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A Statin Affects Cholesterol Levels By

Muscle Pain And Weakness

Statins and Cholesterol

The most common side effect is muscle pain and weakness, a condition called rhabdomyolysis, most likely due to the depletion of Co-Q10, a nutrient that supports muscle function. Dr. Beatrice Golomb of San Diego, California is currently conducting a series of studies on statin side effects. The industry insists that only 2-3 percent of patients get muscle aches and cramps but in one study, Golomb found that 98 percent of patients taking Lipitor and one-third of the patients taking Mevachor suffered from muscle problems.4 A message board devoted to Lipitor at forum.ditonline.com contained more than 800 posts, many detailing severe side effects. The Lipitor board at www.rxlist.com contains more than 2,600 posts .

The test for muscle wasting or rhabdomyolysis is elevated levels of a chemical called creatine kinase . But many people experience pain and fatigue even though they have normal CK levels.5

John Altrocchi took Mevacor for three years without side effects; then he developed calf pain so severe he could hardly walk. He also experienced episodes of temporary memory loss.

Active people are much more likely to develop problems from statin use than those who are sedentary. In a study carried out in Austria, only six out of 22 athletes with familial hypercholesterolemia were able to endure statin treatment.9 The others discontinued treatment because of muscle pain.

Indirect Evidence For The Existence Of Lipid

In a post hoc analysis of the WOSCOPS trial, investigators found, by comparing event rates in two subgroups of individuals whose on-treatment LDL cholesterol levels were in the same range independent of receiving either pravastatin or placebo, that event rates for the two subgroups differed markedly. Subjects treated with pravastatin had a 36% lower risk

Indirect evidence for the existence of a lipid-independent effect of statins on endothelial function in humans is suggested by a study comparing peripheral endothelial function, as measured as flow-mediated brachial arterial dilation , in a group of 23 men with CHD without lipid-lowering medication with that in 22 age- and blood pressure-matched CHD patients with similar lipid levels despite ongoing statin therapy. In this study, FMD of the brachial artery was significantly higher in patients receiving statins than in those without any treatment. Moreover, multivariate regression analysis revealed statin use as the only significant predictor of FMD.

Because of its well-defined mechanism and the fact that a similar effect has not been observed with simple lipid lowering, the increase in the number and functional activity of EPCs found with atorvastatin therapy in patients with CHD represents additional indirect evidence for the existence of non-lipid statin effects in humans.

Muscle Pain And Weakness Is A Side Effect Of Statins

Myopathies, or muscle symptoms such as weakness and pain, are another side effect of statins.

Myopathies range from mild myalgias, or muscle pains, to a life-threatening condition known as rhabdomyolysis. The most common myopathy associated with statin use, myalgia, only occurs in about 1 out of every 1,000 patients taking statins.

The chance of experiencing this statin side effect increases as you get older, with higher doses and while taking certain other medications. These symptoms will usually appear within four months of initiating statin therapy.

Rhabdomyolysis, another myopathy that can occur with statin use, is extremely rare and deadly if not properly treated. It occurs in one person out of 10,000 individuals taking statins.

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Effect On Endothelial Function

Lipid-independent effects of statins on NO and ET-1 synthesis in the endothelial cell. Statins increase endothelial NO synthesis by stabilizing eNOS-mRNA, which results in an increase in eNOS protein, and by promoting eNOS activation via Akt-mediated phosphorylation. Furthermore, statins decrease transcription of prepro ET-1 mRNA resulting in a reduction of endothelial ET-1 production. In addition, NO negatively regulates prepro ET-1 mRNA transcription and, thus, contributes to a decrease in ET-1 production. On the other hand, ET-1 may stimulate NO synthesis via activation of endothelial ETBreceptors. Akt, serine/threonine kinase that activates eNOS by phosphorylation; eNOS, endothelial nitric oxide synthase; NO, nitric oxide; ET-1, endothelin-1; ETB, endothelin type B receptor.

How Statins Act As Cholesterol Lowering Drugs

Statins: A cholesterol cure

Statins are one of the important cholesterol lowering drugs that occupy key role in therapy for high cholesterol. All these drugs are identified by the suffix -statin and drugs in this category mainly include simvastatin, lovastatin, atorvastatin, rosuvastatin and pravastatin. The main goal of all these statins is to lower serum cholesterol levels.

How it can be achieved?

