Living with HIV carries the same lifetime risk of cardiovascular disease (CVD) as having diabetes, even after taking into account smoking, a US study has estimated.
The investigators say that more research is needed to find out whether preventive treatments such as statins could reduce this risk in people who don’t qualify under current guidelines.
HIV infection increases inflammation and causes metabolic changes such as low levels of 'good' HDL cholesterol, all of which contribute to the development of heart disease. These effects are distinct from any harm caused by older antiretroviral drugs or lifestyle factors such as smoking and drinking alcohol.
Although the incidence of cardiovascular disease is known to be higher in people living with HIV compared to the general population, the lifetime risk of cardiovascular disease for people living with HIV has not been calculated. Understanding the lifetime risk can help in planning health services and in raising awareness of cardiovascular risk among people living with HIV and their health care providers.
The study, carried out by a group of researchers at Harvard University, Brigham and Women’s Hospital and Massachusetts General Hospital, was designed to estimate the impact of cardiovascular disease on life expectancy in people living with HIV, taking into account the high prevalence of smoking in people living with HIV.
The model included three cohorts, based on available population data: the US general population, a population at high risk for HIV infection sharing behavioural risk factors with people living with HIV (smoking, alcohol use) and a population of people living with HIV. The second group was included in order to disentangle the effects of lifestyle factors and HIV infection on the risk of cardiovascular disease.
The model used CEPAC, a validated computer model of HIV disease progression that is used to estimate the cost-effectiveness of interventions. It used data on life expectancy and cardiovascular events from US life insurance tables, from the 2010 National Health Interview Survey and the National Centre for Health Statistics. The incidence of cardiovascular disease in the HIV population was calculated by taking the incidence in the general population and adjusting for the prevalence of known risk factors such as lipid elevations and glucose intolerance in people living with HIV.
The researchers modelled the incidence of cardiovascular disease and death at the ages of 40, 50 and 60, taking into account other causes of death, including HIV. The researchers also calculated the lifetime risk of cardiovascular disease and life expectancy. A cardiovascular event was any of the following: a heart attack, a stroke, coronary heart disease or angina.
The model showed that cardiovascular disease risk was highest for people living with HIV and lowest for the general population. By the age of 60, the model projected that one in five men living with HIV (20.5%) would develop cardiovascular disease in some form, compared to 13.8% of women living with HIV.
In comparison, the group of people at high risk of HIV who had a similar prevalence of risk factors to the HIV population had a lower cumulative risk of cardiovascular disease (14.6% for men, 9.7% for women).
In the general US population, the cumulative risk at the age of 60 was 12.8%. By the age of 70, the model estimates that the incidence of cardiovascular disease events will be twice as high in people living with HIV compared to the US general population.
The model projected an average life expectancy of 70 years for people with HIV compared to 77.5 years for the US general population and 76.4 for the at-risk population. By the age of 70, the cumulative risk of cardiovascular disease would be 37.9% (range 30.8-47.8%) for people living with HIV compared to 29.1% in the at-risk population and 25.6% in the general population. The potentially wide range is influenced by the proportion of the population who start treatment early, maintain a fully suppressed viral load and do not die as a consequence of late diagnosis. People diagnosed late were judged to be more likely to die earlier, from non-cardiovascular causes. The range also depends on assumptions about how much harm HIV does to the vascular system.
The at-risk cohort had a similar prevalence of smoking to the cohort of people living with HIV, but only in at-risk men aged 60 and over was the cumulative risk of cardiovascular disease higher than the general population. This finding suggests that although smoking increases the risk of cardiovascular disease for people with HIV to the same extent as the rest of population, the impact of HIV infection on heart disease is more substantial – and is apparent in both men and women.
The findings are likely to be applicable to Europe too, say the researchers; smoking is more common among people with HIV in Europe, and people are living longer as a consequence of earlier treatment.
The researchers say that cardiovascular disease prevention methods need to be tested in people living with HIV, such as primary preventive treatment with statins. Furthermore, “given that the projected CVD (cardiovascular disease) risk among PLWH (people living with HIV) was similar to those with diabetes, we believe that HIV should be considered a major risk factor for CVD and that PLWH could benefit from preventive strategies similar to persons with diabetes mellitus.”
Several sets of guidelines recommend that people aged 40 to 75 years should receive statins as a cardiovascular disease prevention measure. US Preventive Health Services Taskforce guidelines recommend that people should be prescribed statins if they have diabetes and a 10-year risk of cardiovascular disease of 10% or more. UK guidance from NICE recommends an offer of statins to anyone with diabetes over the age of 40.
A large randomised placebo-controlled clinical trial, REPRIEVE, is testing whether giving the statin pitavastatin to people on antiretroviral therapy over the age of 40 will reduce the risk of heart attack, stroke and other major cardiovascular problems in people who don’t meet current criteria for statin treatment. The study is designed to last up to six years and should report its results by 2021.
Background: Cardiovascular disease (CVD) is an increasing cause of morbidity among persons living with HIV (PLWH). We projected cumulative CVD risk in PLWH in care compared to the US general population and persons HIV-uninfected, but at high risk for HIV.
Methods: We used a mathematical model to project cumulative CVD incidence. We simulated a male and female cohort for each of three populations: 1) US general population; 2) HIV-uninfected, at high risk for HIV; and 3) PLWH. We incorporated the higher smoking prevalence and increased CVD risk due to smoking to the HIV-infected and HIV-uninfected, at high risk for HIV populations. We incorporated HIV-attributable CVD risk, independent of smoking.
Results: For men, life expectancy ranged from 70.2–77.5 years and for women from 67.0–81.1 years (PLWH-US general population). Without ART, lifetime CVD risk for HIV-infected males and females was 12.9% and 9.0%. For males, by age 60, cumulative CVD incidence was estimated at 20.5% in PLWH in care compared to 14.6% in HIV-uninfected high risk persons, and 12.8% in the US general population. For females, cumulative CVD incidence was projected to be 13.8% in PLWH in care compared to 9.7% for high risk HIV-uninfected persons, and 9.4% in the US general population. Lifetime CVD risk was 64.8% for HIV-infected males compared to 54.8% in the US general population males, but similar among females.
Conclusions: CVD risks should be a part of treatment evaluation among PLWH. CVD prevention strategies could offer important health benefits for PLWH and should be evaluated.
E Losina, EP Hyle, ED Borre, BP Linas, PE Sax, MC Weinstein, C Rusu, AL Ciaranello, RP Walensky, KA Freedberg