Applied Evidence
Statin adverse effects: Sorting out the evidence
Studies have assessed the incidence of everything from myopathy to diabetes and cataracts, but findings have been inconsistent. Here’s help in...
Use validated criteria to make the diagnosis
Include FH in your differential diagnosis when evaluating patients with very high LDL levels. However, rule out possible secondary causes of elevated LDL before rendering a conclusion. Hypothyroidism, nephrotic syndrome, diabetes, and liver disease are among the most common secondary causes of high LDL cholesterol.13
Several validated criteria sets can be used to establish an FH diagnosis. No single criteria set is more valid or more widely adopted around the world. All 3 of the most commonly used criteria sets take into account family history and a patient’s LDL level, and 2 of the 3 factor in physical findings (TABLE 2).9
Physical exam findings that suggest FH can be subtle (FIGURE). Tendon xanthomas are a thickening of the soft tissue as a result of infiltration by lipid-rich cells. They most commonly occur at the Achilles and metacarpal tendons, but can also be seen at the patellar and triceps tendons. Xanthomas may not be readily visible, so it’s important to run your fingers over these areas to detect nodularity or thickening. While the presence of a tendon xanthoma makes FH highly likely, they are present in less than half of patients with FH.17
Tuberous xanthomas or xanthelasmas are waxy-appearing growths that may look yellow or orange and appear to be pasted on the skin in areas around the face, commonly the eyelids. The presence of xanthelasmas in a patient younger than age 25 suggests FH.
Finally, arcus corneae is an opaque ring around the outer edge of the cornea. When this is seen in patients younger than age 45, it’s suggestive of FH.13 If you note tendon xanthomas, xanthelasmas, or arcus corneae while examining any of your patients, be sure to order an LDL level if it hasn’t already been done.
Is genetic testing necessary?
The only way to make a definitive diagnosis of FH is to find a mutation in a gene known to affect LDL metabolism. However, because genetic testing is expensive—and because more than one thousand different genetic defects can contribute to FH—it’s not practical to test every patient. Furthermore, since an estimated 20% of the mutations that contribute to FH have not yet been clearly delineated, a “normal” result on a genetic test might be misleading.5 Therefore, the diagnosis of FH usually is a clinical one. After clinically diagnosing a patient with FH, it’s imperative to screen first-degree family members by measuring their LDL cholesterol levels.
Lifestyle changes, statins can ward off CHD
Lifestyle modifications (ie, improved diet and exercise) and statins are the treatments of choice for patients with FH. Before starting pharmacotherapy, patients should undergo 3 months of lifestyle modification to assess how well this approach improves their lipid levels, assuming the patient doesn’t have additional risk factors such as hypertension or tobacco use, in which case he or she might require immediate pharmacotherapy. Statins can be initiated simultaneously with lifestyle choices in patients with an LDL >190 mg/dL.18
Lifestyle modification. Although FH is a genetic problem, patients should be encouraged to make healthy choices regarding diet and exercise. While the best choices may not get FH patients to their LDL goal, better choices may mean that patients can take fewer medications, or lower doses of them. Healthy lifestyle choices can also have other positive effects on cardiovascular risk (eg, lowering blood pressure).
Patients can’t be expected to navigate their food choices alone, and several visits with a dietician will likely be needed. It’s important to emphasize the family influence on diet and get the entire family involved with making healthy food choices.
In addition to addressing diet and exercise, be sure to encourage patients to abstain from tobacco and manage stress as part of their overall effort to reduce the likelihood of a cardiovascular event.
Statins. Early treatment of FH with statins can delay initial coronary events and prolong life.19 In a 12.5-year study of 2146 patients with FH, approximately 80% of patients treated with statins survived without experiencing CHD, compared to slightly less than 40% of those who were not treated with statins.19 Patients treated with statins had a 76% reduction in risk of CHD compared to those who didn’t receive statins.19 Even low doses of statins started early have been shown to help avoid myocardial infarction in adults with FH.20
The goal of treatment for FH is to reduced LDL levels by 50%.21 In pediatric patients, treating to an LDL level of 130 mg/dL is an alternative goal.21 Because it’s challenging to achieve this goal with improved diet and exercise alone, treatment with a statin is often necessary.22