By Kathleen Doheny
WebMD Health News
Adding an experimental biologic drug to a course of statin drugs can help lower LDL “bad” cholesterol even more, according to new research.
“These drugs actually start where statins finish,” says Evan Stein, MD, PhD, director of the Metabolic & Atherosclerosis Research Center in Cincinnati.
Known as REGN727/SAR236553, the drug is a monoclonal antibody, a type of biologic. A biologic is created through a biological process instead of chemically synthesized.
Stein compared the effects of taking Lipitor (atorvastatin) along with either injections of the new monoclonal antibody or a placebo injection. He tested it in patients who still had high LDL levels despite taking a starting dose of Lipitor for at least seven weeks.
The study was funded by Sanofi and Regeneron Pharmaceuticals, which make the new biologic. It is published in the New England Journal of Medicine.
Although the results look promising, long-term studies are still needed, says Raymond J. Gibbons, MD. Gibbons is professor of medicine at Mayo Clinic, in Rochester, Minn. He was not involved in the study.
Statins can help lower cholesterol in many people, Stein says. But they don’t work well for everyone.
“About 10% to 20% of patients cannot tolerate statins or high enough doses to get [their cholesterol] under control,” he says.
LDL levels below 100 milligrams per deciliter are recommended for people with established heart disease. Those at highest risk should aim for levels under 70.
The new drug inhibits a protein called PCSK9. In the process, it allows for the removal of LDL from the blood.
Stein’s team studied the new drug in 92 patients. Their average age was in the mid- to late-50s. All had LDL levels above 100 even after taking 10 milligrams of Lipitor for at least seven weeks.
He assigned patients to one of three groups for eight weeks:80 milligrams of Lipitor daily, plus injections of the new drug every two weeks10 milligrams of Lipitor a day, plus injections of the new drug every two weeks80 milligrams of Lipitor daily, plus placebo injections every two weeks.
“It’s a little injection in the abdomen, under the skin,” Stein says.
The researchers followed the patients for eight more weeks.
All those who got the new biologic lowered their cholesterol below 100.
But only 52% of those who got 80 milligrams of Lipitor but placebo injections lowered their LDL below 100.
“More than nine out of 10 of those who got the new drug lowered their LDL to below 70, regardless of whether the statin dose was 10 or 80 milligrams,” Stein says.
Only 17% of those who got the higher dose of Lipitor and placebo injections reduced their LDL levels below 70.
The side effects were similar among the three groups. Some patients reported headache, dizziness, diarrhea, or other gastrointestinal problems or musculoskeletal problems.
However, Stein says, the study was fairly short term, “especially for drugs that will likely be taken life-long.” And larger studies are needed.
He says it is too early to estimate the cost of the new drug.
He reports consulting fees from Amgen, Adnexus Therapeutics, Genentech, Regeneron, and Sanofi related to PCSK9 inhibitors. His institution has received research funds directly related to PCSK9 clinical trials and lab analysis from Alnylam, Amgen, BMS, Genentech, Sanofi, and Regeneron.
Long-term data are needed and critical for further understanding, Gibbons says.
The need to inject the drug may not appeal to some patients, he says. “The inconvenience would be a barrier to many patients, particularly to those who don’t have their own transportation.”
Researchers need to examine whether the new drug results in fewer heart attacks and strokes.
Sanofi and Regeneron Pharmaceuticals are recruiting people for additional studies.
Amgen and other companies are also developing PCSK9 protein inhibitor drugs.SOURCES: Evan Stein, MD, PhD, director, Metabolic and Atherosclerosis Research Center; professor of pathology and laboratory medicine, University of Cincinnati. Roth, E. New England Journal of Medicine, Nov. 15, 2012. Raymond J. Gibbons, MD, Arthur M. and Gladys D. Gray professor of medicine, Mayo Clinic, Rochester, Minn.
For overweight people with diabetes, intensive exercise and dieting not only aids weight loss, it can also help train their fat cells to produce a hormone believed to boost production of “good” cholesterol, according to a new study.
And this so-called “good” cholesterol, or HDL cholesterol, has been linked to positive effects for cardiovascular health.
