests it raises HDL levels and reduces triglyceride levels (Bordia et al 1998).

Familial hypercholesterolemia and statins

Perhaps the most dramatic example of monogenic diseases leading to treatments for common disease concerns familial hypercholesterolemia (FH) and the development of statins (Goldstein et al., 2001). FH is a relatively common dominant condition affecting 1 500 of the population. Individuals with FH have high levels of cholesterol at birth and will develop atherosclerosis and vascular disease in childhood. The risk of fatal heart disease before the age of 40 years is significantly higher than among the general population. Approximately one-third of patients with FH show no symptoms until sudden cardiac death. Through the pioneering work of Brown and Goldstein, we know that FH is caused by loss of function mutations in the LDL receptor gene (LDLR). The LDL receptor removes cholesterol from the blood stream. This piece of genetic detective work proved that high cholesterol is the cause of coronary disease in these patients. Extrapolating from this monogenic condition, these findings...

Hypercholesterolaemia And Hypertriglyceridaemia

Niacin has been used for the treatment of hypercholesterolemia and hypertriglyceridaemia since the 1950s. Large doses of niacin reduce total cholesterol, LDL-cholesterol, triglycerides and lipoprotein (a) levels and also markedly raise HDL-cholesterol C levels (lllingworth et al 1994). Considering these factors are also predictive of cardiovascular events, niacin is used to reduce overall risk of cardiovascular disease (Canner et al 1986). According to a recent meta-analysis effects on LDL- 2007 Elsevier Australia Extended-release niacin (nicotinic acid) has been evaluated in at least four randomised, placebo-controlled trials, with the most efficacious results occurring at doses of 1 500-2000 mg day (Goldberg 1998, Grundy 2002, Guyton et al 2000, Morgan et al 2003). Results were dose- and time-dependent, with trials ranging in length from 4 to 16 weeks. At the 1500 and 2000 mg doses, reductions were noted in total cholesterol (-7 to -12.1 ) total cholesterol to HDL-C ratio (-17 to...

Monogenic hypercholesterolemias

Cetp Pcsk9

Important insights into CHD pathogenesis have come from the study of monogenic hypercholes-terolemias, and have led to the development of the most widely used class of lipid-lowering drugs, the HMG-CoA-reductase inhibitors (statins). Among the many known risk factors for atherosclerosis, very high low density lipoprotein (LDL) cholesterol levels are probably unique in their ability to lead to the development of premature atherosclerosis in humans in the absence of other additional risk factors. Table 24.2 summarizes the main characteristics of the known Mendelian disorders of severe hypercholesterolemia, all of which are associated with premature CHD. Autosomal dominant hypercholesterolemias Familial hypercholesterolemia (FH) was the first genetic disease of lipid metabolism to be clinically and genetically characterized and it represents the most common and most severe form of Mendelian hypercholesterolemia (Goldstein et al., 2001). The disease is caused by mutations in the LDL...

High Cholesterol

Probiotics modestly reduce cholesterol levels in healthy subjects and may have stronger effects in people with hyperlipidaemia. In another study, 32 subjects with serum total cholesterol ranging from 5.7 to 7.25 mg dl_ were randomly assigned to two treatments (1) Intake of a low-fat drinking yoghurt prepared with two ordinary yoghurt starters (Streptococcus thermophilus and Lactobacillus delbrueckii subsp. Bulgaricus placebo group) and (2) Intake of a low-fat drinking yoghurt prepared with the two yoghurt starters plus Bifidobacterium longum strain BL1 (problotlc group). After Intake for 4 weeks at 3 100 mL day, reduction of serum total cholesterol was observed In approximately half of the problotlc group subjects a particularly significant decrease In serum total cholesterol was found among subjects with moderate hypercholesterolemia (serum total cholesterol > 6.2 mg dL). The serum lipid concentrations In the placebo group subjects were almost stable during the experimental periods...

Ulcyte Or Questran

Lipex, Zocor) Cholestyramine (e.g. Questran lite, colestipol e.g. Colestid ) HMG-CoA reductase inhibitors (statins) HMG-CoA reductase inhibitors (statins) Cholestyramine (e.g. Questran lite, colestipol e.g. Colestid ) 1448 tions 1431 Cholestyramine (e.g. Questran lite, colestipol e.g. Colestid ) Cholestyramine (e.g. Questran lite, colestipol e.g. Colestid ) Willowbark

Moving Into the Third Millennium After a Century of Screening

For many decades, the discovery of drugs has depended on screening. From the previous century until the 1960s, chemical compounds and natural products were tested in whole animal assays, and in the case of antibacterial and antitumor testing, the samples were tested in whole cell assays. Although screening was labor intensive and expensive, it was fruitful. A large number of successful drugs such as the cephalosporins, aminoglycosides, tetracyclines, macrolide antibiotics, doxyrubicin, etoposide, and other anticancer agents, steroids and drugs for use in the central nervous system and cardiovascular areas were discovered by screening 1,2 . In many cases, identification of the lead molecule, such as penicillin, cepha-losporin, macrolides, captopril, and mevacor, spawned a large number of analogs through chemistry programs 3-7 . A single lead molecule identified in one company has, in many cases, kept several hundred industrial chemists and biologists busy for several years.

Answers To Patients Frequently Asked Questions

Astragalus appears to have numerous biological effects, such as digestive and immune system stimulation and heart muscle stimulation. Early research suggests that it may have a role in the treatment of asthma, memory deficits, elevated cholesterol levels and as an adjunct to chemotherapy treatment for cancer. When will it start working

Cardiovascular Protection

There are a number of ways in which beta-carotene may act to protect against cardiovascular disease. Free radical scavenging may prevent cellular transformations leading to atherosclerosis and protection of LDL oxidation may further act to protect against atheroma formation (Halliwell 1993). Other mechanisms proposed for the possible favourable effect of antioxidants include an increase of HDL cholesterol and the preservation of endothelial functions (Tavani & La Vecchia 1999). Patients with acute myocardial infarction (AMI) have also been shown to have reduced plasma antioxidant vitamins and enhanced lipid peroxidation upon thrombolysis, suggesting that antioxidants may reduce free radical generation processes in reperfusion injury in AMI (Levy et al 1998). In an animal study, atherosclerosis was inhibited in rabbits fed a high-cholesterol diet supplemented with all-trans beta-carotene. In that study all-trans beta-carotene 2007 Elsevier Australia

Transfer of Cholesterol to the Mitochondrion

Steroid-synthesizing cells have at least three metabolically active pools of cholesterol (1) a small, metabolically active pool of free cholesterol (2) a large storage pool in which cholesterol is stored as cholesterol esters of free fatty acids and (3) a fixed pool of membrane cholesterol, which is not available for steroid synthe-sis.9 The free cholesterol pool is formed from endogenous conversion of acetate to cholesterol via a complex series of reactions and by hydrolysis of cholesterol esters, including those that are part of the storage pool and those that are constituents of low-density lipoprotein (LDL) and high-density lipoprotein (HDL). After cellular uptake of these lipoproteins, LDL is processed through lysozymes, whereas HDL enters the cy-tosolic pool directly. Dietary cholesterol incorporated into LDL is most commonly used for steroid hormone biosynthesis. Although free cholesterol represents only a small fraction of the total cholesterol pool, this fraction can be...

Cardiovascular Disease

In contrast, analysis of the data from the ATBC cancer prevention study, which involved 23,144 male smokers, found that beta-carotene supplementation slightly increased the risk of angina (Rapola et al 1996) and intracerebral haemorrhage while having no overall effect on the risk of stroke (Leppala et al 2000a,b), abdominal aortic aneurysm (Tornwall et al 2001), or symptoms and progression of intermittent claudication (Tornwall et al 1999). Beta-carotene, however, was found to decrease the risk of cerebral infarction modestly among a subgroup with greater alcohol consumption (Leppala etal 2000a,b). In a 6-year post-intervention follow-up study, beta-carotene was found to increase the risk of first-ever myocardial infarction while continuing to have no overall effect on the incidence of stroke (Tornwall et al 2004). An analysis of 52 men from the CARET Study concluded that there was no significant effect on total, HDL- or LDL-cholesterol levels that could account for the observed...

Oral contraceptives

Estrogens can cause nausea, breast tenderness and breast enlargement. Progestins can cause unfavorable changes in LDL and HDL cholesterol. Other adverse effects associated with oral contraceptives, such as weight gain or depression, are more difficult to attribute to one component or the other. Women smokers more than 35 years old who use combination oral contraceptives have an increased risk of cardiovascular disease.

