Men with FH
One of my favorite patients told me that when his dad died at the age of 47, he thought it was a normal occurrence. He thought his dad was “pretty old”. For Brad, this was the norm in his family—relatives on both sides died early of heart disease. After surgery at 53, his mother died at 69. One of Brad’s brothers (who likely inherited 2 genes for FH) died at the age of 23 and another brother had bypass surgery in his mid-30s. Death through young heart attack was always on Brad’s mind and the older he got, the younger age 45 seemed. At age 37, Brad developed chest pain and required bypass surgery. Prior to his chest pain, Brad knew about his high cholesterol, and in fact he had been treated for it—but not adequately—for several years. At the time of his bypass, his LDL-Cholesterol was about 160 mg/dL. That’s certainly better than his baseline level of over 300 mg/dL, but not good enough!
Brad heard the term familial hypercholesterolemia for the first time when he came to my clinic. Giving a name to the disorder for when multiple heart attacks in the family occur, and explaining how FH is inherited, was an important first step. Brad was able to understand his family history, and this motivated him to get much more serious about lowering his cholesterol with both lifestyle and medication. Brad is now on several cholesterol-lowering medications and participates in a long-term clinical trial. His LDL hovers around 70 mg/dL. Brad proactively had his two daughters tested. Although he was disappointed to learn that his younger daughter (Sammy) has FH, he is determined to change the course of his family history. Sammy, now age 12, has been treated with cholesterol-lowering medication since she was 8 years old. Brad is confident that he will dance at Sammy’s wedding and live to meet his grandchildren—a joy his parents never knew.
You may have FH, FH is life-threatening if not accurately diagnosed and proactively treated. Therapies can help you avoid early heart attacks. Please make an appointment to have your cholesterol tested.
Although the answer to this is not 100% certain, there are likely several reasons. The first is puberty. As young men go through puberty, their HDL (protective cholesterol) tends to fall. This does not happen to young women. A low HDL is an additional risk factor for early heart disease. Thus not only is a young man with FH at risk due to his elevated LDL, compared to the women in his family, he very likely has a lower HDL. Additionally, women (even women with FH) tend to be relatively protected from symptomatic heart disease until menopause – probably due to estrogen.
An aside to women reading this: please notice the word symptomatic. Although it is unusual for a woman with FH to have a heart attack before menopause, your elevated LDL cholesterol means you are still putting cholesterol into your artery wall. Women have smaller heart arteries than men, and it doesn’t take long after going through menopause to block those arteries – so women need to be treated early, too!
In the past, but not currently, more men than women smoked. Smoking is poison for everyone, but for people with FH, smoking is doubly poisonous. Smoking can lower the HDL and leads to chemical modifications (oxidation) of LDL. Oxidized LDL is more dangerous than non-oxidized LDL. It is therefore possible that in the past, smoking set men with FH up for earlier heart disease than their non-smoking female relatives. The bottom line is that if you smoke you should quit!
Once a man develops heart disease, there is no evidence that men are less likely to be aggressively treated for their cholesterol. In fact, in the past there was even evidence that women were less aggressively treated for their heart disease than were men.
FH is treatable if accurately diagnosed.
The fact is, the only way you will know if you have high cholesterol is if you get tested. The current national recommendation is that all Americans undergo cholesterol testing between ages 9-11.
If you have not yet been tested, especially if you have a strong family history of heart disease, I urge you to be tested. Knowledge is power. If you are found to have FH, get treated, and work to reduce all other risk factors. If you are overweight, try hard to get to a healthier weight. If you smoke, please quit. I know, both losing weight and quitting smoking are difficult—but the sooner you do it, the healthier you will be. If you have high blood pressure, then exercise, salt restriction, weight loss, and medications when necessary are all important. Finally, if you have diabetes, work on weight loss through diet and exercise, and, if necessary, take prescribed medications.
Anyone who has FH should also have a measurement for Lp(a), which is an inherited lipid found in the blood. Lp(a) is really the combination of an LDL particle and a clotting particle. People living with FH who also have a high Lp(a) level are at even higher risk for early heart disease than are people who simply have a high LDL level. You can imagine that if Lp(a) contains an LDL particle it can block up the arteries; adding to that a clotting particle makes the risk even higher. Most heart attacks are caused when a cholesterol plaque inside a heart artery ruptures and subsequently a blood clot forms on top of the ruptured plaque. The combination of a ruptured plaque and a blood clot might completely prevent blood from flowing in the heart artery. If the blockage is not opened quickly, a heart attack will ensue.
Lp(a) can be measured in two different ways. If your test is measured in mg/dL then a normal level is less than 30 mg/dL. Some labs measure in nmols/L, in which case the goal is a level < 74 nmol/L.
Unfortunately, Lp(a) is quite difficult to treat. If your level is very elevated, it is unlikely to normalize with medication. Although there have not been any formal studies performed to assess whether lowering Lp(a) reduces cardiac risk, it makes sense to try to lower this lipoprotein. Of the currently available cholesterol lowering medications, only niacin significantly lowers Lp(a). Estrogen does have some Lp(a) lowering properties, but estrogen is not used in men.
