Epidemiologic studies suggest that the incidence of myocardial infarction or hospitalization for coronary heart disease (CHD) is increased up to twofold in HIV-infected individuals compared with age-matched controls without HIV infection. This increased risk of ischemic events likely is attributable to a higher prevalence of certain CHD risk factors that are independent of HIV status, such as smoking, as well as to both HIV infection and antiretroviral (ARV) medications. These various factors may interact in ways that are complex and incompletely understood.
Among the traditional CHD risk factors, dyslipidemia is common among persons with HIV infection, and can be caused both by HIV itself (e.g., resulting in low high-density lipoprotein [HDL] cholesterol) and by ARV therapy (ART); see chapter Dyslipidemia. Insulin resistance and diabetes also appear to be more prevalent in HIV-infected patients. (See chapter Insulin Resistance, Hyperglycemia, and Diabetes on Antiretroviral Therapy.) Visceral fat accumulation, a poorly understood complication of HIV or ART, also may contribute to CHD risk in certain patients (see chapter Abnormalities of Body-Fat Distribution).
Several studies have suggested that low CD4 cell counts are associated with myocardial infarction and stroke. Additionally, a number of studies suggest that inflammation and immune activation owing to uncontrolled HIV infection also likely contribute to atherosclerosis. For example, in the Strategic Management of Antiretroviral Therapy (SMART) study, CHD events were more common in patients on intermittent ART than in those on continuous ART, possibly because of adverse effects of intermittent HIV viremia on inflammation, coagulation, and lipid parameters. There is even preliminary evidence that so-called elite controllers - patients with undetectable HIV viremia and preserved CD4 counts in the absence of ART - have increased carotid intima-medial thickness (a marker of atherosclerotic burden) compared with HIV-uninfected subjects, after adjusting for other CHD risk factors. Limited data also suggest that initiation of ART leads to improvement of endothelial dysfunction (an early marker of atherosclerosis that is predictive of future CHD events) and to improvement in markers of inflammation and immune activation. Taken together, these observations suggest that earlier initiation of ART could reduce CHD risk.
On the other hand, even patients with virologic suppression on ART appear to have higher levels of various physiologic markers of cardiovascular risk than the HIV-uninfected persons, perhaps owing to persistent immune activation. Additionally, exposure to ARVs has been linked to risk of myocardial infarction in large cohort studies such as the D:A:D study. In particular, the risk has been associated with use of ARV regimens that are based on protease inhibitors (PIs) rather than nonnucleoside reverse transcriptase inhibitors (NNRTIs). The risk is attributable in part to adverse changes in lipid profiles, but there appears to be additional risk associated with PIs that is not accounted for by changes in lipids; this remains poorly understood. Among the nucleoside reverse transcriptase inhibitors (NRTIs), abacavir and didanosine have been associated with increased risk of myocardial infarction in some but not all studies. The mechanism of this potentially increased risk has not been determined.
Clinicians should ask all patients about CHD, CHD risk equivalents, and CHD risk factors. Assess the following during the history:
- Age (>45 for men, >55 for women)
- History of angina, myocardial infarction, or other heart disease
- Family history of premature CHD in first-degree relatives (men aged <55, women aged <65) and diabetes mellitus
- Smoking history
- Glucose intolerance or diabetes mellitus
- CHD risk-equivalent states:
- Diabetes mellitus
- Peripheral vascular disease
- Cerebrovascular disease
- Abdominal aortic aneurysm
- Use of cocaine or amphetamines
- Physical inactivity
Perform a physical examination to include the following:
- Vital signs, including blood pressure, pulse, weight, and body mass index (BMI); see chapter Dyslipidemia
- Jugular venous distention
- Heart and lung examination
- Auscultation for carotid or femoral bruits
- Peripheral pulses and evaluation of extremities for peripheral edema
- Abdominal examination for fat accumulation, ideally with measurement of waist circumference
- Determine whether the patient has established CHD or a CHD risk-equivalent state (see above).
- Stratify risk based on the number of CHD risk factors and the Framingham risk calculator if two or more major CHD risk factors are present. The risk calculator is available at cvdrisk.nhlbi.nih.gov/calculator.asp.
- Check fasting lipids and glucose annually; more frequently if abnormal.
- Patients with established or suspected CHD should undergo standard evaluations such as electrocardiography and exercise stress testing; refer to a cardiologist as appropriate.
- Work closely with patients to reduce their risks of CHD events.
- For patients who smoke, smoking cessation is the single most important intervention to reduce risk of CHD events (see chapter Smoking Cessation).
- Manage dyslipidemia according to established guidelines (see chapter Dyslipidemia).
- Manage hypertension by lifestyle intervention (e.g., sodium restriction, exercise, weight loss) and pharmacologic therapy as indicated.
- Optimize glycemic control in patients with diabetes mellitus (see chapter Insulin Resistance, Hyperglycemia, and Diabetes on Antiretroviral Therapy).
- Encourage weight loss in overweight and obese patients, with referral to a dietitian as appropriate.
- Encourage exercise, ideally 30 minutes at moderate intensity 5-6 times per week.
- Encourage a healthy diet that is low in saturated fats.
- Consider aspirin 81 mg QD for primary prevention of CHD in patients at moderate to high risk who do not have contraindications to aspirin use.
- For patients who use cocaine or amphetamines, encourage cessation.
- Both HIV infection and ARV medications may contribute to the risk of CHD, and the available data suggest that the risk of CHD is increased in HIV-infected patients relative to the general population.
- Review the benefits of smoking cessation.
- Review exercise possibilities to determine which activities might be realistic and acceptable for the patient.
- Review the patient's eating habits and explain the need to work with a dietitian to optimize lipid levels and keep blood glucose within normal ranges.
- Emphasize the importance of other lifestyle modifications, such as weight loss (if appropriate).
- Educate patients about any pharmacologic therapy that is indicated.
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