Common diseasecommon variant or not

At the time of writing, there are not enough data to be able to evaluate the extent to which the CD-CV hypothesis is true. There are a number of examples of common variants for complex diseases that are known (Lohmueller et al., 2003), and also clear examples of moderate allelic heterogeneity (at NOD2 CARD15, involved in Crohn's disease Hugot et al., 2001) and functional rare variants (associated with plasma levels of HDL cholesterol and LDL, and rates of sterol absorption Cohen

Evidence That Exosomes Play A Role In Stressinduced Hsp72 Release

Independently of the classical secretory pathway (based on the inability of Brefeldin A treatment to inhibit stress-induced HSP72 release), and that non-specific processes such as cell lysis could not account for stress-induced release of HSP72 (Lancaster and Febbraio, 2005). However, and in contrast to the results of Broquet and coworkers, we were unable to confirm a role for lipid rafts in stress-induced HSP72 release. Using methyl- -cyclodextrin (the cholesterol depleting agent) to disrupt lipid raft function, our results demonstrate that lipid rafts do not play a role in stress-induced HSP72 release from human peripheral blood mononuclear cells (PBMCs) (Lancaster and Febbraio, 2005). Importantly, our data demonstrate that methyl- -cyclodextrin highly effectively depleted intracellular cholesterol levels in a dose-dependent manner, confirming that our methyl- -cyclodextrin treatment regimen was efficacious.

Lipidlowering Activity

Although the mechanism of action is yet to be fully explained, studies show that chromium supplementation may decrease triglyceride levels, total and LDL-cholesterol and modestly increase HDL-cholesterol (Bahijri 2000, Lee & Reasner 1994, Press et al 1990, Preuss etal 2000).

What Should Be Clarified Beforehand

Interactions are important in the choice of combination regimens. Whereas interactions between antiretroviral drugs are well known, interactions with other concomitant medications are often less well characterized. The urgent need for more research was recently demonstrated in a study investigating the interactions between HAART and statins. In healthy volunteers, the measurement of plasma levels showed that levels of simvastatin were elevated by 3,059 after concurrent dosing with ritonavir or saquinavir (Fichtenbaum 2002). One case of fatal rhabdomyolysis on simvastatin and nelfinavir has been described (Hare 2002). Many drugs should be avoided in combination with particular antiretroviral drugs, as incalculable interactions may occur. These include certain contraceptives. Even drugs that seem unproblematic at first glance can have unfavorable effects one study that received a lot of attention showed that plasma levels of saquinavir were

Frequency Distributions

A set of unorganized data is difficult to digest and understand. Consider a study of the serum cholesterol levels of a sample of 200 men a list of the 200 levels would be of little value in itself. A simple first way of organizing the data is to list all the possible values between the highest and the lowest in order, recording the frequency ( ) with which each score occurs. This forms a frequency distribution. If the highest serum cholesterol level were 260 mg dl, and the lowest were 161 mg dl, the frequency distribution might be as shown in Table 1-1

Relative frequency distributions

As Table 1-2 shows, a grouped frequency distribution can be transformed into a relative frequency distribution, which shows the percentage of all the elements that fall within each class interval. The relative frequency of elements in any given class interval is found by dividing , the frequency (or number of elements) in that class interval, by n (the sample size, which in this case is 200). By multiplying the result by 100, it is converted into a percentage. Thus, this distribution shows, for example, that 19 of this sample had serum cholesterol levels between 211 and 220 mg dl.

Hormone replacement therapy administration and regimens

In those women with a uterus, a progestin should be given continuously (2.5 mg of medroxyprogesterone per day) or in a sequential fashion 5-10 mg of medroxyprogesterone (Provera) for 1214 days each month . The most common HRT regimen consists of estrogen with or without progestin. The oral route of administration is preferable because of the hepatic effect on HDL cholesterol levels. modulator, FDA-labeled for prophylactic treatment of osteoporosis. This agent offers an alternative to traditional HRT. The modulator increases bone density (although only one-half as effectively as estrogen) and reduces total and LDL cholesterol levels.

Relationship to Classical Indexes

It is important to analyze whether the previous analysis methodology for parameterizing the vessel behavior during the flow-mediated dilation test is linked to other clinical parameters and CVD risk factors traditionally used in the medical literature. Serum lipids, particularly cholesterol and the cholesterol fraction carried by low-density lipoproteins (LDL cholesterol) are recognized as a main causal factor of atherosclerosis 34 . In this disease lipids accumulate in the vessel wall, disturbing the vascular function of delivering sufficient blood flow to the affected territories, which ends with the manifestation of a vascular clinical event like heart attack or stroke. Moreover, knowing patients' lipid levels and modifying them with drugs and diet is the main preventive tool against cardiovascular diseases. From this point of view, cholesterol and LDL cholesterol are considered as risk factors, as higher levels identify individuals with higher risk whereas the cholesterol fraction...

Liver X and Farnesoid X Receptors

In addition, FXR activates expression of yet a fourth orphan receptor, SHP-1, which then dimerizes with the constitutively active LRH-1 and attenuates LRH LXR-mediated transcription of CYP7A, preventing further synthesis of bile acids from cholesterol.417 Despite its crucial role in gating bile acid biosynthesis and cholesterol clearance, LXRa is apparently not essential for survival as deletion of mouse LXRa yields phenotypically normal mice.418 However, when challenged with a high-cholesterol diet, these animals accumulate cholesterol in the liver due to failure to induce CYP7A activity, in spite of the presence of functional LXRj. Oxysterols apparently also upregulate expression of proteins involved in sterol lipid transport. For example, certain ABC transporters involved in lipid transport and cholesterol ester transfer proteins are activated through LXR signaling.419-421 An additional level of regulation may include transcriptional induction of...

Feedback Regulation Is Not Synonymous With Feedback Inhibition

In both mammalian and bacterial cells, end products feed back and control their own synthesis, in many instances by feedback inhibition of an early biosyn-thetic enzyme. We must, however, distinguish between feedback regulatio n, a phenomenologic term devoid of mechanistic implications, and feedback inhibition, a mechanism for regulation of enzyme activity. For example, while dietary cholesterol decreases hepatic synthesis of cholesterol, this feedback regulation does not involve feedback inhibition. HMG-CoA reductase, the rate-limiting enzyme of cholesterologenesis, is affected, but cholesterol does not feedback-inhibit its activity. Regulation in response to dietary cholesterol involves curtailment by cholesterol or a cholesterol metabolite of the expression of the gene that encodes HMG-CoA reductase (enzyme repression) (Chapter 26).

FMD Response Eigen Parameterization

As can be concluded from Table 5.7, a weak but significant correlation was found between AFMDc and LDL cholesterol in a damaging way and between AFMDc and HDL cholesterol in a protective way. This had been previously reported when studying dyslipidemic populations with a similar correlation magnitude, association that could be slightly attenuated in our population due to a narrower range of lipids variation. For instance, Kuvin et al. 38 found a correlation coefficient of HDL cholesterol and AFMDc of 0.3. The correlation between classical flow-mediated dilation and LDL cholesterol (r -0.40) had been previously reported by Aggoun et al. 39 in hypercholesterolemic patients. Other studies report one of these associations but rarely both or with stronger association coefficients 40 and never in natural large populations with normal lipid levels 41 . EigenFMD modes are also related to cholesterol fractions. Interestingly, this analysis highlights that each fraction exerts a different...

Clinical manifestation

Frequently, complex metabolic alterations are associated with the described body shape alterations. These include peripheral and hepatic insulin resistance, impaired glucose tolerance, type 2 diabetes, hypertriglyceridemia, hypercholesterolemia, increased free fatty acids (FFA), and decreased high density lipoprotein (HDL). Often these metabolic abnormalities appear or deteriorate before the manifestation of fat redistribution. The prevalence of insulin resistance and glucose intolerance has been reported in the literature at 20 to 50 depending on the study design and measurement methods. Frank diabetes is less frequent with a prevalence of between 1 and 6 . Lipodystrophic patients present with the highest rates of metabolic disturbances. The therapy-induced dyslipidemias are characterized by increased low density lipo-proteins (LDL) and triglyceride-rich very low density lipoproteins (VLDL). Detailed characterization revealed an increase of apoplipoprotein B, CIII and E. Raised...

