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How to monitor prostate cancer using active surveillance

If you’re among the one in three American adults with high blood pressure, be sure you’re getting plenty of the B vitamin known as folate. Doing so may lower your odds of having a stroke, an often disabling or deadly event linked to high blood pressure, a new study suggests.

Folate occurs naturally in many foods, but especially green leafy vegetables, beans, and citrus fruits. Here in the United States, add to the list most grain products, including wheat flour, cornmeal, pasta, and rice. They are fortified with the synthetic version of folate, known as folic acid.

That’s not the case in many countries around the world, including China, where the new study was done. Published online this week in the Journal of the American Medical Association, it included more than 20,000 adults in China with high blood pressure who had never had a stroke or heart attack. Participants who took folic acid supplements along with the blood-pressure lowering medicine enalapril (Vasotec) were less likely to have had a stroke over the 4½-year trial than those who took enalapril alone.

The cardiovascular benefits of folate have been known for decades. Studies begun in the 1970s (including Harvard’s Nurses’ Health Study and Health Professionals Follow-up Study) have shown that people who said they consumed more folate had fewer strokes and heart attacks than those who reported consuming less. Folate, along with other B vitamins, helps break down homocysteine, an amino acid that may damage the inner walls of arteries. Such damage can boost the risk of a stroke or heart attack.

However, clinical trials in the United States that compared people who took folic acid supplements with those who took placebos showed no benefit from taking folic acid supplements. One likely explanation is that supplements are most helpful for people who don’t get enough folate in their diets. Nearly a quarter of Americans fell into that category before 1998. But beginning that year, food companies were required to fortify grain products with folic acid. Within a year, the percentage of people with low folate levels dropped dramatically.

The Chinese study found that the stroke prevention benefit of folic acid was biggest in people with low baseline folate levels. Also, most of the earlier folate studies were done in people who’d already had a stroke or heart attack. Such people are likely already taking an array of medications to prevent another event, which could obscure any effect from the folate.

The new findings are most relevant for people in countries without folate fortification. Still, they’re a good reminder to take a close look at your diet to make sure you’re getting enough of this crucial nutrient.

“Fruits and vegetables are important sources of folate in the diet, and they also bring lots of other benefits, such as potassium and phytonutrients, that also help lower cardiovascular disease,” says Dr. Walter Willett, professor of epidemiology and nutrition at Harvard T.H. Chan School of Public Health who co-authored an editorial about the new study.

In the U.S., the average person gets about 100 to 150 micrograms (mcg) of folic acid a day from fortified grain products—roughly a quarter of the recommended daily intake of 400 mcg a day. Certain groups of people might fall a little short, however, such as those in the southwestern US who use the corn flour known as masa, which is not folate-fortified. People on gluten-free diets who don’t eat foods made with wheat flour might also be a little low in folate, says Dr. Willett.

Everyone—and especially those with high blood pressure—should eat a generous amount of fruits and vegetables every day, advises Dr. Willett. And to cover any gaps, “it still makes sense for most people to take a multivitamin, multimineral supplement every day,” he recommends. Is brain damage an inevitable consequence of American football, an avoidable risk of it, or neither? An editorial published yesterday in the medical journal BMJ poses those provocative questions.

Chad Asplund, director of sports medicine at Georgia Regents University, and Thomas Best, professor and chair of sports medicine at Ohio State University, offer an overview of the unresolved connection between playing football and chronic traumatic encephalopathy, a type of gradually worsening brain damage caused by repeated mild brain injuries or concussions.

This condition was first described in a football player in 2005, after University of Pittsburgh experts performed an autopsy on Pittsburgh Steelers center Mike Webster, whose life had taken a downward turn after his retirement from professional football. Since then, researchers have linked chronic traumatic encephalopathy to the wasting away of brain tissue, the buildup of brain proteins linked to dementia and Alzheimer’s disease, memory loss, depression, anger, and other behavioral and emotional problems.

So far, all cases of autopsy-proven chronic traumatic encephalopathy have been in players who sustained repeated blows to the head. That’s a fact of life for almost all professional football players. But some of those with the condition had never been diagnosed with a concussion. According to Asplund and Best, this suggests that a series of head injuries that don’t cause concussions may lead to chronic traumatic encephalopathy or be an important risk factor for it.

