Muscle Problems Associated with Statins

Statin-associated muscle symptoms are the most common side effects noted with statins, reported in 10% to 25% of patients receiving statin therapy. A very severe form of muscle problems is noted in less than 0.1% of patients receiving statin therapy and will not be discussed here.

Muscle symptoms associated with statin use include muscle weakness, muscle aches, stiffness, soreness, tenderness or cramps associated with exercise. Usually the muscle symptoms are symmetric and involve the thigh, shoulder or calf muscles. Symptoms generally occur within two to twelve weeks of starting the offending statin but may occur at any time in the course of treatment particularly if an additional factor is introduced.

Symptoms generally resolve over several weeks after discontinuing the medication although total resolution of symptoms may require several months. Risk factors include advanced age, female sex, lower muscle mass, vitamin D deficiency and physical disability. An increase in statin dose can also provoke muscle symptoms as can the introduction of another medication or substance that increases the concentration of the statin in the blood.

Because of a certain type of metabolism lovastatin (Mevacor), simvastatin (Zocor) and atorvastatin (Lipitor) are more prone to interactions with other medications. Additionally, tropical juices such as grapefruit, starfruit and pomegranate can greatly increase the blood levels of these statins thereby increasing the risk of adverse effects.

The flowing statins are associated with less risk of interaction: pravastatin (Pravacol), fluvastatin (Lescol), pitavastatin (Livalo) and rosuvastatin (Crestor).

Muscle problems are more common with simvastatin, particularly at higher dose, than with other statins. Pravastatin (Pravacol), fluvastatin (Lescol), pitavastatin (Livalo) and rosuvastatin (Crestor) are less commonly associated with muscle symptoms than other statins.

If you suspect muscle symptoms related to statin use it is important to call your doctor immediately to work on a plan. Often changing the medication or dose is effective in resolving the issue.



Tendon Problems with Levaquin, Cipro, Avelox and Other Fluoroquinolone Antibiotics

Recently the U.S Food and Drug Administration issued a warning to doctors against the routine prescribing of fluoroquinolone antibiotics to those patients with bronchitis, sinusitis and uncomplicated urinary tract infections who have other treatment options.

The most common serious side effects associated with these medications are problems involving the tendons, however, the overall incidence is less than one percent. The most common tendon involved is the Achilles tendon (90% of fluoroquinolone-associated tendinopathy) which can be inflamed and painful or, in some cases, rupture. However, all weight bearing tendons can be involved.

The usual symptoms of Achilles tendon disorders are swelling and tenderness with sharp pain on walking. Rupture is usually preceded by these symptoms but may occur spontaneously. Symptoms usually occur 9-13 days after the initiation of fluoroquinolone therapy with most occurring in the first month. However, symptoms may occur many months after the start of therapy.

Most patients have a satisfactory recovery within two to four weeks although some patients can have prolonged symptoms, occasionally persisting for six months. Long-term problems with the tendon (swelling, pain, etc.) are estimated to occur in about 10% of cases.

Risk factors for fluoroquinolone-associated tendon problems include older age (older than 60 years in 70% of cases), receiving concomitant corticosteroid therapy (including inhaled nasal and pulmonary corticosteroids) and kidney dysfunction. Higher fluoroquinolone doses appear to be associated with greater risk.

Although all fluoroquinolones have been responsible for this side effect levofloxacin (Levaquin) and ofloxacin (Floxin) may possess a substantially greater propensity than other fluoroquinolones to cause tendon problems. The reason for this association is unknown.

When a fluoroquinolone must be used avoiding strenuous physical activity is important to prevent tendon trauma and rupture. Special caution must also be used in patients with pre-existing tendon disorders.


Am I on the Right Dose of Thyroid Medication?

In 95% of cases low thyroid hormone levels in a person are the result of the failure of the gland itself rather than a failure of the gland to receive the appropriate signal (thyroid stimulating hormone) from the pituitary gland. To correct a low thyroid state thyroid hormone is given as T4 in a tablet form calibrating the dose by measuring the thyroid stimulating hormone (TSH) which exists in a reciprocal relationship with T4. In other words, TSH is elevated when the thyroid dose is too low and TSH is suppressed when the thyroid dose is too high.

Thyroid hormone is given as T4 which is a prohormone converted to the active hormone (T3) by the body. Over the years some authorities have claimed that giving thyroid supplementation as a combination of T4 and T3 is superior to administering T4 alone. Multiple studies have not demonstrated any advantage of the combination preparation. Additionally, producing a standardized dose of this preparation is more difficult and subject to variation.

