HAART to heart
A timely chat with your HIV doctor about the risks of heart disease just might
save your life, writes Dr Mervin Tryer
More
people living with HIV will die from causes other than opportunistic diseases
as evermore potent and sophisticated HAART regimens extend life expectancy.
Cardiovascular disease (CVD) accounts for 39 per cent of all deaths in the
UK, killing 238,000 people annually, usually from heart attacks and strokes.
As people living with HIV continue to live longer, more will develop and succumb
to CVD. People with HIV taking HAART may be more at risk of CVD than the rest
of the population. This is because the very presence of HIV in the body, as
well as abnormal blood fats (cholesterol) caused by some antiretroviral drugs,
may make heart attacks and strokes more likely. However both you and your
doctor could potentially reduce the risk.
What is CVD?
CVD begins when factors such as smoking, infections or excessively high blood
pressure (hypertension) damage the delicate layer of cells (endothelium) lining
the blood vessel. As a response to this, white blood cells invade the endothelium.
CVD occurs when, rather than repairing the vessel, the cells and other processes
produce further damage.
White blood cells that invade the endothelium become engorged with cholesterol
and form a ‘fatty streak’ along the endothelium. Almost everyone
has ‘fatty streaks’. They are even common among children before
their tenth birthday. The streaks develop, eventually forming advanced fibrous
plaques. These are layers of muscle and collagen (‘fibrous tissue’
- gristle) covering a porridge-like core of fat and white blood cells (see
photo overleaf).
Fats within the bloodstream move into this ‘plaque’ and, as it
grows, the plaque bulges into the vessel. This reduces the vessel’s
diameter and slows the supply of blood to the organs. Now, for the first time
since the streak developed, symptoms may emerge. The crippling pain of angina,
for example, arises when the narrowing creates an imbalance between supply
and demand for oxygen and nutrients by the heart. This forces the patient
to slow down and so restores this balance.
In some cases, the plaque ulcerates or ruptures - often because of the stress
imposed by hypertension (high blood pressure). The core’s contents escape,
triggering a blood clot. If the clot blocks the vessels, the tissues supplied
by them die. When this occurs in the vessels supplying the heart or brain,
the patient suffers a heart attack (myocardial infarct) or ‘ischaemic’
stroke respectively. Ischaemia (lack of blood flow/oxygen supply) causes around
80 per cent of strokes.
HIV, HAART and CVD
HIV potentially contributes to CVD in several ways. Firstly, HIV can activate
monocytes (a type of white blood cell) making them more likely to invade the
endothelium. Secondly, HIV may trigger inflammation that undermines the blood
vessel’s defences, again making the invasion more likely. Thirdly, HIV
can increase the amount of specialised proteins (appropriately called adhesion
molecules) that ‘stick’ white blood cells to the endothelium.
HAART (Highly Active AntiRetroviral Therapy) can also contribute to CVD by
altering the balance of fats (lipids) in the body. This may be responsible
for increasing CVD risk. HAART can also result in a change in body fat distribution.
As well as causing problematic cosmetic issues, this may also contribute to
CVD.
Your blood contains numerous lipids. It also contains specialised proteins
that carry lipids in the blood. The liver makes cholesterol from saturated
(‘animal’) fat in your diet. Low Density Lipoprotein (LDL) carries
cholesterol from the liver to fatty tissue, muscles and other tissues. High
density Lipoprotein (HDL) carries cholesterol from the tissues back to the
liver. (A way of remembering the good and bad lipid is: LDL is ‘Lethal’,
HDL is ‘Healthy’).
Triglycerides are the most common type of lipid. These act as an energy source
for cells and are an integral part of the lipoproteins. They also become incorporated
into plaques encouraging further growth.
HAART and lipid balance
It is perfectly normal and healthy to have cholesterol and triglycerides in
your blood. However, some HAART regimens affect the lipid balance. In particular,
certain protease inhibitors may increase blood levels of triglycerides and
LDL (bad cholesterol).
If you are on a HAART regimen it is important to have your blood fats measured
on a regular basis. UK guidelines for the general population - not specific
to patients on HAART - recommend the following:
UK cholesterol targets
(Report of the fourth working party of the British Hypertension Society, 2004-BHS
IV)
• Optimal therapeutic goal:
Total cholesterol <4 mmol/l or
LDL-cholesterol <2 mmol/l
• Audit standard (minimum):
Total cholesterol <5 mmol/l or
LDL-cholesterol <3 mmol/l
If your cholesterol is high and particularly if you have other risk factors,
you and your doctor should work together to reduce your risks.
Strategies may include:
• Modifying diet
• Introducing exercise
• Changing your antiretrovirals
• Introducing a lipid lowering agent such as a statin.
Other areas that may help reduce risk of CVD include stopping smoking and
controlling high blood pressure
HAART
and fat redistribution
Some HAART regimens change the distribution of fat around the body, which
may increase the risk of CVD. In the past, around 40 per cent of people on
HAART developed lipodystrophy, the sometimes dramatic changes to appearance
and body shape associated with some antiretrovirals.
Lipodystrophy can arise in many places around the body. Some people gain fat
(lipohypertropy) in their lower trunk, others may develop a pad of fat at
the back of the neck and upper back. When it enlarges, the latter can produce
a characteristic ‘buffalo hump’ appearance. In some men and women,
the lipohypertropy results in breast enlargement.
Others can lose an amount of fat beneath the skin. This is called lipoatrophy
and usually occurs in the arms, legs, buttocks and face. Not surprisingly,
one survey suggests 97 per cent of patients felt lipoatrophy undermined their
confidence and 71 per cent of people with lipoatrophy either needed treatment
for anxiety or were on the borderline of needing help. Some people experience
both lipohypertropy and lipoatrophy.
Several factors seem to increase the risk of developing lipoatrophy. For example,
the likelihood of developing lipoatrophy roughly doubles among those who have
lived with HIV for more than 80 months (just over six and a half years) compared
with those diagnosed more recently. Men who lose more than 7kg are roughly
four times more likely to develop lipoatrophy than those who lose less weight.
Genetic factors also contribute to lipoatrophy risk. Nucleoside reverse transcriptase
inhibitors (NRTIs) may directly change body shape. Quite how this happens
remains unclear, although there is evidence they damage mitochondria (important
components of the cell) within fat tissue.
As well as the cosmetic complications, it is thought that lipohypertrophy
may increase the likelihood of cardiovascular risk factors.
Preventing CVD
Against this background, preventing CVD has become an important part of HIV
management. Everyone should quit smoking, which, apart from the other dangers,
increases the risk of heart disease by around 50 per cent. As is the case
among people without HIV, diet and exercise can reduce abnormal lipid levels
and lower blood pressure.
Changing your lifestyle can often be difficult, and many people need drugs
to control their blood pressure and lipid levels. The choice of lipid lowering
drug depends on many factors, including the profile of changes in the blood
- whether LDL is especially low or HDL is particularly high for example. The
choice also depends on the risk of interactions of any lipid lowering drug
with HAART components and any other medications.
HAART’s components also differ in the extent to which they change the
body’s fats. As mentioned, some NRTIs are linked to body shape changes
and there may be an additive effect if protease inhibitors are also used.
Some antiretrovirals cause more blood lipid changes than others. In certain
situations, switching between drugs may reduce the risk.
• Dr Tryer is associate specialist in HIV Medicine at the Royal Free
Hospital, London
This article was supported by Bristol-Myers Squibb
