Anticoagulant Use Could Be Driving Rise in Risk of Intracerebral Hemorrhage

Vasileios-Arsenios Lioutas, MD

Despite marked advances in the fights against cardiovascular disease and stroke, results of a National Institutes of Health-funded study suggests rates of intracerebral hemorrhages have increased among older adults over the last 3 decades.

Using data from the Framingham Heart Study, investigators found rates have remained consistent among most age groups but increased in those 75 and older, while also pointing out the increased rate of anticoagulant use during the same time period.

"One of the possible explanations for why we saw more bleeds in older Framingham participants is that, by using these anticoagulant medications, we prevented adverse events that would potentially have killed them earlier in life," said lead investigator Vasileios-Arsenios Lioutas, MD, a stroke neurologist at Beth Israel Deaconess Medical Center and Harvard Medical School, in a statement. "We prolonged their life expectancy and then, because we did, they were at risk to have a hemorrhage later in life."

With the Framingham Heart Study containing information back to 1948, Lioutas and a team of colleagues from the University of Texas Health Science Center obtained data from more than 10,000 subjects. In an effort to assess the long-term population-based trends of intracerebral hemorrhage and whether risk profiles vary based on the region of the brain, investigators designed a longitudinal prospective analysis using data from participants and their offspring.

Of note, the first cohort of the Framingham Heart Study was enrolled in 1948 and included 5209 individuals; the offspring cohort was enrolled in 1971 and contained 5124 individuals. The first cohort was examined biennially and the offspring cohort was examined every 4 years. During each follow-up examination, investigators recorded interim history, lifestyle risk factors, comorbidities, and medication use, as well as blood pressure, height, and weight of participants.

As definitions have changed over time, investigators pointed out the presence or absence of a cardiovascular risk factor was defined in accordance with the accepted definition at the time data was recorded. Additionally, hypertension systolic blood pressure (SBP) of more than 140 mm Hg, diastolic blood pressure (DBP) of more than 90 mm Hg, or the use of an antihypertensive medication

Of those included in the Framingham Heart Study, 180 experienced an intracerebral hemorrhage event during the 68-year study period. Upon application of inclusion criteria, investigators included 99 patients who experienced a first, primary intracerebral hemorrhage event. Of these, 55 were identified as a lobar intracerebral hemorrhage and 44 were identified as a deep intracerebral hemorrhage.

Using these 99 subjects, investigators created a control cohort of 396 age- and sex-matched patients without any stroke event. Furthermore, analyses were designed to compare the adjusted and unadjusted rates of intracerebral hemorrhage across 3 different periods—from 1948-1986, from 1987-1999, and from 2000-2016.

Results of the investigators’ analyses indicated the unadjusted incidence rate of intracerebral hemorrhage increased over time with a rate of 25 per 100,000 person-years in period 1 and a rate of 73 cases per 100 000 person-years in period 3. However, the age-adjusted incidence rate experienced a decline between the second and third periods from 51 cases per 100 000 person-years to 46 cases per 100 000 person-years.

Among patients 75 years of age and older, the incidence rate increased from 88 per 100,00 person-years in period 1 to 176 cases per 100,000 in period 3. Between periods 2 and 3, cases per 100,000 person-years increased from 158 to 176. Investigators pointed out use of anticoagulant mediations increased from 4.4% during period 2 to 13.9% in period 3.

Investigators highlighted both higher systolic and diastolic blood pressure and statin medication (odds ratio [OR], 4.07; 95% CI, 1.16-14.21; P=.03) were associated with a greater incidence of deep intracerebral hemorrhage while higher systolic blood pressure and apolipoprotein E e4 allele homozygosity (OR, 3.66; 95% CI, 1.28-10.43; P=.02) were associated with the incidence of lobar intracerebral hemorrhage.

This study, “Assessment of Incidence and Risk Factors of Intracerebral Hemorrhage Among Participants in the Framingham Heart Study Between 1948 and 2016,” was published in JAMA Neurology.