When Mark was in his mid-20s, he had his cholesterol tested for the first time.
It seemed like a good idea. His father had died at the age of 50 from a heart attack and his grandfather had died from the same thing at the age of 60.
The results, however, were shocking.
His cholesterol levels were drastically elevated for someone his age.
Mark learned that he had familial hypercholesterolemia, a genetic condition that affects approximately 1 in 250 to 500 people.
The condition impairs the body’s ability to clear excess cholesterol from the bloodstream. This information would change his life forever.
A Global Epidemic
Mark isn’t alone.
People with high cholesterol levels have twice the risk of heart disease as people with low levels. Heart disease is the leading cause of death both in the United States and around the world.
Because high cholesterol has no immediate symptoms, it’s easy to overlook or ignore.
High cholesterol also often co-occurs with other, far more visible conditions like obesity or diabetes, making it easy to push cholesterol concerns to the side.
For many people, there aren’t any outward signs that anything is wrong at all. As a result, less than half of American adults with high cholesterol are getting treatment for their condition. Less than a third have their condition under control.
Mark, a 59-year-old Orange County resident, has a combined cholesterol level of 330 mg/dL — far above the maximum of 200 mg/dL recommended by the Centers for Disease Control and Prevention (CDC).
Other than that, he’s in good health. He’s at a healthy weight. He’s eating well and he enjoys softball, tennis, and cycling. But despite his wholesome lifestyle, his cholesterol levels remain out of control.
A new documentary, Heart Felt, explores the lives of people like Mark around the world living with the invisible specter of high cholesterol. Director Cynthia Wade sought to bring to light this under-discussed problem.
“It’s not dialogue that we have. We might touch upon it in a doctor’s office, but there’s always a sense of either fear, or shame, or trepidation, or ‘Ugh, do I really wanna know?’ because what if the numbers aren’t what they should be?” she said in an interview with Healthline. “We all do as best as we can, but we all know that we could do better, and it’s a hard conversation to have, it’s a hard thing to look at.”
Cholesterol in the Body
Cholesterol is a fatty substance that the body uses to manufacture a range of chemicals, including the hormones estrogen and testosterone.
The body generates enough cholesterol to serve these purposes on its own, meaning that any cholesterol that a person eats in his or her diet is unnecessary.
Small amounts of LDL cholesterol, or “bad” cholesterol, stay dissolved in the bloodstream until the liver digests them to excrete from the body. When these levels get too high, though, sticky patches of cholesterol can begin to form on the walls of blood vessels, forming plaques.
As these plaques grow larger, they narrow the amount of available room inside the blood vessels, raising blood pressure and reducing the oxygen supply to the heart, brain, and other organs. This increases the risk for heart attack and stroke.
“We know from some epidemiological studies that high cholesterol is one of the strongest risk factors for future heart attack,” said Nicholas J. Leeper, assistant professor of vascular surgery and cardiovascular medicine at Stanford University, in an interview with Healthline. “This has been known from landmark studies, like the Framingham study that’s been conducted over a period of many decades now.”
Genetics plays a major role, making alterations in the chemical pathway that the liver uses to eliminate cholesterol from the body.
“Our genes establish a range in which our cholesterol levels can orbit,” explained Donald Lloyd-Jones, professor and chair of the Department of Preventive Medicine at Northwestern University’s Feinberg School of Medicine, in an interview with Healthline. “Then, our eating patterns are what determine where within that range we fall. In general, it’s hard to break out of that range without an extreme dietary change or without medication.”
Typically, there are two different types of gene patterns that can cause high cholesterol levels.
“All of us have a greater or lesser predisposition to high cholesterol, which is contributed to by many small genetic variants with small effects,” said Joshua Knowles, assistant professor of cardiology at Stanford University, in an interview with Healthline. “Working in concert, tens to hundreds of these genetic variants can slightly increase your risk of high cholesterol. That’s what happens to most of us.”
However, Knowles continued, there are rare genes where even a single mutation can cause large effects, such as the one that causes Mark’s familial hypercholesterolemia (FH). These genes are dominant, meaning that if you have even a single copy of the gene, it will activate.
“If you inherit one bad copy of the gene from one of your parents, you’ll manifest high cholesterol,” Knowles said. “If you inherit a bad copy from both parents, you’ll have astronomically high LDL cholesterol.”
Managing Risk: Diet
“Diet and exercise are the cornerstones of therapy for everybody,” Knowles advises.
Together, they can lower LDL cholesterols levels by 10 to 15 percent, he says. For people without FH, this can often be enough.
To registered dietician Maria Bella, founder of Top Balance Nutrition and a clinical nutrition coordinator at the NYU School of Medicine, the key part of a cholesterol-fighting diet is fiber.
“Fiber is found in any fruit, any vegetable, and many whole grains,” she said in an interview with Healthline. “Fiber forms a gel-like substance in the small intestine, partially blocking the cholesterol receptors and promoting bile acid and cholesterol excretions, lowering the cholesterol levels.”