Well, first of all lets see how cholesterol is distributed within the body by various mechanisms and how statins stand as cholesterol lowering drugs by acting on any of these pathways.

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So Are Statins Worth It

It depends on who you are, what your cardiovascular risk is, and the possible benefits.

At a population level, this is something known as the number needed to treat . Or, to put it another way, how many people have to take statins to prevent one heart attack?

For people with a low risk for cardiovascular disease, 217 people would have to take a statin to prevent one non-fatal heart attack. So 217 is the NNT. But when you look at people with a high risk for cardiovascular disease, only 39 people have to take a statin to prevent one non-fatal heart attack. So the NNT for high-risk people is much lower than for low-risk people.

The higher your risk of cardiovascular disease, the more the benefits of statins outweigh the risks of side effects.

The professional guidelines and the online risk estimator go a long way toward identifying people who should take a statin. But each person is unique. The information here should be a starting point for discussion rather than a final answer. Talk with your healthcare provider to make a decision on whether you should take a statin.

How Statin Drugs Protect The Heart

More than 200 million people around the world take statin drugs for theirheart health. Shifting ideas about the risks and benefits of statins overthe years, however, have left some new patients confused about whetherthese drugs are rightor safefor them.;

Traditionally, statins were viewed as purely;cholesterol-lowering;drugs. So it made sense just to use them for people with high cholesterol, explains Johns Hopkins cardiologist;Michael Blaha, M.D.But weve learned that they also benefit people with lower levels of cholesterol who are at a high risk of heart disease. So we now think of statins as;risk-reducing;drugs.

This dramatic change in thinking means that people who once were;not;candidates for statins are now prescribed them to lower their risk of heart attack and stroke.

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Are There Any Food Or Drinks I Should Avoid

Some foods affect the way your liver can process the statin, increasing the risk of side effects. Grapefruit is a common food that has this effect with some statins. Doctors generally recommend that you eat no more than half a grapefruit or drink no more than a 200ml glass of grapefruit juice each day if you are taking some statins. Check with your pharmacist if this applies to the statin you are taking.Statins;can affect your liver, so you should avoid;regularly drinking large quantities of alcohol while taking them. This can increase your risk of muscle problems.

Effect Of Mipomersen On Clinical Outcomes

Statins Impact on CoQ10 Levels

There are no clinical outcome trials but it is presumed that lowering LDL-C levels in patients with Homozygous Familial Hypercholesterolemia will reduce cardiovascular events. In a study comparing cardiovascular events in patients with Homozygous Familial Hypercholesterolemia in the 24 months prior to initiating mipomersen therapy and after initiating mipomersen revealed a decrease in events . In this trial mipomersen resulted in a mean absolute reduction in LDL-C of 70 mg/dL , non-HDL cholesterol of 74 mg/dL , and Lp of 11 mg/dL .

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List Of Statin Medications

The following tables list statins that are currently available in the United States. The majority of these drugs are available in generic versions. Generic drugs are typically less expensive than brand-name drugs. Theyre also more likely to be covered by health insurance plans.

All seven statins come in regular-release forms. This means that the drug is released into your bloodstream all at once. Two of the statins also come in extended-release forms, which are released into your bloodstream more slowly.

Statin

What Fibrates Are Available To Treat High Cholesterol Levels

Fibric acid derivatives

  • Increased bleeding time.

Adenosine triphosphate-citric lyase inhibitors

The FDA has approved bempedoic acid to lower cholesterol. Bempedoic acid works in the liver to slow down cholesterol production. The medication comes in 180-mg tablets taken once per day with or without food. It should be taken with statin medications, but there are dosage limitations if taken with simvastatin or pravastatin.

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Is There Any Difference Between The Different Statins

There are a few statins available in New Zealand atorvastatin , pravastatin , rosuvastatin and simvastatin . Rosuvastatin is not subsidized – you will need to pay for the cost of this medicine in full.; ;In New Zealand, atorvastatin is the preferred statin and is most widely used.;If;you have side effects with atorvastatin, your doctor may;consider lowering the dose or changing to another statin.

Effect Of Ezetimibe Therapy On Clinical Outcomes

Side Effects of Statin Cholesterol Medications on CoQ10 ...

