Over the long, slow unfolding of the HIV/AIDS story, one thing has remained constant: there always seems to be some new symptom, side effect, syndrome or infection to be worried about.
Lately, the potential of some anti-HIV drugs to cause cardiovascular disease has been the focus of attention. It’s become something of a commonplace that ‘protease inhibitors cause heart disease’. But like most things in HIV disease, the reality is somewhat more complex. Some antiretrovirals can cause increases in blood cholesterol and triglyceride levels, but increased blood lipid levels do not automatically mean heart disease.
Positive people would be well-advised, then, to look further before leaping to fatalistic conclusions, or ditching the drugs and hurling themselves into the latest cardio-craze being pimped by some personal trainer, gay gym junkie or ageing TV starlet.
The link between HIV treatment and heart disease is far from clear-cut or well understood. While a growing body of evidence indicates that some anti-HIV drugs can increase the risk of developing cardiovascular disease, it’s important to also consider the extent to which other risk factors for heart disease — factors independent of either HIV or its treatment — play a role in the apparently higher rates of heart disease in HIV found in some (but by no means all) epidemiological studies.
So just how can you untangle all this?
The first — and most useful — fact to remember is that coronary artery disease is very common in the Australian community, and remains the country’s leading cause of death. Coronary artery disease is a form of heart disease in which the arteries which pump blood to the heart become narrowed, due to the accumulation of fatty deposits and cell debris over a long period of time. As a result of the build-up of this ‘arterial plaque’, the flow of blood through these arteries to the heart is reduced, which can cause damage to the heart muscle. In severe cases the blood flow may be blocked altogether, resulting in angina (chest pain) and possibly a heart attack.
Coronary artery disease is one medical condition we know a great deal about. Its causes, natural history, and patterns of occurrence are extremely well documented. You’d have to have been living under a rock not to have been exposed to information of one sort or another about coronary artery disease, and the ways we can prevent it.
Men in general are at increased risk of this form of heart disease as they get older, but there are other major risk factors, including obesity, high levels of fat and certain types of cholesterol in the blood, smoking, alcohol consumption, high blood pressure (hypertension), family history, and diabetes.
Women appear to have the benefit of some hormonal protection from heart disease, at least until menopause, but are far from immune, especially as they get older: coronary artery disease remains the number one killer of Australian women. Dutch researchers recently announced that smoking and obesity dramatically increased the risk of heart disease for women such that a combination of these two factors is now thought to knock an average of a whopping 13.3 years off your lifespan. And women who smoke may be up to six times more likely to have a heart attack than women who do not smoke.
With this background in mind, HIV researchers have been asking if HIV or its treatment increase the risk of heart disease developing sooner, or occurring more seriously. And do the lipid elevations associated with HIV treatment present the same long-term cardiac risk as in HIV negative populations?
Neither studies nor experts agree on the answers to these important questions. But the consensus seems to be that if protease inhibitors, other anti-HIV drugs or HIV itself do increase the risk of a person developing heart disease, then it is more important than ever to understand the role of risk factors in exacerbating this, and to minimise or modify these risks as far as is practical.
HIV, antiviral treatment and your heart
Most people think of heart disease as synonymous with arterial hardening, described above, but there are varying forms of heart disease — some of which have entirely different causes to the much-invoked unholy trinity of age/fat/smoking. Conditions like congestive heart failure, for example — where the heart is unable to properly pump blood — can be due not only to disease of the coronary arteries, but may also be caused by damage to the heart valve, or cardiomyopathy (a series of chronic disorders which can damage, weaken or enlarge the heart). Cardiomyopathy may have congenital causes, or may be caused by some specific, unusual factors — like having had an illness or infection which weakens the heart.
There are several reasons why some believe there is a link between HIV itself, independent of HIV treatment, and an increased risk of developing certain forms of heart disease.
- Some researchers believe that chronic HIV infection may lead to consistently high levels of certain immune proteins which can interfere with the way your body metabolises fats.
- HIV infection has been associated in the past with higher rates of cardiomyopathy.
- Chronic inflammation (which can occur as a result of chronic viral infection) may contribute to the hardening of the arteries.
- People with compromised immune systems may be more likely to develop infections which directly involve the heart.
- Some steroids and hormones can increase the thickness of the blood, and may lead to high blood pressure, a risk factor for heart disease.
This apparently alarming list should not be taken to mean that all people with HIV are at dramatically increased risk of the immediate development of some bizarre or fatal form of heart disease. But it does suggest that it may be prudent for people with HIV to pay some attention to the question of heart health.
At the 2001 International Workshop on HIV-associated Lipodystrophy and Adverse Events, Dr Vincent Mooser, of Lausanne University in Switzerland, related a cautionary tale in the form of epidemiological modelling. In isolation, he suggested, neither HIV nor its treatment presents a necessarily higher risk of developing cardiovascular disease. However, he pointed to research which shows that, among people who have heart attacks, their average number of collective risk factors for this is just two. Mooser’s point was this: while HIV or its treatment is unlikely to lead to a pandemic of heart disease among positive people, in the presence of other risk factors, the risk of coronary artery disease could certainly be aggravated.
One of the reasons why this subject has received so much attention is precisely this concomitant risk. For a start, many HIV positive people are men, now approaching middle age and older — that is to say, they are already at or nearing the age where heart disease may become a serious health issue. Perhaps more significantly, the HIV Futures III report identified smoking rates — at nearly 55 percent of all those surveyed — as much higher among positive people than smoking rates among the Australian population more generally. (Smoking rates in the non-HIV-affected community have actually been in decline: less than 30 percent of Australian men and women smoke).
For an older HIV positive man who smokes, for example, the risk of heart disease may already be significant, independent of the question of HIV treatments.
