ICH Rates Rising in the Elderly

June 10, 2020

A new analysis shows that rates of intracerebral hemorrhage (ICH) have not fallen during recent years, as has been seen with ischemic stroke, and rates appear to be increasing in the elderly.

"Our findings suggest we should be preparing for an increase in ICH rates with the ageing of the population," lead author Vasileios-Arsenios Lioutas, MD, Beth Israel Deaconess Medical Center, Boston, Massachusetts, told Medscape Medical News.

The researchers also discuss whether the increased use of certain medications such as anticoagulants and statins may be playing a role in ICH trends.  

The analysis examined data from more than 10,000 individuals from the Framingham study. "This is the longest running population-based cohort with a follow-up period of 68 years, so gives us a unique opportunity to look at ICH trends in a large population over a long period of time," Lioutas said.

The paper was published online June 8 in JAMA Neurology.

There were 129 cases of a primary ICH incident in the study, with an incidence rate of 43 cases per 100,000 person-years. The unadjusted incidence rate increased over time, but the age-adjusted incidence rate showed a slight decrease since 1987.

An age-stratified analysis indicated a continued increase in ICH incidence among patients aged 75 years or older, reaching 176 cases per 100,000 person-years in the period 2000-2016.

"In general, there has been a stabilization of ICH rates since the mid-80s. The rates have flattened out, but we have not seen a large decline in ICH in the past 30 years as has been seen for ischemic stroke. This leads us to ask whether we could be doing better with regard to ICH," Lioutas commented.

"In particular, we saw an increase of ICH since 1985 in older people (aged over 75) whereas there was a slight decrease in those under 75. As the population is aging, we should brace ourselves for an increase in ICH," he added.

Hypertension Contributes to Both Deep and Lobar ICH

The researchers looked at the two different subtypes of ICH, deep and lobar, which are believed to represent different underlying processes.

"We have always thought that deep ICH is generally related to hypertension and lobar ICH is related to amyloid angiopathy — the deposit of amyloid protein in the blood vessel walls. But our current results suggest this is not as straightforward as we may have believed," Lioutas explained.

"We found that while deep ICH is indeed related to hypertension, we also found hypertension to be a pretty robust risk factor for lobar ICH as well."

The incidence rate increased substantially with age for both the lobar and deep types of ICH.

"These results suggest we need to be even more aggressive with blood pressure control. This is the one modifiable risk factor we can absolutely act upon and make a difference," Lioutas stressed. 

Why are ICH Rates Not Falling?

Many risk factors for ICH and ischemic stroke are similar, so, if ischemic stroke rates are falling, why are ICH rates not falling too? "This is the million-dollar question," Lioutas noted. 

He said that the current data do not answer that question, but he put forward some suggestions including increased use of certain medications, particularly anticoagulants.  

"There has been a sharp increase in the use of anticoagulants — these drugs are great at reducing ischemic stroke but they do increase bleeds. The rate of use of anticoagulants has tripled since 1985. This is not a surprise," Lioutas commented.  

In the study, use of anticoagulant medications increased from 4.4% in period 2 (1987-1999) to 13.9% in period 3 (2000-2016).

The researchers also discuss the increased use of statins in relation to the ICH rates seen.

"Statins have been linked to ICH but this association is not strong. The jury is out on this as the evidence is conflicting, but statin use has increased dramatically since the mid-1980s," Lioutas commented.

In the paper, the researchers write: "In our cohort, patients with deep ICH had a 4-fold higher likelihood of using statin medications compared with matched individuals in the control group despite no significant differences in cardiovascular disease prevalence. However, we approach this finding with caution given the relatively low number of exposed individuals."

Lioutas added: "We are not making a direct link between our results and the use of either anticoagulants or statins, but only to say that this may be one possible explanation for our observations."

"The beneficial effects of statins and anticoagulants in reducing ischemic events are well proven and their benefits definitely outweigh their risks when used in the right patient populations," he added. "They also probably allow people to live longer so that they may then go on to experience an ICH, but perhaps we could make sure we select patients for these medications more carefully and think about dosage and each individual's risk of hemorrhagic complications."

Competing Risks?   

Commenting on the study for Medscape Medical News, Michael Szarek, PhD, professor Chair of the Department of Epidemiology and Biostatistics at the SUNY Downstate Health Sciences University, New York City, said, "The finding that hemorrhagic stroke incidence appears to be increasing in older patients over time may be explained, at least in part, by competing risks.  

"Specifically, as the risk of death from vascular causes, including ischemic stroke, has decreased due to more effective treatments that modify the risk of these events, patients consequently remain at risk for non-modifiable events. Therefore, patients who would have otherwise died at a younger age from vascular causes appear to have higher rates of other negative outcomes, including hemorrhagic stroke."

On the issue of statins and ICH, Szarek points out that meta-analyses of individual patient data from randomized studies have not found statins to be associated with a significantly increased risk for ICH. 

"Importantly, these analyses have consistently found substantial benefits of statin therapy in terms of vascular events including ischemic stroke, which are much more frequent than hemorrhagic stroke overall as well as in older patients," he said. "Therefore, even if statin therapy results in an increased risk of hemorrhagic stroke, the possible absolute increase in risk is small relative to the definitive absolute decrease in these other events, indicating the benefits of treatment far outweigh this potential risk."

This study was supported by grants from the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, and the National Heart, Lung, and Blood Institute.

Lioutas reported receiving grants from the National Institutes of Health and the National Institute on Aging during the conduct of the study, and personal fees from Qmetis outside the submitted work. Disclosures for other authors appear in the paper.

JAMA Neurol. 2020. Published online June 8. Abstract.

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