There is about a six week lag between an adjustment in T4 and the final change in the TSH level. Therefore, one cannot assume that more thyroid medication is required after a dose increase because of a failure of TSH to normalize until six weeks have passed. Additionally, T4 has a seven day half-life which insures a constant blood level throughout the day even though the tablet is taken only once a day and makes changes in blood level slow to appear.

Although TSH is used as the marker for thyroid dose adjustment checking the actual level of free thyroid hormone in the blood is important when initiating therapy and occasionally over the years to monitor therapy.

As mentioned in a previous blog, there is some debate about what is the proper TSH target. Traditionally normal TSH is defined as about 0.5 to 5 mU/L. These normal values are based on wide population studies that, by necessity, include individuals with low thyroid hormone levels and, therefore, elevated TSH levels. Using a proper sample population that excludes all individuals with thyroid abnormalities produces a value of 2.5 mU/L as an upper limit for TSH. It may be possible for a person to feel not quite right with a TSH of 4.9, for example, and to feel better with a TSH of 1.9.

Even when an appropriate dose of thyroid is started other factors can interfere with delivering the correct dose to the blood stream. The amount of hormone delivered to the blood steam from a particular thyroid hormone preparation (bioavailability) is standardized by the pharmaceutical firm and supervised by the government. While it used to be thought that a particular name brand was more reliable this has not proven to be the case. However, different generic preparations can have different bioavailability. If there is some concern after a different generic has been started checking the TSH will determine if altered bioavailability is an issue.

Thyroid hormone may not be properly absorbed thereby confusing attempts to find the proper dose. Ideally, it should be taken on an empty stomach one hour before breakfast or in the evening two hours after the last meal. Taking it with food or even coffee can diminish absorption. Taking it with certain other medications or supplements such as calcium, iron or Prilosec can interfere with absorption.

Many medications interfere with T4 becoming active in the blood steam even if they are not taken simultaneously with the thyroid dose. Practically speaking, if a person is on certain medications that interact with thyroid medication the dose can be altered to correct the issue. Problems usually only arise when a new interfering medication is initiated and the TSH is not checked to make the necessary adjustments in dose.

Your thyroid dose may need adjustment upwards if you put on weight. Additionally, your thyroid may be producing some hormone that might decrease over years requiring an increase in the thyroid dose. In any case, it is important to check the TSH yearly and, of course, if symptoms develop to insure that the thyroid dose is proper.

Is a Thyroid Problem Causing My Fatigue?


Is a Thyroid Problem Causing My Fatigue?

Fatigue is definitely one of the symptoms of thyroid deficiency (hypothyroidism.) Thyroid hormones (T4, thyroxine and T3, triiodothyronine) regulate the metabolic processes and an insufficient amount of the hormone causes a generalized slowing of these processes, cold intolerance, weight gain, constipation, dry skin and other problems in addition to fatigue.

The best way to determine thyroid hormone deficiency is through measuring the thyroid stimulating hormone. Thyroid stimulating hormone (TSH) and thyroid hormone exist in a reciprocal relationship where a drop in the thyroid hormone level produces a rise in TSH which serves to stimulate the thyroid gland to make more thyroid hormone.

TSH is not the sole measure of thyroid status although it is often used as the solitary screen for hypothyroidism. In the event of a problem with the pituitary gland’s ability to regulate TSH an individual may have low thyroid hormone level in the setting of a low or normal TSH and the diagnosis of hypothyroidism might be missed.

Measuring thyroid hormone directly can uncover a situation as described above. In such a case thyroid hormone, measured as free T4, would be low indicating thyroid deficiency in the presence of a normal or low TSH.

Why not simply rely on a direct measurement of thyroid hormone (free T4) to screen for a hypothyroidism? A low free T4 almost always defines a low thyroid state but thyroid hormone is very precisely gauged to the individual where a particular free T4 level, although in the normal range, might be insufficient for a particular person. TSH when functioning correctly increases when the thyroid hormone drops below a specific set point even though that set point might be in the normal range for the general population.

Therefore, measuring TSH and free T4 can almost always correctly identify a hypothyroid condition. TSH alone can identify hypothyroidism 95% of the time which is why it is often used separately as a screen for thyroid disease.