There have been a limited number of ezetimibe clinical outcome trials. Two have studied the effect of ezetimibe in combination with a statin vs. placebo making it virtually impossible to determine if ezetimibe per se has beneficial effects. However, one study has compared ezetimibe plus a statin vs. a statin alone and one study compared ezetimibe vs. placebo.

SEAS TRIAL

SHARP TRIAL

The SHARP Trial was a randomized trial of 9,270 patients with chronic kidney disease with no known history of myocardial infarction or coronary revascularization . Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily vs. placebo. The primary outcome was first major atherosclerotic event . Treatment with simvastatin plus ezetimibe resulted in a decrease in LDL-C of 0·85 mmol/L . This decrease in LDL-C was associated with a 17% reduction in major atherosclerotic events. In patients on hemodialysis there was a 5% decrease in cardiovascular events that was not statistically significant. Unfortunately, similar to the SEAS Trial, it is impossible to determine whether the addition of ezetimibe improved outcomes above and beyond what would have occurred with statin treatment alone.

IMPROVE-IT TRIAL

EWTOPIA 75

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Potential Risks And Side Effects

People who take statins should avoid grapefruit. Grapefruit can interact with certain statins and make side effects worse. This is especially true with lovastatin and simvastatin. Be sure to read the warnings that come with your medications. If you have questions, talk to your doctor or pharmacist. You can also read more about grapefruit and statins.

Most people can take statins without too many side effects, but side effects can occur. Its hard to say if one type of statin will cause more side effects than another. If you have persistent side effects, your doctor may be able to adjust your dosage or recommend a different statin.

Some of the more common side effects of statins include:

  • constipation
  • diarrhea
  • nausea

These side effects are generally mild. However, statins can also cause more serious side effects. These include:

Why Dont Doctors Prescribe Pantethine Or Niacin

Well, the answer is, he may just not know about it. Unlike drugs companies that spend millions of dollars on advertising and have sales reps whose only job is to push their statin drug, Pantethine and Niacin are naturally occurring compounds.

Because they are natural and common compounds, nobody can patent them. Because a drug companies cannot patent and therefore have exclusive right to sell the compounds, no significant investment in marketing or education for Pantethine and Niacin has been made. Subsequently, your doctor may just not know.

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Effect On Bempedoic On Lipid And Lipoprotein Levels

EFFECT WITHOUT STATINS

In a study that randomized 345 patients with hypercholesterolemia .and a history of intolerance to statin to bempedoic acid or placebo bempedoic acid decreased LDL-C by 21.4%, non-HDL-C by 17.9%, and apolipoprotein B by 15% . One third of patients were on background non-statin therapy most commonly ezetimibe and fish oil. Triglyceride levels were not altered but there was a small decrease in HDL-C levels that was statistically significant .

IN COMBINATION WITH STATINS

Notably, the addition of bempedoic acid to atorvastatin 80mg per day was still capable of significantly decreasing LDL-C , non-HDL-C , and apolipoprotein B compared to placebo . The addition of bempedoic acid to high dose atorvastatin therapy did not cause meaningful changes in atorvastatin pharmacokinetics.

IN COMBINATION WITH STATIN AND EZETIMIBE

Biliary Secretion Of Cholesterol

Effects of Statin Therapy on Exercise Levels

This is recycling mechanism of cholesterol in between liver and intestine. Cholesterol can be secreted into bile which then empties into the intestine.

Here some of the cholesterol is excreted into faeces but major portion is reabsorbed again into the liver.

Okay, these are three pathways by which cholesterol is distributed within the body.

Now, where these statins act to lower cholesterol levels?

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How Statin May Impact Your Health Negatively

Apart from diabetes, statin is associated with various other health problems. However, the benefits of these drugs outweigh the risks, say experts. While there is no doubt about the efficacy of statins as cholesterol-lowering drugs, one needs to be aware of the side effects too.

Like every other drug, the most common side-effects of statins include headache, nausea and overall weakness. Muscle weakness or tendonitis may also be seen. Gastro-intestinal problems like constipation, diarrhea and vomiting can occur. Rare side-effects like memory loss, difficulty in concentrating, forgetfulness, amnesia and memory impairment have also been reported. For these rare side-effects, the symptoms may start one day to years after starting treatment and may resolve within a median of three weeks after stopping the statin.

Here we take you through some of the major health conditions linked to the use of statins.

