American College of Physicians: Internal Medicine — Doctors for Adults ®

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Lipid disorders

From the September ACP Observer, copyright © 2005 by the American College of Physicians.

Usually treatable and arguably preventable, lipid disorders are rarely isolated medical conditions. Often, they go hand-in-hand with other widespread cardiovascular risk factors, including diabetes, obesity, smoking, high blood pressure, impaired glucose tolerance, metabolic syndrome and lack of exercise.

However, even in patients with no additional comorbidities, abnormal cholesterol levels can provide clues to looming cardiovascular trouble. But when should you start looking for those clues?

According to the National Cholesterol Education Program's Adult Treatment Panel III (ATP III) guidelines, physicians should begin screening adults age 20 or over, while the U.S. Preventive Services Task Force (USPSTF) argues for regular screening starting at age 35 for men and age 45 for women, unless patients have other existing risk factors.

The two groups also don't agree on the value of regular triglyceride screening. ATP III guidelines recommend screening for hypertriglyceridemia, saying high triglyceride levels may indicate metabolic syndrome, while the USPSTF has found insufficient evidence to recommend either for or against routine triglyceride screening.

And when it comes to treating lipid disorders, there is also debate about how low some patients' cholesterol levels should go. Last year, the ATP III guidelines were updated to include an optional therapeutic LDL target of less than 70 mg/dL in patients at very high risk.

"Many patients can reach this level on medium or high-dose statins—and sustain few additional side effects, save for myopathy at high doses," said Michael Pignone, ACP Member, who authored the PIER module on dyslipidemia screening. "The tough question is whether to add a second drug [to reach that target]." The costs and risks of side effects go up with combination therapy, Dr. Pignone pointed out, "and such an approach has not been tested in trials with coronary heart disease endpoints."

How should physicians reconcile guideline differences? By concentrating, experts say, on patients' global risk.

"Physicians talk about cholesterol, then talk about blood pressure—but these things work together," said Dr. Pignone. "Even a modest level of dyslipidemia, along with other risk factors, may need treatment."


This colored scanning electron micrograph of a coronary artery cross section shows atherosclerosis, with fatty plaque (in yellow). A fatty diet high in cholesterol can reduce blood flow and lead to clots or blockages.



William B. Kannel, FACP, a senior investigator with the Framingham Heart Study, agreed that patients' global risk scores are critical in treatment decisions for lipid disorders. He also has his own views about when to begin lipid screening.

"Physicians should start looking at this in the early teen years, because occasionally you'll see someone with a genetic problem," Dr. Kannel said. "It's particularly appropriate for children whose mother and father developed coronary disease at an early age"—a factor that doubles children's risk of developing coronary heart disease (CHD).

This edition of ACP Observer Special Focus is designed to help optimize your ability to treat dyslipidemia, with recommendations for screening, therapy and thorough follow-up.

ATP III CLASSIFICATIONS

LDL cholesterol

  • Optimal: less than 100 mg/dL
  • Near or above optimal: 100-129 mg/dL
  • Borderline high: 130-159 mg/dL
  • High: 160-189 mg/dL
  • Very high: greater than or equal to 190 mg/dL

Total cholesterol

  • Desirable: less than 200 mg/dL
  • Borderline high: 200-239 mg/dL
  • High: greater than or equal to 240 mg/dL

HDL cholesterol

  • Low: less than 40 mg/dL
  • High: greater than or equal to 60 mg/dL

SCREENING

Initiate screening for men at age 35 and women at age 45 to identify candidates for intensive diet and drug therapy. Continue screening patients over age 65 who are in generally good health, unless they have a short-term life expectancy.

While you should get a fasting lipid profile every five years for these adults, screen patients more frequently if they exhibit changes in diet or weight that put them at higher risk for lipid disorders. If the patient is not fasting, use total cholesterol and HDL cholesterol levels for initial screening; if initial results are abnormal, get a fasting lipid profile to calculate LDL cholesterol. Draw two separate measurements to ensure an accurate assessment of serum lipids.

Screen adults in their 20s and early 30s who have increased risk or evidence of hyperlipidemia on physical exam, or increased risk of cardiovascular disease due to other risk factors. Risk factors include diabetes, a positive family history of premature cardiovascular disease (CVD) and a family history of dyslipidemia.

DIAGNOSIS

Use history, physical exam and lab evaluation, including a second fasting profile, to confirm the diagnosis of a primary or secondary lipid disorder, and identify other risk factors.

Get a history of coronary disease including myocardial infarction, angina, and coronary artery bypass graft or percutaneous transluminal coronary angioplasty.

Note CHD equivalent status in patients who test positive for one of the following indicators of accelerated atherogenesis:

  • Diabetes mellitus.
  • Noncoronary vascular disease, such as aortic aneurysm, claudication, ankle-brachial index of less than 0.9, and symptomatic carotid disease including stroke and transient ischemic attack.
  • A greater than 20% risk of a cardiovascular event occurring within 10 years.