Specific interventions

Coronary heart disease (CHD) includes history of myocardial infarction, unstable angina, stable angina, coronary artery procedures, or evidence of clinically significant myocardial ischemia. CHD risk equivalents include clinical manifestations of non-coronary forms of atherosclerotic disease, diabetes, and > 2 risk factors with 10-year risk for hard CHD > 20 . Risk factors (RF) include age (male > 45 years, female > 55 years or premature menopause without hormone replacement), positive family history for premature CHD (in first-degree relatives < 55 years and first-degree female relatives < 65 years), cigarette smoking, hypertension (blood pressure > 140 90 mmHg or taking antihypertension drugs), HDL < 40 mg dl (1.0 mmol l). If HDL cholesterol is over > 60 mg dl (1.6 mmol l), subtract one risk factor from the total (adapted from Dub 2000 and Schambelan 2002). Coronary heart disease (CHD) includes history of myocardial infarction, unstable angina, stable angina,...

Prevention Of Morbidity And Mortality Of Cardiovascular Disease

For over 25 years, fish and fish oils have been linked to cardiovascular health. This association was first recognised when significantly lower death rates from acute myocardial infarction (Ml) were found among Greenland's Inuit population, despite only moderate differences between the Inuits' blood cholesterol levels and those of other populations (Holub 2002). A high dietary omega-3 fatty acid intake in the form of marine mammals (seal, whale) and various fish were thought responsible for the protective effect (Bang et al 1980). In 1989, results from the first large, randomised, clinical trial investigating the effects of fatty fish consumption on survival and risk of secondary Ml confirmed a link to cardiovascular health (Burr et al 1989). The DART (Diet and Reinfarction study) found a modest intake of 2-3 portions weekly of fatty fish reduced mortality in men who had previously experienced a Ml and produced a relative reduction in total mortality of 29 during the 2-year follow-up,...

Elevated Triglyceride Levels

DHA and EPA supplementation significantly reduces triglyceride levels and is used as sole therapy in cases of elevation or as adjunctive therapy with cholesterol-lowering medication when indicated. According to Din et al, omega-3 fatty acids reduce triglyceride concentrations in a dose-dependent manner, with intakes of about 4 g day lowering serum triglycerides by 25-30 (Din et al 2004).

Bacterial Cholesterol Metabolism

The intestinal tract has a major impact on cholesterol metabolism (34-36). A major source of intestinal cholesterol comes from the de novo synthesis of the sterol compound. Cholesterol also can enter the intestine from dietary sources. It has been estimated that 34-57 of dietary cholesterol is absorbed from the intestine (37). In humans cholesterol synthesized by the intestinal cells is introduced into the lumen by exfoliation of these cells. An additional source of intestinal cholesterol is via biliary excretion.

Individual and Population Examples

As a general rule, individual-directed interventions bring about significant benefits to the individuals but have little impact on the population rates of disease or condition in question and vice versa for population-based interventions, which generally bring little benefit to each individual but have the potential to influence the prevalence or incidence of the condition (7). With obesity, this discrepancy is even more exaggerated (compared to, say, hypertension or hypercholesterolemia) because available individual interventions, apart from surgery, have modest long-term effects for the individuals under treatment (8,9). The efforts on population-based interventions related to obesity are much needed but are still in their infancy (1,10,11).

Cholesterol Lowering Conjugates Designed to Function Through the Hepatic Lectin

In contrast to the approaches described above in which molecules designed to function within the liver are delivered through their interaction with the hepatic lectin, a strategy to use the hepatic lectin to eliminate unwanted species from serum has also been investigated. Specifically, Biessen et al. attempted to take advantage of hepatic lectin mediated endocytosis and subsequent ligand proteolysis to lower serum cholesterol levels 134 . It was anticipated that targeting the proteins responsible for serum cholesterol transport, high-density lipoprotein (HDL) and low-density lipo-protein (LDL), to hepatocytes via the hepatic lectin would lead to their degradation, thereby lowering serum cholesterol. Bifunctional ligand 29 was designed, in which cholesterol was linked to a trivalent galactose derivative (Fig. 20). When added to serum, compound 29 formed complexes with HDL and LDL. Intravenous injection of 29 into rats resulted in a decrease in detected serum cholesterol levels by 44 ....

Cardiovascular Effects

Antihyperlipidaemic Ginsenoside Rb1 has been shown to lower triglyceride and cholesterol levels via cAMP-production in the rat liver (Park et al 2002b). P. ginseng extract (6 g day) for 8 weeks resulted in a reduction in serum total cholesterol, triglyceride, LDL and plasma malondialdehyde levels and an increase in HDL (Kim & Park 2003) in eight males. Ginseng has also been reported to decrease hepatic cholesterol and triglyceride levels in rats, indicating a potential use of ginseng in the treatment of fatty liver (Yamamoto et al 1983).

Public Health Aspects Of

Of major public health interest are the results of treatment trials of hypertension and use of statins in the elderly showing decreased incidence of dementia. Treatment of other risk factors for VaD is also indicated, including smoking, hyperfibrinogenemia, orthostatic hypotension, cardiac

Cholesterol Synthesis Is Controlled By Regulation Of HmgcoA Reductase

Regulation of cholesterol synthesis is exerted near the beginning of the pathway, at the HMG-CoA reductase step. The reduced synthesis of cholesterol in starving animals is accompanied by a decrease in the activity of the enzyme. However, it is only hepatic synthesis that is inhibited by dietary cholesterol. HMG-CoA reductase in liver is inhibited by mevalonate, the immediate product of the pathway, and by cholesterol, the main product. Cholesterol (or a metabolite, eg, oxygenated sterol) represses transcription of the HMG-CoA reductase gene and is also believed to influence translation. A diurnal variation occurs in both cholesterol synthesis and reductase activity. In addition to these mechanisms regulating the rate of protein synthesis, the enzyme activity is also modulated more rapidly by posttransla-tional modification (Figure 26-4). Insulin or thyroid hormone increases HMG-CoA reductase activity, whereas glucagon or glucocorticoids decrease it. Activity is reversibly modified by...

Definition Of Obesity And Bmi Cutoff Points

Figure 5 Risk factors elevated serum cholesterol (> 6.2 mmol L), elevated total cholesterol HDL cholesterol ratio (> 4.4), elevated triglyceride (> 1.8 mmol L), elevated blood pressure (> 140 90mmHg), diabetes mellitus (OGGT > 11.1 mmol L). Data are corrected for age, ethnicity, educational level, occupation, physical activity, smoking, and waist hip ratio. (From Ref. 20.) Figure 5 Risk factors elevated serum cholesterol (> 6.2 mmol L), elevated total cholesterol HDL cholesterol ratio (> 4.4), elevated triglyceride (> 1.8 mmol L), elevated blood pressure (> 140 90mmHg), diabetes mellitus (OGGT > 11.1 mmol L). Data are corrected for age, ethnicity, educational level, occupation, physical activity, smoking, and waist hip ratio. (From Ref. 20.)

Assessment of Risk Factors

Overall, the greatest danger of overweight obesity is the development of cardiovascular disease. Moreover, in the long term obesity predisposes to type 2 diabetes, which is itself a risk factor for cardiovascular disease. ATP III provides useful classifications for lipid and nonlipid risk factors. These classifications are shown in Tables 1 and 2, respectively. In ATP III, estimates are made of a person's absolute risk using Framingham risk scoring, which is available through the NHLBI (http htm). This scoring estimates the 10-year risk for developing myocardial infarction or coronary death. It is based on absolute levels of the following risk factors total cholesterol, HDL cholesterol, blood pressure, smoking history, and age. Framingham scoring can be carried out either by manual scoring or with a simple computer program, both of which are available on the NHLBI website. In addition, ATP III defines the metabolic syndrome for clinical practice according to five clinical features...

