Statins: Good for the Heart, Maybe Not So Good for Diabetes

Steven Reinberg wrote . . . . . . . . .

Statins are proven to lower cholesterol, but they may also come with a downside for patients with diabetes: A new study finds they may make the blood sugar disease worse.

Researchers found that among those taking statins, 56% saw their diabetes progress, compared with 48% of those not taking statins. And the higher the dose of the statin, the faster the progression of the diabetes.

“This study should be a start to more research examining the balance of benefits and harms of statins in patients with diabetes,” said senior researcher Dr. Ishak Mansi. He is a professor in the Departments of Medicine and Data and Population Science at the University of Texas Southwestern in Dallas.

“We know well about the benefits of statins, but the harms are much less investigated,” Mansi said. “Specifically, what is the population that may benefit less from the use of statins for primary prevention or be harmed? Answering these questions impact hundreds of millions of patients and cannot be postponed.”

He cautioned that based solely on this one finding, no patient should stop taking their statins and that association does not prove causation.

For the study, Mansi and his colleagues collected data on more than 83,000 diabetic patients who used statins and more than 83,000 who didn’t.

Those who were taking statins were more likely to see their diabetes progress and need to start using insulin and other types of drugs to lower high blood sugar levels sooner than those who weren’t taking statins.

“The study may alert clinicians that they may need to pay close attention and expect to adjust anti-diabetes medications when they initiate statins,” Mansi said.

Dr. Joel Zonszein, an emeritus professor of medicine at the Albert Einstein College of Medicine in New York City, said that blood sugar is not the only key to managing type 2 diabetes.

“Management of type 2 diabetes is not centered on lowering blood sugars,” explained Zonszein, who wasn’t part of the study. “In addition to lifestyle changes, medications are often necessary to prevent or attenuate complications. Statins are highly effective in lowering cholesterol and protecting against heart attacks and strokes.”

Statins do not cause diabetes and the modestly increased rate in precipitating new-onset diabetes is well-known, though the exact mechanism remains unknown, he said.

“The benefits of statins in patients with type 2 diabetes are far greater than the potential side effects,” Zonszein added.

Millions of people have been treated with statins, and its widespread application has been a major public health advance, he noted.

Treatment of obesity, hypertension and high cholesterol is as important as improving glycemic control, Zonszein added, and statins are one of the best medications for these in patients with type 2 diabetes.

“When prescribing any medication, a careful balance between benefits and side effects is discussed between the health care provider and the patient,” Zonszein said. “In the case of statins, the benefits, particularly in patients with type 2 diabetes, are by far better than potential side effects.”

The report was published online in the journal JAMA Internal Medicine.

Source: HealthDay

Could a Type of Statin Raise Dementia Risks?

Amy Norton wrote . . . . . . . . .

Certain cholesterol-lowering drugs might speed dementia in some older adults whose memories are starting to fail, a small, preliminary study suggests.

The researchers found that of 300 older adults with mildly impaired thinking and memory, those using “lipophilic” statins were more likely to develop dementia over the next eight years.

Lipophilic statins include such widely used medications as simvastatin (Zocor), atorvastatin (Lipitor) and lovastatin (Altoprev).

They’re considered lipophilic because they are attracted to fat and can cross into many body tissues, including the brain. That’s in contrast to hydrophilic statins — like rosuvastatin (Crestor) and pravastatin (Pravachol) — which act mainly in the liver.

In this study, there was no link between those statins and increased dementia risk.

The findings do not prove that lipophilic statins directly raise dementia risk, experts cautioned. But they add to a conflicting body of evidence on statins and brain function.

“This adds another piece to a complicated puzzle,” said Dan Berlau, a professor of pharmacy at Regis University in Denver, who was not involved in the new investigation but studies memory and disorders of the brain.

He said that high cholesterol in middle-age is linked to a higher risk of dementia later on. As for whether taking statins might curb that risk, Berlau said, studies have mostly come to either of two conclusions: the drugs show no effect, or a protective one.

If statins are protective, one reason may be their cardiovascular benefits: They cut “bad” cholesterol and help prevent fatty plaques from clogging arteries that supply the brain.

But other types of cholesterol medications have not been tied to lower dementia risk, Berlau noted, which hints at something special about statins. Animal research has suggested the drugs might reduce Alzheimer’s-related “plaque” buildup or counter inflammation in the brain, for instance.

Yet there is also evidence tying statins to short-term problems with cognition (thinking and memory), Berlau noted. Some statin users have developed cognitive problems while taking the drugs — issues that go away when the medication is stopped. (Statin labels now carry a warning about that.)

It’s been theorized that in some people, lipophilic statins might lower cholesterol levels in the brain below the threshold needed for normal cognition.

According to Berlau, it’s difficult to know how to square that with large population studies showing a lower dementia risk among statin users, most of whom were on lipophilic medications.

This latest study dug deeper, said project leader Prasanna Padmanabham, of the molecular and medical pharmacology student research program at the University of California, Los Angeles (UCLA).

The researchers separated older adults into groups based on three factors: their initial cognitive status; initial cholesterol levels; and the type of statin they were using.