Now let’s add HIV treatments into this picture. There are a series of now well-documented metabolic anomalies and changes which often occur in people with HIV, thought to be directly caused or greatly exacerbated by antiviral drugs. Research has most strongly linked the protease inhibitor class, in particular but not only ritonavir, with elevated levels of cholesterol and triglycerides — the blood fats associated with the development of coronary artery disease. Efavirenz has also been implicated.
At least one recent study has found that the nucleoside analogue class of drugs (AZT, 3TC, abacavir, d4T, ddI and ddC) are not associated with this problem. US guidelines point to this class of drugs as an option for patients who already have high cholesterol or triglycerides and other pre-existing risk factors.
No-one fully understand the mechanism by which PIs and efavirenz can interfere with the normal metabolism of fats and sugars in the body. Insulin resistance, often a precursor condition to developing diabetes and a sign of metabolic disturbance, is also reported to be associated with PI treatment.
And these effects are not limited to men. In women, it has been suggested that protease inhibitor use can increase the thickness of the wall of the carotid artery, increasing the risk of developing atherosclerosis and heart disease at an earlier age than HIV negative women, implying that there are good reasons for women, too, to pay heed to their cardiac health.
If the last few paragraphs have you clutching your chest in horror, it’s time for a reality check: it would be absurdly melodramatic to suggest that because of this, all people taking anti-HIV drugs are teetering on the brink of imminent cardiac arrest. This is not borne out by the evidence.
And there is certainly some bright news on the treatment front. A lot more is now known about how HIV treatments work, and how to use them more carefully and strategically, with a view to minimising side effects. And some of the drugs in development, in both existing and new classes, promise to have much more amenable cardiac profiles than their predecessors.
In the meantime, however, it is certainly sensible for positive people to look at ways of minimising their risk of developing heart disease — particularly for those people who may already have other risk factors.
Some risk factors, of course, you can’t do much about. Getting older and your genetic inheritance are hardly matters over which you can exercise much control. But there are lifestyle changes that can help reduce the risk of developing heart disease — having a healthy diet, getting regular exercise, avoiding stress and minimising alcohol intake will all help.
And there is one risk factor which can dramatically escalate your risk of heart disease, and which many believe to be a key plank in a risk reduction strategy: smoking.
Does diet make a difference?
There are mixed views about whether or not modifying your diet to reduce consumption of saturated fats and cholesterol will be effective in lowering cholesterol or triglycerides which have become elevated due to HIV treatment.
Some researchers have expressed reservations about whether the usual diet guidelines which would be applied to people diagnosed with or at risk of heart disease are as effective in the context of HIV. Most people agree that maintaining, as far as possible, a diet low in cholesterol and sodium (salt), and substituting the saturated fats found in butter and palm oils with monounsaturated fats (eg olive oil) and polyunsaturated fats (most vegetable oils) may be a useful strategy to keep lipid levels under control. As long as your diet contains the nutrients and calories you need, reducing cholesterol and saturated fats certainly won’t do any harm.
Still, say HIV-experienced dieticians, there is no need to adopt this approach with a missionary zeal: there is usually some room for manoeuvre, and also for pleasure. Avoiding a meal with friends, for example, because of fears you may consume a little fat, would be shortsighted. Maintaining a healthy diet is an overall strategic puzzle, not an exercise in total asceticism and self-mortification.
Diets designed for people at risk of heart disease often focus on weight loss, which is not necessarily appropriate — and may in fact be harmful — for people with HIV, who may require higher calorie intakes and more energy. So out the window with Pritikin, Zone Diets and candida diets, in favour of a balanced approach to eating which makes use of a variety of foods, freshly prepared — especially fruits and vegetables.
Switching from the drugs
With an increasing number of HIV treatments available, it may be possible to choose your treatments in such a way as to minimise the risk of developing heart disease — especially for people with several pre-existing risk factors.
British HIV researcher Matthias Egger reckons it’s a question of weighing up the long-term risk of developing heart problems from a given HIV regimen against the short-term risk of becoming ill from HIV disease progression. So, he says, a young woman who doesn’t smoke, whose viral load is high and whose CD4 count is low, might well be advised to take a protease-based combination: she needs the most powerful drugs to fight HIV in the short term. But a middle-aged man who smokes and whose father had a heart attack, but who has stable HIV infection, may well be advised to avoiding PIs, minimising his long-term exposure to those drugs that may push up his cholesterol or triglycerides.
In reality, many people with HIV do not have the luxury of switching combinations at will: this again reinforces the need to try, as much as possible, to minimise those risk factors that we have control over.
Lipid-lowering drugs
For people with stubbornly high cholesterol or triglyceride levels, it may be an option to force them down with medication, at least in intractable cases, where lifestyle changes or switching drugs doesn’t work. This is usually done with one of two classes of drugs: statins or fibrates. Some research does suggest that the fibrates might achieve and overall better result, and could be considered ‘first-line’ therapy in these cases. However, these drugs should not be seen as a ‘quick fix’ in lieu of modifying other real risks — and they do have some potential side effects which are not inconsequential.
In conclusion, positive people should be aware of the possibility that HIV treatment may cause elevations of blood lipids which, in the long term, could constitute a risk factor for coronary artery disease, and react appropriately.
Regular monitoring of blood lipid levels (ideally these blood tests should be performed after an 8-12 hour fast) should certainly be a regular feature of the lives of anyone taking antiretrovirals. Elevated blood lipids should be discussed with your doctor, but in the absence of other risk factors, they should not be a major cause for alarm. Quitting smoking, maintaining a healthy diet and taking regular exercise are wise moves for everyone, regardless of HIV status.
*Kirsty Machon is NAPWA’s HIV Health Policy Officer._
