HIV linked to greater increase in cardiovascular disease risk for women than men

Women living with HIV have almost twice the risk (a 93% increased risk) of cardiovascular disease compared to women without HIV, while men with HIV have a 44% increased risk compared to those without HIV, a study published recently in the journal AIDS has found.

Since the introduction of antiretroviral therapy, HIV has become a manageable long-term condition, but people living with HIV remain at increased risk of cardiovascular disease. This includes heart attacks, heart failure and stroke. Previous work has established that people with HIV have a 50 to 100% increased risk for cardiovascular disease. This is thought to be due to both lifestyle risk factors for cardiovascular disease, such as smoking and obesity, as well as inflammation and immune activation that occur as a result of HIV infection, both before and after initiation of HIV treatment.

Men and women in the general population have different risk profiles when it comes to cardiovascular disease. Although the likelihood of having cardiovascular disease is higher in men, women have a higher risk of serious consequences such as death when they experience cardiovascular events. This has only begun to be understood relatively recently, and may have important implications for how health systems monitor and treat people.

Previous studies looking at sex differences in cardiovascular disease risk for people living with HIV have shown conflicting results. A narrative review of studies looking into the issue found that HIV increases the risk of cardiovascular disease in women more than it does in men, and suggested this may be down to increased cardiovascular risk factors in women living with HIV, and less effective management of these risk factors when they occur. In contrast, a cohort study, which looked over time at cardiovascular disease risk, found that although the difference between cardiovascular risk in men and women was less noticeable compared to people without HIV, the risk of atherosclerotic cardiovascular disease in men with HIV was still higher than in women with HIV.

Whether these differences are truly present in people living with HIV is what a recent study by Dr Fanghui Shi and colleagues at University of South Carolina in the United States, sought to understand.  

The study

The study matched 4,803 people living with HIV with a control population of 24,276 people who shared similar demographic characteristics (age, sex, and race/ethnicity) and similar cardiovascular disease risk factors (e.g. socioeconomic status, BMI and smoking status), but who did not have HIV.

The researchers investigated whether HIV control affected these differences. HIV control was measured by whether people had a suppressed viral load and normal CD4 count. Researchers looked at data from participants living in the United States who had opted to be enrolled in population research. Data was reviewed over a decade, with the rate of cardiovascular disease, viral suppression, and immune status (CD4 count) measured and statistically examined for significant differences. Cardiovascular disease was defined as a composite of coronary artery disease or haemorrhagic or ischaemic stroke.

Results

No one at the start of the study had established cardiovascular disease. Over a decade, people living with HIV were found to have approximately 60% higher risk of developing cardiovascular disease compared to those who did not have HIV. This increased risk persisted amongst people with a suppressed viral load (around 50% higher) or high CD4 count (around 35% higher).

Women with HIV in particular were at an increased risk of cardiovascular disease compared to women who did not have HIV. Their specific risk was 90% higher than matched women who did not have HIV, while men’s risk was 40% higher compared to men without HIV.

Furthermore, whereas effective HIV suppression in men with HIV was associated with a cardiovascular risk profile similar to those without HIV, a preserved immune function (normal CD4 count) alone wasn't enough. Those with a normal CD4 count still had a significantly higher risk, around 32%, than men without HIV.

The increased risk remained for women living with HIV, irrespective of whether their viral load was suppressed or they had a strong CD4 count. Comparing men and women with HIV directly, this gap was clearest among those with a suppressed viral load: women's cardiovascular risk was 36% higher than men's in this group.

Women are at increased risk, but what is the cause?

This work agreed with previous research that has suggested that women with HIV were at higher risk of cardiovascular disease than their male counterparts. What it was also able to suggest is that women, unlike men, may not benefit from a reduced cardiovascular disease risk if their HIV is well controlled.

While the researchers used a large cohort of patients, over 90% had health insurance, which may not be generalisable to the average population in the US.

Previous explanations for why women with HIV may be at increased risk from cardiovascular disease have included less optimal management of cardiovascular disease risk factors compared to men, and greater levels of immune activation and inflammation. The researchers in this study highlighted previous studies that showed that women may experience higher levels of inflammation even when their HIV is well controlled. Other physiological factors could also play a role. For example, during menopause, oestrogen levels decrease and this is associated with increased cardiovascular disease risk. As women with HIV age, this may therefore be an important factor.