Background And Relevant Pharmacokinetics

Lower serum concentrations of zeaxanthin have been associated with male gender, smoking, younger age, lower non-HDL cholesterol, greater ethanol consumption and higher BMI (Brady et al 1996). Lutein and zeaxanthin, together with other carotenoids, have also been found to be lower in people with chronic cholestatic liver disease, which can be attributed to malabsorption of fat-soluble vitamins, as well as other mechanisms of hepatic release (Floreani et al 2000). In an epidemiological study

Using Hormonal Strategies To Improve Mammographic Density And Sensitivity Of Screening Mammograms

There may be women in whom reducing hormone levels will not result in reduced density. For such women and for women who due to medical (high cholesterol) or other reasons do not wish to reduce their hormone levels, alternative imaging techniques, currently being developed and tested, may be a good alternative.52

Body Size At Birth And Later Body Composition

Associated with body mass index and with the area of thigh muscle but not with subcutaneous fat on the thigh. The association between birth weight and body mass index may therefore have reflected an association with lean tissue rather than fat. Waist-hip ratio and truncal fat also have different metabolic associations. Waist-hip ratio is more strongly associated with serum triglyceride and HDL cholesterol concentrations than is the sub-scapular-triceps skinfold ratio (22). The associations between low birth weight and these two measures of body composition are likely to reflect influences in the intrauterine environment that are either different or act at different times.

Children Of Centenarians

Offspring of centenarians have been found to have lipid profiles associated with lower risk for cardiovascular disease (Barzilai, Gabriely, Gabriely, Iankowitz, and Sorkin, 2001). Other findings show that middle-aged sons of long-lived parents had better systolic pressures, cholesterol levels, and decreased frequencies of the apoE fi-4 allele, compared to middle-aged sons of shorter-lived parents. Using a questionnaire-based cross-sectional study design, Terry and colleagues (2004) assessed the

The Maternal UPD14 Syndrome

With the exception of one case of no apparent phenotype (Papenhausen et al., 1995), which was insufficiently documented at the molecular level (Robinson and Langlois, 1996), all other cases further illustrated this emerging syndrome (Coviello et al., 1996 Tomkins et al., 1996 Sirchia et al., 1994 Barton et al., 1996 Linck et al., 1996 Walgenbach et al., 1997 Splitt and Goodship, 1997 Robinson et al., 1994 Desilets et al., 1997 Miyoshi et al., 1998 Ralph et al., 1999 Harrison et al., 1998 Fokstuen et al., 1999 Martin et al., 1999). The birth is often premature and the birthweight low for gestational age. In about 30 of cases, the head grows rapidly in the postnatal period, owing to a hydrocephalic condition that, however, arrests spontaneously. A suggestive facies with prominent forehead (in association with arrested hydrocephalus) and supraorbital ridges, a short philtrum, and downturned mouth corners are present (Figure 2). There is hypotonia, hyperextensible joints, mild to moderate...

Transduction of the Liver

Kim et al. (66) investigated correction of hypercholesterolemia in apolipoprotein E (apoE)-deficient mice by using either an FGAd-encoding mouse apoE cDNA (FG-Ad5-cE), an HDAd-encoding mouse apoE cDNA (HD-Ad5-cE), or an HDAd-bearing mouse genomic apoE locus (HD-Ad5-gE). Intravenous injection of ApoE-deficient mice with 5 X 1012 particles kg of FG-Ad5-cE resulted in an immediate fall in plasma cholesterol levels to within normal range (Fig. 6A). However, this effect was transient and plasma cholesterol levels increased after 28 days, returning to pretreatment levels by 112 days. Correlative with the plasma cholesterol levels, the levels of plasma apoE immediately increased shortly after injection but rapidly declined to pretreatment levels by day 28 (Fig. 6B). Similarly, intravenous injection of 7.5 X 1012 particles kg of HD-Ad5-cE produced a complete and immediate lowering of plasma cholesterol to normal levels, but in contrast to FG-Ad5-cE, the reduced levels lasted about 1 year...

Preventing Cardiovascular Disease

A double-blind, placebo-controlled study investigating the effects of a quercetin-containing supplement on plasma quercetin status, risk factors for heart disease and serum platelet fatty acid levels was conducted on 27 healthy men and women with cholesterol levels of 4.0-7.2 mmol L (Conquer et al 1998). The subjects consumed a quercetin-containing supplement (1 g quercetin day) or rice flour placebo for 28 days. Quercetin intakes were approximately 50-fold greater than dietary intakes previously associated with lower coronary heart disease mortality in epidemiologic studies. Plasma quercetin concentrations were approximately 23-fold greater in subjects consuming the quercetin capsules than in the placebo group. Quercetin supplementation did not alter serum total, LDL- or HDL-cholesterol or triglyceride levels, or other cardiovascular disease or thrombogenic risk factors such as platelet thromboxane B2 production, blood pressure or resting heart rate. This is in contrast to a previous...

Other Targets for AntiHDV Therapy

Because the production of mevalonate by the enzyme HMG-CoA reductase is a committed step in both the cholesterol and prenyl lipid biosynthetic pathways (Zhang and Casey 1996), it has been suggested that HMG-CoA reductase inhibitors-which are in widespread clinical use to treat hypercholesterolemia-might be used to inhibit prenylation. Prenylation can indeed be inhibited in vitro by an HMG-CoA reductase inhibitor, but the doses required are cy-totoxic (Sinensky et al. 1990). Because cellular needs for cholesterol can be exogenously supplied via the low density lipoproteins receptor system, synergy between HMG-CoA reductase inhibitors and FTIs can be considered. Similar potential synergistic effects might also be achieved by combining FTIs with other classes of drugs which inhibit additional steps in the pathway of prenyl protein synthesis. For example, most prenylated eukaryotic proteins are further processed by the sequential activity of the products of the Rce-1 (CXXX-box...

Osteoporosis and Cardiovascular Disease in the Elderly

Osteoporosis and cardiovascular disease are common disorders that increase with aging. Accumulating evidence indicates that both disorders may share common pathophysiologic mechanisms as well as risk factors. Besides age and sedentary lifestyle, diabetes, hypertension, dyslipidemia, estrogen deficiency, and hyperhomo-cysteinemia are common risk factors for both disorders. Furthermore, therapeutic agents for osteoporosis have antiatherosclerotic properties and agents such as statins that are atheroprotective, and appear to increase bone mass and perhaps protect against fractures.

Etiology and Pathogenesis

The relationship between depression and cardiovascular disorders also provides insight into the mechanisms of depression. Abnormalities in neurotransmitters (including serotonin), platelet-activating factor, and nitric oxide, which are involved in atherosclerotic processes, have been implicated in the pathogenesis of depression (Plante, 2005). Moreover, vascular consequences of depression such as heart rate and pulse pressure variations may lead to endothelial dysfunction in critical microcirculation networks (cerebral, myocardial, and renal) and initiate physicochemical alterations in interstitial compartments adjacent to vital organs. Worsening depressive symptoms after a coronary event were associated with impaired autonomic control of the heart, and mortality was almost three times higher among the patients with MDD at the time of the initial event compared to those without depression (de Guevara et al., 2004). The finding of higher rates of relapse of depression among patients...

Genetic and environmental contributions to CHD pathogenesis

Whilst environmental influences account for a significant part of individual and population susceptibility to CHD, the longevity of some individuals with multiple risk factors (e.g. smoking, hypercholesterolemia, hypertension), and the consistent and highly significant risk conferred by a positive family history of CHD, point to the importance of genetic factors in CHD pathogen-esis. Genes which control plasma lipids and lipoproteins are amongst the clearest examples of genetic risk factors for CHD (Table 24.1). Raised LDL cholesterol, triglycerides reduced HDL cholesterol

Evidence for the genetic basis of CHD

Family history of the disease is one of the strongest and most consistent risk factors for CHD. Relative risk estimates of between 1.5 and 5 have been derived from a range of family and population studies (Hawe et al., 2003 Lusis, 2003). At least a part of the risk of family history is conferred by the monogenic dyslipidaemias, including familial hypercholesterolemia (FH) (Goldstein et al., 1973), which carry a high penetrance of CHD. However, since the frequency of the FH heterozygous state, and of other monogenic dyslipidaemias, is only at

Oligopolygenic complex genetic hyperlipidemias

Combined hyperlipidemia, characterized by increased serum triglyceride and or cholesterol and decreased HDL cholesterol is the most common disorder of lipid metabolism affecting 1-2 of individuals in Western societies. The term familial combined hyperlipidemia (FCHL) was coined by Goldstein et al. to describe a pattern of lipid abnormalities (Goldstein et al., 1973) in survivors of myocardial infarction who had raised blood cholesterol and triglyceride levels. Originally, FCHL was described as a dominant disorder with a primary effect on blood triglyceride levels, a secondary effect on cholesterol levels, and with incomplete penetrance until the third decade (Goldstein et al., 1973). However subsequent segregation analyses (Austin, 1992

Genetics of human coronary heart disease

The heritability of known risk factors that were included in this linkage study (including type 2 diabetes mellitus and hypertension) was high, suggesting that these intermediate phenotypes are genetically determined to a moderately high extent. However, whereas age, gender, diabetes and hypertension contributed significantly to the myocardial infarction phenotype, high cholesterol levels did not. Since many of the individuals in the study were on lipid-lowering therapy, this suggests that hypercholesterolemia now appears to be a less significant risk factor for myocardial infarction than diabetes and hypertension.

