Statin use, hypertension, and APOE-ε4 gene associated with intracerebral hemorrhage risk in the Framingham Heart Study

1. Incidence of intracerebral hemorrhage in older patients has increased since 1948.

2. Hypertension and statin use are both associated with intracerebral hemorrhage.

Evidence Rating Level: 3 (Average)

Study Rundown: Of all stroke types, intracerebral hemorrhage (ICH) possesses the highest mortality rate and is the greatest cause of disability. While stroke incidence has been reported to be decreasing over time, much of this can be attributed to a decrease in ischemic stroke rather than ICH events. Underlying pathophysiological mechanisms involved in ICH are non-uniform, such that deep and lobar brain regions suggest variable processes. Given that individuals older than 75 years may be at greater risk due to other comorbidities, further investigation into these factors may help to clarify ICH incidence and identify those at greatest risk.

This case-control study analyzed data from participants of the longitudinal community-based cohort Framingham Heart Study, a study that has been ongoing since 1948. It aimed to characterize ICH incidence rates, investigate temporal trends of these rates during a follow-up period of 60 years or more, and identify major risk factors for ICH based on brain region. Results suggested that older patients were at greatest risk of ICH and that the incidence rate has not decreased over time. Hypertension, statin use, and apolipoprotein E (APOE) ε4 homozygosity were also identified as major risk factors that were significantly associated with higher ICH risk. Findings re-emphasize the importance of controlling hypertension as a modifiable risk factor for cardiovascular events, and presents additional factors that may be used for risk stratification.

Click to read the study in JAMA Neurology

Relevant Reading: Contributions of the Framingham Heart Study to Stroke and Dementia Epidemiologic Research at 60 Years

In-Depth [case-control study]:

This observational longitudinal nested case-control study included a total of 10,333 participants and their offspring from the Framingham Heart Study, all of whom had experienced a spontaneous ICH event based on pathologic testing or imaging.

Of the 10,333 individuals between 1948 and 2016, both original participants (n = 5,209; age range 28 to 62 years) and their offspring (n – 5,214; age range 5 to 70 years), 129 were identified with having experienced a primary incident of ICH. Following exclusions, 99 participants were separated into two case-control samples, stratified by the first ICH incident’s brain region (44 deep ICH, 55 lobar ICH). These individuals were matched by sex and age with a 1:4 ratio with 396 control participants without stroke history.

During a follow-up period of 68 years (301,282 person-years), 129 of the 10,333 participants (mean [SD] age = 77 [11] years; 55.8% female) experienced a primary ICH. The incidence rate was 43 cases per 100,000 person-years. While incidence rate increased over time, age-adjusted findings suggested a decrease between periods 2 (1987 to 1999) and 3 (2000 to 2016). Age stratification demonstrated a continuous increase in ICH incidence among those 75 years of age and older, up to 176 cases per 100,000 person-years in period 3. Period 3 also verified a 300% increase in anticoagulant use relative to period 2, with incidence of both deep and lobar ICH increasing during this time. Hypertension and statin use were significantly associated with deep ICH incidence (OR 4.07, 95% CI 1.16 to 14.21, p = 0.03). Lastly, high systolic blood pressure and APOE ε4 homozygosity were associated with lobar ICH incidence (OR 3.66, 95% CI 1.28 to 10.43, p = 0.02).

Image: PD

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