And how do we get enough fiber?
“We talk about eating on a rainbow, consuming six colors of produce per day,” she said. “It’s focusing on the fun things instead of restriction. This way eating healthy becomes really fun, versus sad.”
Adding fiber isn’t the only change you can make in your diet.
Mary G. George, deputy associate director for science and senior medical officer at the CDC’s Division for Heart Disease and Stroke Prevention, offers more advice. Avoid trans fats (found in many packaged cookies and pastries that have long shelf lives) and saturated fats (found in whole diary, red meat, and many oils), which boost the body’s cholesterol production.
Instead, choose foods high in monounsaturated and polyunsaturated fats, such as nuts and olive oil, which can help raise levels of HDL (“good”) cholesterol. The American Heart Association (AHA) also reports that good sources of lean protein include low-fat dairy, poultry, fish, and legumes.
Bella offers an important perspective on regulating your diet.
“Set your goals in such a way that you always feel successful, that way you’re more likely to keep on going,” Bella said. “Focus on setting more realistic goals like the 80/20 rule: make 80 percent of your diet healthy, and allow for small cheats here and there.”
Managing Risk: Exercise
Dietary changes, while helpful, aren’t enough. George also urges people with high cholesterol to exercise.
“Be physically active on a regular basis, such as brisk walking, swimming, cycling, or even gardening,” she said. “The Surgeon General recommends that adults engage in moderate-intensity exercise for two hours and 30 minutes every week, and children and teenagers should do at least one hour of activity each day.”
For people with a busy workday, Bella suggests taking a short break each hour to get up and take a brief walk or run a flight of stairs. If done throughout the day, it adds up to the 40 minutes daily that is recommended by the AHA.
“You do not need to go to the gym,” she points out.
And for people who don’t have the job flexibility to step away from their desk or station every hour, there are other options.
“The New York Times has a fantastic exercise app,” Bella recommends. “It’s a seven-minute app based on High Intensity Interval Training. If you’re traveling, or you’re at home, or you cannot afford to save for the gym, it’s a great way to exercise. All of us have seven minutes.”
George rounds out this advice with a few other factors to keep in mind.
“Maintain a healthy weight,” she said. “Being overweight or obese can raise your cholesterol levels, while reducing weight can lower them.”
She also advises, “Quit smoking and avoid secondhand smoke. If you don’t smoke, don’t start.”
Drugs to the Defense: Statins
For the majority of people with high cholesterol levels that don’t respond sufficiently to diet and exercise, the drug of choice will be statins.
These drugs inhibit an enzyme in the liver called HMG CoA reductase, which is involved in cholesterol production.
Not only does this slow the body’s rate of cholesterol production, it also prompts the liver to grow more LDL receptors, the bonding sites that the liver uses to absorb cholesterol from the bloodstream to be excreted.
“It’s sort of like a recycling program for LDL cholesterol,” explained Knowles. “LDL cholesterol is basically a waste product. You activate the recycling program with the use of statins.”
Statins have been around since the 1980s. Many have gone generic, driving prices down to less than $100 a year.
“[With] statins, we have data on hundreds of thousands of people who’ve been carefully monitored on them,” said Lloyd-Jones. “We know that they have substantial and significant effects on reducing LDL cholesterol, and in turn, pretty dramatically reducing rates of heart attacks, strokes, and overall mortality in essentially every group of patients we’ve looked at.”
“These medicines are actually quite interesting, because they seem to have additional benefits we don’t fully understand, above and beyond their cholesterol-lowering capacity,” added Leeper.
Those benefits may soon be extended to a much larger number of people. In 2013, the American College of Cardiology and the American Heart Association (ACC/AHA) jointly released a new set of guidelines that would increase the number of people eligible to take statins.
With the low cost of generic statins, improved quality of life from better health, and the reduced risk of death, increasing statin use will actually be cost-effective, according to a report in JAMA. The researchers quantified health gains using quality-adjusted life-years.
“We found that the risk threshold used in the current ACC/AHA guidelines (above 7.5 percent) is good value for money,” said Ankur Pandya, assistant professor of health decision science at the Harvard T.H. Chan School of Public Health and lead author of the study, in an interview with Healthline. “It could be cost-effective to recommend statin treatment for up to two-thirds of the U.S. population over the age of 40 (using a risk threshold of 3.0 percent).”
Expanding use of statins this broadly raises the question of potential side effects.
“A major side effect from statins is increased longevity, honestly,” Knowles said.
About 15 percent of statin users experience muscle aches, but Knowles said there is no increase in cancer risk and the risk of liver disease is extremely low.
Knowles concluded, “Statins get a bad rap, but they’re extremely good medications. They’ve been around for a long time.”
Unfortunately for Mark, he falls into the small category of people with adverse side effects.
Although statins lowered his cholesterol levels by 30 percent, the side effects were too much to bear. And he tried just about every statin in the book, going so far as to enroll in nearly a dozen clinical trials for newer versions of the drug in his quest for one he could tolerate.
