Cardiac dysfunction in relation to vascular brain injury, cognitive impairment and depressive symptoms; The Heart-Brain Connection Study
Authors: Amier R P , Marcks N , Leeuwis A E , Nijveldt R , Biessels G J , Kappelle L J , Van Oostenbrugge R J , Van Der Geest R J , Bots M L , Niessen W J , De Bresser J , Mooijaart S P , Van Der Flier W M , Brunner-La Rocca H P , Van Rossum A C 
Published: October 2022

Abstract

Introduction
Cardiovascular disease is an independent contributor to cognitive impairment. With an imminent rise in chronic cardiovascular disease, a better understanding of its effects on brain health is warranted. Impaired blood flow to the brain is one of the main hypothesized mechanisms linking cardiovascular disease with abnormal brain aging.

Purpose
To investigate relations between (subclinical) cardiac dysfunction and vascular brain injury, cognitive impairment and depressive symptoms, with a side-by-side comparison of cardiac biomarkers and imaging parameters.

Methods
Multicenter, cross-sectional, observational cohort study among 559 participants: 431 with manifest cardiovascular disease (heart failure [HF], carotid occlusive disease or vascular cognitive impairment) and 128 control participants, all without dementia. Participants underwent 3T heart-brain MRI and cognitive testing. Determinants were cardiac biomarkers (NT-proBNP and high-sensitive Troponin-I) and left ventricular (LV) functional parameters by MRI (LV ejection fraction, cardiac output, LV global function index). Outcome measures were cerebral small vessel disease (CSVD) by MRI (presence of white matter hyperintensities, microbleeds, lacunar infarcts or perivascular spaces), CSVD score (0–4), cognitive impairment in ≥1 domain (memory, language, attention-psychomotor speed and executive functioning) and depressive symptoms (Geriatric Depression Scale-15 score &gt;5). Interaction analyses were used to investigate effect modification by patient group; results are reported pooled or stratified accordingly.

Results
In patients with cardiovascular disease and controls, but not in those with manifest HF, LV functional parameters were associated with CSVD and cognitive impairment, with the following associations: LVEF &lt;50% with CSVD (OR 4.67 [1.37–15.95]) and CSVD score (RR 1.38 [1.06–1.81]); LV global function index with CSVD (OR 0.71 [0.58–0.86]), CSVD score (RR 0.90 [0.84–0.96]) and cognitive impairment (OR 0.84 [0.72–0.97]). LV global function index (OR 0.82 [0.71–0.95]) and cardiac output (OR 0.81 [0.71–0.93]) were also associated with depressive symptoms in all. These relations were independent from age, sex, hypertension, diabetes, waist-hipratio, history of ischemic heart disease, transient ischemic attack or stroke. Cardiac biomarkers were univariably associated with brain outcome measures, but not in multivariable analysis.

Conclusion
This study indicates that subclinical cardiac dysfunction, as assessed by cardiovascular MRI, is independently associated with vascular brain injury, cognitive impairment and depressive symptoms. Of all parameters, LV global function index showed the most robust relations, indicating that global cardiac performance is more closely related to poorer brain outcome than merely LV systolic function. In those with clinically manifest HF, the severity of cardiac dysfunction was related to depressive symptoms but not to other brain outcome measures.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Netherlands CardioVascular Research Initiative; The Dutch Heart Foundation