The new study, from researchers at The Methodist Hospital in Houston, included data on overweight and obese people with type 2 diabetes who were taking part in a multicenter clinical trial examining how increased physical activity and reduced calorie intake affected their risk for cardiovascular disease.
The participants were randomly assigned to either an intensive diet and exercise program (the “lifestyle intervention” group) or a program that offered only diabetes support and education and no lifestyle changes (the “control” group).
After one year, the lifestyle intervention group had achieved significant improvements in a measure of total fat called “adiposity,” fitness, blood sugar levels and fat levels, the investigators found.
In addition, while levels of “bad” LDL cholesterol did not change, levels of the fat hormone adiponectin and HDL cholesterol did increase: Total adiponectin produced by fat cells increased about 12 percent and HDL cholesterol increased nearly 10 percent in the people who made lifestyle changes, compared to those in the control group, the research showed.
It’s well established that adiponectin plays a role in fat burning and sugar storage. This study suggests that the hormone also encourages the liver to produce HDL cholesterol, the study authors pointed out in a hospital news release.
“What we’re learning is that even overweight people who are physically active and eating a healthy diet are getting benefits from the lifestyle change,” principal investigator Dr. Christie Ballantyne, director of the Center for Cardiovascular Disease Prevention, part of the Methodist DeBakey Heart and Vascular Center at The Methodist Hospital in Houston, said in the news release.
“When you exercise and diet, you’re improving the function of your adipose tissue, your heart and vascular systems, and even muscle performance. You’re getting a lot of benefits that you may not see by just looking at the weight on a scale,” he added.
The study was released online in advance of publication in an upcoming print issue of the Journal of Lipid Research.
By Denise Mann
WebMD Health News
Cholesterol levels are dropping among U.S. adults, new research shows.
That’s a good thing, as high levels of total cholesterol and LDL (“bad”) cholesterol are risk factors for heart disease.
From 1988 to 2010, average levels of total cholesterol, LDL, and blood fats called triglycerides fell for all groups of U.S. adults. Levels of HDL (“good”) cholesterol started to rise during this time frame.
Heart disease risk is based on more than just your cholesterol profile, says CDC researcher Margaret D. Carroll, MSPH. High blood pressure, obesity, and smoking also play a role.
“We show that one risk factor may be decreasing and we will have to see what happens,” Carroll says. “Hopefully, progress will be made with the other risk factors as well.”
Carroll’s study doesn’t show why cholesterol levels dropped. The change may be due, at least in part, to the growing numbers of U.S. adults who take cholesterol-lowering medications such as statins.
From 1988 to 1994, 3.4% of adults took a statin. This percentage jumped to 15.5% in 2007-2010.
“Statins dramatically reduce LDL levels and reduce risk of heart attack and stroke, and people live longer,” says cardiologist Holly Andersen, MD, director of education and outreach for the Perelman Heart Institute at New York-Presbyterian Hospital/Weill Cornell Medical Center.
Yet, a drop in cholesterol levels was also seen in adults not taking statins or other drugs to lower cholesterol. This suggests there may be other things going on, such as efforts to remove trans fats from our diets.
According to the new study:Average levels of total cholesterol fell from 206 milligrams per deciliter of blood (mg/dL) in 1988-1994 to 196 mg/dL in 2007-2010.Average LDL dropped from 129 mg/dL in 1988-1994 to 116 mg/dL during 2007-2010.Average triglyceride levels increased from 118 mg/dL in 1988-1994 to 123 mg/dL in 1999-2002, and then declined in 2007-2010 to 110 mg/dL.
According to the American Heart Association, total cholesterol should be less than 200 mg/dL of blood, and optimal LDL should be less than 100 mg/dL. Triglycerides, too, should be less than 100 mg/dL, and HDL should be 60 mg/dL or above for optimal heart health.
These positive cholesterol trends have already started to make a dent in rates of heart disease, says Steven Nissen, MD. He is the chair of cardiovascular medicine at the Cleveland Clinic in Ohio.
“We know that the single best predictor of heart disease is cholesterol levels, and they have been going down,” Nissen says.
