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Ingle letter in human genome linked with elevated cholesterol levels identified

A group of researchers claims to have identified a single letter in the human genome that points to the risk for high cholesterol.

Led by Rockefeller University scientists, the consortium says that the letter they have identified is linked with elevated LDL cholesterol levels, one of the leading health concerns.

Research leader Jan L. Breslow, head of the Laboratory of Biochemical Genetics and Metabolism, says that this study brings a new level of understanding to an enzyme called HMGCR, the rate-limiting catalytic engine of cholesterol biosynthesis and the target of the much-revered cholesterol-lowering drugs known as statins.

For years, HMGCR has been known to play a key role in cholesterol metabolism. However, there was no evidence that common genetic variants existed in the gene that could affect how people metabolise cholesterol, an artery-clogging fat when produced (or consumed) in excess.

“In fact, HMGCR became the poster boy for how genes without common variation can still be good drug targets,” Science Daily quoted first author Ralph Burkhardt, a postdoctoral fellow in the Breslow lab, as saying.

The researchers have revealed that their current study builds upon ongoing research involving the inhabitants of the Micronesian island of Kosrae, who have a higher burden of risk factors associated with obesity and heart disease.

Burkhardt, Breslow and their colleagues took advantage of the growing power of genomic databases and genetic and biochemical techniques to show that a single letter difference, known as a single nucleotide polymorphism or SNP, in the HMGCR gene was linked to higher LDL cholesterol levels in the 4,947 people whose blood was analysed: a population of 2,346 Kosraeans and a European sample that was included for statistical power.

“At this point, nobody had an idea what biological effect this SNP would have. So we went on to look for a mechanism, one that could explain how this variant affects HMGCR expression and/or function,” says Burkhardt.

The researchers said that the literature already made it clear that people produce two forms of the HMGCR enzyme: a short form and a long one.

They said that their latest study had led to the discovery that the SNP in question modulates how much of each form each person produces, and that those with higher cholesterol levels produce more of the long form than the short one.

Relying on a process called alternative splicing, the researchers also showed that when the cell transcribes the HMGCR gene, it skips a region of it called exon 13, leading to the shorter enzyme.

They believe that this process ultimately reduces cholesterol production in the body.

“Genes that affect the synthesis, processing and breakdown of these lipoproteins are closely linked to heart disease. This research has helped us to better understand atherosclerosis susceptibility and its complex genetic basis,” says Burkhardt. (ANI)

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A new national study has shown that nearly 75 percent of patients hospitalized for a heart attack had cholesterol levels that would indicate they were not at high risk for a cardiovascular event, according to current national cholesterol guidelines.

Specifically, these patients had low-density lipoprotein (LDL) cholesterol levels that met current guidelines, and close to half had LDL levels classified in guidelines as optimal (less than 100 mg/dL).

“Almost 75 percent of heart attack patients fell within recommended targets for LDL cholesterol, demonstrating that the current guidelines may not be low enough to cut heart attack risk in most who could benefit,” said Dr. Gregg C. Fonarow, Eliot Corday Professor of Cardiovascular Medicine and Science at the David Geffen School of Medicine at UCLA and the study’s principal investigator.

While the risk of cardiovascular events increases substantially with LDL levels above 40–60 mg/dL, current national cholesterol guidelines consider LDL levels less than 100–130 mg/dL acceptable for many individuals. The guidelines are thus not effectively identifying the majority of individuals who will develop fatal and non-fatal cardiovascular events, according to the study’s authors.

Researchers also found that more than half of patients hospitalized for a heart attack had poor high-density lipoprotein (HDL) cholesterol levels, according to national guidelines.

Published in the January issue of the American Heart Journal, the study suggests that lowering guideline targets for LDL cholesterol for those at risk for cardiovascular disease, as well as developing better treatments to raise HDL cholesterol, may help reduce the number of patients hospitalized for heart attack in the future.

“The study gives us new insight and intervention ideas to help reduce the number of heart attacks,” said Fonarow, who is also director of the Ahmanson–UCLA Cardiomyopathy Center.

“This is one of the first studies to address lipid levels in patients hospitalized for a heart attack at hospitals across the entire country.”

The research team used a national database sponsored by the American Heart Association’s Get with the Guidelines program. The database includes information on patients hospitalized for cardiovascular disease at 541 hospitals across the country.

Researchers analyzed data from 136,905 patients hospitalized for a heart attack nationwide between 2000 and 2006 whose lipid levels upon hospital admission were documented. This accounted for 59 percent of total hospital admissions for heart attack at participating hospitals during the study period.

