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HIV and AIDS
infarction was significantly associated with duration of exposure to in PI-naïve HIV-positive individuals and HIV-negative controls,
38–40
abacavir (ARR 1.14, 95% CI 1.08–1.21 per year of exposure; p=0.0001) whereas other studies have reported no significant association between
and didanosine (ARR 1.06, 95% CI 1.01–1.12 per year of exposure; PI exposure and abnormal carotid IMT.
41–44
In these latter studies,
p=0.03), but not zidovudine, stavudine or lamivudine. This excess risk traditional cardiovascular risk factors such as age, male gender, low-
appeared to arise from recent exposure to these two specific NRTIs: density lipoprotein (LDL) cholesterol and smoking were more strongly
patients receiving abacavir or didanosine during the previous six months associated with abnormal IMT levels than antiretroviral-related factors,
were at 90 and 49% higher risk, respectively, of myocardial infarction emphasising the continued importance of traditional risk factors in the
than those who had never been treated, or who had been treated more development of CVD in this patient group. Similarly, the use of PI-based
than six months previously with these drugs. Although patients with HAART in HIV-infected subjects was associated with impaired flow-
recent exposure to abacavir were more likely to be older men and to have mediated vasodilatation in the brachial artery, which was explained in
hypertension, diabetes, dyslipidaemia or a history of CVD, after further part by the atherogenic dyslipidaemia induced by PIs.
45
adjustment for predicted 10-year risk of coronary heart disease recent
use of abacavir remained significantly associated with increased risk of Pathogenesis of Cardiovascular Disease in HIV
myocardial infarction (ARR 1.89, 95% CI 1.47–2.45; p=0.0001), as did There are several possible explanations for the increase in coronary
recent use of didanosine (ARR 1.49, 95% CI 1.14–1.95; p=0.004). events seen in HIV-infected patients undergoing HAART. In addition to
Adjustment for HIV disease activity (viral load, CD4
+
count) and metabolic the higher prevalence of traditional risk factors for CVD within the
risk factors likely to be modified by antiretroviral therapy did not HIV-infected population, proposed pathogenic mechanisms include
appreciably weaken these associations. pro-atherogenic conditions arising from HIV infection itself, as well as
direct and indirect effects of antiretroviral therapy.
Clinical and Subclinical Features of
Cardiovascular Disease in HIV Effects of HIV Infection
The clinical presentation of CVD in HIV-infected patients differs from that Progressive HIV disease is associated with increased T-cell proliferation
in the general population, insofar as the typical HIV-positive patient and activation and high levels of circulating inflammatory markers,
presenting with acute myocardial infarction is a male smoker, has a low with immune activation persisting long after initiation of HAART.
46
high-density lipoprotein (HDL) cholesterol level, is at low risk of ischaemic Evidence indicates that inflammatory immune responses play a pivotal
events and death, as determined by his Thrombolysis in Myocardial role in the pathogenesis of atherosclerosis,
47,48
and inflammation,
Infarction (TIMI) risk score, and is significantly younger than his endothelial dysfunction and impaired fibrinolysis may contribute to the
HIV-negative counterpart.
29
As might be expected in this population, increased cardiovascular risk observed in the HIV-infected population.
single-vessel disease is common, which suggests a favourable early The pro-inflammatory state associated with HIV infection may give rise
prognosis.
29–31
Coronary angioplasty and stenting yield excellent initial to atherogenic lipid changes.
49,50
The lipid profile in antiretroviral-naïve
results in these patients, although restenosis rates are reported to be HIV-infected subjects is characterised by low total cholesterol, HDL
higher than in the general population.
29,32
Coronary lesions in HIV- cholesterol and LDL cholesterol and elevated triglyceride levels, with
infected patients show similar histological features to those in non- the latter mainly appearing as very-low-density lipoprotein (VLDL).
51–55
HIV-infected patients
33
but tend towards higher coronary artery calcium
scores, which indicates an increased atherosclerotic burden.
34
Effects of Antiretroviral Therapy
The increased risk of myocardial infarction arising from exposure to
Electrocardiographic (ECG) evidence of asymptomatic CVD, such as the HAART would appear to be due in part to the adverse metabolic
presence of Q-waves and/or ST-segment depression, appears to be a effects of these drugs.
25,27
ART has been linked to the development of
frequent feature in HIV-infected patients receiving HAART.
35
Among the lipid and carbohydrate metabolic abnormalities and increased central
cohort of HIV-infected patients (n=4,831, mean age 44 years) enrolled in adiposity, which are established risk factors for CVD in the non-HIV-
the Strategies for Management of Antiretroviral Therapy (SMART) study, infected population. The typical lipoprotein pattern in patients
none of whom had clinically overt CVD, 10.9% showed ECG receiving long-term HAART is one of decreased HDL cholesterol,
abnormalities (5.9% had Q-waves, 5.5% had ST-segment depression).
35
increased triglyceride and increased LDL cholesterol levels,
56–60
not
However, no clear association between HAART type or duration and ECG unlike the phenotype observed with the metabolic syndrome. In
abnormalities was noted. addition, increased levels of potentially atherogenic remnant
lipoproteins are noted, which would serve to increase the availability
Vascular imaging can be used to evaluate abnormalities in vascular of fatty acids for peripheral lipid deposition. The pattern and severity
function that may precede symptomatic ischaemic heart disease. of dyslipidaemia varies substantially between antiretroviral drug
Available techniques include B-mode high-resolution ultrasound imaging classes and individual drugs, occurring most frequently with PI-
of the carotid and femoral arteries and flow-mediated vasodilatation of containing (particularly ritonavir and lopinavir) regimens.
58,61,62
Overall,
the carotid and brachial arteries, assessed by high-resolution ultrasound evidence would suggest that the use of PI-based HAART results in
after periods of arterial occlusion.
36
Findings from such studies suggest an decreased peripheral lipolysis, increased hepatic production of
increased prevalence of subclinical atherosclerosis and higher rates of triglyceride-rich lipoproteins and impaired clearance of lipoprotein
carotid atherosclerotic disease progression in HIV-positive individuals remnants.
63,64
NNRTIs have a more modest effect than PIs on total
than in age-matched HIV-negative controls.
37
Several studies have cholesterol and LDL cholesterol levels, and are less likely to be
indicated significantly higher rates of abnormal carotid and femoral associated with lower HDL cholesterol levels.
58
Within this class,
artery intimal-media thickness (IMT) and/or carotid and femoral artery nevirapine is associated with lower total cholesterol and triglyceride
plaque lesions in HIV-infected individuals receiving PI-based HAART than levels than efavirenz.
58
14 EUROPEAN INFECTIOUS DISEASE
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