Idiopathic Intracranial Hypertension May Double Cardiovascular Risk

July 12, 2019

Idiopathic intracranial hypertension (IIH) in women appears to be associated with an increased cardiovascular risk, new research shows.

"This is a landmark study in that the possible long-term sequelae of idiopathic intracranial hypertension have not really been considered before," senior author Alexandra J. Sinclair, PhD, University of Birmingham, United Kingdom, told Medscape Medical News.

"Our results show that patients with idiopathic intracranial hypertension have double the risk of future cardiovascular events compared to controls even after adjusting for body mass index (BMI)," she said. "This implies that idiopathic intracranial hypertension is actually a systemic metabolic condition, and that patients need to have their cardiovascular risk strictly managed."

The study was published online July 8 in JAMA Neurology.

Young, Female, and Obese

The authors note that IIH is a condition of unknown origin and characterized by elevated intracranial pressure typically manifesting as papilledema, with a consequent risk of visual loss and chronic disabling headache.

Patients are typically young and female, and more than 90% are obese. The incidence and economic burden of idiopathic intracranial hypertension are rising in line with global obesity figures.

Management focuses on preserving vision and reducing headache morbidity, but long-term consequences of having the condition are unknown.

Noting that IIH has recently been linked to a unique profile of androgen excess, another key driver of increased cardiovascular risk, the researchers conducted the current study to try to define cardiometabolic risk in these patients, independent of BMI.

They analyzed data over a 28-year period from The Health Improvement Network (THIN), an anonymized, nationally representative electronic medical records database in the UK, and identified 2760 female patients with IIH (mean age 32 years, 60% obese) who were each matched with up to 10 controls by BMI and age. A total of 27,125 controls were included in the study.

Results showed that women with IIH had higher absolute risks for all cardiovascular outcomes vs controls. Hazard ratios were 2.10 for all cardiovascular events, 1.97 for heart failure, 1.94 for ischemic heart disease, 2.27 for stroke/transient ischemic attack, 1.30 for type 2 diabetes, and 1.55 for hypertension. All of the findings were statistically significant.

Data also showed that the prevalence of IIH in female patients tripled between 2005 and 2017, from 26 to 79 per 100,000 women, with rates increasing markedly in individuals with BMI over 30.

"To our knowledge, no previous cohort study has evaluated cardiovascular risk in idiopathic intracranial hypertension," the authors write.

The findings are the first indication that morbidity in this condition may extend beyond the typically considered areas of visual loss and chronic headaches, they add.

The investigators acknowledge that the predominant occurrence of obesity in patients with IIH may be expected to increase the cardiovascular risk, but in this study the increased risk was seen despite matching for BMI and age and controlling for other important covariates, including migraine (which can also be linked to increased cardiovascular risk).

Intervention Opportunity

"This has always been thought of as a condition affecting the eyes and the brain and is managed by ophthalmologists and neurologists. But our results suggest we need a broader view," said Sinclair.

"These are mainly young women," she noted, "and so we have the opportunity to intervene early to reduce their raised cardiovascular risk with weight modification, lifestyle advice on diet, quitting smoking and taking exercise, and close monitoring and treatment of lipids, blood pressure, and blood sugar levels."

As many of these patients are overweight or obese, facilitating weight loss needs to be a priority, Sinclair says. "This will help with the acute symptoms of the condition and can also lead to very significant cardiovascular benefits."

Noting that weight loss is a complex issue that requires specialist management and support, Sinclair urged health professionals to do more to encourage these patients to seek medical advice, get help with weight management, and engage with specialist weight loss services.

She also reported that new drugs are in development for IIH, including the new class of diabetes agents, glucagon-like peptide 1 (GLP1) receptor agonists, which may lead to new treatment approaches.

Prevalence Rising

Commenting on the findings for Medscape Medical News, Sweta Sengupta, MD, Duke University School of Medicine, Durham, North Carolina, said IIH was historically termed a rare disease, but is becoming increasingly more prevalent with the global rise of obesity and increased awareness of this condition. "Therefore, studying the implications of this disease is important," stressed Sengupta, who was not involved with the current research.

"This was a well-done, comprehensive retrospective cohort study that followed a large sample size of women for a significant period of time. Idiopathic intracranial hypertension disproportionately affects women, so this study focusing on women is appropriate," she said.

Sengupta added that the study gives patients and practitioners awareness about potential comorbid conditions that can develop and may increase the frequency of screening for cardiovascular risk factors, including hypertension and diabetes.

Sinclair reports grants from the NIHR Clinician Scientist Fellowship, the Medical Research Council, and the Idiopathic Intracranial Hypertension UK Charity. Sengupta has disclosed no relevant financial relationships.

JAMA Neurol. Published online July 8, 2019. Full text

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