Insights from rodent models

Early loss-of-function studies focused on molecules previously identified as potentially important modifiers of lipid handling. From these studies, apoE (Plump et al., 1992 Zhang et al., 1992) and the LDL receptor (Ishibashi et al., 1993) were confirmed as important modifiers of cholesterol levels. Mice lacking either apoE or the LDL receptor develop significant atherosclerotic lesions when fed a high fat diet. This observation paved the way for a deluge of studies looking at genetic influences on atherosclerosis lesion size in apoE and LDL receptor knockout mice (Glass and Witztum, 2001). Consequently, a solid body of new information has emerged on the mechanisms regulating plasma lipoprotein levels and controlling the initial stages of atherogenesis. The obvious advantage of studying the effect of a gene in mice predisposed to developing atherosclerosis is that anti-atherogenic effects of a gene may be more readily detected (Table 24.3). QTL studies of atherosclerosis with...

Hiv And Tryptophan Depletion

An open, prospective trial has also concluded that extended-release niacin therapy is safe and effective for the treatment of dyslipidaemia associated with antiretroviral therapy 2000 mg day was given to 14 subjects for 14 weeks and resulted in significant reductions in serum levels of triglycerides, total cholesterol, and non-HDL-cholesterol (Gerber et al 2004).

Potential risks of PEP

The risks of PEP mainly concern the adverse effects of the antiretroviral substances. Most frequently this refers to gastrointestinal symptoms such as nausea, vomiting or diarrhea. Also possible are changes of hematology, transaminases or creatinine. There have been reports about elevated triglyceride and cholesterol levels and insulin resistance even in short term use of protease inhibitors.

Keep Your Heart Healthy

Cardiovascular disease (CVD) is the leading cause of death among New Yorkers, with 27,000 CVD-related deaths reported each year (New York City Department of Health and Mental Hygiene, 2004b). One quarter of New York City adults have been diagnosed with high blood pressure, and a similar number have been diagnosed with high cholesterol, with many more remaining undiagnosed. One-sixth of New York City adults are obese, and three-fourths of New Yorkers do not get at least 30 minutes of physical activity four or more days per week. More than 500,000 adult New Yorkers (9 ) have been diagnosed with diabetes, a 2 2-fold increase in the past decade. Another 250,000 New Yorkers may have diabetes and not know it, and close to a million more with pre-diabetes are likely to eventually develop diabetes. Blood pressure and cholesterol can be controlled with diet, exercise and medications. Control of blood pressure with medications significantly reduces the incidence of stroke, heart attack and...

Biomedical Demography

Demographers over the past half century have increasingly become involved with the design of surveys and the analysis of survey data, especially pertaining to fertility or morbidity and mortality. Recently, various kinds of physical measurements (height and weight), physiological measurements (of blood pressure and cholesterol levels), nutritional status (assessed by the analysis of blood or urine and other methods), physical performance (hand-grip strength or ability to pick a coin up from the floor), and genetic makeup (as determined by analysis of DNA) have been added to surveys, including those conducted by Christensen, Goldman, Weinstein, Zeng, and others. Such biological measurements can be used as covariates in demographic analyses in much the same way that social and economic information is used. These kinds of analyses are an important activity of biomedical demographers (Finch et al. 2000).

Endothelium Derived Vasoactive Substances

Endothelium-derived hyperpolarizing factors appear to play important roles, especially in the microvascula-ture (82). The chemical identity of EDHF has been related to several factors, such as epoxyeicosatrienoic acid (EET) (83), K+ (84), and anandamide (85). There is an emerging consensus that EDHF is unlikely to be a single factor and that considerable tissue and species differences exist for the nature and cellular targets of the hyperpolarizing factors. One of the potential targets is a KCa channel. Randall and Kendall (85) showed that anandamide, an endogenous cannabinoid derived from arachidonic acid, causes vasodilatation via opening of KCa channels. Hayabuchi et al. (86) demonstrated that EET also opens KCa channels via G-protein without changes in cAMP or cGMP. It is of interest that aging and hypercholesterolemia impair EDHF-mediated relaxation however, the mechanisms of impairment are not clear (82).

Current applications of pharmacogenetics

The ability to individualize the use of currently used drugs will not only permit the identification of individuals vulnerable to drug side effects but, perhaps more importantly, will allow us to identify those patients who will or will not respond to a particular drug treatment. As discussed above, there are certain research areas where this is of vital importance, e.g. in the treatment of cancer, but also for other diseases such as the control of serum cholesterol with statins or the use of non-steroidal anti-inflammatory drugs, where a significant proportion of the population do not respond to these agents. For certain drugs there are already prescribing guidelines for example, in the treatment of childhood leukaemia with 6-mercaptopur-ine (Armstrong et al., 2004) and in the use of Glivec (Vastag, 2004) and Herceptin (Bell et al., 2004). There is, however, still an urgent need for new studies to identify genes which influence drug metabolism and efficacy, and to correlate...

Monogenic genes as genetic risk factors in common disease

Mobogenic Sexy Video

Figure 10.1 Mortality from familial hypercholesterolemia according to sex and time. Mortality was estimated among 250 persons with 0.5 probability of carrying the V408M. Probands and the first 20 years of life were ignored. From Sijbrands et al., 2001. Figure 10.1 Mortality from familial hypercholesterolemia according to sex and time. Mortality was estimated among 250 persons with 0.5 probability of carrying the V408M. Probands and the first 20 years of life were ignored. From Sijbrands et al., 2001. Goldstein, J., Hobbs, H. and Brown, M. (2001). Familial hypercholesterolemia. In Scriver, C., Beaudet, A., Sly, W. and Valle, D., eds., The Metabolic and molecular bases of inherited disease. New York McGraw-Hill. pp. 2863-913. in Alzheimer's disease. Annu Rev Med, 47, 387-400. Rozmahel, R., Wilschanski, M., Matin, A. et al. (1996). Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor. Nat Genet, 12, 280-87....

Atherosclerosis and Aging

There are two explanations for the increased prevalence of vascular disease in the elderly (1) the increased risk represents a longer duration of exposure to conditions that promote atherosclerosis (i.e., the time-dose product of the risk factors) and (2) atherosclerosis is a specific aging-associated process. It is important to note that these possibilities are not mutually exclusive and that from the perspective of a given elderly individual at risk for vascular disease, this distinction may not matter much. However, discrimination between these hypotheses has important implications for prevention of vascular disease, particularly at the population level. In the former case, preventive therapies should focus on early interventions on established risk factors such as hypercholesterolemia, hypertension, diabetes, obesity, and smoking in the latter case, specific therapies may be required to target the aging-associated mechanisms that accelerate atherosclerosis in the elderly.

Ginseng And Atherosclerosis

Ginseng was suggested as a medicament for the control of cholesterol levels and for the treatment of anaemia. Experimental evidence does shew that ginseng is capable of increasing the red blood cell count, of promoting serum protein synthesis and of stimulating RNA formation in the liver and DNA synthesis in bone marrow. Cholesterol, a steroid alcohol, occurs naturally in the body and is found particularly in the bile and gall bladder and in the lipoproteins of the blood plasma. Although endogenous cholesterol can be formed in all cells of the body, blood cholesterol is usually produced in the liver, the body organ that controls the normal cholesterol level in the blood. High levels of cholesterol can occur in insulin and thyroid hormone deficient subjects or in persons consuming a high fat, high cholesterol containing diet. Dietary cholesterol, also called exogenous cholesterol, derives from foods such as milk, cream, butter, cheese, eggs, beef dripping, offal and other meats....

