- Inheriting issues with cholesterol
- How common is it?
- Causes of FH
- Diagnosing FH
- Treatment of FH
- When high cholesterol is a family affair
- Genetic roots
- Detecting FH
- Treating FH
- Alerting others
- Familial Hypercholesterolemia
- Familial hypercholesterolemia prognosis
- Familial hypercholesterolemia FAQs
- High Cholesterol Facts
- High Cholesterol
- What is high cholesterol?
- What are the symptoms of high cholesterol?
- What are the causes of high cholesterol?
- How is high cholesterol diagnosed?
- What is the conventional treatment of high cholesterol?
- What therapies does Dr. Weil recommend for high cholesterol?
- Nutrition and Supplements For High Cholesterol
- High Cholesterol: Is It Hereditary?
- 10 Things You Need to Know About Inherited High Cholesterol
- Some high-cholesterol genes differ between countries
- When very high cholesterol runs in the family
- Faulty receptors
- Familial hypercholesterolaemia
- Tests and diagnosis
- Treatment for familial hypercholesterolaemia
- When to see your doctor
Inheriting issues with cholesterol
Familial hypercholesterolemia or FH is an inherited defect in how the body recycles LDL (bad) cholesterol. As a consequence, LDL levels in the blood remain very high – in untreated adults, above 190 milligrams per deciliter (mg/dL) of blood.
People with FH are essentially born with high LDL cholesterol. Everyone’s cholesterol levels tend to rise with age. But those with FH have LDL levels that start high and go even higher over time.
Just like with non-inherited cholesterol issues, this contributes to atherosclerotic plaques, leading to a much higher-than-normal risk of coronary heart disease. Compared to people with average LDL cholesterol levels (less than 130 mg/dL), people with FH have a five times higher risk for coronary heart disease over a 30-year span.
Men with FH get coronary heart disease up to 20 years earlier. Half of men with untreated FH will have a heart attack or angina before they turn 50. For some it will be as early as their 20s. In women, coronary heart disease appears up to 30 years earlier. Thirty percent of untreated women will have a heart attack before they turn 60.
These increased risks are independent of other risk factors, which can make matters worse. The good news, familial hypercholesterolemia is treatable, with a combination of lifestyle changes and medications.
How common is it?
One in 250 adults (an estimated 834,000 people) have the FH genetic mutation, according to results from the 1999-2012 National Health and Nutrition Examination Survey (NHANES).
Men and women are affected equally by FH.
Causes of FH
Familial hypercholesterolemia is caused by mutation in the gene for the LDL cholesterol receptor, which is involved in passing LDL from the body. Mutations in other genes can also cause inherited high cholesterol. Those genes include the PCSK9 gene and the gene for Apolipoprotein B. All these genes are connected with one another. If you inherit a specific type of mutation in any of these three genes, you can develop FH.
Familial hypercholesterolemia can be inherited from one parent (heterozygous FH), or, in rare instances, from both (homozygous FH). People with this rarer form of FH can have very high LDL cholesterol levels. Many may need bypass surgeries before adulthood. Without treatment, people with homozygous FH rarely live into their 20s.
Some people with FH have physical symptoms. Many don’t.
One symptom is cholesterol deposits in the Achilles tendons or the tendons of the hands or elbows. People with FH can also develop cholesterol deposits in unusual places, such as around the eyes.
Familial hypercholesterolemia is often diagnosed based on a combination of physical exam findings and lab results, as well as personal and family history. FH can also be discovered through molecular diagnosis, genetic diagnosis or genetic testing. It’s helpful when genetic testing reveals FH, because it can alert relatives to their risk.
If one person in a family has FH, it’s advisable for all first-degree relatives – parents, siblings, children – to be checked for it. Similarly, if someone in a family has an early heart attack, it’s a good idea for other family members to get tested.
Children with increased risk for FH should be evaluated between the ages of six and 12. Children may be started on medication as early as age eight or 10 if their cholesterol is high enough or if their family history makes it prudent.
If there’s no sign of FH or heightened LDL levels by the time a child becomes a teenager, it’s unlikely that FH will show up later in life.
Treatment of FH
People with FH have an excellent prognosis, provided the condition is identified early and treated appropriately.
Familial hypercholesterolemia can’t be treated by diet and exercise alone. These lifestyle changes can help, but medications are required when LDL cholesterol levels need to be reduced significantly. (As much as 50 or 75 percent.)
Treatment usually involves a statin drug, and it’s not uncommon for other cholesterol-lowering medications like ezetimibe to be required too. People with extremely high LDL, like those with homozygous familial hypercholesterolemia, may need to undergo a treatment called LDL apheresis. This is a dialysis-like procedure that’s done every few weeks to remove cholesterol from the blood.
Another class of lipid-lowering medications, bile acid sequestrants (such as cholestyramine or colesevelam), may also be used. These drugs reduce the amount of cholesterol absorbed by the intestines. This, in turn, lowers the amount of cholesterol that gets into the bloodstream.
Two newly developed injectable antibodies, known as PCSK9 inhibitors, can also be used to lower cholesterol levels. These medications target and block the PCSK9 protein, which frees up more receptors on the liver to remove LDL cholesterol from blood. Although FDA-approved, PCSK9 inhibitors are a new, somewhat costly treatment option, with limited use.
- Read more about FH in Heart Insight magazine’s Cholesterol in the Family
When high cholesterol is a family affair
Published: September, 2007
An inherited form of high cholesterol — familial hypercholesterolemia — demands serious action.
Most of us with high cholesterol have the garden-variety type brought on by eating too much cholesterol and saturated fat and too few fruits, vegetables, and whole grains. More than half a million Americans, though, have a more dangerous type. It stems from an inherited error that can send harmful low-density lipoprotein (LDL) cholesterol into the stratosphere. This often undetected condition, called familial hypercholesterolemia, can cause an early heart attack, stroke, or premature death. Since the name of the disease is a mouthful, we’ll refer to it as FH.
The cholesterol in your bloodstream comes from two sources. Food provides some of it; your body makes the rest. Because cholesterol is a waxy substance, it can’t dissolve in the watery bloodstream. To get around this problem, the body packages it with proteins and other fats into a variety of particles that mix easily with blood. One important cholesterol carrier is LDL.
When a cell needs cholesterol, proteins on its surface called LDL receptors pull in LDL from the bloodstream. If these receptors don’t work properly, LDL lingers longer in the bloodstream. This allows more LDL to get into artery walls and other undesirable places.
A single main gene codes for the LDL receptor protein. People with FH have a malfunctioning gene. Those who inherit just one copy of the bad gene (from one parent) have what’s called heterozygous FH. Although half their LDL receptors don’t work, the other half do. Individuals who get a malfunctioning gene from both parents don’t have any functioning LDL receptors. This is called homozygous FH.
Heterozygous FH is much more common, affecting about 1 in 500 people, or about 600,000 Americans. They have LDL levels as high as 350 milligrams per deciliter (mg/dL), three times higher than is generally considered ideal. Homozygous FH affects about one person in a million. People with it have LDL levels ranging from 400 to 1,000 mg/dL.
Facts about FH
One person in 500 has it.
Signs of the disease include very high LDL and possibly cholesterol deposits in the tendons or skin.
Only about 10% to 20% of people with FH know they have it.