Of 303 participants with mild cognitive impairment, 200 had total cholesterol levels that were normal or near-normal. It turned out that lipophilic statins were linked to higher dementia risk only among those individuals.

In that group, 24% of lipophilic statin users developed dementia over the next eight years, versus 10% of people not using any statin and 11% of hydrophilic statin users.

In addition, brain scans revealed certain changes linked to dementia among lipophilic statin users, but not people on hydrophilic statins, the researchers said.

Padmanabham presented the findings at the annual meeting of the Society of Nuclear Medicine and Molecular Imaging, held online, and the findings were recently published in a supplement of the Journal of Nuclear Medicine.

No one should toss their statins based on these findings, cautioned senior researcher Dr. Dan Silverman, a professor of molecular and medical pharmacology at UCLA.

For one, he said, the elevated dementia risk was seen only in a select group of people.

And in general, the decision to use statins — and the choice of medication — depends on various factors, Silverman added.

Those factors include an individual’s personal risk of cardiovascular disease and whether there are any co-existing medical conditions, like kidney disease.

That said, if people with mild cognitive impairment and fairly low cholesterol levels are on a lipophilic statin, they might want to talk to their doctor about a switch, Silverman said.

Hydrophilic statins can help keep blood cholesterol in check, he noted, without crossing into the brain.

It’s not clear why lipophilic statins carried a higher dementia risk only among study participants with lower cholesterol. But it’s possible, Silverman said, that in those with higher cholesterol, the benefits of the medications outweighed any potential ill effects on the brain.

Berlau echoed the message that patients should not abandon their statins. “We have lots of evidence tying statins to a protective effect against dementia,” he noted.

And based on their well-established cardiovascular benefits, Berlau said, “I’d still recommend them.”

Source: HealthDay

Cholesterol Lowering Drugs – Statins – are Linked to Improved Gut Bacteria Composition in Obese People

The human gut microbiota consists of trillions of bacteria, fungi and virus constituting an inner chemical factory producing a multitude of microbial compounds affecting immunity, neurobiology and metabolism of the human host.

It has for long been known that imbalances in the composition of gut microbes link with a variety of chronic human disorders spanning from obesity, diabetes inflammatory bowel diseases to depression, schizophrenia, autism and Parkinson. In addition, it is known that unhealthy dieting and use of some medications, for instance stomach acid neutralizers, the so-called proton pump inhibitors, are associated with a further disruption of the microbial communities of the gut.

Now, in a new paper in the scientific journal Nature, The MetaCardis investigators explore gut bacteria in almost 900 individuals from Denmark, France and Germany.

The intestinal microbiota in obese individuals had previously been shown to differ from those in lean subjects with a poor bacterial diversity, a relative depletion of health promoting bacteria and the remaining bacteria dominated by an inflammatory tone.

In their Nature article, the researches now define a cluster of bacteria called Bact2 enterotype, which is found in 4% of lean and overweight people but in 18% of obese individuals who did not use statin drugs, a group of cholesterol lowering medications.

However, in other obese study participants who were treated with statins, the prevalence of the unhealthy Bact2 enterotype was significantly lower (6%) than in their non-treated counterparts (18%) – comparable to levels observed in non-obese participants (4%). The same trend was validated in a Flemish study sample of about 2000 participants.

Statins are commonly prescribed to reduce risk of developing cardiovascular diseases like myocardial infarction and stroke. It is estimated that more than 200 million people worldwide are prescribed statins. Besides their cholesterol-lowering effects, statins also tend to appease patients’ systemic inflammation levels which in part may be related to a disrupted gut microbiota.

The results suggest that statins could potentially modulate the disrupted gut microbiota and linked inflammation in obesity. Previous experiments in rodents have shown an impact of statins on bacterial growth, which might benefit non-inflammatory bacteria and underlie the anti-inflammatory effects of statin therapy. Obviously, clinically controlled human trials are needed to address whether statins mediate some of their anti-inflammatory effect via an improvement of the Bact2 enterotype of an aberrant gut microbiota.

Source: University of Copenhagen

Research Suggests Statins Could Lower Ovarian Cancer Risk

A genetic study has found evidence to suggest that women who take statins in the long term could be less likely to develop ovarian cancer, according to new research funded by Cancer Research UK published recently.

The same result was also found in women who carry the BRCA1/2 gene fault. Having the BRCA1/2 fault puts women at a higher risk of ovarian cancer than the general population.

The research published in JAMA studied genes and the extent to which they inhibit the enzyme HMG-CoA reductase – which is responsible for regulating cholesterol in the body – and is the exact enzyme targeted by statin drugs to reduce cholesterol.

While the study suggests that statins could lower ovarian cancer risk, more research needs to be done specifically looking at their use and impact on women’s risk of developing the disease.

The researchers based at the University of Bristol looked at 63,347 women between the ages of 20 and 100 years old, of whom 22,406 had ovarian cancer. They also looked at an additional 31,448 women who carried the BRCA1/2 fault, of whom 3,887 had ovarian cancer. The study used an approach called Mendelian randomization, which involves analysing the genetic data from thousands of people.