Tools and Targets of Gene Therapy

Ada Deficiency Symptoms

The liver is a very important focus of gene therapy because it controls many bodily functions and because it can regenerate. A gene therapy that corrects just 5 of the 10 trillion cells of the liver could produce an effect. For example, a liver gene therapy targets heart disease. Normal liver cells have low-density lipoprotein (LDL) receptors on their surfaces, which bind cholesterol in the bloodstream and bring it into the cell. When liver cells lack LDL receptors, cholesterol accumulates on artery interiors. Liver cells genetically altered to have more LDL receptors can relieve the cholesterol buildup. Such gene therapy could be lifesaving for children who have inherited familial hypercholesterolemia (see fig. 24.7). familial hypercholesterolemia

Fenugreek Seed And Leaf

In Indonesia, fenugreek is used to promote hair growth. In India, Southeast Asia, and Ethiopia, the seeds are soaked in water (the seeds swell because they are coated with mucilage) and are then drained and eaten to aid digestion, as a laxative, to treat bronchitis, and to cure sore throats. It is used to prevent sharp rises in blood sugar and to lower cholesterol.

Clinical Terms Related to the Cardiovascular System

A variety of inherited and environmental factors contribute to causing cardiovascular disease. Many cases are probably due to a fatty diet and sedentary lifestyle, against a backdrop of genetic predisposition. Disorders of the heart and blood vessels caused by single genes are very rare, but understanding how they arise can provide insights that are useful in developing treatments for more prevalent forms of disease. For example, widely-used cholesterol lowering drugs called statins were developed based on analyzing the molecular malfunction behind the one-in-a-million inherited condition familial hypercholesterolemia. Low-density lipoprotein (LDL) receptors on liver cells admit cholesterol into the cells, keeping the lipid from building up in the bloodstream and occluding arteries. When LDL receptors bind cholesterol, they activate a negative feedback system that temporarily halts the cell's production of cholesterol. In the severe form of familial hypercholesterolemia, a person...

Apolipoprotein E APOE

Specifically, reduction in cellular cholesterol availability results in significant changes in APP trafficking and processing, with the resultant reduction in Ab formation (Runz et a ., 2002). In addition, patients who have taken statins for hypercholester-olemia appear to have a reduced incidence of Alzheimer's disease (Fassbender et a ., 2001 Jick et a ., 2000 Wolozin et a ., 2000).

Significant Interactions

X-v cholesterol-lowering medication Policosanol 941 Considering the mode of action of policosanol, it is likely to increase the cholesterol-lowering effects of statin drugs. However, a theoretical concern exists as to whether concurrent use will also increase the likelihood of adverse effects.

Increased Physical Activity

Increased physical activity improves cardiorespira-tory fitness, with or without weight loss. The latter improves the quality of life in overweight patients by improving mood, self-esteem, and physical function in daily activities. Physical activity reduces elevated levels of CVD risk factors, including blood pressure and triglycerides, increases HDL cholesterol, and improves glucose tolerance with or without weight loss. Furthermore, the more active an individual is, the lower the risk for CVD morbidity and mortality, and diabetes. Physical activity apparently has a favorable effect on distribution of body fat. Several studies showed an inverse association between energy expenditure through physical activity and several indicators of body fat distribution. Only a few randomized controlled trials that have tested the effect of physical activity on weight loss measured waist circumference. In some (but not all) studies, physical activity was found to produce only modest weight loss and...

Typical vs Atypical Ischemia

Once we consider it more likely than not that this patient had ischemic disease, the question of whether it was typical or atypical is somewhat more difficult to ascertain. First, it is necessary to define these two terms. Typical ischemic heart disease is generally considered secondary to coronary atherosclerosis, with atherosclerotic plaque (s) narrowing the lumen and causing damage to the coronary artery wall. The presence of atherosclerosis may increase the possibility of superimposed coronary artery lesions including acute plaque hemorrhage or rupture, luminal thrombosis, and or coronary artery spasm. The presence of atherosclerosis does not provide information concerning the pathogenesis of the plaque, whether it is idiopathic but associated with cigarette smoking, hypercholesterolemia, hypertension, or diabetes mellitus (or combinations of all of these), or whether it may be secondary to less common risk factors such as hyperhomocysteinemia, cocaine use, or radiotherapy (chest...

Monogenic disorders causing impaired reverse cholesterol transport

Low HDL cholesterol is a common finding in patients with premature CHD and usually precedes clinically apparent CHD (Goldbourt et al., 1997). Low HDL concentrations are most frequently associated with the components of the metabolic syndrome X and are rarely due to single-gene disorders (Durrington, 2003). The rare Tangier disease, characterized by very low or even Conversely, cholesterol ester transfer protein deficiency, which is a common cause for high HDL concentrations (> 2.5 mmol l) in Japan is thought to be a state of impaired reverse cholesterol transport, which may lead to premature CHD (Nagano et al., 2002). Thus, HDL cholesterol levels, efflux of cellular lipids as well as the kinetics of HDL metabolism are important determinants of the antiatherogenic effect of HDL (Tall, 1998 von Eckardstein, 2001).

Warfarin Resistance and Unstable INRS

It is less common for medicines to inhibit the action of warfarin than to potentiate it. Common drugs which inhibit warfarin action are barbiturates, rifampin, and nafcillin. Patients on these medications may require 20 mg of warfarin per day to maintain a therapeutic INR. Since most drug-warfarin interactions are mediated through induction of liver enzymes, it may take several days for the warfarin resistance to be noticed after starting the drug and several days for the effect to wear off after stopping the drug. Cholestyramine uniquely interferes with warfarin absorption.

Gh Treatment Of Patients With Abdominal Obesity

We have learned that GH can improve several of the aberrations that occur both in GH deficiency and Syndrome X. Thus, in GH-deficient adults the lipolytic effects of GH results in a preferential reduction in visceral adipose tissue (66). Furthermore, GH reduces the diastolic blood pressure (103), reduces total cholesterol, LDL-cholesterol (57,104-106), and increases HDL-cholesterol concentrations (78,105,107). Furthermore, long-term GH treatment does not impair insulin sensitivity (82). With this background we have studied the effects of GH on the metabolic, circulatory, and anthropodometric aberrations associated with abdominal visceral obesity and Syndrome X (108).

Present Role Of Laboratory Animals

The atherosclerotic lesion mouse contributes to progress in the fight against atherosclerosis and related illnesses. Apo E3 transgenic mice express the human dysfunctional apo E variant of the apoli-poprotein. The Apo E3 transgenic mouse develops hyperlipidemia and atherosclerosis on a high fat high cholesterol diet. Plasma cholesterol levels in the apo E3 mice increase in 4 months, and they develop atherosclerotic lesions in their aortas. Because these lesions resemble those in human patients with atherosclerosis, the apo E3 mouse is a valuable animal model for studies on the genetics, development, and therapy of atherosclerosis.13

Mutations Affecting Membrane Proteins Cause Diseases

Amino acids, sugars, lipids, urate, anions, cations, water, and vitamins across the plasma membrane. Mutations in genes encoding proteins in other membranes can also have harmful consequences. For example, mutations in genes encoding mitochondrial membrane proteins involved in oxidative phosphorylation can cause neurologic and other problems (eg, Leber's hereditary optic neuropathy LHON). Membrane proteins can also be affected by conditions other than mutations. Formation of autoantibodies to the acetyl-choline receptor in skeletal muscle causes myasthenia gravis. Ischemia can quickly affect the integrity of various ion channels in membranes. Abnormalities of membrane constituents other than proteins can also be harmful. With regard to lipids, excess of cholesterol (eg, in familial hypercholesterolemia), of lysophospho-lipid (eg, after bites by certain snakes, whose venom contains phospholipases), or of glycosphingolipids (eg, in a sphingolipidosis) can all affect membrane function....

Diabetes

Although no clinical studies are available, three in vivo studies suggest that andrographis exerts significant dose-dependent hypoglycaemic activity comparable to that of metformin (Borhanuddin et al 1994, Zhang & Tan 2000a, b). A 49.8 reduction in fasting serum triglyceride levels was also achieved with andrographis treatment compared with 27.7 with metformin however, neither treatment affected cholesterol levels. A more recent animal trial also concluded that andrographolide (1.5 mg kg) lowers plasma glucose by enhancing glucose utilisation in diabetic rats (Yu et al 2003).