Among individuals without any prior cardiovascular disease or diabetes, 72.1 percent had admission LDL levels less than 130 mg/dL, which is the current LDL cholesterol target for this population. Thus, the vast majority of individuals having their first heart attack would not have been targeted for effective preventative treatments based on the criteria used in the current guidelines.

The team also found that half of the patients with a history of heart disease had LDL cholesterol levels lower than 100 mg/dL, and 17.6 percent of patients had LDL levels below 70 mg/dL, which are guideline targets for LDL cholesterol in those at fair risk and at high risk for cardiovascular disease, respectively.

The study also showed that HDL cholesterol, or “good cholesterol,” levels have dropped in patients hospitalized for heart attack over the past few years, possibly due to increasing rates of obesity, insulin resistance and diabetes.

Researchers found that 54.6 percent of patients had HDL levels below 40 mg/dL. Developing more effective treatments to boost HDL levels may help reduce the number of patients hospitalized for heart attacks, according to the authors.

“We found that less than 2 percent of heart attack patients had both ideal LDL and HDL cholesterol levels, so there is room for improvement,” said Fonarow.

Fonarow said that only 59 percent of patients in the database had their lipid levels checked upon admission, which should be increased, since these early measurements can often help guide treatment decisions.

He also noted that only 21 percent of patients in the study were taking lipid-lowering medications before admission, despite almost half having a prior history of cardiovascular events, which would prompt treatment.

The national cholesterol guidelines are set by the National Cholesterol Education Program, part of the National Heart, Lung and Blood Institute of the National Institutes of Health.

The study was sponsored by the Get with the Guidelines program, which is supported by the American Heart Association in part through an unrestricted education grant from the Merck Schering Plough Partnership.

Fonarow has conducted research for GlaxoSmithKline and Pfizer and serves a consultant and has received honorarium from Abbott, AstraZeneca, GlaxoSmithKline, Merck, Pfizer and Schering Plough companies. He is also chair of the Get with the Guidelines steering committee.

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People have to eat food in order to have energy to do certain things. Some are able to make three or four trips to the buffet table while others are satisfied after one round. In any case, the type of food brought to the plate could be healthy or harmful, and the choice is really up to the person.

Cholesterol

Those who love to eat red meat and other dishes that are fatty or oil are at risk of getting sick. This is not diarrhea but something worse which could be life threatening because of the amount of bad cholesterol that is being taken into the body.

The high levels of cholesterol in the body are happening more often now than ever before. This is because of the variety of food offered now in the Grocery and in restaurants. The person can still recover from this by eating foods that are not high in saturated fats.

Is there one food product that can be called the best to lower cholesterol?

The answer is no because a well balanced diet must come from all the food groups. Instead of drinking full cream milk or mixing this with corn flakes or whole grain, it is best to use non-fat milk instead. The taste is almost the same is much healthier than the regular brand bought in the supermarket.

Instead of having steak when having a cookout or picnic, this should be changed with lean meats instead. These things do not have that much fat in the center or at the edges and taste just as good as the big slab served with mash potatoes.

The healthier thing to have is food that comes from the ocean

This can be fish or shellfish that is known to carry Omega 3, which is very effective in lowering the levels of cholesterol in people.

Eating a candy bar or a slice of cake does not see so bad but these things are rich in fat. Those who need to fill the stomach with something should try nuts or fruits instead. These products are rich in fiber as well as have vitamins and minerals that are healthier to consume.

Must not forget to add some fruits in the plate

A salad works best or having a few carrots or potatoes as a side dish. Must there always be a balance whenever the individual decides to have meat or fish.

Chicken is not good if this is peaceful. Those who want to eat it for a change can still do as long as the skin has been removed. This can also be Steamed which is a healthier way of cooking it before this is served in a plate.

Many ways to cook the food

The individual can get a cookbook or download some recipes from the Internet to be able to come up with something delicious and at the same time lower one’s cholesterol levels.

If following the instructions are hard, there are always shows on television that teach home makers and other people the basics into something cooking fat free which is good for the diet.

It is never too late to make some lifestyle changes and in order to live a longer and healthier life.

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The new dietary advice is actually based on a rather old finding that predates the mantra to eat a low-fat diet. In the Seven Countries Study started in 1958 and first published in 1970, Dr. Ancel Keys of the University of Minnesota and co-authors found that heart disease was rare in the Mediterranean and Asian regions where vegetables, grains, fruits, beans and fish were the dietary mainstays. But in countries like Finland and the United States where plates were typically filled with red meat, cheese and other foods rich in saturated fats, heart disease and cardiac deaths were epidemic.