What Are Statins And How Do They Work

“Statins” is a class of drugs that lowers the level of cholesterol in the blood by reducing the production of cholesterol by the liver. Statins block the enzyme in the liver that is responsible for making cholesterol. This enzyme is called hydroxy-methylglutaryl-coenzyme A reductase . Scientifically, statins are referred to as HMG-CoA reductase inhibitors.

Cholesterol is critical to the normal function of every cell in the body. However, it also contributes to the development of atherosclerosis, a condition in which cholesterol-containing plaques form within arteries. These plaques block the arteries and reduce the flow of blood to the tissues the arteries supply. When plaques rupture, a blood clot forms on the plaque, thereby further blocking the artery and reducing the flow of blood. When blood flow is reduced sufficiently in the arteries that supply blood to the heart, the result is angina or a heart attack. If reduced flow is caused by plaques in the arteries of the brain, the result is a stroke. If reduced flow is caused by plaques in the arteries of the leg, they cause intermittent claudication . By reducing the production of cholesterol, statins are able to slow the formation of new plaques and occasionally can reduce the size of plaques that already exist. In addition, through mechanisms that are not well understood, statins may also stabilize plaques and make them less prone to rupturing and develop clots.

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Mechanisms Accounting For Bile Acid Sequestrants Induced Lipid Effects

Bile acid sequestrants bind bile acids in the intestine, preventing their reabsorption in the terminal ileum leading to the increased fecal excretion of bile acids . This decrease in bile acid reabsorption reduces the size of the bile acid pool, which stimulates the conversion of cholesterol into bile acids in the liver . This increase in bile acid synthesis decreases hepatic cholesterol levels leading to the activation of SREBPs that up-regulate the expression of the enzymes required for the synthesis of cholesterol and the expression of LDL receptors . The increase in hepatic LDL receptors results in the increased clearance of LDL from the circulation leading to a decrease in serum LDL-C levels . Thus, similar to statins and ezetimibe, bile acids lower plasma LDL-C levels by decreasing hepatic cholesterol levels, which stimulates LDL receptor production and thereby accelerates the clearance of LDL from the blood.

The mechanism by which treatment with bile acid sequestrants improves glycemic control is unclear .

Mechanisms Accounting For The Ezetimibe Induced Lipid Effects

Antihyperlipidemic Drugs

NPC1L1 is highly expressed in the intestine with the greatest expression in the proximal jejunum, which is the major site of intestinal cholesterol absorption . Knock out animals deficient in NPC1L1 have been shown to have a decrease in intestinal cholesterol absorption . Ezetimibe binds to NPC1L1 and inhibits cholesterol absorption . In animals lacking NPC1L1, ezetimibe has no effect on intestinal cholesterol absorption, demonstrating that ezetimibeâs effect on cholesterol absorption is mediated via NPC1L1 . Thus, a major site of action of ezetimibe is to block the absorption of cholesterol by the intestine . Cholesterol in the intestinal lumen is derived from both dietary cholesterol and biliary cholesterol ; thus the majority is derived from the bile . As a consequence, even in patients that have very little cholesterol in their diet, ezetimibe will decrease cholesterol absorption. While ezetimibe is very effective in blocking intestinal cholesterol absorption it does not interfere with the absorption of triglycerides, fatty acids, bile acids, or fat-soluble vitamins including vitamin D and K.

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Can Natural Remedies Lower High Cholesterol Without Statins

Exercise on its own doesnt lower your LDL much often only a few points. Exercise helps minimize many heart disease risk factors, including obesity and Type 2 diabetes. Make a point to exercise five days a week for at least 30 minutes each day.Diet is incredibly important in managing your cholesterol.Every patient who comes to our preventive cardiology clinic for cholesterol management sees a nutritionist as part of the visit because we feel so strongly about the importance of diet. There are many patients for whom weve delayed prescribing statins, or suggested that they get off their medication if it isnt appropriate for their level of risk.Some patients think, Im on a statin I dont have to exercise, and I can eat whatever I want! But thats not the case. Lifestyle choices absolutely matter. For high-risk patients, its not a question of either improving the diet or getting on a medication, its both lifestyle changes and taking a statin together are necessary to protect high-risk patients against heart attack and stroke.If your cholesterol is borderline but not yet high, changing your diet and incorporating healthier food choices can help lower your cholesterol a decent amount. Eating more fiber and lowering your intake of saturated fat definitely can help. For people with relatively low risk, this may be enough to lower heart attack and stroke risk.;

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