If untreated, 85% of men and 50% of women with FH will have a heart attack, stroke, or cardiac arrest before age 65.
Individuals with FH will pass it on to about half of their children.
Many people with FH don’t know they have it. Instead, they (and their doctors) often think they just have tough-to-treat high cholesterol. Your doctor might want to work you up for FH if you have one or more of the following:
total cholesterol above 300 mg/dL (250 mg/dL in children)
LDL above 200 mg/dL (150 mg/dL in children)
early heart disease or very high cholesterol in your immediate family (a father or brother under age 55, a mother or sister under age 65)
cholesterol deposits in the Achilles or other tendons.
Cholesterol control is the centerpiece of coping with FH. It starts with diet, exercise, and lifestyle changes, then extends to cholesterol-reducing drugs.
Cutting back on foods rich in cholesterol and saturated fat, such as red meat and full-fat dairy products, helps lower LDL. So does eating fish, whole grains, vegetables, and vegetable oils — all good sources of unsaturated fats. Other cholesterol-cutting foods include beans, oats, soy protein, nuts, and foods or supplements containing plant sterols or stanols. Controlling blood pressure, exercising, and not smoking are also essential for protecting the heart and blood vessels.
A cholesterol-lowering statin is the usual starting point for drug therapy. Adding a drug such as ezetimibe (Zetia), niacin, or colesevelam (WelChol) can cut LDL even further. The goal is an LDL under 100 mg/dL or, if that’s not possible, at least a 50% reduction.
People with homozygous FH don’t benefit much from statins and other drugs, which work in part by increasing the body’s production of LDL receptors. They periodically need LDL apheresis, a dialysis-like procedure to filter LDL out of the bloodstream.
“As the name indicates, familial hypercholesterolemia is a family problem,” cautions Dr. Paul N. Hopkins, a professor of internal medicine at the University of Utah and an expert on this disorder. If you have FH, it’s important that your family members be tested for it, too. Children of a parent with heterozygous FH have a 50% chance of inheriting the defective gene; it’s 100% if a parent has homozygous FH.
Early testing, followed by aggressive cholesterol control, can delay or prevent the early heart attacks and death that often accompany FH.
More information on FH is available from Make Early Diagnosis to Prevent Early Deaths (www.medped.org), a registry and information center hosted by the University of Utah.
As a service to our readers, Harvard Health Publishing provides access to our library of archived content. Please note the date of last review on all articles. No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician.
Familial hypercholesterolemia prognosis
The prognosis for familial hypercholesterolemia is dependent on how closely an individual follows the lifestyle and diet recommendations, as well as how well the body responds to the medication. Lifestyle changes and medications can help significantly delay heart disease or heart attack.
Those with homozygous FH will generally receive a less positive prognosis, as will those who experience early complications, such as heart problems in childhood.
Familial hypercholesterolemia FAQs
Q: What is the life expectancy for those with familial hypercholesterolemia?
A: Without treatment, the life expectancy of those with familial hypercholesterolemia can be reduced by approximately 15-30 years. However, in people with homozygous familial hypercholesterolemia, the life expectancy may only be 20 years or less. Treatment, however, can manage the condition and lead to a significantly improved prognosis.
Q: Can familial hypercholesterolemia be treated without the use of statins?
A: Statins are normally the preferred medication for treating high cholesterol. However, if side effects occur, or statins are not an available option for various reasons, there are other medications which can be used instead. These include cholesterol absorption inhibitors, sequestrants and niacin or vitamin B-3. The choice of treatment route should always be decided based on the recommendations of a medical professional.
Patient. “Familial Hypercholesterolaemia.” August 1, 2017. Accessed August 2, 2017. ↩ ↩ ↩
National Heart, Lung, and Blood Institute. “What is Cholesterol?” Accessed August 2, 2017. ↩
FH Foundation. “Familial Hypercholesterolemia.” November 15, 2014. Accessed August 2, 2017. ↩
Healthline. “Familial Hypercholesterolemia.” February 9, 2016. Accessed August 2, 2017. ↩
Heart UK. “Treatment for People with Familial Hypercholesterolemia (FH).” Accessed August 2, 2017. ↩
MedlinePlus. “Familial hypercholesterolemia.” May 5, 2016. Accessed August 2, 2017. ↩
LifeExtension. “Familial Hypercholesterolemia.” July, 2006. Accessed August 2, 2017. ↩
Healthline. “Alternatives to Statin for Lowering Cholesterol.” January 20, 2016. Accessed August 2, 2017. ↩
Today, it is estimated that 50% of the American population have cholesterol levels that fall outside the accepted healthy range, and the prevalence of cardiovascular disease reflects this. However, the idea that cholesterol is a major risk factor for the development of heart attacks and strokes was one that was rejected by the scientific community for decades. Although high cholesterol is now a universally accepted warning sign, some medical professionals are starting to question the current standard of care when it comes to statin therapy, as these cholesterol-lowering medications may not benefit all patient populations equally. Will history repeat itself? Here I will present the story of cholesterol, and how it has – and continues to be – a controversial component of modern medical history.
A cholesterol narrative and the uphill battle linking it to cardiovascular risk
In the early 1900s, a young Russian scientist named Anitschkow serendipitously conducted what would be one of the founding experiments for cardiovascular disease research. Instead of disproving his colleague’s hypothesis on ageing, Anitsckow discovered a link between cholesterol and vascular damage (atherosclerosis) after feeding rabbits purified cholesterol. Yet, despite these findings, cholesterol research in the context of human health was not of interest, mostly because many leading scientists did not consider the rabbit – an herbivore by nature – to be relevant to human disease. Furthermore, atherosclerosis was thought to be a natural and inevitable component of ageing and most scientists didn’t see cholesterol as being causative. Therefore, cholesterol research as it relates to cardiovascular disease remained stagnant for several decades.
Approximately 40 years after Anitschkow published his cholesterol studies in rabbits, Gofman had great interest in the concept of cholesterol as being a determinant of cardiovascular disease. An American scientist with a penchant for biomedical research, Gofman was aware of Anitschkow’s cholesterol feeding experiments and, unlike most other scientists during that era, he took these results quite seriously. He was convinced of a between cholesterol and atherosclerosis, which ultimately lead him to question exactly how cholesterol was transported in the blood stream. Using newly established techniques, he started to examine the different chemical forms of cholesterol found in the blood, and identified the components that make up total cholesterol (such as HDL and LDL, which will be discussed in detail below). Unfortunately, the significance of this research would not be realized until many years later.
As time went on and rogue supporters of the “lipid hypothesis” increased in number, the notion that high levels of cholesterol in the bloodstream, a phenomenon known to physicians as hypercholesterolemia, was a causative factor for heart disease started to catch on. It was becoming clearer that diet had an impact on cholesterol levels, and therefore, the incidence of heart attacks. In 1955, Ancel Keys, a prominent nutritional scientist at the University of Minnesota, suggested that, despite the costs and length of time required, it was important to conduct large-scale clinical studies where diet and health were researched :
“There are good reasons for the current great interest in the effects of the diet on the blood lipids. It is now generally agreed that there is an important relationship between the concentration of certain lipid fractions in the blood and the development of atherosclerosis and the coronary heart disease it produces. The outstanding characteristic of atherosclerosis is the presence of lipid deposits, mainly cholesterol, in the walls of the arteries. And both in, man and animals the most obvious factor that affects the blood lipids is the diet.”