“Levels of LDL cholesterol have declined substantially, and along with that decline, we are seeing a reduction in age-related heart disease,” he says. Rates of heart disease have declined steadily since the 1960s, according to the CDC.
“This is a good news story, but there are storm clouds on the horizon,” Nissen says. Soaring rates of obesity and diabetes threaten to overshadow this progress.
“The most likely and plausible explanation is that the decline in cholesterol is due to the more extensive use of medication in the at-risk population,” he says. “We are not moving more or getting lighter, and this didn’t happen by accident.”
The new study serves to back up some of these points. There was not a decrease in how much cholesterol-raising saturated fat U.S. adults ate as a percentage of their daily calories, and there was little progress made in boosting physical activity among adults.
The health message is clear and applies to all adults. “Know your LDL,” he says. “If it is above the optimal level, ask your doctor if you have a high enough risk to warrant treatment.”
By Denise Mann
TUESDAY, Sept. 4 (HealthDay News) — Boosting vitamin D with supplements may not improve blood cholesterol levels among people who have low vitamin D levels, a new study suggests.
In the small new study of people who were deficient in vitamin D, those who received 50,000 international units (IU) of vitamin D3 for eight weeks did not show any improvements in their cholesterol profile when compared to their counterparts who received a placebo.
Those who took vitamin D showed a decrease in levels of parathyroid hormone and increases in calcium levels. These changes corresponded with an increase in low-density lipoprotein or “bad” cholesterol levels, the study showed.
“Correcting a vitamin D deficiency with oral vitamin D supplements does not improve cholesterol levels in the short term,” said study author Dr. Manish Ponda, assistant professor of clinical investigation in the laboratory of biochemical genetics and metabolism at Rockefeller University in New York City. “This is not the definitive answer on vitamin D and cholesterol, though it is an important step toward determining how they are related.”
Participants’ vitamin D levels roughly tripled as a result of taking these mega-doses.
The study findings appear Sept. 4 in the journal Arteriosclerosis, Thrombosis and Vascular Biology.
Vitamin D is known as the “sunshine vitamin” because humans make it in response to the sun’s rays. In recent years, vitamin D deficiency has been linked to heart disease, certain cancers, osteoporosis and diabetes, among other conditions. Vitamin D is added to milk and other foods, and is found in fatty fish, beef, liver, cheese and egg yolks, but supplements are often needed. The Institute of Medicine recently raised the recommended daily intake to 600 IU for people aged 1 to 70 and 800 IU for adults older than 70. Other groups set the bar even higher.
The new findings “pose a strong challenge to a causal role for vitamin D deficiency in high cholesterol levels,” Ponda said. Still, he said, it could be that vitamin D from other sources, namely ultraviolet light, may have beneficial effects on blood cholesterol levels.
“It is possible that oral vitamin D, compared to vitamin D made in the skin in response to sunlight or ultraviolet light, would affect cholesterol levels in different ways,” he said. Ponda and colleagues are conducting a study comparing the effect of oral vitamin D to ultraviolet light exposure on cholesterol levels to see if the source makes any difference.
Dr. Michael Holick, professor of medicine, physiology and biophysics at Boston University School of Medicine, said the findings should not be interpreted to say vitamin D is not beneficial for heart health.
“We knew that the supplements did not affect cholesterol levels,” he said. “Vitamin D’s effect on reducing risk of cardiovascular disease is much more fundamental. There is a lot of data related to vitamin D and cardiovascular health, but this relationship is not necessarily mediated through cholesterol.”
By Alan Mozes
FRIDAY, Aug. 24 (HealthDay News) — The millions of adults who currently use prescription statins to control their cholesterol levels may be inadvertently increasing their risk for developing age-related cataracts, new research suggests.
The bump in cataract risk linked to statin use appears comparable to the elevated risk already known to exist among people with type 2 diabetes, the study team observed.
That said, the study authors cautioned that more research is needed before being able to definitively say there is a cause-and-effect relationship between statins and cataract risk.
“The bottom line is that there appears to be an increased risk among people taking statins as far as getting cataracts,” said study lead author Elizabeth Irving, research chairwoman in the School of Optometry and Vision Science at the University of Waterloo in Ontario, Canada. “That was actually a surprise, because most of the previous literature had suggested the opposite. However, it doesn’t mean that one is causing the other.”