Evaluate patients for other CHD risk factors, including:

  • Age and sex: men age 45 or older, women age 55 and older.
  • Family history of premature coronary disease in a first-degree relative (CHD in male first-degree relative, age 54 or younger; in female first-degree relative, age 64 or younger).
  • Current use of cigarettes.
  • Hypertension, with blood pressure greater than 140/90 mm Hg, or the use of anti-hypertensive medications.
  • HDL cholesterol of less than 40 mg/dL. (Having HDL cholesterol of greater than 60 mg/dL is considered a protective risk factor.)

Coronary patients have a 10-year risk of more than 20% of having another coronary event or dying from CHD. However, patients without CHD also often have a 10-year risk of greater than 20% for major CHD events when they have both increased LDL cholesterol levels and two or more risk factors.

For patients without CHD or CHD-equivalent status but with two or more risk factors, assess their 10-year absolute risk of myocardial infarction or of dying from CHD using the Framingham risk equation, which includes age, total cholesterol and HDL cholesterol levels, blood pressure, presence of diabetes, and smoking status. (Framingham point scores are online.)

Classify patients by their global risk status:

  • High: CHD or CHD risk equivalent, including odds of more than 20% of an event occurring within 10 years.
  • Moderate: 10% to 20% risk of an event occurring in that same time period.
  • Low: less than a 10% chance of an event occurring in that time period.

HDL cholesterol

Draw fasting lipid profiles in patients with HDL cholesterol levels of less than 40 mg/dL. In terms of CHD risk, HDL cholesterol of less than 40 mg/dL identifies a greater progression for men than for women. Many clinicians use a level of less than 50 mg/dL to identify women at high CHD risk.

While no goals for HDL cholesterol levels have yet been set, two randomized trials of gemfibrozil, one in primary prevention and one in secondary prevention, have shown that increasing HDL cholesterol or lowering triglyceride levels is associated with a reduction in cardiac endpoints.

TREATMENT

Non-drug therapy

Patients should derive no more than between 25% and 35% of total daily calories from fat. Patients should increase their intake of vegetables, fruits and high-fiber foods, and maintain a plant-base diet enriched with plant stanols—found in plant foods such as wheat, rye and corn—and soluble fiber.

This type of diet can reduce LDL cholesterol levels by between 5% and 15%—and, if adopted nationwide, would cut Americans' need for cholesterol-lowering drugs by two-thirds.

To reduce high LDL cholesterol levels, start dietary changes either before or at the same time as drug interventions, according to patients' risk for a coronary event. Consider recommending lifestyle changes to young adults (men age 20-35, women age 20-45) if LDL cholesterol is equal to 130 mg/dL or higher.

Patients can more effectively lower their LDL cholesterol with dietary changes (as well as drug regimens) if they maintain an ideal body weight, with a body mass index of less than 25. Consider referring patients to a nutritionist or cardiac risk-factor counselor familiar with LDL cholesterol-lowering diets to help achieve significant dietary changes.

For patients with high triglycerides or low HDL cholesterol, consider a weight-reduction diet low in saturated fat, cholesterol and simple carbohydrates, with limited alcohol consumption and abundant aerobic exercise. Patients can substantially reduce risk—independent of serum lipid levels—with a diet that limits red meat and animal fats, includes fish rich in n-3 fatty acids; is rich in fruits, vegetables, nuts, and whole grains; and incorporates monounsaturated oils, such as olive and canola oils.

Note, however, that very low-fat diets can adversely raise triglyceride levels and lower HDL cholesterol when compared to low-calorie diets enriched with complex carbohydrates and monounsaturated fats.

Drug therapy

Base the aggressiveness of therapy on patients' risk of a CHD event.

Begin drug therapy in all high-risk patients when non-drug therapies do not reduce LDL cholesterol levels below ATP III goals, depending on age, risk factors and CHD status. LDL cholesterol-lowering drug therapies include:

  • HMG-CoA reductase inhibitors, or statins
  • niacin
  • bile acid-binding resins
  • intestinal cholesterol absorption blockers

For low-risk patients who have less than a 10% chance of a coronary event within the next 10 years, recommend six months of dietary changes and exercise before starting drugs. (Keep in mind that treating dyslipidemia in patients at low short-term risk of CHD events to prevent future events is controversial—and that the cost effectiveness of such treatment is unclear.)

Consider drug therapy sooner for high-risk patients who are free of heart disease but who have a 10-year event risk of more than 20%, especially those with LDL cholesterol levels greater than 15% above threshold.

Identify and treat high-risk young adults, such as those with positive family history, familial hypercholesterolemia and diabetes mellitus. Institute LDL-lowering drug therapy for male smokers under age 35 who have LDL cholesterol of between 160-189 mg/dL. If their LDL level is greater than 190 mg/dL, consider immediate drug therapy.

For patients with severe genetic forms of hypercholesterolemia, consider combination LDL-lowering drugs, such as a statin plus a bile acid sequestrant.