As a result, we started to see an increase in clinical studies examining the impact of diet on cardiovascular health, including Keys’ own Seven Countries Study beginning in 1958. This study, which was the first of its kind, examined the connection between lifestyle, diet, and prevalence of cardiovascular disease in men from different world populations. Though the study design is considered to be flawed by today’s standards, the major finding that linked high intake of dietary cholesterol to heart disease, regardless of cultural background, were quite influential.
Alongside the Seven Countries Study, the National Heart Institute (now known as the National Heart, Lung, and Blood Institute – NHLBI) decided in 1948 to begin following people between the ages of 30 and 62 living in the town of Framingham, MA. Perhaps one of the most well-known and cited clinical studies aimed to determine common patterns related to the development of cardiovascular disease, the currently ongoing Framingham Heart Study identified a number of factors related to heart health, including smoking, high blood pressure, and – you guessed it – high blood cholesterol. However, the latter was not a reported cardiovascular disease risk factor until 1961.
Despite the rejection of the lipid hypothesis by several “old-schoolers,” many scientists and physicians began to see the link between blood cholesterol and human health. But, even more brazen was the idea that negative health effects stemming from high cholesterol could be treated and reversed. In the early 1950s, research from the laboratories of Laurance Kinsell (Institute for Metabolic Research, Highland General Hospital) and Edward H. Ahrens (The Rockefeller University) concluded that eliminating dietary saturated fats and replacing them with unsaturated fats has a profound effect on reducing blood cholesterol. This finding was strengthened by the results of three pre-1970s clinical studies: The Paul Leren Oslo Study (1966); The Wadsworth Veterans Administration Hospital Study (1969); and The Finnish Mental Hospitals Study (1968).
Yet, the reaction of medical professionals was still mixed. Some embraced these new data and organizations such as the American Heart Association went on record with a (carefully worded) message urging a reduction in saturated fat consumption. However, others were more pessimistic of these findings, perhaps because they did not feel that the American population would be willing to dramatically change their current lifestyle and dietary habits. Or, perhaps the non-universal acceptance of the lipid hypothesis was because there wasn’t enough information regarding the biochemistry surrounding how cholesterol wreaks havoc in our bodies. And then the work of Gofman became more relevant.
Enter Donald S. Fredrickson. Fredrickson realized the potential of Gofman’s findings regarding how cholesterol was carried in the blood and became convinced that the pattern of cholesterol carriers – known as lipoproteins – was a valuable approach to determining cardiovascular disease risk. Building on Gofman’s research, Frederickson and his colleagues brought lipoprotein science into the clinical setting, busting open the field of lipoprotein metabolism as it relates to atherosclerosis. Still, there were many questions regarding the regulation of lipoprotein level in the blood, especially that which surrounded the matter of nature versus nurture.
Whether there was a genetic component to high cholesterol and cardiovascular risk was a question that fueled a young postdoctoral scientist working in the laboratory of Arno G. Motulsky at the University of Washington. In 1973, Joe Goldstein, now considered to be one of the founders of modern cholesterol research, was one of the first to genetically classify the types of cholesterol-carrying lipoproteins in the blood. However, it was when Goldstein teamed up with Michael Brown – a collaboration that would lead to the 1985 Nobel Prize in Physiology or Medicine – that the genetic regulation of cholesterol metabolism was realized. In a series of research papers published in the 1970s and 1980s, Brown and Goldstein not only how a critical enzyme involved in the generation of cholesterol was regulated, but also elegantly showed that there is a genetic basis behind the inability to remove a pro-heart disease form of cholesterol called low density lipoprotein (LDL) from the blood.
Thanks to Brown and Goldstein, a target for cholesterol therapy was finally identified; however, there was yet to be an actual drug on the market. Proof was still needed that lowering LDL cholesterol will lower ones risk of heart attacks and strokes, and this had to be accompanied by proof of efficacy. The clinical trial that sealed the deal, ending cholesterol’s long road to being taken seriously as a primary cardiovascular disease risk factor, was the Coronary Primary Prevention Trial (CPPT), launched in 1973 by the NHLBI Lipid Research Clinics. This randomized, double blind study showed that lowering blood cholesterol (in this case using cholestryamine – a compound that prevents the intestinal reabsorption of cholesterol and promotes its removal via excretion in the feces) leads to a reduction in heart attacks.
When these data were published in the early 1980s1, there was a consensus among many in the medical community that the lipid hypothesis was correct. Furthermore, the evidence linking cholesterol to cardiovascular disease resulted in many programs and policies aimed at both educating the public about dietary management of blood cholesterol levels and exploring new methods for treatment. This opened up a new area for research and, of course, a new area for cholesterol controversy.
Deconstructing Cholesterol: “Bad” is still bad, but is “good” still good?
Now that a “lipid panel” has become a standard part of the medical check-up, we are easily provided with an extremely valuable, personalized metabolic snapshot. But, the information can also be overwhelming. In the lipid panel, we will see cholesterol broken down into basic components: HDL, which stands for high density lipoprotein; and LDL, an acronym for low density lipoprotein. Added together, they make up most of our total cholesterol.
Because high levels of LDL cholesterol in the blood have been shown to promote atherosclerosis, this form of cholesterol has been appropriately nicknamed “bad cholesterol.” However, whether or not HDL – known to many as “good cholesterol” – can save the day is up for debate. When studying cholesterol characteristics in the population, there is some indication of an inverse relationship between HDL levels and cardiovascular risk. In other words, it seems like high HDL is correlated with low heart attack numbers.
From a mechanistic standpoint, this makes sense. In the body, HDL acts to remove cholesterol from specialized cells called macrophages, which helps to prevent the build-up of cholesterol in our blood vessels. Furthermore, it has been proposed that HDL has antioxidant and anti-inflammatory properties, which are beneficial when it comes to heart disease. But, it isn’t always that simple. In some contexts, HDL can become damaged, transforming into something that actually promotes damage to our blood vessels. Thus, HDL levels may not be an informative parameter at the individual level.
The idea that raising HDL might be beneficial came from clinical studies, including the coronary Drug Trial (1965-1974), where the effects of niacin were examined. To date, niacin is the most effective FDA approved means of raising HDL-cholesterol. Interestingly, niacin also lowers LDL-cholesterol, as well as another type of blood lipid called triglycerides. Because of this, it is hard to tease out whether the protective effects of niacin are actually related to raising HDL levels. Fibrates, such as TriCor or Lopid, are another class of compounds that can significantly raise HDL levels, but, like niacin, these drugs also affect LDL and triglycerides.
Despite some of the uncertainties, several pharmaceutical companies were driven to explore potential cardio-protective effects of specifically raising HDL levels in the blood stream. Based largely on the work of Alan Tall at the Columbia University Medical Center, many pharmaceutical labs are working on targeting a molecule in our body called cholesteryl ester transfer protein, more easily referred to as CETP. Studies have shown that blocking the action of CETP leads to an increase in HDL levels in the blood, and, based on the notion that increased HDL is beneficial, it is thought that these drugs would be a great option to what we already have on the market. However, the first drug trial investigating a CETP-inhibitor had disastrous consequences.