“I would also say we are not now suggesting that statin patients do anything except follow their doctor’s advice with respect to statins,” Irving added. “They’re taking statins for a reason. If you’re going to have a heart attack or get cataracts, what would you choose?”
Irving and her colleagues discuss their findings in the August issue of the journal Optometry and Vision Science.
The authors noted that previous animal research has already pointed to a possible link between high-dosage statin use and a bump in the risk for cataracts, which are characterized by a significant clouding of the eyes’ lenses.
To explore the potential link between statins and eye health in humans, the investigators focused on nearly 6,400 cataract patients who were being treated at the University of Waterloo between 2007 and 2008.
Of those patients, more than 450 had type 2 diabetes, and both diabetes status and statin use were looked at possible risk factors for cataracts.
After accounting for factors such as gender, cigarette use and high blood pressure, the team found that statin use was associated with a 57 percent increased risk for developing cataracts.
Statin users were more likely to develop cataracts at a younger age, the study found. For patients without diabetes, the average age for which the odds of developing cataracts were at least 50 percent was 57.3 years for those not using statins compared with 54.9 years for those taking statins. Patients with diabetes had the same cataract risk at 55.1 years if not using statins and 51.7 years if taking them.
Some overlap existed between diabetes and statin use, the team noted, with 56 percent of the diabetic cataract patients regularly taking statins. The authors pointed out that patients with diabetes who also took statins were found to have developed cataracts a full 5.6 years earlier than those who neither had diabetes nor took statins.
Yet the team nevertheless determined that statin use appeared to be, by itself, an independent risk factor for cataracts.
“Again, we don’t think these findings should turn the world upside down,” Irving stressed. “However, we do think that it once again shows that it’s good to think about what drugs do to the people who take them, and that the people who make drugs might want to consider making better drugs than statins, given the possibility that they do raise the risk for cataracts.”
Dr. Alfred Sommer, professor of ophthalmology and dean emeritus of the Bloomberg School of Public Health at Johns Hopkins University in Baltimore, strongly suggested that statin users should “not be alarmed” by the current findings.
“It’s not to put down this kind of exploratory study, but this simply doesn’t prove anything. This only suggests that there may be some association between the two,” he noted. “For now, statins are really the most important way we have to prevent heart attacks. We don’t have any alternatives at this point, so this is really just a teaser for more research. Nobody should change what they’re doing.”
MONDAY, Nov. 5 (HealthDay News) — An experimental drug may help patients who can’t tolerate statins lower their cholesterol, a new Australian study suggests.
The 12-week, phase 2 clinical trial was conducted at 33 international sites and included adults who suffered muscle problems when taking statins, a class of cholesterol-lowering drugs that includes Crestor and Lipitor. They received injections of a placebo or different doses of AMG145, which is a human monoclonal antibody.
Human monoclonal antibodies are naturally occurring human antibodies that are genetically altered in a laboratory, cloned in large numbers and introduced into the patient to target disease sites.
The patients who received AMG145 had 41 percent to 63 percent reductions in “bad” (LDL) cholesterol and did not experience significant muscle-related side effects, said study leader Dr. David Sullivan, of the Royal Prince Alfred Hospital in Australia, and colleagues.
The reductions in LDL cholesterol seen in these patients were comparable to those that occur in patients taking the highest doses of the most effective statins, the researchers added.
One expert found the results intriguing.
“The most interesting aspect of this study is use of a novel approach using monoclonal antibodies — a subtype of antibodies — in the management of elevated LDL cholesterol,” said Dr. Kenneth Ong, acting chief of cardiology at the Brooklyn Hospital Center.
“In this phase 2 study, the results are certainly impressive and warrant further investigation,” Ong said. “Of note is the reduction in the number of myalgias (muscle pains) for patients compared to the number of myalgias experienced by people taking statins. If larger trials and longer durations of observation confirm these initial findings, many patients whose LDL cholesterol are otherwise untreated or under-treated could benefit.”
Another expert agreed.