However, there is a controversy about whether a normal TSH (usually 0.4 to 5.0 mU/L) is actually normal. The point of those who would reduce the TSH upper limit of normal to 2.5 mU/L is that an upper limit of 5.0 mU/L was extracted from a general population that included many people with thyroid disease thereby distorting the notion of normal. Using a population free of thyroid disease produces an upper limit of 2.5 mU/L.

To complicate matters further, TSH increases somewhat with age in the absence of anything to suggest a hypothyroid state. The upper limit of normal for patients in their eighties could be as high as 6 to 8.

There are additional tests used to define thyroid status including the T3-resin uptake and antithyroid peroxidase (anti-TPO.) The latter is usually abnormal in patients with hypothyroidism and can, if present, can predict that hypothyroidism will eventually develop.

Thyroid disease characterized by a TSH of 10 or less and a normal free T4 is termed “subclinical hypothyroidism” the treatment for which is controversial with some experts recommending no treatment and others recommending thyroid hormone supplementation.

Attempts to define symptoms have been unsuccessful although many patients have complaints suggesting hypothyroidism, including fatigue. Statistical analysis of symptoms cannot separate this group from those with normal thyroid function. Most physicians think that patients with a TSH that is less than 10, although it is in the abnormal range, do not have symptoms attributable to thyroid disease. However, I have seen patients in this category with fatigue who have definitely responded to thyroid hormone treatment.


Do you have high blood pressure?

High blood pressure (hypertension) is defined as a systolic (top number) blood pressure of greater than 140 and/or a diastolic (bottom number) greater than 90. When one of these numbers is abnormal doctors generally consider treatment. However, a single reading indicating a mild abnormality by itself is not enough to merit medication.

About 20 to 25 percent of people with a mildly abnormal blood pressure reading in a doctor’s office have “white coat hypertension,” or blood pressure abnormality only when measured by the physician. Readings done at home or at work are normal.

White coat hypertension does not carry the cardiovascular risks (heart disease and stroke) that regular hypertension does. Documenting home blood pressure requires about 12 measurements over one week that include both morning and evening readings. Of note, normal readings for home determinations (<135/<85) are defined slightly lower than those in a physician’s office.

Additionally, the white coat hypertension effect often wears off with repeated measurement even in the physician’s office. If the doctor notes multiple normal values after an initial elevated reading the initial elevation is not considered evidence of hypertension.

Sometimes the measurement results are quite erratic and the presence or absence of hypertension is unclear. A device that measures blood pressure frequently throughout an entire day can settle the issue. Ambulatory blood pressure monitoring (ABPM) is the best method of defining whether a person has a blood pressure problem.

ABPM measures blood pressure every 15 minutes during the day and every half hour during the night. The nighttime readings are very important since an elevated blood pressure during sleep is a concern.

The ABPM criteria for hypertension are somewhat lower than those for blood pressures taken in a physician’s office: a 24-hour average of 130/80 or above; a daytime average of 135/85 or above; or, a nighttime (sleeping) average of 120/70 or above.

Since blood pressure medication is usually a lifetime commitment it is important to insure that the diagnosis of hypertension is correct.

Sick Building Syndrome: Tired and Stuffy? Think of Your House or Your Office.

BuildingSick building syndrome is a term coined to describe symptoms associated with a structure such as an office building or house. The illness is characterized by fatigue, headache and upper-respiratory symptoms (cough, scratchy sore throat, sinus problems, etc.) Although the symptoms usually resolve when a person leaves the offending structure symptoms can persist.
The lack of fresh air is associated with respiratory tract irritation, fatigue and headaches. An office building has numerous irritants, the most pernicious of which are volatile organic chemicals. Sources of irritants include off-gassing from carpet chemicals, copying machines, insecticides, cleaning compounds, etc. Engineers are aware of the need for fresh air and are required to provide a certain inflow from external air ducts. However, there is a great temptation to reduce the external air input in cold winter months or hot summer days in an effort to reduce energy consumption.
Additionally, air taken from outside vents isn’t necessarily “fresh air.” I have investigated building where the external air intake was very close to the exhaust of diesel trucks that unload supplies for the building.
Mold is an additional and quite severe cause of troublesome building-associated symptoms. It can often be suspected by the characteristic odor of mold and is often noted in buildings with excessive humidity or history of water leaks.
The emphasis on energy conservation that started in the 1970s and construction advances have resulted in buildings and homes that can be almost air-tight. Most new office buildings do not have windows that can be opened. Additionally, the modern home can have very little fresh air intake in hot or cold months when trying to save on heating or air conditioning costs.
There is no specific test for sick building syndrome. Definitely suspect this illness as a cause of upper-respiratory complaints that clear up after you leave the building. If you feel well on weekends and poorly during the work week a building with poor air quality might be the cause. Similarly, if you feel better when you are absent from your home and have a return of symptoms when living in the home an investigation into the air quality might be quite helpful.
A symptom that is more subtle that is more subtle than a typical building-associated cough or runny nose is fatigue. Of course, fatigue in the workplace or home can be due to innumerable physical or psychological causes. However, keep in mind that that poor air quality can cause serious fatigue.
Careful observation of symptoms, the timing of the symptoms and the location can help determine in an office building or home is the cause.

