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Depression increases risk of heart attack for adults with HIV

Major depression is associated with an increased risk of heart attack for middle-aged HIV-positive patients, investigators from the United States report in JAMA Cardiology. Overall, presence of a major depressive disorder (MDD) increased the risk of heart attack – acute myocardial infarction (AMI) – by almost a third. Use of antidepressants weakened the association between depression and heart attack risk, and there was no evidence that milder forms of depression – dysthymic disorders – were associated with an elevated risk of heart attack.

It’s already known that depression is associated with an increased risk of cardiovascular disease (CVD) in the general population. The present study is the first research to show that major depression is also a heart attack risk factor for patients with HIV.

“We report novel evidence suggesting that MDD is independently associated with AMI in the HIV-infected population,” comment the authors. “We found that MDD at baseline was associated with an increased risk for incident AMI over 5.8 years of follow-up. Specifically, after adjustment for demographics, CVD risk factors and HIV-specific factors, HIV-infected adults with MDD had a 30% greater risk for having an AMI than did HIV-infected adults without MDD.”

The investigators believe their research had identified a new target for cardiovascular disease prevention in HIV-positive patients that should be explored in further studies.

Improvements in treatment and care mean that most patients with HIV now have an excellent life expectancy. Diseases associated with older age are an increasingly important cause of illness and death in HIV-positive patients, and prevention of cardiovascular disease is a care priority.

Research in the general population has shown that individuals with a depressive disorders are up to 60% more likely to develop cardiovascular disease compared to individuals with good mental health.

Investigators from the Veterans Aging Cohort Study wanted to see if there was a similar relationship between depression and heart attack risk in patients with HIV.

They therefore designed a prospective study involving 26,144 HIV-positive patients who entered care between 1998 and 2003. Patients were followed between 2003 and 2009 to see if the presence of a major or minor depressive disorder at baseline increased the risk of heart attack during follow-up. The investigators adjusted their findings in several models to take account of traditional cardiovascular risk factors, HIV-related factors, co-infection with hepatitis C virus (HCV), drug use and use of antidepressants.

The majority of participants (>95%) were male and the average age at baseline was approximately 47 years.

A major depressive disorder is defined by psychiatrists as a period of at least two weeks of persistently low mood accompanied by symptoms such as feelings of worthlessness, anxiety, pessimism, impaired concentration, disturbed sleep, loss of interest in everyday activities, reduced energy, and sometimes, thoughts of death or suicidal feelings. On entry to the study, 19% of patients had a major depressive disorder with a further 9% having a milder form of depression.

Patients were followed for a median of 5.8 years. During this time, there were 490 incident heart attacks (2% of study population).

Patients with a major depressive disorder at baseline had an increased risk of heart attack compared to patients without major depression. The association was significant in models that took into account demographics (HR = 1.31; 95% CI, 1.05-1.62), cardiovascular risk factors (HR = 1.29; 95% CI, 1.04-1.60) and HIV-specific factors (HR = 1.30; 95% CI, 1.05-1.62).

The association was weakened but still of borderline significance when the investigators took into account other factors, such as HCV infection, substance abuse and haemoglobin level (HR = 1.25; 95% CI, 1.00-1.56).

The authors also adjusted their results to take account of baseline antidepressant therapy. Overall, use of antidepressants meant that the association between major depression and heart attack was no longer significant.

There was no evidence that milder forms of depression increased the risk of heart attack.

The investigators suggest several reasons why major depression increased the risk of heart attack for patients with HIV, including:

Systemic inflammation.

Changes in the autonomic nervous system.

Poor health behaviours, such as smoking, a sedentary lifestyle and sub-optimal adherence to treatment.

Social isolation.

“We report novel evidence that HIV-infected adults with MDD have a greater for AMI than HIV-infected adults without MDD after adjustment for many potential confounders,” conclude the investigators. “There is a need for clinical trials designed to evaluate the effect of high-quality depression treatment on CVD risk markers and incident events in HIV-infected adults with depression.

The a**lysis presented today was preliminary (data collection was only completed a month ago). Dabis said that further a**lyses will attempt to gain a better understanding of how results differed between men and women, and for people of different ages.

The researchers will try to clarify the reasons people did not link to care – does the explanation lie in the way health services are provided, individual factors or community stigma? They will seek to better understand the differences between the profile of individuals reached and not reached by interventions.

During discussion, Myron Cohen of the University of North Carolina suggested that delays in linking to care could have meant that individuals with recent HIV infection disproportionately contributed to onward transmission. Moreover, it will be important to understand the impact of migration and s*xual networks which reach outside the study area, which may contribute to new HIV infections.