In patients with CHD or its equivalent, guidelines recommend an LDL cholesterol goal of less than 100 mg/dL, although achieving that level may require maximum drug doses or drug combinations. To reduce events and disease progression, clinicians may consider seeking even lower levels for patients who've received post-coronary artery bypass grafting.

For high-risk patients with low HDL cholesterol and high triglyceride levels, you should increase HDL cholesterol to greater than 40 mg/dL and reduce triglycerides to less than 150 mg/dL, after attaining LDL cholesterol goals.

Consider combination therapy in patients with severe lipid elevations, keeping in mind that you may need to prescribe three drugs for some disorders. Be aware of drug interactions, such as those between P-4503A4 metabolized drugs like statins and fibrates, which in combination may induce rhabdomyolysis, myalgia or myositis. Statins may also cause myopathy, renal failure and liver toxicity.

And keep in mind that complications are more common in patients who take more than one lipid-lowering drug; who take other medications that interfere with statin metabolism; or who have other conditions that increase risk, such as immunosuppressive therapy for organ transplantation or renal or hepatic dysfunction.

PATIENT EDUCATION

Work with health care team members to help patients make necessary lifestyle changes that will normalize their lipid profile and lower cardiac risk. A multidisciplinary approach that includes physicians, nurses, dieticians, psychologists and exercise specialists often improves patient compliance.

Patient information should focus on smoking cessation, weight and blood pressure control, regular aerobic exercise, heart-healthy diet and diabetes management. Individualize risk factor identification and intervention for each patient and focus on outcomes. To boost the likelihood of successful lifestyle modification, use mutually agreed-upon goals and outcomes.

Recognize that many patients require repeated attempts to modify often lifelong habits. Use encouragement, empathy and a nonjudgmental approach to foster patients' emotional withdrawal from those habits, as well as written or audiovisual patient education materials to reinforce recommendations. Surveys suggest that more than half of all patients prescribed cholesterol-lowering drugs do not continue taking them 12 months after initial treatment. Reasons for discontinuing therapy include a lack of knowledge about why the medicine was prescribed and a perception that the drugs are not working.

Research shows that community-based intervention programs—such as counseling and follow-up provided by a pharmacist—improve cholesterol management in high-risk patients.

FOLLOW-UP

Regularly screen low-risk patients for lipid disorders. Get a fasting lipid profile at least every five years for those not on a specific diet or drug regimen.

Routinely see high-risk patients on drug therapy to monitor risk, adjust therapy, reinforce adherence to therapy and look for potential side effects. See these patients every few months and get a fasting lipid profile at least once a year.

Studies show that it takes at least one year of drug treatment before clinical endpoints are reduced. Structured, consistent follow-up can enhance patient compliance. Telephone calls, progress letters, reminder postcards, flow charts and a reward system—sending congratulatory certificates, for instance—can be useful.

Access to PIER's lipid disorders module is online; access to its lipid disorders screening module also is online.

The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP.

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Factors to weigh when choosing treatment

Launched in 1948, the watershed Framingham Heart Study has scrutinized the cardiovascular conditions of the residents of Framingham, Mass., for more than 50 years. The study first began reporting on the association between cholesterol levels and heart disease in the early 1960s.

Since then, the study has consistently informed heart disease treatment, as well as cholesterol management guidelines. William B. Kannel, FACP, joined the study near its inception, directed the study from 1966 to 1979 and is now a senior investigator. He spoke with ACP Observer:

On triglycerides:

Physicians don't pay enough attention to the ratio between high triglycerides and low HDL levels. This is a bad profile because it reflects insulin resistance and the presence of small dense LDL, which is highly atherogenic.

On other risk factors:

The one risk factor I would single out is high blood pressure; blood pressure control is extremely important in treating the dyslipidemic patient. If you had a cross section of an artery and vein, side by side, you will find the vein completely free of plaque, where the artery may be completely occluded. The reason? Despite being bathed by the same lipid-laden blood, the vein is free because its pressure is very low.

On treatments:

Some statins work better than others under certain situations. But the connection between the degree of lipid lowering and benefit isn't that highly correlated because of other pleiotropic effects of statins—such as on platelet aggregation and endothelial dysfunction—that accrue.

One interesting combination therapy is ezetimibe with simvastatin. Ezetimibe prevents cholesterol absorption, while simvastatin—a HMG-CoA reductase inhibitor—cuts down hepatic cholesterol production. This combination allows physicians to get a good effect on a lower dose of the statin, thereby diminishing the possibility of myositis, which is apt to occur at a higher dosage.

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Suggestions for selecting treatment

Fortunately for dyslipidemic patients, drug therapies can be tailored to different types of lipid disorders. Below are choices for initial therapy, listed in preferential order.

High LDL
only
1. Statins
2. Resins or absorption blockers
3. Niacin


High LDL/
low HDL
1. Statins
2. Niacin


High LDL/
low HDL/
high triglycerides
1. Niacin and statins
2. Fibrates


High triglycerides with/without
low HDL
1. Fibrates
2. Niacin
3. Statins


Low HDL
only
1. Niacin
2. Fibrates

 

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