When administered alone, torcetrapib – a CETP inhibitor drug produced by Pfizer – was shown to increase HDL levels without significantly affecting LDL levels. The hope was that this biochemical data would translate into a heart-protective effect in humans. However, a clinical trial showed that when provided in combination with another cholesterol-lowering medication called a statin (we will get to these later), torcetrapib treatment was associated with a 50% increase in deaths from cardiovascular disease compared to placebo. These results occurred because torcetrapib was reported to increase blood pressure.
Some of the criticisms regarding torcetrapib surrounded the idea that this was not a “pure” medication, especially considering that the blood pressure effect does not seem to be associated with the mechanism of torcetrapib action. And it is this reasoning that the idea of CETP inhibition has not been totally abandoned.
Many have high hopes for Merck’s CETP inhibitor anacetrapib. In a Phase III study, it was reported that anacetrapib had significant HDL-raising effects when administered to patients already taking a statin, and this was without any of the off-target effects seen with torcetrapib.
However, do HDL levels really matter if LDL levels are in check? In other words, is their any benefit to raising HDL levels if LDL levels are adequately treated? Conclusions from the AIM-HIGH study suggest that the answer is no. In May of this year, the NHLBI announced that they would be prematurely halting this clinical study, which was investigating the effects of taking niacin on top of a statin, citing futility. This decision was made after taking into consideration the negative results from the ACCORD lipid study, which showed that taking a fibrate in combination with a statin provided no extra benefit for diabetic patients.
This certainly creates a fair amount of confusion when it comes to the current “HDL is good” dogma, and many doctors are reconsidering how they treat patients with low HDL levels if LDL is low or normal. Given the currently available data, LDL appears to be the major risk factor when it comes to cardiovascular disease susceptibility. Should we re-interpret the early studies showing an association between high HDL and a lower incidence of heart attacks?
As the investigation into the efficacy of anacetrapib moves forward, perhaps we will become more informed. But what is the point if it is only being tested on top of a statin? To truly know the benefits of raising HDL, pwe need to find a way to only study the effects of altering HDL levels. However, there are always ethical considerations to take into account. It is not good practice to prevent a patient from taking a medication that is known to be beneficial to their condition, just so we can make a point in the name of science.
But, science and medicine is not (and should never be) a “one size fits all” philosophy and there are many who would benefit from knowing if raising HDL levels is a true, stand-alone alternative. This is certainly quite relevant when speaking about the percentage of the population who just cannot tolerate statin therapy because of unwanted side effects. There has got to be a way to ensure that everyone has an equal chance at fighting heart disease and perhaps it is time to restructure our current approach.
Cholesterol confusion and why we should rethink our approach to therapy
For many high-risk patients who do not respond to diet and exercise, getting their LDL levels in check is as simple as taking a statin. Statins are drugs that inhibit the natural ability of our body to generate cholesterol and result in the reduction of LDL cholesterol in the blood. These medications have certainly helped many, especially those who are genetically predisposed to high cholesterol levels due to heredity. However, there are some who just cannot tolerate statin therapy and, therefore, we need to be able to provide them with more options.
All statins have been reported to be associated with adverse side effects, especially when administered at high doses2. These side effects include memory problems, sleeping issues, and, most commonly, that which is associated with muscle. For some, these muscle issues might just be minor. For others, however, statin use may come with more serious muscle problems, and this is catching some attention (see this post by Laura Newman). Based on this, as well as results published in November of 2010 in the Lancet, which reported a significant increase in the number of patients experiencing a muscle condition called myopathy as a result of high-dose statins (80mg per day), the FDA has issued the following safety announcement:
The U.S. Food and Drug Administration (FDA) is recommending limiting the use of the highest approved dose of the cholesterol-lowering medication, simvastatin (80 mg) because of increased risk of muscle damage. Simvastatin 80 mg should be used only in patients who have been taking this dose for 12 months or more without evidence of muscle injury (myopathy). Simvastatin 80 mg should not be started in new patients, including patients already taking lower doses of the drug. In addition to these new limitations, FDA is requiring changes to the simvastatin label to add new contraindications (should not be used with certain medications) and dose limitations for using simvastatin with certain medicines.
The reported frequency of adverse side effects relating to statin usage is 5% in randomized clinical trials, but can reach up to 20% in the clinic3,4. It is thought that this discrepancy arises because of patient selection in these randomized clinical trials, which generally tend to exclude groups (such as women or the elderly) who have a higher rate of statin intolerance. Furthermore, patients who are heavy drinkers, those who have a pre-existing condition (such as diabetes), or those taking a cocktail of medications are typically excluded. Yet, these people are prescribed statins in real life.
As of right now, there is no standardized treatment for patients who develop adverse side effects to statin therapy. In a perspective article published in the New England Journal of Medicine (online November 15, 2011)5, Patricia Maningat and Jan Breslow from The Rockefeller University address this issue, citing the need for pragmatic clinical trials for statin-intolerant patients.
As opposed to randomized clinical trials, which usually involved a homogenous patient population, pragmatic clinical trials would be more applicable to a real-world setting, providing detailed information so that caregivers and policy makers can determine more personalized treatment options. These authors also note the fact that most new therapies are tested on top of statins, therefore making it impossible to determine if these drugs are effective as stand-alone treatments for patients who cannot tolerate statins.
There are many who joke that statins should be added to the drinking water, and with the exponentially growing number of those prescribed statins, they might as well be. There is no doubt that the rising number of statin users will be associated with increased reports of negative side effects. The implementation of pragmatic clinical trials may not be the most cost-effective strategy, nor would the study design prove to be easy, but it is important that we effectively meet the needs of every patient who has high cholesterol. The current standard of care is out of date and it is high time that we began a dialogue to correct this.
- The Journal of Lipid Research’s thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy: Part I; Part II; Part III; Part IV; Part V
- The Donald S. Fredrickson Papers
- Trial puts niacin—and cholesterol dogma—in the line of fire
- The Cholesterol Wars: The Skeptics vs the Preponderance of Evidence
References not hyperlinked
The Lipid Research Clinics Coronary Primary Prevention Trial Results. I. Reduction in incidence of coronary heart disease. JAMA 1984 Jan 20;251(3):351-64.
Bays H. Statin safety: An overview and assessment of the data—2005. AmJ Cardiol 2006;97(8A):6C-26C.
Armitage J. The safety of statins in clinical practice. Lancet 2007; 370(9601):1781-90.
Radcliffe KA, Campbell WW. Statin myopathy. Curr Neurol Neurosci Rep 2008; 8(1):66-72.
Maningat P, Breslow JL. Need: Pragmatic clinical trials for statin-intolerant patients. NEJM 2011
High Cholesterol Facts
Find up-to-date facts about high cholesterol in the United States.
High Cholesterol in the United States
- In 2015–2016, more than 12% of adults age 20 and older had total cholesterol higher than 240 mg/dL, and more than 18% had high-density lipoprotein (HDL, or “good”) cholesterol levels less than 40 mg/dL.1
- Slightly more than half of the U.S. adults (55%, or 43 million) who could benefit from cholesterol medicine are currently taking it.2
- 95 million U.S. adults age 20 or older have total cholesterol levels higher than 200 mg/dL. Nearly 29 million adult Americans have total cholesterol levels higher than 240 mg/dL.3
- 7% of U.S. children and adolescents ages 6 to 19 have high total cholesterol.4
- High cholesterol has no symptoms, so many people don’t know that their cholesterol is too high. A simple blood test can check cholesterol levels.