The finding resulted in the well-known advice to reduce dietary fat and especially saturated fats (those that are firm at room temperature), and to replace these harmful fats with unsaturated ones like vegetable oils. What was missed at the time and has now become increasingly apparent is that the heart-healthy Mediterranean diet is not really low in fat, but its main sources of fat — olive oil and oily fish as well as nuts, seeds and certain vegetables — help to prevent heart disease by improving cholesterol ratios and reducing inflammation.

Virtues Confirmed

It was not until 1999 that the value of a traditional Mediterranean diet was confirmed, when the Lyon Diet Heart Study compared the effects of a Mediterranean-style diet with one that the American Heart Association recommended for patients who had survived a first heart attack.

The study found that within four years, the Mediterranean approach reduced the rates of heart disease recurrence and cardiac death by 50 to 70 percent when compared with the heart association diet.

Several subsequent studies have confirmed the virtues of the Mediterranean approach. For example, a study among more than 3,000 men and women in Greece, published in 2004 by Dr. Christina Chrysohoou of the University of Athens, found that adhering to a Mediterranean diet improved six markers of inflammation and coagulation, including CRP, white blood cell count and fibrinogen.

The same year Kim T. B. Knoops, a nutritionist at Wageningen University in the Netherlands, and co-authors published a study showing that among men and women ages 70 to 90, those who followed a Mediterranean diet and other healthful practices, like not smoking, had a 50 percent lower rate of deaths from heart disease and all causes.

“The Mediterranean diet is one people can stick to,” said Dr. Ozner, author of “The Miami Mediterranean Diet” and “The Great American Heart Hoax” (BenBella, 2008). “The food is delicious, and the ingredients can be found in any grocery store.

“You should make most of the food yourself,” Dr. Ozner added. “When the diet is stripped of lots of processed foods, you ratchet down inflammation. Among my patients, the compliance rate — those who adopt the diet and stick with it — is greater than 90 percent.”

Among foods that help to reduce the inflammatory marker CRP are cold-water fish like salmon, tuna and mackerel; flax seed; walnuts; and canola oil and margarine based on canola oil. Fish oil capsules are also effective. Dr. Ozner recommends cooking with canola oil and using more expensive and aromatic olive oil for salads.

Other aspects of the Mediterranean diet — vegetables, fruits and red wine (or purple grape juice) — are helpful as well. Their antioxidant properties help prevent the formation of artery-damaging LDL cholesterol.

Other Steps

Several recent studies have linked periodontal disease to an increased risk of heart disease, most likely because gum disease causes low-grade chronic inflammation. So good dental hygiene, with regular periodontal cleanings, can help protect your heart as well as your teeth.

Reducing chronic stress is another important factor. The Interheart study, which examined the effects of stress in more than 27,000 people, found that stress more than doubled the risk of heart attacks.

Dr. Joel Okner, a cardiologist in Chicago, and Jeremy Clorfene, a cardiac psychologist, the authors of “The No Bull Book on Heart Disease” (Sterling, 2009), note that getting enough sleep improves the ability to manage stress.

Practicing the relaxation response once or twice a day by breathing deeply and rhythmically in a quiet place with eyes closed and muscles relaxed can help cool the hottest blood. Other techniques Dr. Ozner recommends include meditation, prayer, yoga, self-hypnosis, laughter, taking a midday nap, getting a dog or cat, taking up a hobby and exercising regularly.

He noted that in a 1996 study, just 15 minutes of exercise five days a week decreased the risk of cardiac death by 46 percent.

Even very brief bouts of exercise can be helpful. A British study published in the current American Journal of Clinical Nutrition found that accumulating short bouts — just three minutes each — of brisk walking for a total of 30 minutes a day improved several measures of cardiac risk as effectively as one continuous 30-minute session.

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If last week’s column convinced you that surgery may not be the best way to avoid a heart attack or sudden cardiac death, the next step is finding out what can work as well or better to protect your heart.

Many measures are probably familiar: not smoking, controlling cholesterol and blood pressure, exercising regularly and staying at a healthy weight. But some newer suggestions may surprise you.

It is not that the old advice, like eating a low-fat diet or exercising vigorously, was bad advice; it was based on the best available evidence of the time and can still be very helpful. But as researchers unravel the biochemical reasons for most heart attacks, the advice for avoiding them is changing.

And, you’ll be happy to know, the new suggestions for both diet and exercise are less rigid. The food is tasty, easy to prepare and relatively inexpensive, and you don’t have to sweat for an hour a day to reap the benefits of exercise.

The well-established risk factors for heart disease remain intact: high cholesterol, high blood pressure, smoking, diabetes, abdominal obesity and sedentary living. But behind them a relatively new factor has emerged that may be even more important as a cause of heart attacks than, say, high blood levels of artery-damaging cholesterol.