But it was to no avail. Not only did he experience painful muscle aches, but he also experienced emotional disturbances.
“I am generally a pretty even-keeled, relaxed type of person,” he told Healthline. “On statins I felt sensitive to everyday minor challenges, much more irritable, and even angry at times.”
A New Alternative: PCSK9 Inhibitors
Although Mark is currently living without taking any medications, there are new options just around the corner.
Two new drugs are making their way through the approval process.
Praluent (alirocumab), manufactured by Sanofi-Aventis and Regeneron, received approval Friday from the U.S Food and Drug Administration (FDA).
Amgen’s Repatha (evolocumab) is in the final stages of approval by the FDA. Repatha was approved on July 21 for use in Europe.
These drugs, called PCSK9 inhibitors, work to block the action of an enzyme called PCSK9 that breaks down LDL cholesterol receptors on the liver. By blocking the enzyme, more receptors stay on the liver and can suck more cholesterol out of the bloodstream.
Instead of taking a pill, patients taking Repatha or Praluent would inject themselves with their medication. Praluent is administered using a single-dose disposable pre-filled pen while Repatha uses an auto-injector. Mark enrolled in a clinical trial for Repatha and although he was assigned to the placebo group, he was still using the auto-injector technology.
“The auto-injector is very easy to use,” he said. “I thought I would not be able to inject myself, but with the auto-injector there is nothing to it.”
The PCSK9 inhibitors may offer a promising alternative for people who can’t tolerate statins, or for whom statins don’t do enough to lower LDL cholesterol levels.
“Approximately 25 to 33 percent of patients at high risk for cardiovascular events in the U.S. cannot adequately lower their LDL-C levels with statins and/or other currently approved lipid-lowering agents,” said Scott M. Wasserman, vice president at Amgen, in an interview with Healthline. “Repatha has the potential to offer patients a treatment option that will further lower their cholesterol levels.”
Alongside their upcoming release of Praluent, Sanofi/Regeneron sponsored the documentary Heart Felt and set up the website TakeDownCholesterol.com.
One possible concern about the new drugs is that, because they are under patent, they may cost as much as $10,000 a year, says Knowles.
Another question is whether the PCSK9 inhibitors will cause long-term side effects.
“They seem to be extremely effective on their own at lowering LDL cholesterol, and particularly if you add them to a statin, they drive LDL cholesterol levels extremely low,” said Lloyd-Jones. “So far, they appear to be quite safe. I think it’s important to say that we haven’t had the large clinical trials that establish long-term safety and long-term effectiveness in terms of reducing heart attack and stroke. But in these shorter trials of up to 18 months, we do see reduced rates of heart attack and stroke, and we do see a pretty good safety profile.”
Both Amgen and Sanofi/Regeneron have such clinical trials underway, which are expected to conclude in 2017.
Until then, Lloyd-Jones thinks that PCSK9 inhibitors should be used only in patients, like Mark, who need them most.
“There should be caution about when and in whom we use them until we have more extensive data from longer-term trials,” he said. “My personal feeling would be that they should be reserved just for the highest-risk patients who, for whatever reason, can’t take a statin or can’t take it at the doses where it would be most effective. I don’t think they’re ready for widespread prime time yet until we have longer-term data on safety and efficacy.”
Mark is excited to give the PCSK9 inhibitors a try once they hit the market.
“This new drug looks to be really great,” he said. “From what I have heard, I would be thrilled to take the drug.”
What Can I Do?
Many experts agree that regular screening for cholesterol is crucial.
“There’s no way to know your cholesterol level just sitting there,” said Lloyd-Jones. “You have to have a blood test to know what your cholesterol numbers are.”
It’s recommended that adults aged 20 and older get their cholesterol levels checked every five years. However, people with FH or other risk factors should get checked more frequently. And to detect FH early, all children between the ages of 9 and 11 should get their levels checked at least once.
Learning your family history is one of the most important ways to know your risk level.
“Family histories are really key indicators, especially if that family history is occurring in first-degree relatives at young ages,” said Lloyd-Jones. “If people have had a heart attack or stroke in one’s family at ages lower than 60, that’s something that one should definitely be aware of and get the facts on, and share with their doctors.”
And if family history and a cholesterol test show warning signs, there are genetic tests for FH that can pinpoint the problematic gene mutation about 60 to 80 percent of the time, says Knowles.
And while Lloyd-Jones says that statins are necessary for many people, he concluded, “You can’t expect a medication to take the place of lifestyle. They have to work together. You should never think, ‘Because I’m taking cholesterol medication I get a free pass.’ You have to work on everything.”
Mark has come to terms with his high cholesterol levels.
“Obviously, I wish it were not so, but I also wonder if my high cholesterol has some other effects making me who I am,” he said. “While we wait for a medical alternative, take care of your body in ways you know are healthy. Develop a positive attitude, establish a healthy lifestyle of eating, being active, [and] connecting with others. And look for your funny bone to help you navigate life’s challenges.”