François Dabis said that, although the study was hypothesised to show an effect of TasP after four years of follow-up, it may be that it will take longer to have an impact on incidence, in light of the slowness of linkage to care.

Other delegates suggested that the intervention clusters may not have received a package of interventions that was sufficiently intensive, in comparison with the control clusters. For example a more intensive approach to help people link to care, such as home-based initiation of HIV treatment, could have had a greater impact.

Sheri Lippman of the University of California, chairing the session, commented that it may take more than technical solutions to deal with the structural barriers to engagement with care that exist.

Activists say that a United Nations Political Declaration on Ending AIDS, due to be finalised this week at a UN High Level Meeting on Ending AIDS in New York, could exclude language recognising the critical importance of key populations for the prevention and treatment of HIV, unless sympathetic governments intervene to ensure the inclusion of language reaffirming the needs of marginalised and criminalised populations.
In particular, activists say that interventions by Russia, Iran, Indonesia and a group of Gulf States have resulted in the removal of references to the need to repeal discriminatory and punitive laws affecting s*x workers, people who use drugs and men who have s*x with men.
References to ensuring access to tailored HIV combination prevention services for key populations have also been removed, and an explicit list of key populations is missing from the draft declaration.
References to the burden of HIV infection in key populations in different regions of the world have been diluted, and key populations are referred to only in the context of risk, rather than as groups of people in especially high need of effective HIV prevention services and treatment.
Key populations have disproportionately high rates of HIV infection and yet, have poorer access to essential HIV services. For example, people who inject drugs are 24 times more likely to acquire HIV, s*x workers are ten times more likely to acquire HIV and transgender people are 18 times more likely to acquire HIV.
Key populations face criminalisation, discrimination and a lack of provision of essential evidence-based prevention and treatment services, and are increasingly left behind as the coverage of HIV treatment is scaled up. In Eastern Europe, for example, only 20% of people living with HIV are receiving antiretroviral treatment and half of all new infections are estimated to be occurring in people who inject drugs. Most governments in Eastern Europe express strong opposition to harm reduction measures that could limit HIV infection, continue to promote aggressive policing of drug users and publicly endorse discrimination against men who have s*x with men and transgender people.
“After 35 years of the AIDS epidemic, it is reprehensible that some governments would still rather criminalise communities and obstruct access to evidence based HIV services than work together to end this epidemic,” said George Ayala of the Global Forum on MSM & HIV. “We are demanding leaders that oppose this deadly approach to take a stand today, by requesting the Co-Chairs of the High Level Meeting to open the draft Declaration today for further negotiation. We believe evidence and human rights will carry the day—but only if politicians are willing to work, and to speak out for what is right.”
Activists are calling on the government representatives of the United States, European Union countries, Australia, South Africa, Brazil, Argentina and Colombia to mount a last-ditch defence of the rights of key populations, by pushing for an inclusion of specific acknowledgement of the key populations affected by HIV and the burden of stigma, violence and discrimination faced by these groups. Activists are also calling for the needs of key populations to be addressed in all sections of the declaration that discuss strategies for ending the epidemic, and language concerning s*xual and reproductive health and rights of women and key populations to be retained.
UN human rights experts have also called for a strong focus on key populations and harm reduction for people who inject drugs in the final declaration.
In a statement issued last week , the Office of the United Nations High Commissioner for Human Rights said “states must commit to removing the punitive frameworks that fuel mass incarceration, HIV epidemics, and negative health outcomes,” and recommendeds that the declaration “adopt a new target to prevent HIV among people who inject drugs, and commit to ensuring availability and access to evidence-based treatment, including harm reduction programmes.”
The draft declaration is designed to commit national governments to endorse the Fast-Track approach to achievement of the 90-90-90 targets, and to provide a framework for the global HIV response over the next five years. The UNAIDS 90-90-90 Fast-Track target calls on countries to reach the following goals:
90% of people living with HIV diagnosed by 2020
90% of diagnosed people on antiretroviral treatment by 2020
90% of people in treatment with fully suppressed viral load by 2020.
The declaration also commits national governments to work towards reducing TB-related deaths by 75% by 2020, and to reduce new infections among young women to less than 100,000 per year by 2020.
“Without commitments on advancing the response among marginalised and criminalised groups, the very goal of the declaration—to guide the world in ending AIDS as a global epidemic by 2030—will not be achieved,” said Asia Russell of Health GAP (Global Access Project).
Activists are calling on organisations to lobby their national government representatives and use social media platforms to express the strength of feeling on the issue. In particular they encourage advocates to "urge your government and missions in NYC to avoid rushing into approving a seriously flawed document," and to demand that "your delegations emphatically speak against weakened or misleading language or language that renders key populations invisible."