- Having high blood cholesterol raises the risk for heart disease, the leading cause of death, and for stroke, the fifth leading cause of death.
High Total Cholesterol Levels Vary by Race, Ethnicity, and Sex
The chart below shows the prevalence of high total cholesterol (240 mg/dL or more) among adults age 20 and older in the United States from 2015 to 2016.1
Americans Are Making Progress on High Cholesterol
About two-thirds of U.S. adults say they have had their cholesterol checked within the last 5 years.5
Most healthy adults should have their cholesterol checked every 4 to 6 years. Some people, such as people who have heart disease or diabetes or who have a family history of high cholesterol, need to get their cholesterol checked more often.6
- Heart Disease
- Heart Attack
- Aortic Aneurysm
- High Blood Pressure
- Carroll M, Fryar C, Nguyen D. HDL, National Health and Nutrition Examination Survey: Total and High-density Lipoprotein Cholesterol in Adults: United States, 2015–2016. NCHS data brief, no. 290. Hyattsville, MD: National Center for Health Statistics; 2017.
- Mercado C, DeSimone AK, Odom E, Gillespie C, Ayala C, Loustalot F. Prevalence of cholesterol treatment eligibility and medication use among adults—United States, 2005–2012. 2015;64(47):1305–11.
- Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. Heart disease and stroke statistics—2017 update: a report from the American Heart Association. 2017;135(10):e1–458.
- Nguyen DT, Kit BK, Carroll MD. Abnormal Cholesterol Among Children and Adolescents in the United States, 2011–2014. NCHS data brief, no. 228. Hyattsville, MD: National Center for Health Statistics; 2015.
- Carroll MD, Kit BK, Lacher DA, Yoon SS. Total and High-Density Lipoprotein Cholesterol in Adults: National Health and Nutrition Examination Survey, 2011–2012. NCHS data brief, no. 132. Hyattsville, MD: National Center for Health Statistics; 2013.
- HealthFinder.gov. Get Your Cholesterol Checkedexternal icon. Washington, DC: U.S. Department of Health and Human Services; 2018.
Our liver cells and many other cells in our bodies have small structures attached to them called LDL receptors. They have an important job in keeping blood cholesterol down.
When LDL cholesterol in the blood passes by, it attaches to an LDL receptor which takes it into the cell. The cholesterol is used or stored for later, or broken down by liver cells. The LDL receptor then returns to the surface of the cell, ready to bind to more cholesterol in the blood.
With FH, the liver cells can’t take LDL out of your blood. And this is down to faults or mutations in a few specific genes.
LDL receptor genes
Most people with FH have a fault in one of these genes. It means you don’t have enough LDL receptors, so cholesterol builds up in the blood.
APOB gene (apolipoprotein B)
Only two or three out of every 100 people with FH have a fault with this gene. It means LDL cholesterol can’t bind well to LDL receptors. LDL is taken out of the blood too slowly, and cholesterol in the blood stays high.
Only a few people have this type of FH. A fault with this gene means that LDL receptors are broken down in the liver, so they can’t take cholesterol out of your blood.
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What is high cholesterol?
High cholesterol is a well-known risk factor for heart disease. Cholesterol itself is a waxy, fat-like substance that is primarily made by the liver, although some comes from the diet. It is an essential component of cell membranes and is used by the body to produce hormones and vitamin D.
Cholesterol is carried through the bloodstream attached to two different compounds called lipoproteins: low-density lipoproteins (LDL) and high-density lipoproteins (HDL). LDL is commonly known as the “bad” cholesterol because it transports cholesterol from the liver throughout the body, and potentially allows it to be deposited in artery walls. HDL, known as the “good cholesterol,” picks up cholesterol from the blood and delivers it to cells that use it, or takes it back to the liver to be recycled or eliminated from the body.
Too much cholesterol in the blood builds up on artery walls causing hardening of the arteries (atherosclerosis). The buildup of cholesterol narrows arteries, slowing or blocking the flow of oxygen-carrying blood to the heart, which can manifest as chest pain. If blood flow to the heart is cut off because of clogged arteries, the result is damage to the heart muscle – a heart attack.
What are the symptoms of high cholesterol?
High cholesterol itself does not cause symptoms, so there are no outward signs that your levels are too high and thereby posing a risk to your heart.
What are the causes of high cholesterol?
The tendency toward high cholesterol appears to be genetic although diet also influences cholesterol levels. Other factors that can influence cholesterol levels include being overweight and being physically inactive. The older you get, the more likely your cholesterol levels are to rise. Before menopause, women tend to have lower cholesterol levels than men of the same age, but after menopause, women’s LDL levels often increase.
There is considerable controversy over whether high cholesterol is in itself a cause of heart disease (the lipid hypothesis), or a symptom of an inflammatory condition that is the true cause of heart disease (the inflammation hypothesis). According to the latter theory, chronically high levels of inflammation creates small lesions on arterial walls; the body sends LDL to heal those lesions, but it ultimately accumulates and oxidizes, causing blockages. From this perspective, the best lifestyle approach to lower cardiovascular disease risk is to lower inflammation in the body rather than LDL levels.
The two theories are not mutually exclusive; they may both be true to some extent.
How is high cholesterol diagnosed?
Your cholesterol levels can be measured by a blood test done after you’ve fasted for nine to 12 hours. Results will reveal your total cholesterol level, your LDL and HDL levels as well as levels of triglycerides, the most common type of fat in the body. Some doctors also obtain tests for LDL particle size and number.
Desirable levels of total cholesterol are 200 mg per deciliter of blood or less; levels between 200 mg/dL and 239 mg/dL are considered borderline high; 240 mg/dL or higher is considered high cholesterol and raises your risk of heart disease to twice what it would be if your total cholesterol were 200 mg/dL or lower.
A desirable level of heart protective HDL cholesterol is 60 mg/dL or higher; levels below 40 mg/dL for men and less than 50 mg/dL for women increase the risk of heart disease. According to the American Heart Association, the mean level of HDL cholesterol for American adults age 20 and older is 54.3 mg/dL.
A desirable level of LDL (“bad”) cholesterol is less than 100 mg/dL – the lower your LDL, the better in terms of heart disease risk. Levels between 139 and 150 mg/dL are borderline high and those between 160 to 189 mg/dL are considered high, while LDL levels above 190 mg/dL are classed as very high. According to the American Heart Association, the mean level of LDL cholesterol for American adults age 20 and older is 115.0 mg/dL.
Normal triglyceride levels are considered 150 mg/dL or lower; those from 150 to 199 mg/dL are considered borderline high while those from 200-499 mg/dL are considered high, and those above 500 mg/dL are deemed very high. The American Heart Association reports that the mean triglyceride level for American adults age 20 and older is 144.2 mg/dl.
What is the conventional treatment of high cholesterol?
