Associations of early-onset coronary heart disease and genetic susceptibility with incident dementia and white matter hyperintensity: A prospective cohort study - 01/01/25

Doi : 10.1016/j.tjpad.2024.100041

Jie Liang ^a,^{^{1
J. Liang and Y. Zhang contributed equally to this work.}}, Yanyu Zhang ^b,^c,^d,^{^{1
J. Liang and Y. Zhang contributed equally to this work.}}, Wenya Zhang ^a, Yang Pan ^a, Darui Gao ^b,^c,^d, Jingya Ma ^a, Yuling Liu ^a, Yiwen Dai ^a, Mengmeng Ji ^b,^c,^d, Wuxiang Xie ^b,^c,^d,^⁎ , Fanfan Zheng ^a,^⁎
^a School of Nursing, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
^b Department of Endocrinology, Peking University First Hospital, Beijing, China
^c Clinical Research Institute, Institute of Advanced Clinical Medicine, Peking University, Beijing, China
^d Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China

^⁎Corresponding author at: Clinical Research Institute, Institute of Advanced Clinical Medicine, Peking University, No. 38 Xueyuan Road, Haidian District, 100191 Beijing, China.Clinical Research Institute, Institute of Advanced Clinical MedicinePeking UniversityNo. 38 Xueyuan Road, Haidian DistrictBeijing100191China^⁎⁎Corresponding author at: Department of Clinical Nursing, School of Nursing, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 33 Ba Da Chu Road, Shijingshan District, 100144 Beijing, China.Department of Clinical NursingSchool of Nursing, Chinese Academy of Medical Sciences & Peking Union Medical CollegeNo. 33 Ba Da Chu Road, Shijingshan DistrictBeijing100144China

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Abstract

Background

The associations of early-onset coronary heart disease (CHD) and genetic susceptibility with incident dementia and brain white matter hyperintensity (WMH) remain unclear. Elucidation of this problem could promote understanding of the neurocognitive impact of early-onset CHD and provide suggestions for the prevention of dementia.

Objectives

This study aimed to investigate whether observed and genetically predicted early-onset CHD were related to subsequent dementia and WMH volume.

Design

Prospective cohort study.

Setting

UK Biobank.

Participants

500 671 individuals without dementia at baseline.

Measurements

Early-onset CHD (male ≤55 years; female ≤65 years) was ascertained using hospital inpatient records. Incident dementia including all-cause dementia, Alzheimer's disease, and vascular dementia was ascertained using hospital inpatient records, mortality register data, and self-reported data. WMH volume was measured through brain magnetic resonance imaging (MRI). Cox proportional hazards models and linear regression models were used to analyze the associations of early-onset CHD with incident dementia and WMH. Subsequently, a polygenetic risk score (PRS) analysis was conducted to investigate the associations of genetically predicted early-onset CHD with outcomes.

Results

Among 500 671 individuals (female: 272 669, 54.5%; mean age: 57.0 ± 8.1 years), 9 294 dementia occurred during a median follow-up of 13.8 years. Compared with the non-CHD group, both early-onset (n = 16 133) and late-onset CHD (n = 43 944) groups had higher risks of developing dementia (hazard ratio [HR]: 1.99, 95% confidence interval [CI]: 1.81 to 2.19 for early-onset group; HR: 1.20, 95% CI: 1.14 to 1.27 for late-onset group). Among CHD participants, early-onset CHD was associated with a significantly higher risk of incident dementia, compared with late-onset CHD (HR: 1.56, 95% CI: 1.39 to 1.75). In a subset of 40 290 individuals who completed brain MRI scans during a median follow-up of 9.3 years, participants with early-onset CHD exhibited the largest WMH volume among the three groups (early-onset CHD, late-onset CHD, and non-CHD, P_trend<0.001). The PRS analysis supported the associations of early-onset CHD with dementia (odds ratio [OR] for the highest quartile: 1.37, 95% CI: 1.28 to 1.46, P_trend<0.001) and WMH volume (β for the highest quartile: 0.042, 95% CI: 0.017 to 0.068, P_trend=0.002).

Conclusions

Early-onset CHD and genetic susceptibility are associated with a higher risk of incident dementia and a larger WMH volume. Additional attention should be paid to the neurocognitive status of individuals with early-onset CHD.

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Keywords : Early-onset coronary heart disease, Dementia, White matter hyperintensity, Genetic susceptibility, Polygenetic risk score