Intracranial Hemorrhage Incidence Increases With Age

Vasileios-Arsenios Lioutas, MD

Results from the Framingham Heart Study, a longitudinal prospective community-based cohort study, revealed that the incidence of intracranial hemorrhage (ICH) increased in the oldest patients, with unadjusted incidence rates increasing over time.

The study contained 10,333 original and offspring patients, with 129 patients (72 women [55.8%]; mean age, 77 years [standard deviation (SD), 11]) who experienced a primary ICH incident during a follow-up period of 68 years (30,1282 person-years), along with an incidence rate of 43 cases per 100,000 person-years.

Over time, researchers noted that the unadjusted incidence rate of ICH increased, but the age-adjusted incidence rate decreased slightly between Period 2, from 1987 to 1999, and Period 3, from 2000 to 2016. The steady increase from 25 cases per 100,000 person-years in Period 1 grew to 73 cases per 100,000 person-years in Period 3.

The age-stratified analysis revealed that the incidence rate remained low in the group aged 45 to 74 years and increased slightly in the group aged 75 to 84 years (from 96 cases per 100,000 person-years to 113 cases per 100,000 person-years between Periods 1 and 3). However, the incidence rate increases substantially between Periods 1 and 3 in the group 85 years and older, from 39 cases per 100,000 person-years to 287 cases per 100,000 person years.

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The data were collected by Vasileios-Arsenios Lioutas, MD, assistant professor, Beth Israel Deaconess Medical Center, Harvard Medical School, and colleagues, and showed a substantially higher incidence rate with age for both lobar and deep ICH. Additionally, higher systolic and diastolic blood pressure and statin medication use (odds ratio [OR], 4.07; 95% CI, 1.16—14.21; P = .03) were associated with the incidence of deep ICH.

These results indicated that hypertension is a treatable risk factor for both deep and lobar ICH, while the use of statin medications is normally associated with the risk of a deep ICH event. Lioutas and colleagues also noted that higher systolic blood pressure and apolipoprotein E ε4 allele homozygosity (OR, 3.66; 95% CI, 1.28-10.43; P = .02) were associated with the incidence of lobar ICH.

The study originally comprised of 10,333 participants (n = 5209; age range, 28­­ to 62 years) and offspring patients (5124; age range, 5 to 70 years) were followed up from January 1, 1948, to December 31, 2016. Data for these patients were analyzed in October 2019.

Original and offspring patient cohorts were confirmed to have experienced a spontaneous ICH event through imaging or pathologic testing. Among the 129 participants who identified having a primary incident of ICH, 99 were divided into 2 nested case-control samples after exclusions. Within those nested case-control samples, researchers stratified patients based on the brain region of the ICH, which led to 55 patients included in the lobar ICH sample and 44 patients included in the deep ICH sample.

Following that, patients were matched by age and sex (1:4 ratio) with 396 individuals without any stroke event acting as the control group. Through this, the objective of the study was to assess long-term population-based trends in the incidence of ICH, examine incidence rates stratified by deep and lobar locations, and characterize location-specific risk factors. It had been previously noted that ICH has the highest mortality of all stroke types but had conflicting data trends regarding ICH incidence and location-specific factors.

Patients were measured on incidence trends in 3 periods; Period 1, from 1948 to 1986, and the aforementioned Periods 2 and 3, using unadjusted and age-adjusted ICH incidence rates. Researchers used the nested case-control samples to examine baseline risk factors and medication exposures with the incidence events located in the lobar and deep brain regions within the 10 years before participants experienced a stroke event.

“Given the lack of therapy to treat ICH, emphasis should be placed on prevention, which needs to be optimized and intensified. The aging of the population and the more widespread use of anticoagulant medications suggest the need for more precise and accurate risk stratification strategies to mitigate the competing risks of ischemia and hemorrhage, especially in older individuals,” Lioutas and colleagues concluded.

REFERENCE

Lioutas V, Beiser AS, Aparicio HJ, et al. Assessment of incidence and risk factors of intracerebral hemorrhage among participants in the Farmingham Heart Study between 1948 and 2016. JAMA Neurol. Published online June 8, 2020. doi: 10.1001/jamaneurol.2020.1512.