“For those patients with elevated LDL who are intolerant to statins, this provides a viable option,” said Dr. Suzanne Steinbaum, a preventive cardiologist at Lenox Hill Hospital in New York City. More trials need to be done of this unique treatment, she added.
The study was published online Nov. 5 in the Journal of the American Medical Association, to coincide with a planned presentation at the American Heart Association’s annual meeting in Los Angeles.
Cholesterol Screenings Are Up, Some Groups At Risk
Sept. 6, 2012 — The number of adults who say they have had high cholesterol at some point in their lives has gone up, and that may not be a bad thing, according to the CDC.
A new survey of adults nationwide suggests that they are learning the importance of checking their cholesterol. This awareness, not new cases, is likely the reason the numbers have gone up, the report’s authors write.
This may well be true. In a CDC report published earlier this year, researchers found that the overall level of high cholesterol among adults over 20 had dropped from 18% to 13% between 2000 and 2010.
High cholesterol is a major risk factor for heart attack and stroke.
The report drew on data from the Behavior Risk Factor Surveillance System (BRFSS), a telephone survey conducted by the CDC. More than 350,000 American adults take the survey each year. Questions about cholesterol are asked every two years.
In 2005, 72.7% of U.S. adults over 18 said they had had their cholesterol checked at least once in the previous five years. By 2009, that percentage had risen to 76%.
Among those who had been tested in 2005, a third of them reported being told they had high cholesterol at some point in their lives. Four years later, in 2009, 35% said their cholesterol was high or had been so in the past.84.5% of Washington, D.C., adults said they had been tested for high cholesterol, compared to 67.7% of Idaho adults.Most states showed a big rise in testing between 2005 and 2009. Eastern states had generally higher rates of testing than Western states.94.7% of adults 65 and older said they had been tested, compared to 63.2% of adults ages 18 to 44.54.4% of adults 65 and older said they currently had or had had high cholesterol, compared to 23.7% of adults ages 18 to 44.More men reported high cholesterol than women: 37.5% vs. 32.6%.More Hispanics and Asian/Pacific Islanders reported high cholesterol than other groups (36.3% and 37.5%, respectively) — 33.1% of African-Americans said they had or had had high cholesterol.New Mexico, at 30.5%, had the lowest percentage of adults reporting high cholesterol. Texas, at 38.8%, had the highest. About a third of all states showed an increasing number of adults who reported high cholesterol.
Finding high blood cholesterol early through testing is the first important step to treatment and lowering the risk for heart attack and stroke, the report’s authors write.
Public health experts, medical experts, and health educators should emphasize cholesterol testing, especially for young adults, men, Hispanics, and those with lower levels of education, they write.SOURCE: Morbidity and Mortality Weekly Report, Sept. 7, 2012.
(HealthDay News) — Risk factors for high cholesterol include things you can’t control, such as age, gender and family history. But lifestyle choices — factors you can control — are a big part of the equation, too.
The Cleveland Clinic says controllable risk factors for high cholesterol include:Whether your diet is high in saturated fat and cholesterol.Whether you’re overweight/obese.Whether you’re getting enough regular exercise.Whether you have emotional stress and turn to unhealthy habits to help manage that stress.
By Brenda Goodman, MA
WebMD Health News
Nov. 12, 2012 — The requirement to fast before a cholesterol check can be a major inconvenience.
People who forget to fast may be told to reschedule their appointments. For those who remember, sitting in a doctor’s waiting room with a growling stomach can make for a rough start to the day.
Now a large new study shows that cholesterol levels aren’t radically different in people who ate compared to those who fasted before their blood was drawn.
The study, which is published in the Archives of Internal Medicine, suggests that people may not need to fast before they get a cholesterol test.
Experts who were not involved in the research called the results an eye-opener.
“This information is actually very, very interesting. It might change how we approach a patient,” says Suzanne Steinbaum, DO, a preventive cardiologist at Lenox Hill Hospital in New York City.
For the study, researchers looked at the results of all the cholesterol tests processed at the same lab during a six-month stretch in 2011. Because the lab does all the testing for the entire city of Calgary, Canada, that amounted to test results for more than 200,000 people. Doctors also recorded how long it had been since the patient had last eaten.
