What is the clinical evidence from this study?

Study design: Cohort. Population: Premature cardiovascular disease (n=3146). Intervention: Premature cardiovascular disease (CVD) vs. No premature CVD. Primary outcome: Accelerated cognitive decline over 5 years (OR 3.07, 95% CI 1.65-5.71).

January 25, 2023Open Access

Premature Cardiovascular Disease and Brain Health in Midlife

Key Result

Premature cardiovascular disease was associated with a 3.07-fold increased odds of accelerated cognitive decline over 5 years compared to individuals without premature CVD.

Study Design

Type

Cohort (n=3,146)

Multicenter

Yes

Structured PICO

Does premature cardiovascular disease reduce midlife cognition and white matter health in young and middle-aged adults?

Population

3,146 adults from the CARDIA prospective cohort study (aged 18-30 years at baseline), mean age 55.1 years, 57% female, 48% Black, followed up to 30 years. A subset of 656 participants had brain MRI measures.

Intervention

Incident premature cardiovascular disease (CVD) event (defined as occurring at ≤ 60 years of age), including coronary heart disease, stroke/TIA, congestive heart failure, carotid artery disease, and peripheral artery disease.

Comparator

No premature cardiovascular disease events.

Outcome

Cognitive performance (z-standardized) across 5 domains (global cognition, verbal memory, processing speed, executive function, verbal fluency), cognitive decline over 5 years, and brain MRI measures of white matter hyperintensity (WMH) and white matter integrity at year 30.surrogate

Premature cardiovascular disease is associated with worse midlife cognition, accelerated cognitive decline, and poorer white matter health, independent of traditional cardiovascular risk factors.

Main Result

Effect estimate: OR 3.07 (95% CI 1.65-5.71)

Absolute Event Rate: 13% vs 5%

Limitations

Lack of baseline cognitive and MRI assessments limits causal inferences
Small number of premature CVD events limited statistical power to detect differential associations by CVD duration and age at onset
Potential unmeasured confounding from social, structural, and environmental factors
Findings may not be generalizable to other racial/ethnic groups as the cohort only included Black and White adults

Abstract

BACKGROUND AND OBJECTIVES: To understand the role of premature (defined as ≤ 60 years) cardiovascular disease (CVD) in brain health earlier in life, we examined the associations of premature CVD with midlife cognition and white matter health. METHODS: We studied a prospective cohort in the Coronary Artery Risk Development in Young Adults study, who were 18-30 years at baseline (1985-1986) and followed up to 30 years when 5 cognitive tests measuring different domains were administered. A subset (656 participants) had brain MRI measures of white matter hyperintensity (WMH) and white matter integrity. A premature CVD event was adjudicated based on medical records of coronary heart disease, stroke/TIA, congestive heart failure, carotid artery disease, and peripheral artery disease. We conducted linear regression to determine the associations of nonfatal premature CVD with cognitive performance (z-standardized), cognitive decline, and MRI measures. RESULTS: , premature CVD was associated with lower cognition in 4 of 5 domains: global cognition (-0.22, 95% CI -0.37 to -0.08), verbal memory (-0.28, 95% CI -0.44 to -0.12), processing speed (-0.46, 95% CI -0.62 to -0.31), and executive function (-0.38, 95% CI -0.55 to -0.22). Premature CVD was associated with greater WMH (total, temporal, and parietal lobes) and higher white matter mean diffusivity (total and temporal lobes) after adjustment for covariates. These associations remained significant after adjusting for cardiovascular risk factors (CVRFs) and excluding those with stroke/TIA. Premature CVD was also associated with accelerated cognitive decline over 5 years (adjusted OR 3.07, 95% CI 1.65-5.71). DISCUSSION: Premature CVD is associated with worse midlife cognition and white matter health, which is not entirely driven by stroke/TIA and even independent of CVRFs. Preventing CVD in early adulthood may delay the onset of cognitive decline and promote brain health over the life course.

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