Treatment of high cholesterol usually begins with lifestyle changes geared toward bringing levels down. These include losing weight if you’re overweight, and changing your diet to emphasize vegetables and fruits, fish, particularly cold water fish such as wild Alaskan salmon, mackerel, herring and black cod that provide heart healthy omega-3 fatty acids. If lifestyle changes don’t help or if you’re unable to make the changes your doctor recommends, cholesterol-lowering drugs may be prescribed. These include statins, which effectively lower LDL cholesterol; bile acid sequestrants that may be prescribed along with statins to lower LDL; nicotinic acid to lower LDL cholesterol and triglycerides and raise HDL; drugs called fibrates that may be prescribed to lower cholesterol and may raise HDL; and a drug called Ezetimibe to lower LDL by blocking the absorption of cholesterol in the intestine.
What therapies does Dr. Weil recommend for high cholesterol?
Dr. Weil recommends making the following lifestyle and dietary changes in order to lower high cholesterol levels:
- Lose weight. Even a modest amount of weight loss can lower cholesterol levels.
- Reduce the amount of sugar and flour in your diet. Recent evidence indicates that added sugar – in the form of table sugar (sucrose) or high-fructose corn syrup – is probably a greater contributor to heart disease than is consumption of saturated fat. This suggests that the inflammatory hypothesis may in fact have more validity than the conventional lipid hypothesis, although the debate is far from settled. As a general rule, Dr. Weil advises against consuming foods with added sugars, particularly soft drinks and highly processed snack foods, which can cause rapid spikes and dips in blood sugar levels. The result can be overeating, obesity and heart disease.
- Avoid trans-fatty acids. These heart-damaging fats can reduce HDL (“good”) cholesterol levels and raise levels of LDL (“bad”) cholesterol. The tip-off that trans-fatty acids are present in foods is the listing of “partially hydrogenated oil” on a food’s ingredient list. Trans-fats are found in many brands of margarine and in most heavily processed foods, as well as in snack foods such as chips, crackers and cookies, and in the oils used to cook fast-food French fries, doughnuts and movie popcorn.
- Exercise. Daily aerobic exercise can help increase HDL levels.
- Don’t smoke. Smoking itself is a risk factor for heart disease. It can also significantly lower HDL cholesterol.
- Relax. Emotional stress may prompt the body to release fat into the bloodstream, raising cholesterol levels. Counter stress by practicing daily breathing exercises and other stress-reduction techniques such as yoga, meditation, guided imagery or tai chi.
Nutrition and Supplements For High Cholesterol
Dr. Weil recommends the following dietary changes that may help lower cholesterol levels.
- Eat some nuts every day. Choose almonds, walnuts and cashews, all of which contain heart-healthy monounsaturated fat.
- Substitute whole soy protein for animal protein. Soy protein such as tofu, tempeh, soy milk, whole soy beans and roasted soy nuts has been shown to lower cholesterol levels. Choose organic products where possible.
- Use fresh garlic regularly. Garlic has been shown to lower both cholesterol levels and blood pressure. Use one or two raw or lightly cooked cloves a day.
- Drink green tea daily. The antioxidants it contains help lower cholesterol and prevent the cholesterol in your blood from oxidizing.
- Eat plenty of soluble fiber. Beans and lentils, apples, citrus fruits, oats, barley, peas, carrots and ground flax seed are all good sources of soluble fiber, which has a powerful cholesterol-lowering effect.
- Limit refined carbohydrates. These include cookies, cakes, crackers, fluffy breads, chips and sodas, all of which can worsen cholesterol levels by lowering HDL and also increase triglyceride levels.
- Take coenzyme Q10 (CoQ10). This powerful antioxidant benefits heart health by protecting LDL cholesterol from oxidation and by re-energizing the mitochondria in the heart cells, which is where energy metabolism occurs. CoQ10 may also help lower blood pressure.
- Take fish oil. Fish oil contains an abundance of essential omega-3 fatty acids (omega-3s) that have been shown to lower triglyceride (blood fat) levels, minimize inflammation and clotting, and increase HDL (“good”) cholesterol. Research indicates that omega-3s may help reduce the risk and symptoms of a variety of disorders influenced by inflammation, including heart attack and stroke. You can add omega-3s to your diet by eating more cold water fish such as wild Alaskan salmon, sardines, herring, mackerel and black cod. If that’s not possible, Dr. Weil recommends taking two grams daily of a fish oil supplement that contains both essential omega-3 fatty acids, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). When choosing a supplement, look for one derived from molecularly distilled fish oils – these are naturally high in both EPA and DHA and low in contaminants. Also choose a supplement brand that has been independently tested and guaranteed to be free of heavy metals such as mercury and lead, and other environmental toxins including polychlorinated biphenyls, also known as PCBs.
Updated, December 17, 2012
High Cholesterol: Is It Hereditary?
There are two main forms of cholesterol. The first, LDL cholesterol, is often called “bad” cholesterol. It’s considered unhealthy to have high levels of LDL cholesterol in your body. The other, HDL cholesterol, is sometimes referred to as “good” cholesterol. Higher levels of HDL cholesterol can be a sign of good health.
If your doctor tells you that you have high cholesterol, they’re usually referring to either high levels of LDL cholesterol or a high level of total cholesterol. Total cholesterol is also sometimes called serum cholesterol. It’s the sum of LDL and HDL cholesterol and 20 percent of your triglycerides. LDL cholesterol and total cholesterol can be used as indicators of your risk of developing cardiovascular disease and other complications.
Learn more: What is serum cholesterol and why is it important? “
A variety of risk factors contribute to unhealthy levels of cholesterol, including genetics, lifestyle choices, or a combination of the two.
Familial hypercholesterolemia vs. high cholesterol
If you have a close relative, such as a parent, sibling, or grandparent, who has high levels of cholesterol, you’re more likely to have it yourself. This is largely due to the passing on of genes from parents to children that increase levels of cholesterol in the blood, such as a gene that codes for a defective receptor. This is known as familial hypercholesterolemia.
Familial hypercholesterolemia is a form of inherited high cholesterol. People with this condition generally have higher cholesterol levels than people without this condition, despite lifestyle choices. That’s because people with this condition aren’t able to regulate cholesterol levels as efficiently as other people. People with familial hypercholesterolemia can’t control their cholesterol through diet and exercise alone, and may instead need to also use medication.
Having a genetic risk for high cholesterol doesn’t guarantee that you’ll have high cholesterol. It just means that you have an increased risk. Let your doctor know about your concerns. They can help you manage your cholesterol and monitor your levels so that if you do develop high cholesterol, you can begin treatment right away.
Obesity or large waist circumference
Some people are genetically predisposed toward obesity or a large waist circumference. Both can increase your risk for high cholesterol. Lifestyle factors also play a role in these two risk factors.
Obesity is defined as a body mass index (BMI) of 30 or higher.
A large waist circumference is 40 or more inches for men and 35 or more inches for women. Fat that accumulates in your waist increases your risk of elevated cholesterol and other cardiovascular complications.
Elevated blood sugar
High levels of glucose can increase LDL cholesterol and decrease HDL cholesterol. High levels of glucose in your blood can also damage the lining of arteries. That can increase your risk of fatty deposits building up in your arteries.
Like obesity and waist circumference, some people are more genetically predisposed toward high blood sugar. Lifestyle choices, like diets high in soda, candy, or other foods containing large amounts of sugar, can also contribute to high blood sugar levels.
Some risk factors for high cholesterol can be completely controlled by lifestyle choices. These include diet, exercise, and smoking.