When researchers broke down the results by fasting time, they found little change. Overall, total cholesterol and HDL “good” cholesterol varied by less than 2%, depending on when a person had last eaten. Total cholesterol and HDL are important because they are the main measures used to calculate a person’s risk for heart-related events.
LDL “bad” cholesterol was less than 10% different in people who’d recently eaten compared to those who had been fasting for at least eight hours.
Triglycerides, or blood fats, were the most sensitive to food. They varied by no more than 20% between people who had fasted and those who had not.
Because the study is just a snapshot in time, it has important limitations. It doesn’t prove that cholesterol levels don’t change significantly before and after a meal for individual patients.
Researchers say the small differences noted in the study may matter for some, including those who are taking specific medications to lower their cholesterol or triglycerides. Those patients may still need fasting tests.
But for many others, eating may not make a difference.
“For routine screening, we’re suggesting that a 2% variance probably isn’t going to be significant,” says Christopher Naugler, MD, MSc, chief of clinical pathology at the University of Calgary, Canada.
Other experts agree.
“I think we’ve just taken for granted that we should do fasting for lipid testing,” says Samia Mora, MD, a preventive cardiologist at Brigham and Women’s Hospital, in Boston.
Mora wrote a commentary on the study, but was not involved in the research.
She says the requirement to fast before a cholesterol test was based on very small studies where researchers fed subjects very high-fat or high-sugar meals.
“Most people aren’t having big fat loads before they get their lipids measured,” she says.
Currently, guidelines still recommend that people not eat before a cholesterol test. But Mora says a growing body of evidence suggests that fasting isn’t necessary.
“We’ve had several studies now that have all found the same thing,” she says.
By Charlene Laino
WebMD Health News
Nov. 5, 2012 (Los Angeles) — An IV infusion of “good” HDL cholesterol seems to rapidly remove cholesterol out of plaque-clogged arteries following a heart attack, a small, early study suggests.
The goal of the new treatment is to reduce the high risk of a second heart attack in people who have had a heart attack.
In the year after a heart attack, about 12% of people have a second heart attack or stroke. And half of them happen in the first month, says researcher Andreas Gille, MD, PhD. Gille is head of clinical and translational science strategy at CSL Limited (which funded the study) in Parkville, Australia.
Standard heart attack medications, such as aspirin and anti-clotting drugs, prevent clotting but don’t eliminate an underlying factor: cholesterol that has built up on artery walls, he says.
HDL removes cholesterol from artery walls, but current HDL-boosting drugs, such as niacin and fibrates, take years to work, according to Gille.
Gille and colleagues tested CSL112, an infusible and natural human formulation of apolipoprotein A-1 (ApoA-1), in 57 healthy volunteers.
ApoA-1 is the key protein in HDL particles that transports cholesterol from arteries and other tissues into the liver for disposal. Think of it as a garbage truck: It picks up the debris and disposes of it at the dump.
Following a single infusion of CSL112, researchers looked for signs of cholesterol movement. Over the next two hours:Cholesterol removal from cells rose 164%.Levels of ApoA-1 doubled. In contrast, levels of ApoA-1 only rise about 3% in the four weeks after niacin is given, Gille says.
There were no serious side effects.
Robert Eckel, MD, of the University of Colorado Health Sciences Center, says the strategy “is potentially useful. The question is, how important is it to address HDL levels quickly vs. treating them long-term.
“We still don’t know enough about HDL to know how to modify it to best benefit patients,” Eckel says.
The findings were presented here at the American Heart Association’s Scientific Sessions 2012.
The next step is a larger study in which CSL112 will be given as a short series of weekly IV infusions shortly following a heart attack or heart-related chest pain.
These findings were presented at a medical conference. They should be considered preliminary, as they have not yet undergone the “peer review” process, in which outside experts scrutinize the data prior to publication in a medical journal.SOURCES: American Heart Association Scientific Sessions 2012, Los Angeles, Nov. 3-7, 2012. Andreas Gille, MD, PhD, head, clinical and translational science strategy, CSL Limited, Parkville, Australia. Robert Eckel, MD, University of Colorado Health Sciences Center.