Statins may protect against the development of ovarian cancer because they’ve been shown to induce apoptosis – one of the body’s ways of getting rid of old, faulty or infected cells – and to stop tumours from growing in laboratory studies. Another line of thought is that statins lower circulating cholesterol, which helps regulate cell growth, though this research suggests that lower circulating cholesterol was not the method by which statins may reduce ovarian cancer risk.

The findings suggest that long-term statin use could be associated with an estimated 40% reduction in ovarian cancer risk in the general population, although the estimate comes from looking at gene variation rather than statins themselves, and the exact mechanism by which these genes are associated with lower ovarian cancer risk is unclear.

Ovarian cancer is the 6th most common cancer in women in the UK. There are around 7,400 cases each year, and out of those with a known stage at diagnosis, almost 6 in 10 are diagnosed at a late stage. Around 4,100 women die from the disease every year in the UK.

There is no test that reliably picks up ovarian cancer at an early stage, so chemoprevention could be an important approach to saving lives.

Professor Richard Martin, from the University of Bristol, said: “Our findings open up the possibility of repurposing a cheap drug to help prevent ovarian cancer – especially in women who are at a higher risk. It’s incredibly interesting that women whose bodies naturally inhibit the enzyme targeted by statins have a lower risk of ovarian cancer, but we don’t recommend anyone rushes to take statins specifically to reduce ovarian cancer risk because of this study.

“It’s a promising result and I hope it sparks more research and trials into statins to demonstrate conclusively whether or not there’s a benefit.”

Dr Rachel Orritt, Cancer Research UK’s health information manager, said: “This study is a great first step to finding out if statins could play a role in lowering ovarian cancer risk, and justifies future research into this area.

“But there’s not yet enough evidence to know if statins themselves could reduce the risk of developing ovarian cancer safely. And it’s important to remember that the risk of developing ovarian cancer depends on many things including age, genetics and environmental factors. Speak to your doctor first if you have any concerns about your risk.”

Source: EurekAlert!

Cholesterol Drugs Might Help Curb ‘High-Risk’ Prostate Cancers

Drugs that many men with prostate cancer might already be taking — cholesterol-lowering statins — may help extend their survival if they have a “high-risk” form of the disease, new research suggests.

High-risk patients include men with high blood levels of prostate specific antigen (PSA) and a “Gleason score” of 8 or more. Gleason scores are a calculation used to gauge prognosis in prostate cancer. Men with a high Gleason score may develop difficult-to-treat cancers.

Prior research had suggested that statins and the diabetes drug metformin (often prescribed together) have anticancer properties. However, it hasn’t been clear which of the two drugs is the bigger cancer-fighter, or whether either might help against high-risk prostate cancer.

To help answer those questions, a team led by Grace Lu-Yao of the Sidney Kimmel Cancer Center–Jefferson Health, in Philadelphia, tracked data on nearly 13,000 high-risk prostate cancer patients. All were diagnosed between 2007 and 2011.

The study couldn’t prove cause and effect, but it found that statins, taken alone or with metformin, did seem associated with an increase in survival.

Men who took both statins and metformin had higher median survival (3.9 years) than those who took statins alone (3.6 years), metformin alone (3.1 years), or those who did not take either drug (3.1 years).

The study was published in the journal Cancer Medicine.

“Both metformin and statins have been associated with longer life in prostate cancer patients, yet because they are commonly prescribed together, no study we know of has looked at these two medications separately,” Lu-Yao said in a center news release. She’s associate director of population science at the center.

“With respect to prostate mortality, metformin plus statin was associated with a 36% reduction in risk of death followed by statins alone,” Lu-Yao added.

The study also found that those who took one of three types of statin — atorvastatin, pravastatin or rosuvastatin — had longer survival than those who did not take any statins. A similar benefit was not seen with a fourth statin, lovastatin.

Because prostate cancer thrives on testosterone, patients often receive treatments that reduce levels of male hormones (androgens). The new study found that among patients who received such therapies, those who took atorvastatin had a longer median time to prostate cancer progression than those who didn’t take statins.

It’s not clear why such effects were limited to atorvastatin, Lu-Yao said, but it appears to have the best “bioavailability” of the statin drugs and lingers longest in the body.

The research team believes that, based on the existing evidence, a clinical trial should be conducted to assess the effectiveness of statins and the combination of statins/metformin in extending survival of prostate cancer patients.

Two prostate cancer specialists unconnected to the new study agreed that the findings show promise.

“It appears that there may be a place in the treatment of prostate cancer for statins,” said Dr. Elizabeth Kavaler, a urology specialist at Lenox Hill Hospital in New York City. “However, we are not yet at a point where we can use the data to direct patient care.”

She believes testosterone may be key here. According to Kavaler, higher cholesterol levels promote higher levels of androgens, which in turn help encourage the growth of prostate cancer. Statins may help slow that process, Kavaler explained.

Dr. Manish Vira is vice chair for urologic research at The Arthur Smith Institute for Urology in New Hyde Park, N.Y. He agreed that the findings are encouraging, and noted that “a dozen actively recruiting clinical trials using either metformin or a statin in prostate cancer treatment” are already underway.

Source: HealthDay