So here’s the big question: does playing football cause chronic traumatic encephalopathy, or are some people who play football already at higher risk for developing it? Repeated head injuries may, indeed, directly cause chronic traumatic encephalopathy. At the same time, it’s possible that the players who sustain brain injuries are genetically prone to them or to other factors that increase the likelihood of developing dementia, emotional or behavioral issues, or premature death.

It’s essential to answer the cause and effect question, in part because not knowing the answer has generated fear among players. San Francisco 49ers linebacker Chris Borland, one of the National Football League’s top rookies in 2014, recently announced his retirement from professional football because of his worries about the long-term effects of repetitive head injuries. In addition, some parents of even younger players, fearing the potential hazard from head injuries, are keeping their kids from playing football, soccer, and other sports.

The Football Players Health Study at Harvard University aims to provide some solid answers. Its organizers hope it will do for football what the Framingham Heart Study has done for heart health and the Nurses’ Health Study has done for nutrition.

The 10-year study, launched in 2013, aims to explore more than just head injuries. It includes a variety of medical conditions that affect football players’ quality of life and length of life. The study is funded by the National Football League Players Association. It has begun by recruiting former NFL players. Let’s hope that this study and other research on sport-related head injury and later brain damage can provide the guidance that players and parents need. Older adults with new back pain usually end up getting a CT scan or MRI. That’s often a waste of time and money and has little or no effect on the outcome, according to a new study from the University of Washington.

The results contradict current guidelines from the American College of Radiology. The guidelines say that it’s “appropriate” for doctors to order early MRIs for people ages 70 and older with new-onset back pain, and many doctors do just that.

The study followed more than 5,200 men and women over the age of 65 who saw a primary care physician for a new bout of back pain. More than 1,500 of them had some type of back scan within six weeks of the first doctor visit. After reviewing medical records and questionnaires the study participants completed, the researchers found that people who got early scans did no better than those who didn’t have scans. The scans added about $1,400 per person to the overall cost of back pain care — with no measurable benefit. The results were published in this week’s Journal of the American Medical Association.
Watch for red flags

Back pain, especially low back pain, is very common. Most people will have at least one bout of serious back pain at some point in their lives. More often than not, the reason for the pain is never identified. And most of the time the pain gets better on its own.

The University of Washington study offers a common-sense approach to new back pain in most older adults: wait for a bit, use simple strategies to ease the pain, and monitor what happens.

There are, of course, exceptions. An individual with new back pain who also has symptoms or signs that could indicate a fracture, cancer, infection, or other serious problem should get an early imaging test, such as a spine x-ray, CT scan, or MRI. So-called red flags include:

    back pain with a fever
    back pain in someone who has cancer
    back pain that wakes you from sleep (not just waking up and realizing your back still hurts, but pain that wakes you up)
    back pain after an injury
    back pain with loss of control of urine or stool

Just say no to an early back scan

Back pain can be very severe. If you haven’t had it before, it can be frightening. It’s natural to want to know why it is happening. Having a CT scan, MRI, or x-ray of the back might seem like it could pinpoint the problem and guide the way to treatment. But as the University of Washington researchers and others have shown, these scans help only the small percentage of people with new-onset back pain accompanied by red-flag symptoms.

Say the imaging test shows a bulging disc or some other change. It could be the cause of your back pain. More likely, though, it isn’t. There is a good chance that treatment will be directed at what shows up on the scan, and it either won’t ease the pain or will make the problem worse.
Easing back pain

There is no single best remedy for new-onset back pain. Staying in bed for a long time usually makes it worse. Here are some better strategies you can try:

    Try to get up and move around every few hours. Stand and sit until you become too uncomfortable, then lie down again. Try to do a little more each time you get up.
    When you are lying down, position your body and legs in a way that feels most comfortable. Try lying on your side with a pillow placed between bent knees, or lying on your back with two or three pillows under your knees.
    Hot, cold, or neither is a personal preference. If your back pain is clearly injury-related, try applying ice or cold packs for a few minutes several times a day. The cold will help ease inflammation and numb pain. After a few days, switch to heat. Lying on a heating pad on a low setting can feel good.
    For most people, acetaminophen (Tylenol) is the safest over-the-counter pain reliever. Don’t take more than 6 extra-strength (500 milligram) pills or 8 regular-strength (325 milligram) pills in a 24-hour period. Ibuprofen (Advil and others) and naproxen (Aleve and others) are also options, but they can have more serious side effects, especially in seniors.

