HIV and Your Heart

Cardiovascular disease is a general term to describe medical conditions that affect the heart and blood vessels. Examples of major cardiovascular diseases and conditions include coronary artery disease, heart attacks, heart failure and strokes.

Cardiovascular disease is the leading cause of death in the United States and is a growing concern for people living with HIV. This is true, in part, because people with HIV are living longer than ever before, due to the widespread use of antiretroviral (ARV) therapy. And just like their HIV-negative peers, their risk of cardiovascular disease increases once they enter their 50s and 60s.

HIV itself can further increase the risk. Untreated HIV, with its high viral loads, has been linked to cardiovascular disease and experts now recommend starting treatment earlier to avoid cardiovascular damage that many believe is caused by active viral reproduction. However, many of the drugs used to treat HIV can also contribute to cardiovascular disease, notably by raising cholesterol and triglyceride levels.

The good news is that many steps can be taken to help prevent and manage cardiovascular disease. Decades of research, involving HIV-negative and HIV-positive people, have repeatedly shown that lifestyle changes such as diet, exercise and quitting smoking can greatly reduce the risk of cardiovascular disease. When lifestyle changes aren't enough, a number of effective medications and other medical approaches are available. It's also important to take cardiovascular risk factors into account when making crucial HIV treatment decisions, such as when to start or switch treatment and which medications to use.

What are the different types of cardiovascular diseases?
There are a number of cardiovascular diseases. Some directly affect the heart's structure and ability to function. Others indirectly affect the heart by making it harder for blood to circulate through the blood vessels. Some people are born with heart or blood vessel defects (congenital), but most problems occur as a result of disease, lifestyle or age.

Some of the major cardiovascular diseases include:

Aneurysms: An aneurysm is a bulge in the wall of a blood vessel. They usually get bigger over time and can burst.
Angina: Chest pain resulting from reduced oxygen to the heart.
Arrhythmias: An irregular heartbeat. The heart can sometimes beat too slowly (bradycardia) or too quickly (tachycardia), or it can suffer from irregular contractions (fibrillation).
Cardiomyopathy: Disease or damage to the heart muscle, reducing its ability to pump blood.
Congestive Heart Failure (CHF): CHF is when your heart does not pump as strongly as it should, so your body doesn't get the right amount of blood and oxygen. This weakened pumping action can cause fluid to back up in your lungs and other parts of your body.
Coronary Artery Disease (CAD) / Coronary Heart Disease (CHD): The most common form of heart disease, CAD/CHD occurs when fat and scar tissue block arteries in the heart (atherosclerosis), increasing the risk of angina and heart attacks.
Heart Attack (Myocardial Infarction): A heart attack, or myocardial infarction (MI), is an injury to the heart muscle caused by a loss of blood supply. MIs occur when a blood clot blocks the flow of blood through a coronary artery.
High Blood Pressure (Hypertension): High blood pressure is an excessive force of pressure as your blood pumps through the vessels. This can lead to heart attacks, strokes, heart failure and kidney damage.
Peripheral Arterial Disease (PAD): PAD occurs when the blood vessels in the legs and arms become clogged. This can lead to limb pain and increase the risk of a heart attack or stroke.
Stroke: Stroke occurs when blood flow to the brain is interrupted, usually by a blood clot (ischemic stroke) or when a blood vessel in the brain ruptures (hemorrhagic stroke). Both can cause the death of brain cells in the affected areas.
Valve Problems: The heart valves, which open and close in the four chambers of the heart, keep blood pumping in one direction in and out of the heart. They can become narrowed (stenosis) or unable to close properly (prolapse), or they can leak (regurgitation).

What causes cardiovascular disease in people with HIV?
 
Many factors can influence your risk of heart disease. Some can be controlled, others can't. Some factors greatly increase the risk of cardiovascular disease, whereas others may exert only a mild influence. Knowing the combined contribution of your various risk factors can help you and your health care provider determine your overall risk for cardiovascular disease.

Risk Factors You Can't Control:

• Both gender and age strongly influence cardiovascular health. Generally, men have a greater risk than women and at an earlier age. For men, risk begins to increase by age 45 and continues to grow with each passing year. For women, the risk generally doesn't start to climb until after menopause. By age 65, however, the cardiovascular disease risk in women escalates substantially.

• Race also plays a role in heart health, though it isn't entirely clear why. In general, African Americans have a higher risk for health problems such as high blood pressure and diabetes. These two health problems greatly increase a person's risk for cardiovascular disease.

• There is also a genetic risk—cardiovascular disease may be more likely in some families compared with others. If your parents, grandparents or aunts and uncles suffered heart attacks or strokes at an early age, the chance that you will too is higher than if your relatives remained healthy.

Risk Factors You Can Control:

• Diet, exercise and smoking all profoundly influence heart health. The three are often called lifestyle factors. Though a healthy diet and regular exercise both contribute greatly to cardiovascular health, smoking is one of the worst offenders, and aside from its negative impact on blood pressure and atherosclerosis (hardening of the arteries), smoking also increases the risk for lung cancer and emphysema.

