Use of highly active antiretroviral therapy (HAART) for over two years can cause increases in blood pressure, according to a large study presented in the 10th June edition of AIDS. This suggests that patients taking HAART are at an increased risk of problems such as heart disease and stroke, and underscores the need for regular blood pressure monitoring in HIV-positive patients.
Since its introduction in the mid-1990s, HAART has dramatically reduced rates of disease and death in HIV-positive people. However, there are concerns about long-term side-effects, including elevations in the levels of fats and sugars in the blood, changes in body fat distribution and heart disease.
Raised blood pressure is a well-known risk factor for heart disease and other problems in the general population. To assess the risk in HIV-positive patients, investigators from the Multicenter AIDS Cohort Study (MACS) analysed their records from almost 20 years of follow-up. The MACS is an ongoing observational study of men in the United States, who have reported having had sex with men, which started to recruit in 1984.
The investigators analysed six-monthly blood pressure measurements from 5578 (99%) of the 5622 men who were recruited up to 1995. At enrolment, the median age of these men was 32.6 years, 83% were Caucasian and 59% had a history of smoking. A total of 84,800 blood pressure measurements were taken between 1984 and 2003.
Measurement of blood pressure measurement gives two values: a systolic value, taken when the heart is beating, and a diastolic value, which is taken between heartbeats. Blood pressure is usually quoted as the systolic pressure ‘over’ the diastolic.
In this study, high systolic blood pressure or ‘systolic hypertension’ was defined as a value over 140mmHg, and diastolic hypertension as a value over 90mmHg.
“Our study showed that HAART was associated with an increase in the prevalence of hypertension,” the investigators conclude. “Importantly, the effect of the duration of HAART use was different for systolic hypertension versus diastolic hypertension.
“Our findings underscore the importance of monitoring blood pressure and for signs and symptoms of hypertension-related complications among HIV-positive men taking HAART," they write.
The investigators found that 7% of the systolic blood pressure measurements were high, and 8% of the diastolic. In agreement with previous findings, systolic and diastolic hypertension were more common in African-Americans, smokers, older men and men with a higher body mass index (BMI).
After controlling for age, race, BMI and smoking, multivariate analysis showed that HIV-positive men taking HAART for between two and five years had an elevated risk of systolic hypertension (odds ratio [OR]: 1.51, 95% confidence interval [CI]: 1.25 – 1.82).
Men taking HAART for over five years showed a similar elevation in risk of systolic hypertension (OR: 1.70; 95% CI 1.34 – 2.16).
In contrast, men who had taken HAART for less than two years had similar rates of systolic hypertension to HIV-negative men (OR: 1.06; 95% CI: 0.87 – 1.30).
However, HIV-positive men who had not taking any antiretroviral therapy were significantly less likely to have systolic hypertension than HIV-negative men (OR: 0.79; 95% CI: 0.70 – 0.89). Men taking single-drug or other drug combinations that did not fall into the investigators’ definition of HAART had a similarly reduced prevalence of systolic hypertension (OR 0.69; 95% CI 0.59 – 0.80).
In contrast to systolic hypertension, the prevalence of diastolic hypertension was lower in patients having taken HAART for between two and five years than HIV-negative controls (OR: 0.78; 95% CI: 0.63 – 0.96). Being on HAART for over five years was associated with no change in the rates of diastolic hypertension in comparison to HIV-negative men (OR: 1.21; 95% CI: 0.94 – 1.56).
The investigators also examined the contribution of protease inhibitors to the elevated risk of high blood pressure. They saw no additional effect of protease inhibitor use on the observed relationships between HAART and either type of hypertension.
The investigators note that the increased incidence of systolic, but not diastolic hypertension in patients on long-term HAART is similar to isolated systolic hypertension (ISH), a disease usually observed in the elderly.
“Although both systolic and diastolic blood pressure are associated with cardiovascular morbidity and mortality, systolic blood pressure has often been found to be a better predictor of coronary heart disease, stroke, and all-cause mortality,” they explain. “ISH [is] independently associated with an increased risk of these cardiovascular events.”
They explain that the effect of HAART on blood pressure could be due either to a direct effect on blood vessel walls or to an indirect effect of raised blood fats and sugars.
However, they emphasise that their results should not be over-interpreted, particularly since their observations could be explained by factors other than HAART use itself. “Men who take HAART for more than five years may be subset of those who thrive and are subject to other aetiologic mechanisms for essential hypertension such as weight gain,” they write.
In addition, they acknowledge that their measurements of blood pressure were not standardised, and that their cohort was largely restricted to “relatively affluent and educated gay men".
“We cannot generalise our findings to women or other populations of HIV-infected persons such as injection drug users, some minority groups, and haemophiliacs,” they conclude.
Seaberg EC et al. Association between highly active antiretroviral therapy and hypertensions in a large cohort of men followed from 1984 to 2003. AIDS 19: 953-960, 2005.