[Viva] Fwd: CATIE News - HIV and the immune system linked to heart disease in women

[Denise Becker]

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From: CATIE <mailer at catie.ca>
Date: Thu, Sep 26, 2013 at 2:48 PM
Subject: CATIE News - HIV and the immune system linked to heart disease in
women
To: dbecker106 at gmail.com


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    CATIE News - Bite-sized HIV and hepatitis C news bulletins
       CATIE News - HIV and the immune system linked to heart disease in
women

The widespread availability of potent combination anti-HIV therapy
(commonly called ART or HAART) in Canada, Australia, the U.S. and Western
Europe has greatly improved the health of HIV-positive people. Deaths from
AIDS-related infections are now much less common, at least among
HIV-positive people who get tested, make regular clinic visits and take ART
every day exactly as directed.
 Inflammation

HIV infection activates the immune system, causing it to release chemical
signals that incite inflammation throughout the body. This is a normal
response to an infection, as the body mobilizes to contain an invading
germ. However, in many cases, the immune system is not able to squelch HIV.
Treatment for HIV significantly reduces levels of HIV-related inflammation,
but ART does not eliminate the inflammation associated with HIV infection,
perhaps because the virus continues to persist, albeit at relatively low
levels. As a result, inflammation persists and this carries the potential
to gradually degrade many organ systems.
 Gender

Several studies have found a link between an increased risk for serious
cardiovascular disease (heart attack, stroke) and HIV infection,
particularly among men. However, comparatively less is known about the
impact of prolonged HIV infection on the cardiovascular health of women.

Observational studies in France and North America suggest that HIV-positive
women have an increased risk for heart attack, in some cases as high as
three-fold greater than among HIV-negative women. Precisely why this
increased risk occurs has not been clear, until very recently.
 Uncovering risks

Researchers in Boston have intensely studied women, both HIV positive and
negative, to better understand the interactions between their immune and
cardiovascular systems. In the Boston study, all women were free from
symptoms of cardiovascular disease (CVD) and did not have a history of CVD.
Using high-resolution X-ray scans (CT scans) of the women’s arteries,
researchers found that HIV-positive women were more likely to have more
sticky deposits in their arteries called plaque, specifically non-calcified
plaque (NCP). These are unstable deposits of fat and other materials that
can burst and trigger the formation of blood clots. If the clot formed is
sufficiently large, it can block an artery and lead to a heart attack.
Researchers linked the presence of NCP to certain inflammatory signals
produced by cells of the immune system called monocytes. These and other
findings are discussed later in this report.
 Study details

Researchers at New England’s leading medical centre, Massachusetts General
Hospital, recruited 90 women. None of them had a history of or symptoms of
CVD and they were distributed as follows:

   - 60 HIV-positive women
   - 30 HIV-negative women

 All women were recruited from the same communities to ensure that they had
similar CVD risk and socio-economic factors. As our focus will be on the
HIV-positive women, here is their average profile:

   - age – 47 years
   - ethno-racical composition – 75% women of colour, 25% white women
   - time since HIV diagnosis – 15 years
   - 98% were taking ART
   - 84% had a viral load less than 50 copies/ml
   - CD4+ count – 600 cells
   - 17% had higher-than-normal blood pressure
   - 8% were currently taking a class of cholesterol medicines commonly
   called “statins”
   - 15% had type 2 diabetes
   - 50% smoked tobacco
   - 47% were undergoing menopause
   - 5% currently injected street drugs
   - 10% currently used cocaine
   - in general, most women were at least overweight

 Results – Plaque

Overall, HIV-positive and -negative women seemed to have similar amounts of
plaque in their arteries. However, when researchers focused on the presence
of non-calcified plaque, HIV-positive women had significantly more of these
unstable deposits in their arteries.

Even when researchers took into account well-known risk factors for
CVD—such as older age, smoking tobacco, abnormal cholesterol levels and so
on—HIV-positive women were still found to have elevated deposits of NCP.

The research team also compared findings from HIV-positive women to
information in their database of men (with and without HIV) and found that
HIV-positive women had significantly greater average blood sugar levels and
so-called good cholesterol (HDL-C) than men. In contrast, men had
significantly elevated levels of triglycerides in their blood.
 Focus on the immune system

Compared to men with or without HIV infection, HIV-positive women were more
likely to have elevated levels of the following proteins and cells in their
blood:

   - soluble CD163 (sCD163)
   - soluble CD14 (sCD14)
   - activated CD4+ cells

 Other proteins that have previously been associated with HIV-related
inflammation in some studies with HIV-positive people—interleukin-6 and
high-sensitivity C-reactive protein—were not statistically elevated among
HIV-positive women in the Boston study.

Taking many factors into account, researchers found that HIV infection was
significantly linked to the presence of NCP in the arteries of women.
 A key finding

In the present study of relatively young women without symptoms of or a
history of CVD and who had generally good control of HIV, researchers found
increased activation of the immune system and greater amounts of unstable
deposits in the arteries of HIV-positive women compared to HIV-positive men
and HIV-negative women. These deposits, called NCP, are unstable and prone
to rupture; in previous studies with HIV-negative people, they are
associated with an increased risk for heart attacks.
 Different cells and proteins

There are many cells of the immune system. Historically, the main focus of
HIV research has been on T-cells (such as CD4+ and CD8+ cells) as well as
B-cells. A relatively understudied group of immune cells is called
monocytes; in their mature form, they are called macrophages. These cells
play many roles, including alerting the immune system to the presence of
invading germs, amplifying the immune response and attacking infected cells.
 Aging and immune activation

In the present study, researchers found high levels of sCD14 and sCD163 in
the blood of HIV-positive women. These proteins are shed into the blood
when monocytes are activated.

