Malawian study provides strong evidence that HIV infection is an important risk factor for stroke

HIV infection is an important risk factor for stroke among adults in Malawi, investigators report in Neurology. The case-controlled study showed that the association between HIV and stroke risk was most evident in younger patients. HIV-positive individuals who had recently started antiretroviral therapy (ART) had an especially high risk of stroke, which the researchers attribute to immune reconstitution inflammatory syndrome (IRIS).

“HIV infection is an independent risk factor for stroke in Malawian adults,” comment the authors. “Although hypertension was the leading risk factor in this population overall, HIV infection and its treatment were the second most important risk factors and had the highest population attributable risk in younger patients.”

Incidence of stroke is increasing in many southern African countries. Hypertension is thought to be the main cause. However, a substantial proportion of strokes occur in younger patients who have a low prevalence of high blood pressure and other traditional risk factors for stroke.

Glossary

stroke

An interruption of blood flow to the brain, caused by a broken or blocked blood vessel. A stroke results in sudden loss of brain function, such as loss of consciousness, paralysis, or changes in speech. Stroke is a medical emergency and can be life-threatening.

hypertension

When blood pressure (the force of blood pushing against the arteries) is consistently too high. Raises the risk of heart disease, stroke, kidney failure, cognitive impairment, sight problems and erectile dysfunction.

adjusted odds ratio (AOR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 

traditional risk factors

Risk factors for a disease which are well established from studies in the general population. For example, traditional risk factors for heart disease include older age, smoking, high blood pressure, cholesterol and diabetes. ‘Traditional’ risk factors may be contrasted with novel or HIV-related risk factors.

matched

In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 

It has been suggested that HIV and its treatment may increase the risk of stroke. However, the importance of HIV and ART as risk factors for stroke remains unclear, especially in sub-Saharan African settings. A team of investigators therefore designed a case-controlled study to examine the role of HIV, ART and their interaction with hypertension as stroke risk factors among adults in Malawi.

The study population included 222 patients from the Blantyre district who were diagnosed with stroke between 2011 and 2012. These patients were matched with 503 individuals from the general population. The patients and controls were matched for age, sex and place of residence.

Average age was approximately 60 years.

HIV prevalence was higher among stroke patients than the controls (31% vs. 19%).

MRI scans were performed on 190 (86%) of patients, showing that 78% had suffered an ischaemic stroke and 22% a haemorrhagic stroke.

Ischaemic stroke is the most common type of stroke, occurring when a blood clot blocks blood and oxygen from flowing to the brain. Haemorrhagic stroke, usually caused by high blood pressure, occurs when a blood vessel bursts and bleeds into the brain.

Stroke was strongly associated with HIV infection (aOR = 3.29, 95% confidence interval 2.05 to 5.25; p < 0.001). Having started ART within the previous six months was especially associated with stroke (adjusted odds ratio (aOR) = 15.6, (%% CI 4.21 to 46.6; p < 0.001). The authors speculate that this elevated risk might be explained by a form of immune reconstitution syndrome, but say that more research is needed to explain the mechanism. They note that an increased risk of stroke was also seen in the first year after starting treatment in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study.

Overall, HIV was shown to contribute 15% of the risk of stroke (population attributable faction [PAF]) and hypertension 46%. HIV infection significantly increased the risk of ischaemic stroke, but not haemorrhagic stroke (where bleeding in the brain occurs).

HIV was the main risk factor for stroke in younger patients (under 45 years), increasing the odds more than five-fold (aOR = 5.57, 95% CI 2.43 to 12.8; p < 0.001).

Untreated HIV infection was also a risk factor for stroke (p < 0.001), although there was no association between viral load and stroke. 

When combined, HIV and hypertension were associated with a more than 13-fold increase in the risk of stroke (aOR = 13.63; 95% CI, 6.30-29.45). There was no evidence of effect modification between these two risk factors.

Other risk factors included diabetes and smoking.

“Our study, with well-defined cases, carefully selected population controls, and 99% ascertainment of HIV status, provides the clearest evidence yet that HIV is indeed an important risk factor for stroke,” write the authors. “While ART is necessary for improved HIV related outcomes overall, the association between early ART use and stroke events poses an additional (and potentially treatable) risk. How to address this is something that the research community will need to consider in sub-Saharan Africa and beyond.”

References

Benjamin LA et al. HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults. A case-control study. Neurology, 86: 1-10, 2016. (Full text article available here).