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Stroke risk almost twice higher in women with than without HIV.

Compared with similar HIV-negative women, those with HIV had about a 2 times higher risk of stroke,* a serious emergency in which blood stops flowing to part of the brain (Figure 1). (1) The higher stroke risk with HIV persisted even when researchers accounted for other known stroke risk factors. Taking antiretroviral therapy longer lowered stroke risk in women with HIV.

Previous research in a large Boston-area comparison of women with and without HIV found that HIV-positive women had nearly a twice higher risk of stroke, even after researchers accounted for common stroke risk factors.2 But that analysis did not account for sex-specific stroke risk factors like pregnancy, menopause, and estrogen use.

To explore stroke risk factors in women further, researchers working with the Partners HIV group in Boston conducted this comparison of women with HIV and a similar group of women without HIV.

How the study worked. The research team analyzed women in a large database that includes people with or without HIV in two Boston hospital systems. They identified women with HIV in care any time between January 1996 and December 2011. For every woman with HIV, the researchers selected 10 HIV-negative women the same age and race.

Then the researchers checked medical records to see which women had a first-ever stroke during the study period. They also used medical records to determine what stroke risk factors each woman had. They recorded risk factors related to female sex, such as menopause, pregnancy, and use of estrogens for contraception or hormone replacement therapy. For women with HIV, the researchers recorded who used antiretroviral therapy and for how long.

Next the research team figured out stroke incidence--the rate at which women had a first stroke during the study period. Then they compared stroke incidence in women with versus without HIV. Finally, the investigators used a standard statistical method to compare the stroke rate in women with versus without HIV; this method accounted for whatever other traditional stroke risk factors a woman had (like older age, high blood pressure, or smoking). Then they repeated that statistical test to include female sex-specific risk factors (like menopause and estrogen use). This final analysis would indicate whether HIV infection, by itself, affected stroke risk, regardless of whatever other risk factors a woman had.

What the study found. The study involved 1214 women with HIV and 12,041 without HIV. Both groups had 7 years of care considered in this analysis. Women with and without HIV were similar in age (about 39 years) and proportions of whites (about 41%), blacks (about 31%), and Hispanics (about 18%). Among women with HIV, 61% had an undetectable viral load.

The overall new-stroke rate (incidence) was 1.99 per 1000 person-years, meaning 2 of every 1000 women had a stroke every year.

The rate was much higher in women with HIV (4.24 per 1000) than in women without HIV (1.77 per 1000).

Those numbers meant women with HIV had nearly a 2.5-fold higher stroke risk than women without HIV (Figure 2). When the researchers adjusted that statistical analysis to account for classic stroke risk factors (like older age, high blood pressure, and smoking), women with HIV had almost a 2-fold higher stroke risk than women without HIV (Figure 2). After additional statistical adjustment for female sex-specific stroke risk factors (like menopause and estrogen use), women with HIV still had a nearly 2-fold higher stroke risk than women without HIV (Figure 2).

Focusing just on women with HIV, statistical analysis considering age and race identified two factors that affected stroke risk: (1) Every year of antiretroviral therapy was linked to a 14% lower stroke risk, and (2) a history of central nervous system infection or cancer was linked to almost a 3-fold higher stroke risk.

What the findings mean for you. This large 7-year comparison of women with and without HIV linked HIV infection to almost a doubled risk of stroke--a dangerous block in blood flow in the brain (Figure 1). (1) This link between HIV and stroke risk held true regardless of whatever stroke risk factors a woman had. Notably, the researchers included sex-specific stroke risk factors such as menopause and estrogen use.

Although an earlier analysis of women and men in the same Boston healthcare systems did not find that HIV infection by itself raises the risk of stroke in men, (2) a similar study in US veterans tied HIV infection to higher stroke risk in men. (3) And other studies see a higher risk of cardiovascular disease--including stroke--in men with HIV. (4) Older age is a well-known stroke risk factor. Because people with HIV now live into older age thanks to antiretroviral therapy, stroke risk will climb in the HIV population.