New High Blood Pressure Guidelines

Blood pressure 4The guidelines for treating high blood pressure (hypertension) were recently revised. In brief, the authors raised the acceptable limit for systolic blood pressure for individuals 60 years and older. Additionally, they questioned the previous recommendation of aiming for lower blood pressures for patients with diabetes and kidney disease. As was the case with cholesterol, the conclusions were challenged by many experts, particularly challenging the choice of studies that produced the conclusions.

The previous blood pressure treatment goal of less than 140/90 mm Hg for individuals 60 years or older has been raised by the new guidelines to 150/90 mm Hg. The former goal was based on studies showing an increased cardiovascular risk in individuals with blood pressure over 140/90 mm Hg and risk improvement when the blood pressure was lowered. For instance, lowering blood pressure by 10 mm Hg in patients with hypertension reduces the risk of cardiovascular and stroke death by 25% to 40%.

However, the studies documenting results such as the above often had a goal of less than 160 mmHg and often did not examine the subset of patients 60 years and older. Two recent relatively short-duration studies comparing a goal of less than 140 mm Hg with less than 150 mm Hg in patients over 65 years showed no outcome difference. Using a review of many studies, the guideline authors did not find sufficient evidence that the more aggressive treatment goal of 140/90 mm Hg vs. 150/90 mm Hg benefits older adults.

The obvious question is: What is the harm of a more aggressive goal since so many studies, however imperfect, document improvement with lower blood pressure? Medication side effects are the worry. Too many times physicians become cemented on a number and push medications to the point where an individual experiences dizziness (the most common antihypertensive medication side effect.) The risk from falls can exceed the more remote risk from hypertension. Therefore, on balance the guideline authors suggest flexibility when treating patients 60 years and older.

That said, if an older hypertensive individual tolerates a goal of 140/90 without side effects there is no reason to decrease or stop medication allowing an increase in blood pressure to 150/90. Furthermore, many think that there is reason to believe that the lower goal, absent the concern of medication side effects, probably is more beneficial.

New Statin Guidlines


New guidelines from the American Heart Association and the American College of Cardiology have changed both the indications for taking statins and, in some cases, have suggested a lower dose. Also, the use of additional medications to assist in lowering cholesterol values has been called into question.


The new statin dose guidelines require in most cases a calculation of cardiovascular risk over the next ten years. This calculation includes age, sex, race, systolic blood pressure, blood pressure medication history, history of diabetes, smoking history, total cholesterol and HDL cholesterol values. The risk calculation does not include family history. Your risk can be calculated by using the formula included in the following link:


Within days of the announcement experts criticized the cardiovascular calculator as outdated and, as a result, overstating the risk of cardiovascular disease by up to 100%. All cardiovascular calculators rely on historical data which don’t adequately reflect the very significant decrease in cardiovascular risk in more recent years and this one is no exception.


The guidelines recommend abandoning the former goals of reducing LDL, or bad cholesterol, to below 100 or below 70 for people at high risk. The authors of the guidelines stated that those goals resulted in undertreatment of some patients and overtreatment of others.


Instead they suggest individualizing treatment based on risk. For an individual younger than 75 years and over 21 years with known cardiovascular disease high-intensity dosing of statin medication is prescribed with a goal of reducing LDL cholesterol by 50% or more not tied to a specific number. For an individual over 75 years with known cardiovascular disease the goal is an LDL reduction of between 30-50% (moderate-intensity dosing.).


High-intensity statin dosing with a goal of a 50% or more reduction in LDL is also suggested for people between the ages of 40 and 75 years with type 1 or type 2 diabetes, LDL cholesterol between 70 and 189 and a risk of cardiovascular disease that exceeds 7.5% over the next ten years. For people with diabetes between the ages of 40 and 75 years with LDL cholesterol between 70-189 and a less than 7.5% ten year risk for cardiovascular disease moderate-intensity statin dosing is suggested (an LDL reduction of between 30-50%.)