• One very common risk factor for many people is having levels of blood fats—lipids, such as cholesterol and triglycerides—that are out of the healthy range. Unhealthy levels usually mean that your total cholesterol, your "bad" cholesterol (LDL), or your triglycerides are too high, or that your "good" cholesterol (HDL) is too low. Poor diet, smoking, ARV therapy (see the next section) and a lack of exercise can all contribute to lipid problems. If your levels are abnormal, most doctors will first recommend lifestyle changes—healthier diet, exercise and quitting smoking—sometimes combined with changes to your ARV treatment or drugs designed to reduce cholesterol and triglycerides.

• High blood pressure is another risk factor that most people can control. Eating healthy, exercising and quitting smoking can all help control blood pressure. When lifestyle changes don't do the trick, doctors sometimes prescribe drugs to control blood pressure.

• Diabetes is also a major risk factor for cardiovascular disease. In particular, every time your blood sugar climbs too high and stays too high, it contributes to cardiovascular disease. If you have diabetes, a healthy diet and regular exercise are even more important, as are regularly monitoring your blood sugar and appropriately using whatever medication your doctor prescribes to treat your diabetes.

HIV infection itself may also be a risk factor. Studies have shown that HIV-positive people not on ARV therapy have lower "good" HDL cholesterol and higher triglycerides than people not living with the virus. There is also evidence that the body's hyperactive response—inflammation—to the presence of HIV, especially if it is not being treated, can gradually damage to the heart and blood vessels, potentially increasing the risk of cardiovascular disease. And while people living with HIV can't (yet) control whether or not they remain infected with the virus, they can help manage many of the health problems that HIV can cause.

Does HIV treatment increase the risk of a heart attack?
 
A number of studies have investigated the impact that antiretrovirals (ARVs) may have on heart disease risk. While it is true that many HIV drugs can cause side effects that may increase the risk of heart attacks or strokes, studies such as the Strategies for Management of Antiretroviral Therapy (SMART) trial have also demonstrated that ARV therapy as a whole actually protects against cardiovascular disease. The SMART trial found there were more heart attacks among those who delayed or stopped treatment, compared to those who started and remained on therapy.

Still, many ARVs have been linked to side effects that can potentially increase the risk of cardiovascular disease. Many protease inhibitors (PIs), some non-nucleoside reverse transcriptase inhibitors (NNRTIs) and a few nucleoside reverse transcriptase inhibitors (NRTIs) have been found to cause cholesterol and triglyceride abnormalities in people with HIV. PIs and NRTIs have also been tied to diabetes—another cardiovascular disease risk. Some drugs have also been linked to an increased risk of heart attacks, for reasons that are not yet clear.

While experts agree that cardiovascular risks are associated with HIV treatment, there are established cardiovascular—as well as immunological—benefits to treatment. And just as there needs to be a favorable balance between the cardiovascular risks and benefits of ARV therapy, there are ways to maintain a favorable balance in people using these medications. This involves working closely with a health care provider to make sure that all cardiovascular risks—including smoking, diet, exercise, family history, blood pressure and current lipid levels—are considered when making treatment decisions. Monitoring these risk factors during HIV treatment is essential as well.

The following is a guide to the various drug classes and their impact on cardiovascular disease:

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

• Zerit (stavudine) can increase lipids, among other side effects, and most health care providers recommend avoiding it when possible.
• Zidovudine (found in Retrovir, Combivir and Trizivir) can increase the risk of developing diabetes—a risk factor for cardiovascular disease—and, in rare cases, can damage heart muscle.
• A couple of studies have linked abacavir (found in Ziagen, Epzicom and Trizivir) and didanosine (found in Videx and Videx EC) to an increased risk of heart attacks in a couple of studies. Several other studies found no such risk, and experts haven't yet agreed upon a biological explanation for why either drug contributed to an increased heart attack risk.

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)     

• Efavirenz (found in Sustiva and Atripla) can modestly increase triglycerides as well as raise healthy HDL. Viramune (nevirapine) has no impact on cholesterol or triglycerides, except for HDL increases.
• Rescriptor (delavirdine), rarely used because of three-times-daily dosing, can modestly increase cholesterol and triglycerides.
• Intelence (etravirine) and rilpivirine (found in Edurant and Complera), the newest NNRTIs, appear to have a minimal effect on cholesterol or triglycerides.

Protease Inhibitors (PIs)           

• Most of the PIs can raise total and LDL cholesterol and triglycerides, and using Norvir (ritonavir) to boost blood levels of the PIs can exacerbate this effect.
• Neither Reyataz (atazanavir) nor Prezista (darunavir) appears to raise lipid levels. However, when either is combined with Norvir, lipid levels may be affected.

Entry Inhibitors (including fusion inhibitors)

• Fuzeon (enfuvirtide) does not appear to impact lipids.
• Selzentry (maraviroc) does not appear to impact lipids.

Integrase Inhibitors         

• Isentress (raltegravir) does not appear to impact lipids.

How is cardiovascular disease diagnosed and monitored?
 
