Treatment with HAART has been accompanied by a decrease in cardiovascular-related deaths in HIV-positive US veterans according to a study published in the New England Journal of Medicine. However, HIV-positive people suffering a heart attack are more likely to experience a second severe coronary event according to another US study published in the 24th February 2003 edition of the Archives of Internal Medicine.
In a retrospective study investigators examined the medical records of 36,766 HIV-positive patients who received care at US Veterans Affairs hospitals between January 1993 and June 2001. The results were first presented at the Ninth Conference on Retroviruses and Opportunistic Infections in 2001. When compared to the general profile of HIV-positive patients in the US, those receiving care at Veteran Affairs facilities were slightly older (82% over 35), and healthier (36.7% were asymptomatic and had a CD4 count of at least 500 cells/mm3 at diagnosis).
Risk factors for cardiovascular disease including diabetes, high blood pressure, high blood lipids and smoking were present in a little under 24% of patients and 6.6% had received treatment for vascular disease.
In total, 70.2% received anti-HIV therapy for an average of 15 months each. All patients were treated with a nucleoside analogue, 41% with a protease inhibitors and 25% a non-nucleoside analogue.
Overall, there were 1,207 admissions for cardiovascular disease, 1,764 for cardiovascular or cerebrovascular disease and 2,006 deaths from these causes.
However, after the introduction of HAART, the rate of admission for cardiovascular and cerebrovascular disease fell from 1.7 events per 100 patient-years in 1995 to 0.9 events per 100 patient-years in 2001. Death rates from any cause fell from 21.3 per 100 patient-years in 1995 to 5.0 per 100 patient-years in 2001.
Neither the rate of admission or death because of cardiovascular conditions increased with increasing exposure to HAART. Where admission and death for cardiovascular and cerebrovascular disease did occur it was more likely to be amongst older patients with more advanced HIV disease and pre-existing cardiovascular or vascular disease.
Use of all classes of antiretroviral drug was found to be associated with a lower risk of death from all causes including cardiovascular and cerebrovascular disease.
The investigators concluded that the use of HAART did not lead to increased rates of cardiovascular or cerebrovascular disease and fear of vascular disease should not deter the use of HAART (in the short-term at least). However, the extended prognosis of people receiving HAART means that longer-term observation is needed.
However, a study comparing 24 HIV-positive patients experiencing heart attacks to 48 age and sex-matched HIV-negative controls found that the HIV-positive patients were more likely to suffer a second cardiac event within 15 months.
Between 1998 and 2000 all HIV-positive patients admitted with an acute myocardial infarction (AMI) to a Los Angeles hospital were monitored and matched with HIV-negative controls.
HIV patients experiencing AMIs were found to already be in a high risk group for cardiovascular disease, 88% being male with an average age of 47 years.
At the time of the AMI, the average period since the diagnosis of HIV was 10 years, and average CD4 count was 318 cells/mm3. HAART was being provided to 92% of patients with 71% taking at least one protease inhibitor.
Patients treated with protease inhibitors had a similar age and sex profile to the other HIV patients, but tended to have been HIV-positive for longer (10.7 years versus 8.4 years) and to have a lower CD4 count (268 cells/mm3 versus 426 cells/mm3).
Although patients on protease inhibitors were more likely to be treated with lipid lowering agents, their cholesterol, LDL cholesterol, HDL cholesterol and triglycerides were similar to those receiving non-protease containing regimens.
None of the HIV-positive patients died in hospital as a result of their AMI. However, over the next 15 months, 20% of patients had a second AMI, and 45% were rehospitalised for another cardiac event. Vascular illnesses also occurred in the patient group, with 30% having an artherothrombotic event.
Significant levels of more "traditional" HIV-related illness were also observed in the group including dementia, wasting syndrome, chronic diarrhoea and acute pancreatitis.
Although the HIV-positive patients matched the 48 HIV-negative controls for age and sex, the HIV-positive patients had a much higher incidence of second AMI (20% versus 4%) and rehospitalisation for a coronary event (45% versus 11%).
Commenting on their finding, the investigators observed that protease inhibitors did not seem to be solely responsible for abnormally high blood lipids seen in their 24 patients who had had heart attacks, and suggested that premature coronary artery disease was likely to be a result of HIV infection itself rather than treatment with HAART. These conclusions were supported by “necropsy findings of premature atherosclerosis in a high percentage of HIV-positive patients not treated with protease inhibitors and in children who have died of AIDS.”
The investigators conclude that HIV-positive patients who experienced an AMI were more likely to have subsequent cardiac events than HIV-negative patients. However, “the major determinants of prognosis…remain complications associated with HIV infection.”
The findings add to the conflicting data presented earlier this month at the Tenth Conference on Retroviruses and Opportunistic Infections, where the DAD study showed a 26% increase in risk of cardiac events for every year of antiretroviral therapy, whilst the ACTG 5078 study reported no increase in carotid intima media thickness (a marker of atherosclerosis).
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Bozzette SA et al. Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection. New England Journal of Medicine, 348: 702-710, 2003.
Matetzky S et al. Acute myocardial infarction in human immunodeficiency virus-infected patients. Archives of Internal Medicine, 163: 457-460.