Lp(a) can also be lowered by LDL-apheresis. Although LDL-apheresis, a dialysis like procedure, is typically used to lower LDL cholesterol, sometimes the procedure is approved by insurance companies specifically to lower Lp(a).
Some of the cholesterol lowering medications currently in development appear to significantly lower Lp(a).
Although this question cannot be answered precisely, there are statistics that were collected by Dr. Joan Slack and colleagues and published in The Lancet in 1969. This was long before we had the most powerful medications for cholesterol reduction for all ages, including young heart attack.
Again, it is difficult to give you a precise percentage. In any given person, the overall degree of risk reduction will likely depend on the age at which cholesterol-lowering medications are started, and the number of other risk factors a person has for the development of heart disease, such as diabetes, cigarette smoking, high blood pressure, and high Lp(a). Some general statements can be made.
In studies (many 5 or more years in length) performed in people with very high cholesterol, including many with FH, statins have been shown to reduce the risk of a future heart attack by over 30%. In observational studies of FH patients performed in Europe, it appears that long-term statin therapy is capable of lowering lifetime risk to that of the general population.
Thankfully, this is not a common problem, but if it is your situation it can be miserable.. I ran a cholesterol (lipid) clinic for 20 years and this was an issue I encountered on a daily basis. Over time, I learned lots of tricks to help people lower their cholesterol level, even in the face of "statin intolerance."
Studies show statins reduce chances of a future heart attack by 30%.
First, it is important to make sure that a person does not have an underlying condition known to increase the risk for the development of statin myopathy, such as muscle aches when taking a statin.. People with an under active thyroid are significantly more likely to experience statin myopathy than people with a normally functioning thyroid gland, so make sure your health care provider checks this. If you are found to have a hypothyroid problem, once this has been corrected, you may well be able to tolerate statins.
Certain medications can lead to an increase blood level of statins. These include, among others, drugs used to treat HIV, certain antibiotics, and another type of cholesterol lowering medication known as gemfibrozil (Lopid®). If this is your situation, your health care provider should make a change. These medications really should not be used with statins.
People with underlying liver or kidney disease and people who are frail may be more likely to develop statin myopathy. These people are typically treated with lower doses of statins. Some studies have found Asians with heart attacks in the family are more likely to develop statin myopathy and as such, are also often treated with lower doses of statins. Finally, as with so many medical conditions, recently genetic factors have been found to play a role in determining who develops statin myopathy.
When it comes to statins, they are not all created equal. One large study—The PRIMO Study—found that of the statins simvastatin (Zocor®) was most likely to cause muscle aches and fluvastatin (Lescol®) was least likely. Unfortunately, Lescol® is the least potent statin. That said, other more potent statins including atrovastatin (Lipitor®) and rosuvastatin (Crestor®) are less likely than simvastatin to cause aches. In general, my approach to statin intolerance is to try different statins, one at a time. If a statin causes pain, I ask my patients to stop the medication. Once they feel better we can try a different statin, or a lower dose of the same statin. In some cases, every other day, or even every 3rd or 4th day dosing is effective.
If a person with FH can only tolerate low dose, or intermittent statin dosing, he/she will likely need to tighten his/her diet, and almost certainly will require additional medications. Other choices which may be additive to statins include bile acid sequestrants (Welchol®, Questran®, Colestid®), cholesterol absorption inhibitors (Zetia®), or niacin (Niaspan®). See the glossary for a discussion of these medications.
Other options for further LDL reduction include LDL apheresis (see below), and participation in clinical trials. Here at the Family Heart Foundation we are committed to providing you with information on currently available clinical trials in your area. We encourage you to register through the FH Registry. Knowing your current cholesterol profile and medical history will help match you to an appropriate trial.
LDL-apheresis is a dialysis-like procedure, performed every week in people with homozygous FH and every other week in persons with heterozygous FH. A person has homozygous FH if he/she has inherited 2 genes for FH, one from each parent, and a person with heterozygous FH has inherited one gene for FH. Apheresis literally means “to take out.” In the case of LDL-apheresis, LDL cholesterol is physically removed from the blood. Blood is removed from one arm, specially treated to remove the LDL cholesterol, then returned into the other arm. The procedure, which typically takes between 2-4 hours, can lower LDL by as much as 80% and also dramatically lowers Lp(a). Unfortunately, over a short period of time a person’s level rebounds – this is why it needs to repeated frequently.
Although for obvious reasons (scientists will always know who is getting the procedure and who is not), it is impossible to conduct placebo-controlled trials to assess the effectiveness of LDL-apheresis. Several studies have compared the outcomes of patients receiving medications along with LDL-apheresis to those receiving medications without LDL-apheresis. It appears that long term use of LDL-apheresis may reduce cardiac risk anywhere from 44 – 72% above and beyond the use of medications alone.
Finally, if your doctor has recommended LDL-apheresis it is likely that your LDL [or Lp(a)] remains very high despite maximally tolerated cholesterol lowering medications.
If you have HeFH (heterozygous FH), as long as your partner doesn’t also have HeFH, your child has a 50 % chance of having FH. In exactly the same way that you inherited a gene for LDL cholesterol removal from each of your parents, your child has inherited one gene for LDL cholesterol removal from you and one from your partner, which reduces the risk of heart attacks in family.