Lipidlowering

The role of carnitine in fatty acid metabolism suggests a potential role in hyperlipidaemia. Several studies have indicated that oral l-carnitine significantly reduces lipoprotein-a levels however, effects on other lipids are inconsistent, l-Carnitine (2 g day) significantly reduced serum lipoprotein-a levels in 77.8 of subjects receiving active treatment after 12 weeks, according to one placebo-controlled, double-blind randomised study. No significant change was observed in other lipid parameters (Sirtori et al 2000). l-Carnitine (2 g day) was also shown to significantly lower lipoprotein-a levels at 3 and 6 months in a double-blind placebo-controlled trial of 94 hypercholesterolemic patients with newly diagnosed type 2 diabetes (Derosa et al 2003). In a trial of children with hyperlipidaemia, lipoprotein-a levels were only reduced in those with type II homozygotes and other lipid parameters worsened (Gunes et al 2005). l-Carnitine has also been shown to decrease apolipoprotein B...

Hyperlipidaemia

The ability of chitosan to form complexes with various fats, including cholesterol, provides a theoretical basis for its use in hyperlipidaemia. Dietary chitosan has been tested and found to be effective in reducing serum cholesterol levels and atherosclerosis in normal and diabetic mice, and therefore has been investigated in the treatment of hypercholesterolemia in humans (Muzzarelli 1999). A 2002 review states that in humans, dietary chitosan reduces serum total cholesterol levels by 5.8-42.6 and LDL levels by 15.1-35.1 (Ylitalo et al 2002). Based on these figures, the effects of chitosan range from mild to moderate and appear to be inconsistent for total cholesterol. More specifically, lowering of LDL-cholesterol is more consistent, whereas little effect is seen on plasma triglyceride concentration, according to several different experimental and human studies involving obese or diabetic subjects or people with mild to moderate hypercholesterolemia (Bokura & Kobayashi 2003, Tai...

Kidney Failure

One open study of 80 patients with renal failure undergoing haemodialysis found that 1350 mg of chitosan taken three times daily effectively reduced total serum cholesterol levels (from 10.14 4.40 mmol Lto 5.82 2.19 mmol L)and increased serum haemoglobin levels (from 58.2 12.1 g L to 68 9.0 g L) (Jing et al 1997). After 4 weeks, significant reductions in serum urea and creatinine levels were observed. After 12 weeks, patients reported subjective improvements, such as feeling physically stronger, increased appetite and improved sleep, which were also significantly greater than the placebo group. Importantly, during the treatment period, no clinically problematic symptoms were observed.

Risk and Inaction

Decisions in favour of inaction are much less visible. We notice being injected rather than not being injected, an offender being given parole rather than refused. We notice, and tend to register the fact of change, more than we do continuity. But harm can arise from inaction, just as readily as from action. And, at least in theory, there can be legal liability for inaction as readily as for action. The patient, who does not receive medication because the decision was not to take the risk, may experience loss. If that decision, not to risk, was professionally improper then the patient is entitled to complain and receive compensation. But people do not notice negligent omissions as readily as they do negligent commissions. And we do not recognise, as readily, the decisions that were not even mooted, as we do those that were discussed even though not acted upon. I know what my doctor did last time I had an appointment with him. I recall a decision about cholesterol levels. But I do not...

Clinical Summary

The patient's medical history was significant for hypertension, hypercholesterolemia and severe coronary artery disease (80-90 stenosis of left anterior descending coronary artery and 50-60 occlusion of right coronary artery). Eight months prior to her death, the patient underwent percutaneous transluminal coronary angioplasty (PTCA) of the left anterior descending coronary artery (LAD). Four months later, because of post-angioplasty re-stenosis, she underwent coronary artery bypass graft (CABG) using the left internal mammary artery to the LAD (Figure 3).

Diagnosis

Both the lack of a formal definition and uncertainty about the pathogenesis and possible long-term consequences, leads to a continuing discussion about appropriate guidelines for the assessment and management of HIV lipodystrophy syndrome and its metabolic abnormalities. Outside clinical studies, the diagnosis relies principally on the occurrence of apparent clinical signs and the patient reporting them. A standardized data collection form may assist in diagnosis (Grinspoon 2005). This appears sufficient for the routine clinical assessment, especially when the body habitus changes develop rather rapidly and severely. For clinical investigations however, especially in epidemiological and interventional studies, more reliable measurements are required. But so far, no technique has demonstrated sufficient sensitivity, specificity or predictive value to definitively diagnose the HIV lipodystrophy syndrome by comparison with results obtained from a normal population. A recent multicentre...

Hypolipidaemic

An ex-vivo study found that 250 g day of a standardised ginger extract significantly reduced plasma LDL-cholesterol levels, the LDL basal oxidative state, as well as LDL-cholesterol and serum cholesterol's susceptibility to oxidation and aggregation, compared with placebo. Ginger also reduced aortic atherosclerotic lesions by 44 in atherosclerotic mouse aorta (Fuhrman et al 2000).

Syndrome

Elevations of triglycerides and low levels of high-density < lipoprotein (HDL) are common in overweight obese patients. They are especially common when patients have other risk factors of the metabolic syndrome (4-6). 5 ATP III classification of serum triglycerides is shown in Table 8. In patients with atherogenic dyslipidemia (triglyceride > 150 mg dL, small LDL particles, and low HDL cholesterol (< 40 mg dL) , a three-part ther- I

Cholesterollowering

Cholesterol reduction has been demonstrated for silymarin in two studies of rats fed a high cholesterol diet (Krecman et al 1998, Sobolova et al 2006). Although the mechanism of action is unknown, it has been suggested that inhibition of HMG-CoA reductase is involved (Skottova & Krecman 1998a) and inhibition of cholesterol absorption from dietary sources (Sobolova et al 2006). Considering that the herb also contains phytosterols, these too may play a role in cholesterol reduction.

Prevention

Prevention of cardiovascular events is based on the reduction of known risk factors. In recent years, an association between antiretroviral drugs and lipid concentrations, i.e. hypercholesterolemia and hypertriglyceridemia, has been reported (Stocker 1998, Sullivan 1997). The degree of lipid alteration differs between the types and doses of antiretroviral medication. Protease inhibitors (PIs) in particular, are able to increase lipid concentrations. In addition to hyperlipidemia, insulin resistance has also been described in association with PIs (Behrens 1999, Noor 2001). Prevention of coronary heart disease is based on the guidelines for non-HIV-infected patients. (De Backer 2003 Table 1). Diet is the first step in the therapy of hypercholesterolemia. The second step relies on lipid lowering drugs (Dube 2003). Good results were observed using a combination of statin (Atorvastatin 10 mg d) and fibrate (Gemfibrozil 600 mg bid) (Henry 1998). However, an increased risk of rhabdomyolysis...

Dyslipoproteinemia

A common finding in both GH deficiency and Syndrome X is high levels of serum triglycerides and low HDL-cholesterol concentrations. This may be associated with their increased abdominal adiposity (75) and insulin resistance (67,68,76). However, although a dramatic reduction in visceral adipose tissue occurs in response to GH treatment, serum triglyceride concentration is not reduced (66,75,77) and the concentration of HDL-cholesterol is increased (77,78). The lipolytic action of GH treatment probably increases the flux of FFA to the liver (79) and increases the synthesis and secretion of VLDL from the liver. The LPL activity in adipose tissue is attenuated (80) and the post-heparin plasma LPL is not affected by GH treatment (81). As serum triglyceride concentrations do not increase under conditions of increased VLDL secretion the peripheral catabolism must be enhanced. Increased LPL activity in other tissues such as muscle is therefore likely (81). Furthermore, the strong association...

Dyslipidemia

The role of dyslipidemia in atherosclerosis has been clearly established. Both elevated LDL-cholesterol and reduced HDL-C are risk factors for atherosclerosis. This dyslipidemia has been shown to be related to bone mass and bone fragility and might represent a common underlying factor for both osteoporosis and atherosclerotic disease (Yamagushi et al., 2002). In a study of 214 postmenopausal Japanese women, plasma LDL-cholesterol levels were inversely correlated with bone mineral density at the forearm and the lumbar spine (Yamagushi et al., 2002). In this study, plasma HDL-C was positively correlated with BMD at the lumbar spine and at the forearm. Triglyceride (TG) predicted the presence of vertebral fractures in this cohort of post-menopausal women. This indicates that dyslipidemia is common to both atherosclerosis and osteoporosis. Consistent with these findings, the administration of high-fat

Pharmacologic Agents

Agents that commonly are used for prevention and treatment of osteoporosis and CVD such as bisphos-phonates and statins have beneficial effects on both the bone and the vascular wall. That is not surprising given the common pathway and site of actions for each of these agents (McFarlane et al., 2002). Statins (3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors) commonly are used for treatment of dyslipidemia. These agents lower cholesterol by production and enhance LDL clearance. In addition, statins also reduce cellular isoprenoid intermediates, leading to decreased isoprenyla-tion and decreased activity of small GTP binding proteins from the Ras Rho family (McFarlane et al., 2002). Bisphosphonates act one step downstream from the site of action of statins on the mevalonate pathway (McFarlane et al., 2002), which is involved in the regulation of Ras Rho proteins. It is suggested that the inhibition of protein prenylation might be responsible for the antiresorptive...

