Women with HIV have no cardiovascular advantage over men, unlike in the general population

Women with HIV do not have a lower risk of serious heart disease than men, unlike in the rest of the population, an analysis of the REPRIEVE study of statin treatment for people with HIV has found. Moreover, smoking cessation and blood pressure monitoring and management need to be prioritised for all people with HIV at lower risk of serious heart disease, whether or not they choose to take statins.

The REPRIEVE study showed that taking pitavastatin every day reduced the risk of a major cardiovascular event such as heart attack or stroke by 36% in people with HIV judged to be at low-to-moderate risk of a major event when they joined the study.

In response to the findings, guidelines groups in the United States, United Kingdom and Europe have recommended statin treatment for people with HIV who have low-to-moderate cardiovascular risk.

“Women with HIV have higher levels of T-cell activation and experience less reduction in inflammation after beginning ART than men.” 

To further improve cardiovascular care in people with HIV, the REPRIEVE study group also looked at the risk factors associated with a major cardiovascular event (anything heart-related that would require admission to hospital) in study participants. In particular, they wanted to identify which factors had the greatest impact on the risk of a heart attack or stroke and which of the factors could be modified by lifestyle changes.

REPRIEVE recruited 7769 people with HIV aged 40 to 75 years who had been taking antiretroviral treatment for at least six months. Participants were randomly assigned to take either pitavastatin or a placebo and followed for approximately five years.

Participants had a median age of 50 years, 69% were male, 53% were White and 41% Black or African American, 63% were recruited in high-income countries, 18% in Latin America and the Caribbean and 15% in sub-Saharan Africa. At study entry, 36% had high blood pressure, 25% were current smokers, and the median cardiovascular risk score was 4.5%.

To assess the risk of major cardiovascular events associated with modifiable risk factors, the researchers created a multivariable model in which they adjusted for demographic factors, location of recruitment, smoking, substance use, family history of premature cardiovascular disease, metabolic factors, nadir CD4 count, viral suppression and antiretroviral regimen at study entry. Participants were stratified by randomised treatment group and the analysis controlled for statin therapy.

The fully adjusted analysis showed that the risk of a first major cardiovascular event during follow-up was higher for:

• People aged 50-59 (hazard ratio 2.06) and over 60 years (HR 2.53) compared to people aged 40-49 years
• In high-income countries, people of Black or African American race compared to White people (HR 1.65)
• People in high-income countries compared to all other regions except South Asia
• People with a family history of premature cardiovascular disease (HR 1.53)
• Current smokers (HR 2.27)
• People with high blood pressure (HR 1.77) or lower HDL cholesterol (HR 1.21)
• People with unsuppressed viral load (HR 1.40)
• People taking a non-standard combination of antiretroviral drugs (1.53).

The researchers were surprised to discover that female sex was not associated with a lower risk of a major cardiovascular event among people with HIV. In the general population, female sex is associated with a lower risk of serious heart disease. Before menopause, oestrogen promotes lower levels of ‘bad’ LDL cholesterol and helps to maintain healthy blood vessels. After menopause, the difference between men and women in cardiovascular risk diminishes.

In an accompanying editorial, Dr Sonya Krishnan and Dr Eileen Scully of Johns Hopkins University note that women with HIV have higher levels of T-cell activation at any given viral load and experience less reduction in inflammation after beginning antiretroviral treatment than men with HIV.  

The study investigators say that their findings provide guidance on which cardiovascular risk factors should be prioritised for attention in people with lower cardiovascular risk or those who are unwilling to take a statin. Recent studies in the United Kingdom show low uptake of statins in people with HIV, partly due to health system barriers but also because in some clinics, up to half of those offered statins declined treatment.

The REPRIEVE study team highlight the importance of smoking as a risk factor. Current smokers were more than twice as likely as never-smokers to experience a major cardiovascular event during the study. People who had stopped smoking before they joined the study did not have a raised risk of a major event compared to those who never smoked, and the study investigators stress the need for smoking cessation interventions that address loneliness, depression and substance use – factors associated with smoking in people with HIV.

Blood pressure monitoring and control are also critical ingredients of cardiovascular disease prevention, as high blood pressure is common among people with HIV, especially in people over 50. Managing blood pressure in people with HIV is just as essential for people taking statins as it is for everyone else, say the investigators; in the REPRIEVE study, pitavastatin had a greater impact on cardiovascular events in people without hypertension, they point out.

Unsuppressed viral load was also a modifiable risk factor, supporting the need for early and consistent antiretroviral treatment, the investigators conclude.