In general, in people who are aging, excess sCD163 is found in the blood
and monocytes and macrophages appear to be somewhat dysfunctional as they
are less able to control infections.

In the present study, the high levels of sCD163 and other proteins and
activated cells in the blood of HIV-positive women suggests that their
immune systems have prematurely aged, by between 10 and 15 years compared
to HIV-negative women of the same age.

In theory, the chronic immune activation found in HIV-positive women
combined with dysfunctional monocytes/macrophages could play a role in
accelerating the process of CVD. However, this theory remains to be proven.
 What is being done?

Researchers in different countries are testing interventions (such as
low-dose Aspirin, fish oil, exercise and anti-inflammatory drugs) to try to
dampen excess inflammation associated with chronic HIV infection. However,
long-term studies will be required to assess if such interventions can
prevent heart attacks, strokes and other problems. Well-designed studies to
explore these issues are time consuming and very expensive.

In the meantime, cardiovascular researchers note that there are factors
that can be addressed to improve the health of HIV-positive women. For
instance, in the present study there were factors identified among
HIV-positive women that are associated with an increased risk for CVD,
including the following:

   - smoking tobacco
   - being overweight
   - type 2 diabetes
   - injecting street drugs
   - use of cocaine

 All of these factors can begin to be addressed with discussion between
doctor and patient, increased levels of exercise (when possible), changes
to diet, use of medicines to control blood sugar, referrals for
psycho-social support, treatment for smoking cessation and addiction
counselling.

The findings from the present study underscore the unique issues of
HIV-positive women and the need for researchers to begin to develop CVD
risk calculators that take into account substance use and chronic immune
activation.
 A warning

In reviewing the findings from Boston, Dr. Franck Bocarra and Dr. Ariel
Cohen, cardiovascular experts based in France, note that if doctors and
their HIV-positive patients cannot bring these risk factors under control
it is possible that over the coming decade these risk factors could
intensify one another and “generate an explosive cocktail for CVD.”

*Resources*

HIV and cardiovascular
disease<http://www.catie.ca/fact-sheets/other-health-conditions/hiv-and-cardiovascular-disease>–
CATIE fact sheet

How to Say “I Quit”—and Mean
It<http://www.catie.ca/en/positiveside/summer-2013/how-say-i-quit-and-mean-it>–
*The Positive Side*

*—Sean R. Hosein*

REFERENCES:

   1. Fitch KV, Srinivasa S, Abbara S, et al. Noncalcified coronary
   atherosclerotic plaque and immune activation in HIV-infected women. *Journal
   of Infectious Diseases*. 2013; in press.
   2. Boccara F, Cohen A. Immune activation and coronary atherosclerosis in
   HIV-infected women: Where are we now, and where will we go next? *Journal
   of Infectious Diseases.* 2013; *in press.*
   3. Lohse N, Hansen AB, Gerstoft J, et al. Improved survival in
   HIV-infected persons: consequences and perspectives. *Journal of
   Antimicrobial Chemotherapy*. 2007 Sep;60(3):461-3.
   4. Freiberg MS, Chang CC, Kuller LH, et al. HIV infection and the risk
   of acute myocardial infarction. *JAMA Internal Medicine*. 2013 Apr
   22;173(8):614-22.
   5. Boccara F, Lang S, Meuleman C, et al. HIV and coronary heart disease:
   Time for a better understanding. *Journal of the American College of
   Cardiology*. 2013 Feb 5;61(5):511-23.
   6. Pandrea I, Cornell E, Wilson C, et al. Coagulation biomarkers predict
   disease progression in SIV-infected nonhuman primates. *Blood.* 2012 Aug
   16;120(7):1357-66.
   7. Helleberg M, Afzal S, Kronborg G, et al. Mortality attributable to
   smoking among HIV-1-Infected individuals: A nationwide, population-based
   cohort study. *Clinical Infectious Diseases*. 2013 Mar;56(5):727-34.
   8. Zanni M, Lo B, Wai B, et al. Increased coronary atherosclerotic
   plaque vulnerability features on computed tomography angiography among
   HIV-positive subjects vs. matched HIV-negative controls. In: Program and
   abstracts of the *20th Conference on Retroviruses and Opportunistic
   Infections*, 3-6 March 2013, Atlanta, U.S. Abstract 63.
   9. Baker J, Huppler-Hullsiek K, Singh A, et al. Monocyte activation but
   not T cell activation predicts progression of coronary artery calcium in a
   contemporary HIV cohort. In: Program and abstracts of the *20th
   Conference on Retroviruses and Opportunistic Infections*, 3-6 March
   2013, Atlanta, U.S. Abstract 66LB.
   10. Walker J, Burdo T, Miller A, et al. Elevated numbers of CD163+
   macrophages in the hearts of SIV-positive rhesus macaques with cardiac
   diseases are decreased using PA300. In: Program and abstracts of the *20th
   Conference on Retroviruses and Opportunistic Infections*, 3-6 March
   2013, Atlanta, U.S. Abstract 64.
   11. Martin GE, Gouillou M, Hearps AC, et al. Age-associated changes in
   monocyte and innate immune activation markers occur more rapidly in HIV
   infected women. *PLoS On*e. 2013;8(1):e55279.
   12. Hearps AC, Martin GE, Angelovich TA, et al. Aging is associated with
   chronic innate immune activation and dysregulation of monocyte phenotype
   and function. *Aging Cell*. 2012 Oct;11(5):867-75


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www.denise-becker.com
Queen's Gold Jubilee Medal
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cell: 250-870-1714
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