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Lipid Screening and Cardiovascular Risk

Updated June 2007

VI. LIPID SCREENING AND CARDIOVASCULAR RISK

Recommendation:

Clinicians should assess HIV-infected patients for cardiovascular risk factors at least annually.

Lipid screening and prevention of heart disease have assumed increasing importance because of the increased life expectancies of HIV-infected patients receiving HAART. Some studies suggest that heart disease is more common among HIV-infected individuals compared with those without HIV disease.1 Lipid abnormalities can occur rapidly within months of initiation of ARV therapy. The full clinical significance of these laboratory abnormalities is not yet clear, although the abnormalities may contribute to cardiovascular risk and may be associated with premature coronary heart disease (CHD) in some patients, especially those with preexisting risk factors for CHD (see Table 1). In a prospective, observational study of more than 23,000 patients followed with a median cumulative exposure to combination ARV therapy of 1.9 years, a significantly increased risk of myocardial infarction was observed, although the absolute risk of myocardial infarction was low.2

Table 1: Major Risk Factors Exclusive of LDL Cholesterol That Modify LDL Goals*
  • Cigarette smoking
  • Hypertension (blood pressure ≥140/90 mmHg or on antihypertensive medication)
  • Low HDL cholesterol (<40 mg/dL)†
  • Family history of premature CHD  (CHD in male first-degree relative <55 years; CHD in female first-degree relative <65 years)
  • Age (men ≥45 years; women ≥55 years)
From the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP). Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol
Refer also to the Framingham risk prediction calculator, available at: http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof
* Diabetes is regarded as a coronary heart disease risk equivalent.
† HDL cholesterol ≥60 mg/dL counts as a “negative” risk factor; its presence removes one risk factor from the total count.



Hypertriglyceridemia is of special concern for clinicians treating HIV-infected patients taking ARV agents, and the metabolic syndrome has been increasingly recognized in HIV-infected patients receiving HAART.

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A. Monitoring Lipid Profile

Recommendation:

Clinicians should monitor patients receiving ARV therapy for dyslipidemia by obtaining a fasting lipid profile before initiation of ARV therapy, between 3 and 6  months after starting or changing ARV treatment, and at least annually thereafter. More frequent monitoring may be indicated by the presence of persistent lipid elevation, cardiovascular risk factors, or cardiovascular symptoms.

A fasting lipid profile, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides, should be obtained prior to initiation of HAART, then between 3 to 6 months after starting or changing ARV therapy, and annually thereafter. Alternatively, if collection of a fasting sample is not feasible, a nonfasting total cholesterol and HDL-C profile may be obtained. The clinician should proceed with a fasting lipoprotein profile when the nonfasting total cholesterol is ≥200 mg/dL, triglycerides are ≥150 mg/dL, or the HDL-C is <40 mg/dL.

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B. Management of Lipid Disorders

The management of lipid disorders in HIV-infected patients parallels management in non-HIV-infected patients. Individual cardiovascular risk assessments and management of lipid disorders can be accomplished by following current guidelines for assessment and management, such as those published by the National Cholesterol Education Program (NCEP) and the Adult AIDS Clinical Trial Group (ACTG) Cardiovascular Disease Focus Group. The NCEP Adult Treatment Panel (ATP) III guidelines are a useful quick reference (available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/atglance.pdf).

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1. Lifestyle Modifications

Recommendation:

Clinicians should recommend lifestyle modifications, such as smoking cessation, increased exercise, weight loss, nutrition therapy, and substance use treatment.

Evidence suggests that provider-initiated discussions of lifestyle modifications positively impact patient behaviors. It is important to focus on modifiable risk factors, especially smoking cessation (see Health Promotion and Maintenance).3 Careful attention to blood pressure control and weight control can significantly improve health, and the importance of diet and exercise should not be underestimated.

Regardless of whether or not patients have known CHD or CHD equivalents (type 2 diabetes, atherosclerotic disease, or stroke), therapeutic lifestyle changes should be an early intervention for the treatment of lipid disorders. These changes include increased physical exercise, weight reduction when indicated, and dietary changes; however, the use of lipid-lowering drugs may be needed to achieve appropriate goals of the ATP III guidelines of the NCEP.

Consultation with a registered dietitian may be helpful in achieving dietary goals. In general, advising patients to restrict intake of foods high in saturated fats and cholesterol should be beneficial.

Table 2 outlines cholesterol goals and cholesterol levels at which either lifestyle modifications or drug therapy should be initiated.