Moderate-to high-intensity statin dosing is indicated for those people between the ages of 40 and 75 years, LDL cholesterol between 70 and 189 and a 7.5% or more risk of cardiovascular disease in the next ten years.


Only individuals with LDL cholesterol values of 190 or more are designated to receive statin therapy in the absence of known cardiovascular disease, history of diabetes or a 7.5% or more risk of cardiovascular disease over the next ten years. In these situations high-dose statin therapy is suggested.


An example: A 45 year old woman with an LDL cholesterol of 150 and a less than 7.5% risk of cardiovascular disease over the next ten years would not require statin treatment.




Cardiovascular disease is defined as acute coronary syndromes, or a history of myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin.


The authors of the guidelines do not recommend adding additional medications (such as Zetia) to achieve LDL cholesterol goals.


Fish Oil and Prostate Cancer

A recent report in the Journal of the National Cancer institute concluded that men with a high blood concentration of fatty acids (omega-3) had an increased prostate cancer risk. The conclusion is concerning since it appears to contradict the assumption that fish oil and fatty fish consumption improve the overall health of men.

Moreover, the authors had previously found that high concentrations of trans-fatty acids (yes, the ones now restricted in food processing because of a clear association with heart disease) were associated with a decreased risk of aggressive prostate cancer. Trans-fatty acids are found in margarine and frying oils. Omega-6 fatty acids were associated with a lower risk of total prostate cancer.

Other studies have shown numerous health benefits of omega-3 fatty acid. One study showed a two- to three-fold greater risk for prostate cancer in men who ate no fish compared with those who consumed large amounts of fish in their diet. Other studies have also shown a decreased risk of prostate cancer and of metastatic prostate cancer in men who eat fish more than three times a week.

There are a number of problems with the recent study associating omega-3 fatty acid concentration with prostate cancer. We don’t know the source of the fatty acids in the study patients; there was no information on dietary habits or supplements taken. We don’t know anything about the subject’s risk factors for prostate cancer such as ethnicity, PSA levels, age and weight. Additionally, the study was based on a single blood test, not an analysis of concentrations over time.

Of interest, Japanese men consume the most omega-3 fatty acids from their diet in the world and yet are experiencing a declining risk for death due to prostate cancer. Additionally, many studies have demonstrated the cardiovascular benefits of omega-3 fatty acids.

Until more information is available to the contrary, in my opinion, it is prudent for patients with cardiovascular disease to consume oil fish several times a week and use fish oil if a dietary source is unavailable or unappealing.

Reappraising Vitamin D and Calcium Supplementation


Recently the U.S. Preventive Services Task Force (USPSTF) issued a recommendation against routine daily supplementation with vitamin D and calcium in most circumstances. They conclude that there is adequate evidence demonstrating the taking 400 units of vitamin D and 1,000 mg of calcium does not prevent fractures in postmenopausal women. In addition, they note that the aforementioned supplementation does cause an increase in kidney stones and, therefore, is associated with harm.

It is unclear whether higher doses of vitamin D and calcium prevent fractures in men and postmenopausal women. Oddly, vitamin D supplementation is effective in preventing falls in community-dwelling adults aged 65 or older who are at risk for falls. The USPSTF does recommend vitamin D for this group.

Although the routine use of vitamin D and calcium supplements have been called into question the need for adequate levels of vitamin D in the body remains a constant. Those who lack enough vitamin D suffer from inadequate bone formation and, in addition, lack the beneficial effects of vitamin D on muscle strength and balance.

Obtaining vitamin D from dietary sources is best, just as we find that all vitamins are most effective when obtained from dietary sources. Good sources of vitamin D include: fatty fish and fortified foods, such as milk, yogurt and orange juice.

For individuals at risk for vitamin D deficiency supplementation is essential. This group would include the chronically ill, patients with intestinal malabsorption, pregnant women and those being evaluated for osteoporosis.

For now, the best approach might be to measure vitamin D levels in individuals at risk for vitamin D deficiency, including those mentioned above, older women, and women with risk factors for osteoporosis, and use vitamin D supplementation to bring the levels to normal.

Risk factors for osteoporosis include bone fracture, a family history of fractures or osteoporosis, smoking, excess alcohol consumption, malabsorption, the use of certain medications, sedentary life style and small body frame.