Some of the tests to diagnose or monitor heart disease are quite basic, and your doctor probably already checks these:

Lipid Levels – The amounts of fats in your bloodstream. These should be checked regularly, preferably in a fasted state (after 12 hours with no food or drinks other than water).

• Total Cholesterol – Your total mix of good and bad cholesterol. Ideal is less than 200 milligrams per deciliter (mg/dL) of blood. Borderline is 201 to 239 mg/dL, and high is 240 mg/dL and higher.
• LDL Cholesterol – One of the two "bad" types of cholesterol. The ideal level is below 100 mg/dL, while 160 mg/dL or more is considered high.
• VLDL Cholesterol – The other "bad" cholesterol. It is calculated indirectly as a percentage of your triglycerides. A normal VLDL is usually between 5 and 40 mg/dL.
• HDL Cholesterol – The "good" type of cholesterol. The ideal level is 60 mg/dL or higher. Normal is 40 to 59 mg/dL. Below 40 mg/dL is too low.
• HDL/LDL Ratio – The HDL/LDL ratio looks at the ratio of good cholesterol to bad cholesterol. The ratio is determined by dividing the LDL cholesterol into the HDL cholesterol. For example, if a person has an HDL cholesterol of 50 mg/dL and an LDL cholesterol of 150 mg/dL, the HDL/LDL ratio would be 0.33. The goal is to keep the HDL/LDL ratio above 0.3, with the ideal HDL/LDL ratio being above 0.4.
• Triglycerides – Less than 150 mg/dL is ideal, while greater than 200 mg/dL is high.

Blood Pressure – According to the American Heart Association, the top number (systolic) should ideally be less than 120 and the lower number (diastolic) should be less than 80. Usually stated as, "120 over 80." A blood pressure of 140/90 or higher is considered high blood pressure, or hypertension.
Glucose – Normal glucose—the amount of sugar in the blood—is less than 100 mg/dL in a fasted state. Pre-diabetes is 100 to 125 mg/dL fasted, and diabetic is 126 mg/dL or higher. Another blood test calls for testing your blood sugar while in a fasted state, drinking a sugary beverage and then testing your blood glucose again two hours later.
Kidney Function – Kidney damage can be a cause or an effect of cardiovascular disease. BUN (blood urea nitrogen), creatinine and uric acid are three common blood tests of kidney function.

Your health care provider may order additional cardiovascular disease tests. These may include an electrocardiogram (EKG or ECG), an echocardiogram, a chest X-ray, a computerized tomography (CT) scan, a magnetic resonance imaging (MRI) scan, stress testing or cardiac catheterization.

Am I at risk for cardiovascular disease?
 
As has been pointed out, many factors contribute to cardiovascular disease. What's more, not all factors carry the same risk—some are much more serious than others. For example, smoking has been proved to substantially increase the risk of heart disease, as has diabetes. Being 30 pounds overweight might also increase your risk, but not to the same degree as smoking. While these principles have been well established in studies involving HIV-negative people, most experts agree that the same principles apply to HIV-positive people as well.

How can I reduce my risk of cardiovascular disease?
 
It is possible to dramatically reduce your risk of cardiovascular disease. Quit smoking and within 10 years your heart attack and stroke risk drops by nearly 300 percent. Diet and exercise can also profoundly reduce risk. These behavioral changes, along with good medical management, can also help people who've already had a heart attack or have been diagnosed with significantly clogged arteries. For people living with HIV, managing cardiovascular disease risk may also involve decisions about when to start antiretroviral (ARV) therapy and which ARVs to avoid. Here are some options to consider:

• Treat HIV. Federal HIV treatment guidelines recommend starting treatment before CD4 counts fall below 500—and half of the federal guidelines panel recommends starting treatment at higher CD4 counts—in large part because the risk of heart disease increases in people with lower CD4 counts who are not on treatment. This is because, as stated earlier, uncontrolled HIV replication can increase the risk of damage to the blood vessels and heart.
• Choose the Right Treatments. When it comes to heart disease risk, not all ARV drugs are created equal. Some can raise cholesterol and triglycerides, while others may increase the risk for developing diabetes. For more information on choosing ARVs—or switching if necessary—click here.
• Quit Smoking. Smoking causes chronic inflammation of the blood vessels and the heart, negatively affects cholesterol, increases blood pressure and can lead to emphysema and lung cancer. For more information and tips on quitting, click here.
• Watch Your Diet. Eating a lot of saturated fat and processed sugars increases your risk of both heart disease and diabetes. Conversely, people who eat lots of fresh vegetables, fruits, whole grains, nuts and healthy fats—from fish, for example—appear to be protected from heart disease. For more information on diet and nutrition, click here.
• Get Active. Exercise strengthens your heart, reduces blood pressure, improves cholesterol and enhances your mood. For more information on exercise, click here.
• Reduce Stress. Chronic stress can increase your blood pressure and raise stress hormones. Click here to learn more about keeping stress levels in check.
• Consider Medication. When lifestyle changes don't do the trick—or aren't enough to bring your lipid levels under control—a number of drugs can improve cholesterol and triglycerides.

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