PCSK9 inhibitors: a major advance in cholesterol-lowering drug therapy
Posted March 15, 2015, 11:02 am , Updated March 20, 2015, 12:22 pm
Gregory Curfman, MD
Gregory Curfman, MD
Assistant Professor of Medicine

Former Editor-in-Chief, Harvard Health Publishing

Every so often a medical advance comes along that rewrites the script for treating a disease or condition. After today’s announcements of impressive results of a new type of cholesterol-lowering drug, that scenario just might happen in the next few years.

The new drugs, called PCSK9 inhibitors, are monoclonal antibodies. They target and inactivate a specific protein in the liver. Knocking out this protein, called proprotein convertase subtilisin kexin 9, dramatically reduces the amount of harmful LDL cholesterol circulating in the bloodstream. Lower LDL translates into healthier arteries and fewer heart attacks, strokes, and other problems related to cholesterol-clogged arteries.

If you have high cholesterol, it’s best to try to lower it with a healthy diet like the Mediterranean diet and exercise. The combination of diet and exercise does the trick for some people. Others need help from medicine.

Statins have been the first-line drugs for lowering cholesterol since the late 1980s. They’ve been shown to prevent repeat heart attacks in people who have already had one and first heart attacks in a wide range of at-risk individuals. In about one in five people, though, a statin doesn’t lower cholesterol enough. Adding a second drug that lowers cholesterol by a different mechanism doesn’t always help. And some people can’t take a statin because of side effects like muscle pain, liver damage, or the development of diabetes.

The results of three clinical trials presented today at the annual meeting of the American College of Cardiology, and simultaneously published in the New England Journal of Medicine, suggest that an even better cholesterol-lowering medication may be on the horizon.

The trials show that PCSK9 inhibitors are extremely powerful cholesterol-lowering agents. In all three trials, all of the participants took a statin. Half got a PCSK9 inhibitor (either evolocumab or alirocumab) every two to four weeks; the other half got a placebo. After a year, LDL levels were 60% lower in the PCSK9 groups.

“Among people treated with evolocumab, the average LDL after one year of treatment was 48 milligrams per deciliter of blood, the lowest LDL ever seen in the experimental arm of a lipid-lowering trial,” Dr. Marc Sabatine, professor medicine at Harvard-affiliated Brigham and Women’s Hospital, told me. Dr. Sabatine was the principal investigator for two of the trials presented at the cardiology meeting. For comparison, a “healthy” LDL is 100 mg/dL.

In some of the trial participants, treatment with evolocumab lowered LDL below 25 mg/dL, and the individuals appeared to do fine, said Dr. Sabatine.

Cholesterol lowering is good only if it translates into better health. That was the case in the three trials. Participants taking the PCSK9 inhibitors were 50% less likely to have had a heart attack or stroke or develop heart failure over the course of the one-year trials.

As with all drugs, there are downsides. At least for now, PCSK9 inhibitors must be given by injection every 2 to 4 weeks. Neurocognitive problems, such as mental confusion or trouble paying attention, were seen in some of the study participants. And if the cost of other monoclonal antibody drugs is any indication, PCSK9 inhibitors won’t be cheap. CVS officials have estimated that a year’s worth of treatment could cost between $7,000 and $12.000.

PCSK9 inhibitors are still experimental drugs. The three trials presented at the American College of Cardiology meeting were designed to look at how well the drugs lowered LDL, not how well they prevent heart attack, stroke, and other cardiovascular problems. Other trials now underway aim to do just that. The FDA can’t begin to evaluate whether PCSK9 inhibitors should become part of the cholesterol-lowering armamentarium until after the results of these trials have been presented and published, and better information is available about the drugs’ side effects.

If approved, these drugs would probably be used first in people who don’t respond to statins or who develop side effects from them. But because it appears that PCSK9 inhibitors reduce the risk of heart attack and other cardiovascular problems in those taking a statin, combining a statin and a PCSK9 inhibitor may be a good option for people at especially high risk for cardiovascular disease.

We’ve never before had medications that can reduce LDL cholesterol levels this much. Time will tell if PCSK9 inhibitors safely prevent heart attack and stroke. As a cardiologist who has seen many people have their lives cut short by cardiovascular disease or who survived but with a poorer quality of life, I have my fingers crossed that a new class of cholesterol-lowering drugs may someday reduce the burden of heart and blood vessel disease.

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