Table 2: LDL and Non-HDL Cholesterol Goals and Thresholds for Therapeutic Lifestyle Changes and Drug Therapy in Different Risk Categories
Risk Category LDL Goal (mg/dL) LDL Level at Which to Initiate Lifestyle Changes (mg/dL) LDL Level at Which to Consider Drug Therapy (mg/dL) Non-HDL Goal (mg/dL)*
CHD or CHD risk equivalents:
diabetes mellitus, atherosclerotic disease (CAD or stroke), or multiple risk factors (10-year risk >20%)
<100 >100 ≥130 (100-129: drug optional)† <130
2+ risk factors: HDL <40 mg/dL, strong family history, age >45 years, and smoking (10-year risk >20%) <130 ≥130 10-year risk
10%-20%: ≥130
10-year risk <10%: ≥160
<160
0-1 risk factor‡ <160 ≥160 ≥190 (160-189: LDL-lowering drug optional) <190
Modified from the Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/
LDL, low-density lipoprotein; CHD, coronary heart disease; CAD, coronary artery disease; HDL, high-density lipoprotein.
* Non-HDL cholesterol = (total cholesterol – HDL). When LDL cannot be measured because the triglyceride level is >200 mg/dL, non-HDL cholesterol may be used as a secondary goal. The non-HDL cholesterol goal is 30 mg/dL higher than the LDL cholesterol goal.
† Some authorities recommend use of LDL-lowering drugs in this category if an LDL cholesterol level of <100 mg/dL cannot be achieved by therapeutic lifestyle changes (dietary and exercise intervention). Others prefer use of drugs that primarily modify triglycerides and HDL (e.g., nicotine acid or fibrate). Clinical judgment also may suggest deferring drug therapy in this subcategory.
‡ Almost all people with 0 or 1 risk factors have a 10-year risk <10%; thus, 10-year risk assessment in people with 0 or 1 risk factors is not necessary.

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2. Pharmacologic Treatment of Dyslipidemia

Recommendations:

Pharmacologic treatment of dyslipidemia should be guided by currently available clinical guidelines.

When a statin is indicated, clinicians should avoid using simvastatin and lovastatin in patients who are concurrently receiving protease inhibitors (PIs).

Treatment of dyslipidemia with pharmacologic therapies should be combined with lifestyle and cardiovascular risk modification.4-7 For patients at highest risk, an even more aggressive approach may be appropriate, including dual lipid-lowering therapy or changes in their ARV regimens for adequate lipid control. These approaches are based on studies suggesting potential benefit for reductions in LDL-C <100 mg/dL to as low as 70 mg/dL.8

Some lipid-lowering agents have relative and absolute contraindications with certain ARV agents, particularly PIs. For example, lovastatin and simvastatin are contraindicated with PIs. Pravastatin and atorvastatin are the statins with the best-studied pharmacokinetic profile for use with PIs. Higher doses of pravastatin may be needed due to induction and subsequent lowering of drug levels by PIs, whereas lower initial doses of atorvastatin may be appropriate due to increased blood levels with concomitant PI use. The role of newer agents with less cytochrome P450 interaction, such as fluvastatin and rosuvastatin, has yet to be defined, because experience with these agents in the HIV-infected patient population is limited. However, rosuvastatin will not likely interact with PIs and NNRTIs.

For treatment guidelines, refer to the Medical Care Criteria Committee’s Long-Term Complications of Antiretroviral Therapy.

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REFERENCES

1. Klein D, Hurley L, Quesenberry C. Hospitalizations for CHD and MI among Northern California HIV+ and HIV- men: additional follow-up and changes in practice. 12th Conference on Retroviruses and Opportunistic Infections, Boston 2005; Abstract 869.

2. Friis-Moller N, Sabin CA, Weber R, et al. Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med 2003;349:1993-2003. Erratum in: N Engl J Med 2004;350:955.

3. Mamary EM, Bahrs D, Martinez S. Cigarette smoking and the desire to quit among individuals living with HIV. AIDS Patient Care STDS 2002;16:39-42.

4. Dube MP, Sprecher D, Henry WK, et al. Preliminary guidelines for the evaluation and management of dyslipidemia in adults infected with human immunodeficiency virus and receiving antiretroviral therapy: Recommendations of the Adult AIDS Clinical Trial Group Cardiovascular Disease Focus Group. Clin Infect Dis 2000;31:1216-1224.

5. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497. Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/profmats.htm

6. Updated guidelines for cholesterol management. JAMA 2001;285:2508-2509.

7. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. National Heart, Lung, and Blood Institute Obesity Education Initiative, 1998.

8. Grundy SM, Cleeman JI, Merz CNB, et al. Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation 2004;110:227-239.

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