Eating a diet high in saturated and trans fats can increase your cholesterol levels. Foods high in these types of fats include:
- red meat
- full-fat milk and yogurt
- fried foods
- highly processed sweets
Exercise can increase your HDL cholesterol and decrease your LDL cholesterol. That means that adding exercise to your routine can help promote healthy levels of cholesterol in your body.
Aim for 150 minutes of moderate- to high-intensity aerobic exercise each week. You don’t have to initially start out exercising that much if you’re new to exercise. Instead, work your way up to that goal, and be sure to talk to your doctor before starting any new exercise routines. Additionally, add resistance exercises, such as weight lifting or yoga, into your exercise plan.
Smoking can have a negative impact on your heart health. That’s because tobacco damages the wall of your blood vessels. This makes it more likely for fat deposits to build up.
Talk to your doctor about smoking cessation programs that may work for your lifestyle. Sometimes you may need to try more than one method to stop smoking. Having a support group can help.
Learn more: 14 tips for quitting smoking “
10 Things You Need to Know About Inherited High Cholesterol
1. Everyday Health: How common is the inherited high cholesterol condition called familial hypercholesterolemia, or FH, in the United States?
Dr. Underberg: A lot more common than people think: It affects 1 in 400 people in the general population. It’s more common than other genetic diseases that get a lot more airtime. In founder populations — French Canadian and Ashkenazi Jewish populations, for example — FH occurs in 1 in 100 people. This is a genetic condition that shortens lifespan and is treatable.
2. Everyday Health: Is the incidence of this genetic form of high cholesterol stable or on the rise in the U.S. population?
Dr. Underberg: FH incidence is stable as a genetic condition. We’re seeing a slow uptick in awareness now, so that both patients and practitioners are more aware.
3. Everyday Health: How many people do you think have the condition but have not yet been diagnosed?
Dr. Underberg: The diagnosis rate is between 1 and 20 percent. At a maximum, 20 percent are getting diagnosed in the United States. In the Netherlands and in the U.K., there is more awareness .
4. Everyday Health: How is familial hypercholesterolemia diagnosed?
Dr. Underberg: For the majority of people, there are no symptoms until they have a heart attack. Patients may have bumps around the eyes, or bumps on the tendons, but many patients don’t. A white ring around the cornea of the eye is sometimes seen in patients even under the age of 45. The main symptoms are high cholesterol levels and a family history of high cholesterol.
5. Everyday Health: Is FH inherited by all the children in a family or only some of them?
Dr. Underberg: Assuming that a parent has FH, there’s a one-in-two chance that a child will have it — a 50 percent likelihood.
6. Everyday Health: What’s different about the genes in families with this inherited condition?
Dr. Underberg: There are several genes that are involved in how we dispose of cholesterol in the liver. The LDL receptor is a protein in the liver that gets cholesterol out of the bloodstream. In the majority of familial hypercholesterolemia cases, there is a mutation in the LDL-receptor gene. They can’t get rid of cholesterol, so the liver makes more cholesterol because it doesn’t realize it has enough from the bloodstream. This makes it very difficult for people to get cholesterol levels down.
7. Everyday Health: What are the consequences of not treating very high cholesterol?
Dr. Underberg: Lifetime risk of a cardiovascular event — heart attack or stroke — is 20 times greater for someone with FH. And for women in the age group of 20 to 39, there is 125 times greater risk.
Men tend to have cardiovascular events 10 years earlier, in their thirties and forties, and women in their fifties and sixties.
8. Everyday Health: How is high cholesterol treated in patients with inherited high cholesterol?
Dr. Underberg: We encourage a heart-healthy lifestyle: exercise, low-fat diet, not smoking. But this condition starts at birth; cholesterol is high from day one . Diet alone is rarely enough. Statin medication is the cornerstone of treatment for these patients, but it’s often not enough.
PCSK9 inhibitors like Praluent reduce the amount of LDL cholesterol in the circulation, and lower total cholesterol.
Other medications, like ezetimibe and bile acid sequestrants can also be used. Some patients can’t tolerate medication, or their cholesterol is so high that medication doesn’t work. For them, LDL apheresis is a procedure to remove cholesterol from the blood, like dialysis, and is done every one to two weeks.
New medications were approved by the FDA for extraordinary cases — Kynamro (mipomersen sodium) injection, and Juxtapid (lomitapide) — but these have side effects.
9. Everyday Health: Is premature heart disease preventable in people with familial hypercholesterolemia?
Dr. Underberg: There are no prospective trials for ethical reasons; data we have is observational. For FH patients on statins, the risk level is similar to that in people without FH. This fits with the cholesterol hypothesis, that patients born with low cholesterol don’t get heart disease.
10. Everyday Health: What do you do to raise awareness about FH in your community?
Dr. Underberg: This is something I’m really passionate about. I’m the president of the National Lipid Association. We work at health fairs in New York City to promote awareness about FH locally. Nationally, the Foundation of the National Lipid Association offers public service awareness at LearnYourLipids.com. Another source of information is the FH Foundation.
Because people with this condition are at higher risk, we try to make sure that people are identified so their kids can get screened. A child is potentially at risk, but no one may have told them to get screened. By ages 9 to 11, all children should get screened for cholesterol levels. Then if they have FH, they can institute diet and exercise early on as lifestyle changes.
Some high-cholesterol genes differ between countries
The new Nature Communications study adds to evidence that genetic research involved in drug development and risk prediction testing might not apply equally to non-European populations.
“Genome-wide association studies, facilitated by the mapping of the human genome, have transformed our understanding of how our genetics impact our traits, behaviours and disease risks. But the large majority of them have been conducted in people of European descent, so there’s a growing concern that the findings might not uniformly apply to people of diverse backgrounds,” said the study’s lead author, Dr Karoline Kuchenbaecker (UCL Genetics Institute and UCL Psychiatry).
She and her colleagues investigated the known genetic variants that affect blood fat levels, a major cardiovascular risk factor, to test whether they applied to different groups in the UK, Greece, China, Japan and Uganda.
They found that the results were broadly consistent across European and Asian groups, with about three quarters of genetic markers applied similarly across the different groups, but only 10% of the genetic markers for triglycerides (the most common type of fat in the body) were implicated in the same cardiovascular risk factors among people from Uganda.
The researchers point out that even if genetics are nearly universal, environments are more variable, and some genes may have different, undiscovered effects in different environments. Genes predicting high cholesterol may not be risky for people with diets and lifestyles typical of rural Uganda.
“Our findings should serve as a major warning of caution to the field of genetics research — you cannot blindly apply findings from ancestrally European study groups to everyone else,” said Dr Kuchenbaecker.
“We need to ensure that diverse groups are represented in research before proceeding with developing new tests or treatments — otherwise, the consequence will be a very unfair NHS where some new drugs and genetic tests are only suitable for people of European descent.”
When very high cholesterol runs in the family
Fewer than 10% of people who have a genetic condition called familial hypercholesterolemia realize they have it.
Published: April, 2014
More than 600,000 Americans have an inherited condition that can cause heart attacks at an early age.
For most American adults with high cholesterol, the problem stems from eating foods rich in cholesterol and saturated fat. But some have an inherited genetic error that causes cholesterol levels to skyrocket. This often-undetected condition is called familial hypercholesterolemia (FH). If not treated, a person with FH has a 20-fold higher risk of heart attack compared with an unaffected person.