Older HIV-positive patients have a high prevalence of multiple age-related problems, investigators from the United States report in the online edition of the Journal of Acquired Immune Deficiency Syndromes . The research involved patients aged 50 years and older receiving outpatient care in San Francisco. Overall, 40% reported difficulties with daily activities, most reported loneliness, many had mild cognitive impairment and 30% had only poor to fair quality of life.
“This is one of the first studies to have evaluated a wide range of geriatric assessments among HIV-infected individuals in an outpatient clinical setting and provides a comprehensive overview of the health needs faced by the aging HIV-positive population,” write the authors. “We observed a high burden of clinically-concerning deficits in older HIV-infected adults across multiple domains, including functional impairment, falls, depression and social isolation.” The investigators believe their findings have implications for patient care, commenting “our results highlight the importance of systematically providing functional, social and mental health support for the aging HIV-infected population.”
Improvements in treatment and care mean that many patients with HIV are now living well into old age. Over half of HIV-positive adults in the United States are now aged 50 years and over. Previous research has shown that these patients frequently have multiple health problems and develop conditions associated with old age earlier than the traditional cut-off for old age – 65 years.
The Veterans Aging Cohort (VACS) Index, a prognostic tool based on markers associated with HIV and other health conditions, can be used to identify older HIV-positive patients with a high risk of illness and death. VACS Index score has also been associated with risk of fragility fractures, cognitive impairment and exercise capacity. However, less is known about its association with geriatric conditions, such as functional status.
Investigators therefore designed a cross-sectional observational study assessing the physical, cognitive, social and behavioural health of a large sample of older HIV-positive adults receiving outpatient care in San Francisco. A combination of geriatric and other assessments were used to assess psychosocial issues observed in older patients with HIV. The investigators hypothesised that both age and VACS Index would be associated with the geriatric conditions identified in the assessments.
Recruitment was between December 2012 and December 2014 and English-speaking patients aged 50 years and older were eligible to participate.
Assessments included questions on physical, social, mental and cognitive health. The investigators used a combination of assessments that addressed traditional geriatric conditions and also the issues faced by older HIV-positive patients.
Four broad areas of health were assessed:
Physical health and functioning; falls and walking speed (Activities of Daily Living [ADL] and Instrumental Activities of Daily Living [IADL]).
Social support, including physical and perceived support and loneliness.
Mental health, including depression, anxiety, post-traumatic stress disorder.
Behavioural and general health, including adherence to HIV therapy and overall quality of life.
A total of 359 patients were assessed. Most (85%) identified as male, two-thirds were in the men who have s*x with men (MSM) risk category, and approximately 60% were white. Approximately three-quarters had attended college. Half were receiving disability benefits and the majority had an annual income below $20,000. Most (85%) had been living with diagnosed HIV infection for ten years or over. As regards HIV-related markers, 82% had an undetectable viral load and over half had a CD4 cell count above 500 cells/mm3.
Median age was 56 years and two-thirds of patients were in their 50s. Patients aged 60 years and older were more likely to be white, college educated and to have a higher annual income when compared to younger participants.
The patients had a high burden of conditions associated with older age, with 41% reporting a fall in the previous year, almost 60% reported loneliness, half reported receiving low levels of social support and over a third met the criteria for mild cognitive impairment.
Patients aged 60 years and older were more likely to report problems with balance than patients in their 50s (47% vs. 33%). Prevalence of problems with physical health and functioning was similar in the two age groups (12%), but patients in their 60s had slower walking speed.
However, older patients reported less anxiety and had higher levels of adherence to their HIV treatment. Although older patients were more likely to rate their health-related quality of life as “good”, fewer reported that it was “very good” or “excellent”, compared to patients in their 50s (p = 0.04).
A higher VACS Index score – indicative of higher mortality risk – was associated with greater levels of dependence and IADL scores, i.e. falls and slower gait speed (p = 0.003).
“Our data add to the growing body of evidence that older HIV-infected adults are facing increasing medical, psychiatric and social complexity and help to provide insight into how this complexity varies in different age groups in older adults,” conclude the authors. “Our findings highlight the importance of taking a comprehensive approach to identify health issues facing older HIV-positive patients and the critical need to develop interventions to improve the quality of life and address the multifaceted needs of older HIV-infected patients.”