Lipids

Phytosterols are important structural components of plant membranes and stabilize phospholipid bilay-ers in plant cell membranes. Moreau et al. (2002) and Piironen et al. (2000) have recently reviewed phytos-terols in foods and their health promoting properties. Phytosterols have received increased attention in the last 10 years because of their cholesterol-lowering properties. The primary interest in tomato phytos-terols has focused on ripening related events involving phospholipids and their catabolism mediated by phospholipase D (Whitaker et al. 2001 Pinhero et al. 2003). Transformation of tomato with an antisense phospholipase D cDNA construct reduced phospholipase D activity 30 to 40 and resulted in firmer fruit with enhanced lycopene content, vitamin C, and flavor (Oke et al. 2003). Juice and sauce prepared from the transgenic fruit exhibited increased viscosity and levels of major flavor volatiles. Increased membrane stability due to decreased phospholipase D activity may...

Cardiovascular

Several studies also have demonstrated that depression is independently associated with a substantial increase in the risk of heart failure, particularly among women (Abramson et al., 2001 Powell et al., 2005 Williams et al., 2002). Depression had a significant negative effect on health status, including heart failure symptoms, physical and role function, and quality of life in a six-month prospective cohort study (Sullivan et al., 2004). Higher rates of relapse of depression were reported among patients using cholesterol-lowering medications compared to those who were not (Steffens et al., 2003).

Diabetes Assessment

Clinically, overt diabetic symptoms include polyuria, polydypsia, and weight loss. One easy pheno-typing assay is monitoring for glucose in the urine. This test should be performed weekly on at-risk mice. Many other phenotyping procedures and tests have been adapted for evaluating diabetic mouse models. It is beyond the scope of this chapter to discuss all of them. Current procedures available to study diabetic models include urinary glucose and ketones, plasma glucose, lactate, ketones, serum lipids (triglycerides, nonesterified fatty acids, total and HDL cholesterol), plasma insulin, leptin, and corticos-terone, assessment of insulin secretion and sensitivity, and glucose disposal by IVGTT with minimal model analysis, measurement of other circulating hormones, including C-peptide, glucagon, GLP-1 (active and total), pancreatic polypeptide, thyroxine and TSH, renal function parameters urinary albumin excretion, serum creatinine and blood urea nitrogen, in vitro adipocyte metabolism...

Myopathy

Polymyositis mediated by cytotoxic T cells is the most common HIV-associated myopathy. AZT-induced myopathy occurs very infrequently with the AZT dosages used today. Some substances commonly used in HIV medicine (DDI, co-trimoxazole, pentamidine, sulfadiazine, lipid lowering drugs) may rarely cause acute rhabdomyolysis with tetraparesis and marked elevation of serum CK levels. Notably, PIs raise the serum concentration of statins increasing the risk of statin-induced myopathy and rhabdomyolysis (Hare 2002).

Syndrome X

Syndrome X, also known as metabolic syndrome or insulin resistance syndrome, is a highly prevalent condition that significantly increases the risk of coronary heart disease and is associated with elevated triglycerides, low HDL-cholesterol, and LDL-cholesterol. As niacin raises HDL-cholesterol, lowers triglycerides and increases LDL-cholesterol particle size, it may be considered a useful therapeutic option for the treatment of dyslipidaemia in such cases (Ito 2004). The potential for niacin to induce insulin resistance, however, may affect its use in practice.

Rabbits

Lesions primarily in the aorta, and their development is associated with extraordinarily high plasma cholesterol levels (in the 1000-3000 mg dl range), which can compromise other organ systems in ways that affect the experimental utility of this model. Disease of epicardial coronary vessels is rarely described, and though some features of human atheroma are present in the aortic lesions in rabbits, the prominent human concern of plaque instability is not a feature.

Ure 247

Incomplete dominance appears in the plasma cholesterol levels of heterozygotes and homozygotes for familial hypercholesterolemia FH . This condition is one of many that increase the cholesterol level in the blood, raising the risk of developing heart disease. The photograph shows cholesterol deposits on the elbow of young man who is a homozygote for the disease-causing allele.

Risk Factors

There are several different risk factors for ischemic stroke including genetic factors, aging, hypertension, hypercholesterolemia, diabetes mellitus, atrial fibrillation, coagulation disorders, and smoking. Hypercholesterolemia Whether hypercholesterolemia, a major risk factor for coronary heart disease, is associated with stroke is controversial and remains a matter of debate. Elevated levels of circulating cholesterol cause deposits to form inside blood vessels. When the deposits become sufficiently large, they block blood vessels and decrease the flow of blood. These deposits are part of a disease process called atherosclerosis, which can cause blood clots to form that will ultimately stop blood flow. Data from a clinical study, which enrolled healthy men without vascular disease, suggest that patients in the highest quartile of total cholesterol to high-density lipoprotein ratio have an increased risk of stroke (Bowman et al., 2003). There was no evidence of increased risk in...

Clinical Aspects

Ized by the deposition of cholesterol and cholesteryl ester from the plasma lipoproteins into the artery wall. Diseases in which prolonged elevated levels of VLDL, IDL, chylomicron remnants, or LDL occur in the blood (eg, diabetes mellitus, lipid nephrosis, hypothy-roidism, and other conditions of hyperlipidemia) are often accompanied by premature or more severe atherosclerosis. There is also an inverse relationship between HDL (HDL2) concentrations and coronary heart disease, and some consider that the most predictive relationship is the LDL HDL cholesterol ratio. This is consistent with the function of HDL in reverse cholesterol transport. Susceptibility to atherosclerosis varies widely among species, and humans are one of the few in which the disease can be induced by diets high in cholesterol. The reason for the cholesterol-lowering effect of polyunsaturated fatty acids is still not fully understood. It is clear, however, that one of the mechanisms involved is the up-regulation of...

Figure 1221

Ischemic heart disease is defined as the imbalance between the supply and demand of the heart for oxygenated blood. The most common cause of ischemic heart disease is atherosclerosis. In atherosclerosis, the lumina of the coronary arteries progressively narrow because of accumulation oifibrofatty intimal plaques (see Fig. 12.10). Plaques are formed by lipid deposition, smooth muscle proliferation, and increased synthesis of proteoglycans and collagen within the intima. Blood flow becomes critical when it is reduced by 90 . A sudden occlusion of the narrowed lumen by a thrombus, or clot, released from the surface of an atheromatous plaque precipitates an acute ischemic event. Ischemic events are characterized by anginal pain associated with the loss of oxygenated blood to the region of the heart supplied by the affected coronary vessel. Coronary artery thrombosis usually precedes and precipitates a myocardial infarct, i.e., a sudden insufficiency of blood supply that results in an area...

Hypertension

The first meta-analysis was of 31 placebo-controlled trials involving 1356 subjects and detected a statistically significant dose-response effect on blood pressure when studies were grouped by omega-3 fatty acid dose -1.3 -0.7 mmHg at doses < 3 g day, -2.9 -1.6 mmHg at 3.3-7 g day, and -8.1 -5.8 mmHg at 15 g day (Morris et al 1993). The hypotensive effect was strongest in hypertensive subjects and those with clinically evident atherosclerotic disease or hypercholesterolemia, whereas no effect was detected in healthy subjects.

Lower Your Cholesterol In Just 33 Days

Lower Your Cholesterol In Just 33 Days

Discover secrets, myths, truths, lies and strategies for dealing effectively with cholesterol, now and forever! Uncover techniques, remedies and alternative for lowering your cholesterol quickly and significantly in just ONE MONTH! Find insights into the screenings, meanings and numbers involved in lowering cholesterol and the implications, consideration it has for your lifestyle and future!

Get My Free Ebook