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Association of cognitive dysfunction with cardiovascular disease events in elderly hypertensive patients

Yano, Yuichiroa,b; Bakris, George L.a; Inokuchi, Takashic; Ohba, Yusukeb; Tamaki, Noborud; Nagata, Masahikoe; Kuwabara, Masachikaf; Yokota, Naotog; Eto, Takumah; Kuroki, Munetoshii; Shimada, Kazuyukib; Kario, Kazuomib

doi: 10.1097/HJH.0000000000000025

Objectives: This study assesses whether presence of cognitive dysfunction can be a marker associated with the development of cardiovascular disease (CVD) events independent of ambulatory blood pressure (BP) or other indices of target organ damage (TOD) in elderly hypertensive patients.

Methods: We recruited 585 hypertensive patients (mean age, 73 years; 41% men) who were ambulatory, lived independently, and were without clinically overt dementia. Cognitive function was assessed by Mini-Mental State Examination (MMSE) at baseline, and CVD events (coronary artery disease, stroke, congestive heart failure, and sudden death) were prospectively ascertained. Cognitive dysfunction was defined as the lowest quartile of MMSE scores (n = 183, median 24 points).

Results: CVD events occurred in 42 people over an average of 2.8 years (1644 person-years). The prevalence of cognitive dysfunction was higher in patients with CVD events than those without (57 vs. 29%; both P <0.001) at baseline. Cognitive dysfunction was associated with CVD events, after adjustment for nocturnal SBP and evidence of TOD [i.e. albuminuria, cardiac hypertrophy, and carotid-artery intima–media thickness (IMT)], hazard ratio 2.5–2.9 (all P <0.01). Incorporation of MMSE in the risk model (including age, estimated glomerular filtration rate, and preexisting CVD) improved the C-statistics (from 0.691 to 0.741) and resulted in a net reclassification improvement of 17.6% (P = 0.02). In contrast, incorporation of albuminuria, cardiac hypertrophy, and high carotid-artery IMT added little further improvement in the risk prediction.

Conclusion: Cognitive dysfunction is an independent marker associated with increased risk of CVD events in elderly hypertensive patients.

aAmerican Society of Hypertension Comprehensive Hypertension Center, Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Chicago Medicine, Chicago, Illinois, USA

bDivision of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Tochigi

cDepartment of Orthopedics, Chikamorikai Medical Group, Kochi

dTamaki Clinic

eKijo Clinic

fKuwabara Clinic

gYokota Naika

hEto Cardiology Clinic

iKuroki Naika, Miyazaki, Japan

Correspondence to Yuichiro Yano, MD, American Society of Hypertension Comprehensive Hypertension Center, Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Chicago Medicine, 5841 S. Maryland Avenue, MC 1027, Chicago, IL 60637, USA. Tel: +1 773 702 7936; e-mail:

Abbreviations: ABPM, ambulatory blood pressure monitoring; AIC, Akaike's information criterion; BP, blood pressure; CAD, coronary arterial disease; CCA, common carotid artery; CI, confidence interval; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; ICA, internal carotid artery; IDI, integrated discrimination improvement; IMT, intima–media thickness; LVH, left ventricular hypertrophy; LVMI, left ventricular mass index; MMSE, Mini-Mental State Examination; NRI, net reclassification improvement; TOD, target organ damage; UACR, urinary albumin-to-creatinine ratio

Received 23 May, 2013

Revised 23 July, 2013

Accepted 12 September, 2013

Part of this work was presented at the American Society of Hypertension 2013 Annual Scientific Meeting.

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins