Cholesterol

Cholesterol is a fat or lipid that the body uses in cells, hormones and tissues. High levels of cholesterol in the blood are associated with an increased risk of hardening and narrowing of the arteries and heart attack.

Low levels of cholesterol are often seen among people with advanced HIV disease. However, research has shown that people on protease inhibitor therapy have significantly higher levels of total cholesterol when compared with HIV-positive people not on protease inhibitors.

Total cholesterol levels (range):

• Average: 2.3 to 5.8 mM (88 - 224mg/dl).

• High: 5.8 to 6.9 mM (224 to 266mg/dl).

• Very High: over 6.9 mM (over 266mg/dl).

To convert into United States cholesterol measurements in mg/dl, multiply mM by 38.6. To convert United States measurements into mM, multiply by 0.0259.

In the United Kingdom the average adult cholesterol level is around 5.6 mM, but an optimal level is considered to be less than 5.2 mM (200mg/dl).

HDL ('good' cholesterol) levels:

• Normal range in women: 1.0 to 2.0 mM (38 to 77mg/dl).

• Normal range in men: 0.7 to 1.6 mM (27 to 62mg/dl).

British HIV Association guidelines recommend that individuals with total cholesterol above 6.5mM or an LDL to HDL cholesterol ratio of greater than 4 should consider a number of interventions:

• Switching to a PI-sparing regimen if taking your first regimen.

• Stop smoking.

• Increase exercise levels, reduce intake of saturated fat and look at diet with advice from dietitian.

• Treatment with pravastatin (40mg a day) or atorvastatin (10mg a day).

The target for total cholesterol is 5.5mM or less (212mg/dl), with a target LDL to HDL ratio of 3 or less.

Lipids and lipoproteins

Lipid is the general term for fat in the blood. Examples of lipids include cholesterol, phospholipids and triglycerides. Lipids are carried in the blood as lipoproteins.

There are five different types of lipoproteins including low density lipoprotein (LDL) and high density lipoprotein (HDL).

LDL is sometimes known as 'bad' cholesterol because it is associated with atherosclerosis or 'hardening of the arteries'. This can lead to angina, heart attack and stroke. HDL is sometimes known as 'good' cholesterol because it clears cholesterol from the arteries to the liver, where it is removed from the body.

The American National Cholesterol Education Program has graded target LDL levels according to a person's risk of heart disease. For people with no risk factors or one risk factor for heart disease, the target is 4.1mmol/L. For people with two or more risk factors, the target is 3.3 mmol/L. For people with heart disease, the target is 2.5 mmol/L. Key risk factors include: smoking, high blood pressure, diabetes, family history of heart disease, age over 45 years in men, post-menopause in women.

The Quebec Cardiovascular Study found that the ratio of total cholesterol to HDL cholesterol was superior to the LDL:HDL ratio in predicting cardiovascular events, but this formula has not been adopted universally (Lemieux 2001).

Triglycerides

Triglycerides are fats which occur in the human body. They are made by the body from fats and carbohydrates in food, and stored in fat tissue.

A high level of triglycerides, called hypertriglyceridaemia, is associated with coronary artery disease and diabetes mellitus.

High triglycerides have been observed among people with AIDS before the advent of protease inhibitors. However, the recent cases of high triglycerides are among people doing well on protease inhibitors. Early studies found that about 15-20% of people on protease inhibitors had high triglycerides.

Triglyceride levels:

• Normal: 0.5 to 1.8 mM (44 - 160mg/dl).

• Normal to high: 1.8 to 4.5 mM (160 to 400mg/dl).

• High: 4.5 to 11.3 mM (400 - 1000mg/dl).

• Very high: over 11.3 mM (over 1000mg/dl).

To convert triglyceride measurements in mM into United States measurements in mg/dl, multiply by 88.5. To convert mg/dl into mM, multiply by 0.0113.

As tests are done on an empty stomach, results are called fasting levels. Triglyceride levels are always higher after a meal.

British HIV Association guidelines recommend that people with fasting triglyceride levels above 8mM should:

• Consider switching to a PI-sparing regimen if taking their first regimen.

• Stop smoking.

• Increase exercise and adjust diet.

• Consider fenofibrate or gemfibrozil treatment to reduce triglyceride levels.

The target triglyceride level is less than 4mM in individuals with fasting triglycerides currently above 8mM, and less than 6mM in those with fasting triglycerides above 10mM.

Insulin and glucose

Produced by the pancreas, insulin is the substance which allows the body to make use of sugar. Insulin resistance suggests that the body is not responding properly to insulin. A consequence of insulin resistance is a rise in both insulin and sugar levels in the blood. High levels of insulin in the blood and insulin resistance are associated with lipodystrophy.

Impaired glucose tolerance, leading to abnormally high levels of glucose in the blood, is also part of the spectrum of metabolic changes seen in patients taking antiretroviral therapy.

Glucose tolerance is measured either by checking fasting glucose levels or by a two-hour glucose tolerance test, which checks how high blood glucose levels have risen after two hours in response to the infusion of a set amount of glucose.

Fasting glucose levels between 6.1 and 6.9mM are called impaired glucose tolerance if two-hour glucose tolerance lies between 7 and 11 mM. Fasting glucose levels above 7mM and two-hour glucose tolerance above 11.1mM are called diabetes.

To convert glucose measurements from mM to mg/dl, multiply by 18.0. To convert glucose measurements from mg/dl to mM, multiply by 0.0555.

If you are diagnosed with impaired glucose tolerance or diabetes, various interventions will be recommended in order to restore normal glucose tolerance (or to prevent the condition from getting worse):

• Switching from a PI- to a non-PI-containing regimen if it is your first regimen.

• Increasing exercise levels. Exercise improves glucose tolerance.

• Dietary changes as recommended by a dietitian.

• Aim to reduce body mass index (BMI) below 25 kg/m² by a combination of diet and exercise. BMI is calculated by dividing your weight by the square of your height (in metric measures).

• Treatment with metformin to restore a more normal response to insulin, if you do not have severe fat wasting and your BMI is above 25 kg/m² (high body fat).

• In people with intermediate body fat (BMI 18 to 25 kg/m²), sulphonylurea treatment may be recommended.

• If you have severe fat wasting (BMI below 18 kg/m²), rosiglitazone may be recommended instead, because metformin may further increase fat loss, whereas drugs of the glitazone class may encourage the accumulation of some subcutaneous fat.

Monitoring lipodystrophy

Body fat changes can be monitored in a number of ways:

• Skin fold tests: this test needs to be done by a dietitian or doctor experienced in use of the test, and will be used to monitor changes in the amount of subcutaneous fat on the arms or legs, but these changes will not be representative of total body fat changes.

• Bioelectrical impedance: this test passes an electric current through the body and measures impedance of the current. Fat is a poor electrical conductor compared to muscle. This test cannot detect regional changes in body fat, only total body fat changes.

• Dual energy x-ray absorptiometry (DEXA) scan is a method which can show the distribution of fat, muscle and bone in the body, and can detect changes in different parts of the body. It is likely to produce more accurate measurements of fat loss from the limbs, because it cannot distinguish between subcutaneous and visceral fat. However, this test is expensive and is less accurate in very thin or very obese people.

• Computerised tomography (CT) scan: this is a type of x-ray in which the x-ray source and the scanner rotate around the body. It produces detailed cross-sectional images of the body, and is considered the most accurate measure of whole body subcutaneous and visceral fat. Again, this test is expensive and little used expect in small clinical trials.

None of these methods has been validated for monitoring lipodystrophy, and at present International AIDS Society-USA guidelines do not recommend any specific method for routine clinical monitoring.

Monitoring guidelines for metabolic abnormalities

The US ACTG Cardiovascular Disease Focus Group has developed guidelines on the monitoring and management of dyslipidemia (Dubé ²000).

The group has made the following recommendations:

• A fasting lipid profile should be obtained before starting HAART, and again three to six months later. Individuals with elevated triglycerides at baseline may need to be monitored sooner, e.g. within one to two months of starting therapy.

• In the absence of accurate LDL cholesterol level data (usually due to very high triglyceride levels), treatment intervention decisions should be based on total cholesterol and HDL cholesterol level, since total cholesterol levels may be misleading in this context.

• Patients should be routinely screened for other risk factors for heart disease, such as smoking, family history of heart disease, high blood pressure, menopause, physical inactivity, obesity and diabetes.

• Exacerbating factors such as excessive alcohol use, hypothyroidism, liver or kidney disease or hypogonadism should also be taken into account. Drugs used to treat these (or any other conditions) should be considered.

See Treating body fat and metabolic changes in Anti-HIV therapy: Body fat and metabolic changes whilst on treatment for further details of current treatment guidelines in the event of metabolic abnormalities.

References

See References - body fat and metabolic changes in Anti-HIV therapy: body fat and metabolic changes whilst on treatment.