“Familial hypercholesterolemia is a major cause of premature coronary disease,” says Dr. Linda Hemphill, an instructor in medicine at Harvard Medical School and director of the LDL Apheresis Unit at Massachusetts General Hospital. Premature coronary disease refers to heart disease that occurs before age 55 in men or before age 65 in women. People with FH can succumb to a heart attack in their 30s or even 20s, says Dr. Hemphill. That fact—and the condition’s inherited nature—underscores the importance of diagnosing FH as early as possible.
All people have two genes (one from each parent) responsible for making receptors on cell surfaces that clear low-density lipoprotein (LDL, or “bad” cholesterol) from the blood. People who inherit just one copy of the faulty gene have heterozygous FH. Half of their LDL receptors work; the other half don’t. Those who inherit two malfunctioning genes (homozygous FH) have no working receptors. With nothing to pull harmful LDL from the bloodstream, the level stays high.
Heterozygous FH, by far the more common form, can cause LDL levels as high as 350 milligrams per deciliter (mg/dL), more than three times higher than is considered ideal. Among the one in a million people with homozygous FH, LDL levels can reach 1,000 mg/dL.
People often don’t realize they have FH because they (and their doctors) assume they simply have hard-to-treat high cholesterol. If your LDL cholesterol level was 190 mg/dL or higher before you started treatment, FH is a definite possibility, says Dr. Hemphill. For children, an LDL of 160 mg/dL suggests FH. Another red flag is premature heart disease or very high cholesterol in an immediate family member (occurring before age 55 in a father or brother, or before age 65 in a mother or sister).
People with FH may also develop small nodules filled with cholesterol over various tendons, especially the Achilles’ tendons of the lower leg. These growths are called xanthomas. Cholesterol-filled nodules that form on the eyelids are called xanthelasmas.
For people with FH, the standard advice for anyone with high cholesterol still applies: cut back on foods rich in cholesterol and saturated fat, such as red meat and full-fat dairy products, and eat more vegetables, fruit, whole grains, and fish. Other cholesterol-cutting foods include beans, oats, soy protein, nuts, and foods or supplements containing plant sterols or stanols. Controlling blood pressure, exercising, and not smoking are also essential for protecting the heart and blood vessels.
Cholesterol-lowering statins are the drug of choice, but many people with FH also require additional drugs, including ezetimibe (Zetia), niacin, and colesevelam (WelChol). People with homozygous FH often need LDL apheresis, a dialysis-like procedure to filter LDL out of the bloodstream. Last year, the FDA approved lomitapide (Juxtapid) and mipomersen (Kynamro) for people with homozygous FH to further lower their LDL. Because these drugs may cause serious liver problems, they can be given only under a doctor’s close supervision.
If you have FH, your family members should be tested. Children of a parent with heterozygous FH have a 50% chance of inheriting the defective gene; it’s 100% if a parent has homozygous FH. Most of the time, a cholesterol test can verify the diagnosis, but genetic testing can be helpful for borderline cases. More information is available at the FH Foundation (www.thefhfoundation.org), which aims to boost awareness and improve the diagnosis and treatment of FH.
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Familial hypercholesterolaemia (or familial hyperlipidaemia) is an inherited (genetic) condition in which affected members of a family have high levels of LDL cholesterol, the so-called ‘bad’ cholesterol, in their blood.
Too much LDL cholesterol in the blood can cause deposits of fats to build up in the walls of the arteries (atherosclerosis). People with familial hypercholesterolaemia have high cholesterol from birth and are at high risk of developing atherosclerosis at a young age.
Atherosclerosis is the process behind several conditions, including:
- coronary heart disease (which can result in angina and heart attack);
- cerebrovascular disease (which can cause stroke); and
- peripheral artery disease (which causes poor circulation in the legs).
Many people with familial hypercholesterolaemia don’t know they have it. This is because high cholesterol levels by themselves often don’t cause any symptoms.
When cholesterol levels are extremely high, cholesterol can accumulate in certain areas, such as:
- the skin and tissue underneath the skin, causing visible fatty growths known as xanthomas (often seen over tendons in the hands and feet and the Achilles tendon); and
- around the corneas in the eyes, which appears as a white or grey ring (called arcus cornealis or corneal arcus).
Symptoms of premature (early-onset) coronary heart disease, cerebrovascular disease or peripheral artery disease may be the first sign of familial hypercholesterolaemia. These conditions are defined as premature when they occur in men younger than 55 years and women younger than 60 years.
Some families carry genes that lead to high levels of LDL cholesterol. The abnormal genes mean the body has trouble clearing LDL cholesterol from the blood.
Familial hypercholesterolaemia affects about one in 500 people. Children of affected people have a 50 per cent chance of having the condition.
Tests and diagnosis
Your doctor will ask about your medical history, including a family history and perform a physical examination. People with familial hypercholesterolaemia usually have a strong personal or family history of early-onset of diseases caused by atherosclerosis.
Other conditions that can cause high cholesterol levels (such as thyroid or kidney problems) need to be ruled out before a diagnosis of familial hypercholesterolaemia can be made.
- A blood cholesterol test can be used to detect abnormal cholesterol levels. In people with familial hypercholesterolaemia, LDL levels are generally very high for their age.
- Genetic tests may be performed to confirm the diagnosis and help in the identification of other affected family members.
Treatment for familial hypercholesterolaemia
If you have familial hypercholesterolaemia, treatment will be directed at lowering your cholesterol and reducing your risk of coronary artery disease and stroke.
You will almost certainly be prescribed cholesterol-lowering medicine(s).
Cholesterol-lowering medicines include:
- ezetimibe (often used where statins are not suitable, or in addition to statins);
- cholestyramine and colestipol (which can be used where statins are not suitable, or in addition to statins);
- nicotinic acid (sometimes used in addition to other cholesterol-lowering medicines); and
People with very high LDL cholesterol levels usually need to take a combination of medicines to effectively lower their cholesterol levels.
Your doctor will also advise you to take some of the following lifestyle steps.
- Stop smoking if you are a smoker.
- Lose weight, if you are overweight, or maintain a healthy weight if you are not overweight.
- Diet: eat a healthy, balanced diet that is low in saturated and trans fats. Replace foods containing saturated fats with foods that contain unsaturated fats.
- Increase your intake of fibre with foods such as fruits, vegetables, beans and peas. Soluble fibre, called so because it dissolves in water, is found in oat bran and psyllium husk, and is very helpful in lowering blood cholesterol.
- Eat foods shown to have cholesterol-lowering properties, such as tree nuts; olive oil; and foods supplemented with sterols or stanols (such as cholesterol-lowering margarines, yoghurt or breakfast cereals).
- Limit alcohol to no more than 2 standard drinks per day.
- Exercise regularly. Regular physical activity can improve cholesterol levels and lower your risk of coronary heart disease.
Regular monitoring of your cholesterol levels, and for evidence of blood vessel disease, is important.
When to see your doctor
See your doctor for a blood test to check your cholesterol level if you have:
- a close relative who has very high LDL cholesterol levels;
- a family history of early-onset coronary heart disease, stroke or peripheral artery disease; or
- symptoms that suggest you may have high cholesterol or coronary artery disease.
The good news for people with familial hyperlipidaemia is that with medication and a careful lifestyle, the risk of coronary artery disease can be reduced considerably.
Last Reviewed: 19/08/2015