Left ventricular hypertrophy as a risk factor for accelerated brain aging: Results from the Study of Health in Pomerania

Abstract

Previous studies provided evidence for the importance of cardiac structure abnormalities, in particular greater left ventricular (LV) mass, for brain aging, but longitudinal studies are lacking to date. We included 926 individuals (median age 48 years; 53% women) from the TREND cohort of the Study of Health in Pomerania (SHIP) without reduced ejection fraction or a history of myocardial infarction. LV mass index (LVMI) was determined by echocardiography at baseline. Brain morphometric measurements were derived from magnetic resonance images at baseline and 7-year follow-up. Direct effects of baseline LVMI on brain morphometry at follow-up were estimated using linear regression models with adjustment for baseline brain morphometry. At baseline, median LVMI was 40 g/m^2.7 and 241 individuals (26%) met the criterion of LV hypertrophy. After correction for multiple testing, baseline LVMI was directly associated with reduced global cortical thickness and increased cortical brain age at follow-up independent from hypertension and blood pressure. Exposure-outcome relations were nonlinear and significantly stronger in the upper half of the exposure distribution. Specifically, an increase in baseline LVMI from the 50% quantile to the 95% quantile was associated additional 2.7 years (95% confidence interval = [1.5 years, 3.8 years]) of cortical brain age at follow-up. Additional regional analyses yielded bilateral effects on multiple frontal cortical regions. Our findings highlight the role of cardiac structure in brain aging. LVMI constitutes an easily measurable marker that might help to identify persons at risk for cognitive impairment and dementia.

Keywords: brain aging; brain imaging; epidemiology; left ventricular hypertrophy.

FIGURE 1

Flowchart showing the selection of the study sample. The study sample is based on the TREND cohort of the population‐based Study of Health in Pomerania (SHIP). Echocardiography and brain magnetic resonance imaging were performed during the baseline examinations between 2008 and 2012 (SHIP‐TREND‐0). Follow‐up examinations of similar extend were conducted about 7 years later between 2016 and 2019 (SHIP‐TREND‐1).

FIGURE 2

Direct effects of baseline LVMI on changes in brain morphometry. Weighted linear regressions of follow‐up values of the outcomes (brain volume, subcortical grey matter volume, white matter volume, white matter hyperintensities volume, global cortical thickness, cortical brain age, subcortical brain age, and brain age) on baseline LVMI with adjustment for baseline values of the outcomes were performed. Analyses were additionally adjusted for baseline values of sociodemographic variables, anthropometric variables, lifestyle factors, and follow‐up time (model 1). In addition, we adjusted for cardiovascular risk factors and intake of antihypertensive and lipid‐lowering drugs (model 2). Mediation by diastolic function was investigated by including E/e′ ratio, E/A ratio, and left atrial size index (model 3). E/A—ratio of early and late mitral inflow velocities in diastole. E/e′—ratio of early mitral inflow velocity and early mitral annular velocity in diastole. LVMI, left ventricular mass index.

FIGURE 3

Baseline LVMI is associated with global cortical thinning and accelerated cortical aging during the 7‐year follow‐up period. Direct effects of baseline LVMI on global cortical thickness (a; F _2,839 = 9.2, p _FDR = .0004, f ² = 2.2%), and cortical brain age (b; F _2,836 = 10.8, p _FDR = .0002, f ² = 2.6%) at follow‐up are shown (continuous covariates held constant at their median values and categorical ones at their reference categories). Effects adjusted for baseline values of sociodemographic factors, anthropometric variables, lifestyle factors, cardiovascular risk factors (incl. hypertension and blood pressure) and medication, follow‐up time, and baseline value of the outcome (model 2). Grey areas represent the 95% confidence intervals. Point estimates of effects were derived from changes in outcomes when baseline LVMI is increased from the 50% to the 95% quartile (red dashed lines). Red solid lines correspond to the threshold of LV hypertrophy of about 46 g/m^2.7 (women: 44 g/m^2.7, men: 48 g/m^2.7). LV, left ventricular; LVMI, left ventricular mass index.