That factor is C-reactive protein, or CRP, a blood-borne marker of inflammation that, along with coagulation factors, is now increasingly recognized as the driving force behind clots that block blood flow to the heart. Yet patients are rarely tested for CRP, even if they already have heart problems.

Even in people with normal cholesterol, if CRP is elevated, the risk of heart attack is too, said Dr. Michael Ozner, medical director of the Cardiovascular Prevention Institute of South Florida. He thinks that when people have their cholesterol checked, they should also be tested for high-sensitivity CRP.

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Fearing that gorging on chocolate cake and juicy beef roast might send your blood cholesterol levels sky high? Well then here’s your ultimate saviour- synthetic high-density lipoprotein (HDL).Scientists at Northwestern University have designed synthetic HDL, the “good” cholesterol, which could help fight chronically high cholesterol levels and the resulting deadly heart disease.

The researchers have shown that their nanoparticle version of the is a promising new weapon to bind cholesterol irreversibly.

The synthetic HDL, based on gold nanoparticles, is similar in size to HDL and mimics HDL’s general surface composition.

“We have designed and built a cholesterol sponge. The synthetic HDL features the basics of what a great cholesterol drug should be,” said Chad A. Mirkin, George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences, who led the study with Shad Thaxton, M.D., assistant professor of urology in Northwestern’s Feinberg School of Medicine

He added: “Drugs that lower the bad cholesterol, LDL, are available, and you can lower LDL through your diet, but it is difficult to raise the good cholesterol, HDL. I’ve taken niacin to try and raise my HDL, but the side effects are bad so I stopped. We are hopeful that our synthetic HDL will one day help fill this gap in useful therapeutics.”

To create synthetic HDL the researchers started with a gold nanoparticle as the core, which was then layered on a lipid that attaches to the gold surface, followed by another lipid and last a protein, called APOA1.

APOA1 is the main protein component of naturally occurring HDL.

The final high-density lipoprotein nanoparticles are each about 18 nanometers in diameter, a size similar to natural HDL.

“Cholesterol is essential to our cells, but chronic excess can lead to dangerous plaque formation in our arteries. HDL transports cholesterol to the liver, which protects against atherosclerosis. Our hope is that, with further development, our synthetic form of HDL could be used to increase HDL levels and promote better health,” said Thaxton.

Mirkin said: “HDL is a natural nanoparticle, and we’ve successfully mimicked it. Gold is an ideal scaffolding material — it’s size and shape can be tailored, and it can be easily functionalized. Using gold nanoparticles, which are non-toxic, for synthetic HDL bodes well for the development of a new therapeutic.”

The scientists are now planning to further study the synthetic HDL in biologically relevant conditions and measure and evaluate the cholesterol-binding properties.

The study is published online by the Journal of the American Chemical Society (JACS).

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Some of the people were too scared to drink milk, as they thought that the milk is the main cause of high cholesterol. Well, if you’re one of them, then you should read on this article.

According to the report from the USDA, the milk doesn’t contain a very high amount of cholesterol and it contains the miracle substances that can be helped to inhibit cholesterol!

For your information, our liver will need to detoxify all the foods that we’ve eaten everyday. During the detoxification stage, there is a very complex process called “Liver Cholesterol Synthesis” will be taken place inside our liver and it will lead to the increasing of cholesterol in our blood!

By simply drinking milk, the milk whey acid that containing inside the milk will inhibit the liver cholesterol synthesis and hence, it will reduce the cholesterol level as well.

Furthermore, the medical research discovered that milk could also help to reduce the chances of getting coronary heart disease and high blood pressure!

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The FDA reaffirmed its position that elevated amounts of LDL are a risk factor for cardiovascular diseases such as heart attack, stroke, and sudden death and that lowering LDL cholesterol reduces the risk of these diseases.

The FDA’s comments stem from the agency’s review of data from ENHANCE (Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia) Preliminary results from ENHANCE had indicated there was no significant difference between patients in either group in the thickness of the walls of the carotid arteries, although there was greater lowering of the amount of LDL cholesterol in patients who took the combined medication.

The FDA has now completed its review of the final clinical trial report of ENHANCE. After two years of treatment, there was no significant difference in carotid artery thickness, but the levels of LDL cholesterol decreased by 56% in the combination group and decreased by 39% in the simvastatin alone group.

The final ENHANCE results have not changed the FDA’s position on the benefits of lowering LDL. Based on currently available data, says the agency, patients should not stop taking simvastatin/ezetimibe (Vytorin) or other cholesterol-lowering drugs and should talk to their doctor if they have any questions.

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