For all these reasons, people with HIV should be aware of established stroke risk factors (Table 1). Some risk factors, like older age, can't be changed. But many other stroke risk factors can be avoided or managed. (5) In addition to the stroke risk factors listed in Table 1, this study found a higher stroke risk in women with HIV who had a previous central nervous system (brain and spinal cord) infection or cancer. Taking antiretroviral therapy longer lowered stroke risk in women.

People with HIV, especially those with other stroke risk factors, should talk to their providers about what they can do to avoid stroke risk factors or to limit their impact. Smoking is a major risk factor for stroke, other cardiovascular diseases, lung disease, and cancer. If you smoke, talk to your provider about making a plan to quit. Such plans may include nicotine-replacement therapy, medications like Chantix or Zyban, and an effective online smoke-ending program developed especially for people with HIV (click on the link at reference 6 below).

REFERENCES

(1.) Chow FC, Regan S, Zanni M, et al. Elevated ischemic stroke risk among women living with HIV infection. AIDS. 2018;32:59-67.

(2.) Chow FC, Regan S, Feske S, Meigs JB, Grinspoon SK, Triant VA. Comparison of ischemic stroke incidence in HIVinfected and non-HIV-infected patients in a US healthcare system. J Acquir Immune DeficSyndr. 2012;60:351358.

(3.) Sico JJ, Chang CC, So-Armah K, et al. HIV status and the risk of ischemic stroke among men. Neurology. 2015;84:1933-1940.

(4.) Petoumenos K, Reiss P, Ryom L, et al. Increased risk of cardiovascular disease (CVD) with age in HIV-positive men: a comparison of the D:A:D CVD risk equation and general population CVD risk equations. HIV Med. 2014;15:595-603.

(5.) American Stroke Association. Stroke risks. https://www.strokeassociation.org/STROKEORG/AboutStroke/ UnderstandingRisk/Understanding-Stroke-Risk UCM 308539 SubHomePage.jsp#

(6.) PositivelySmokeFree. https://www.positivelysmokefree.com/

* Words in boldface are explained in the Technical Word List at the end of this issue.

Caption: Figure 1. In an ischemic stroke, the kind considered in this study, a clot in a blood vessel cuts off the supply of blood to part of the brain (blue area on right). Lack of blood deprives the brain of oxygen and can cause serious injury. (Illustration from Servier PowerPoint Image Bank, http://smart.servier.com/).
Table 1. Established stroke risk factors

Factors you can control          Factors you can't control

* Smoking                        * Older age
* Poor diet                      * Female sex
* Obesity                        * Family history of stroke
* Physical inactivity            * Prior stroke, transient
* High blood pressure            ischemic attack (TIA, ministroke),
                                 or heart attack
* Diabetes                       * Black race
* High blood cholesterol         * Hispanic ethnicity
* Carotid artery disease
* Peripheral arterial disease
* Atrial fibrillation
(fast heart beat)
* Other heart disease
* Sickle cell disease

Source: American Stroke Association. https://www-strokeassociation-
org/STROKEORG/AboutStroke/UnderstandingRisk/
Understanding-Stroke-Risk_UCM_308539_SubHomePage.jsp#

Figure 2. A comparison of 1214 women with HIV and
12,041 HIV-negative women the same age determined
that women with HIV had almost a 2.5-fold higher risk of
stroke (left). Statistical adjustment for traditional stroke
risk factors (middle) and traditional factors plus female
sex-related factors (right) indicated that women with
HIV had almost a twice higher risk of stroke than HIV-negative
women.

Higher stroke risk in women with than without HIV

HIV+ vs HIV                 2.47
Traditional risk factors    1.93
Traditional and sex risk    1.89

Note: Table made from bar graph.
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Title Annotation:ARTICLE 7
Publication:HIV Treatment: ALERTS!
Geographic Code:1U1MA
Date:May 1, 2018
Words:1356
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