Assessment of Incidence and Risk Factors of Intracerebral Hemorrhage among Participants in the Framingham Heart Study between 1948 and 2016

Abstract

Importance: Intracerebral hemorrhage (ICH) has the highest mortality of all stroke types and is the most serious complication of anticoagulation. Data regarding trends in ICH incidence and location-specific risk factors on the population level are conflicting. Objective: 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. Design, Setting, and Participants: This longitudinal prospective community-based cohort study comprised 10333 original participants (n = 5209; age range, 28-62 years) and offspring participants (n = 5124; age range, 5-70 years) from the Framingham Heart Study who were followed up from January 1, 1948, to December 31, 2016. Original and offspring patient cohorts were confirmed to have experienced a spontaneous ICH event through imaging or pathologic testing. A total of 129 participants were identified with a primary incident of ICH. After exclusions, the remaining 99 patients were divided into 2 nested case-control samples, which were created by stratifying the first incident of ICH by brain region (lobar ICH or deep ICH), with 55 patients included in the lobar ICH sample and 44 patients included in the deep ICH sample. Patients were matched by age and sex (1:4 ratio) with 396 individuals without any stroke event (the control group). No participant in the patient samples was excluded or approached for consent, as their initial consent to participate in the Framingham Heart Study included consent to follow-up of cardiovascular outcomes. Data were analyzed in October 2019. Main Outcomes and Measures: The unadjusted and age-adjusted ICH incidence rates, assessed in 3 periods (period 1, from 1948-1986; period 2, from 1987-1999; and period 3, from 2000-2016) to study incidence trends. Nested case-control samples were used to examine baseline risk factors and medication exposures with the incidence of ICH events located in the lobar and deep brain regions within the 10 years before participants experienced a stroke event. Results: Of 10333 original and offspring participants in the Framingham Heart Study, 129 patients (72 women [55.8%]; mean [SD] age, 77 [11] years) experienced a primary ICH incident during a follow-up period of 68 years (301282 person-years), with an incidence rate of 43 cases per 100000 person-years. The unadjusted incidence rate increased over time, but the age-adjusted incidence rate decreased slightly between periods 2 and 3. An age-stratified analysis indicated a continued increase in ICH incidence among patients 75 years and older, reaching 176 cases per 100000 person-years in period 3. A concurrent 3-fold increase in the use of anticoagulant medications was observed, from 4.4% in period 2 to 13.9% in period 3. The incidence rate increased substantially with age for both lobar and deep ICH. 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. 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. Conclusions and Relevance: This study found that the incidence of ICH increased in the oldest patients. Hypertension is a treatable risk factor for both deep and lobar ICH, while the use of statin medications is associated with the risk of a deep ICH event.