Clinical and Imaging Markers of Cardiac Function and Brain Health

Figures

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  Figure 1. Systolic (A) or Diastolic Function (B) and Brain Volumes Associations between systolic (A) and diastolic function (B) on echocardiography and brain volumes on MRI are depicted as adjusted mean differences, with 95% CIs. Note that neuroimaging markers were standardized (displayed per 1 SD) to facilitate comparison. The normal category is used as reference. Extended details of each plot can be found in eTable 1. Cohorts included for the meta-analysis of systolic dysfunction (n = 10,302): AGES, ARIC, FHS, RS, SHIP-START, and SHIP-TREND. Cohorts included for the meta-analysis of diastolic dysfunction (n = 9,556): AGES, ARIC, RS, SHIP-START, and SHIP-TREND. AGES = Age, Gene/Environment Susceptibility Study; ARIC = Atherosclerosis Risk in Communities Study; CHS = Cardiovascular Health Study; FHS = Framingham Heart Study; RS = Rotterdam Study; SHIP = Study of Health in Pomerania.

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  Figure 2. Associations Between EA-Ratio or Deceleration Time and Brain Volumes Associations between EA-ratio or deceleration time on echocardiography and brain volumes on MRI were obtained using a random-effects meta-analysis (DerSimonian and Laird method). Estimates are displayed as adjusted mean differences, with 95% CIs. Note that all echocardiographic and neuroimaging markers were standardized (displayed per 1 SD) to facilitate comparison. Given that the EA-ratio is known to be nonlinear (U-shaped) in progressively worse diastolic function, a quadratic term (EA-ratio2) was included in the model. The figure displays the formula for the pooled adjusted mean differences, which constitutes of a quadratic estimate and/or a linear estimate. Model 2 is displayed, which is adjusted for age-specific, age2-specific, sex-specific, cohort-specific covariates, APOE-ε4 carriership, smoking, body mass index, ethnicity, systolic blood pressure, diastolic blood pressure, use of blood pressure–lowering medication, total cholesterol, high-density lipoprotein-cholesterol, use of lipid-lowering medication, diabetes, and history of coronary heart disease. Details can be found in eFigure 4.

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  Figure 3. Associations Between Clinical Heart Failure and Brain Volumes Associations between clinical heart failure and brain volumes on MRI were pooled using a random-effects meta-analysis (DerSimonian and Laird method). Estimates are displayed as adjusted mean differences, with 95% CIs. Absence of clinical heart failure was used as reference. All neuroimaging markers were standardized (displayed per 1 SD) to facilitate comparison. Model 2 is displayed, which is adjusted for age-specific, age2-specific, sex-specific, cohort-specific covariates, APOE-ε4 carriership, smoking, body mass index, ethnicity, systolic blood pressure, diastolic blood pressure, use of blood pressure–lowering medication, total cholesterol, high-density lipoprotein-cholesterol, use of lipid-lowering medication, diabetes, and history of coronary heart disease. AGES = Age, Gene/Environment Susceptibility Study; ARIC = Atherosclerosis Risk in Communities Study; CHS = Cardiovascular Health Study; FHS = Framingham Heart Study; GM = gray matter; HV = hippocampal volume; RS = Rotterdam Study; TBV = total brain volume; WM = white matter.

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  Figure 4. Cardiac Function on Echocardiography and Cerebral Small Vessel Disease Associations between echocardiographic measures and white matter hyperintensities (markers of cerebral small vessel disease) on MRI were obtained using a random-effects meta-analysis (DerSimonian and Laird method). Estimates are displayed as adjusted mean differences, with 95% CIs. All echocardiographic and neuroimaging markers were standardized (displayed per 1 SD) to facilitate comparison. Given the nonlinear (U-shaped) association of the EA-ratio in worsening diastolic function, we included a quadratic term (EA-ratio2) in the model. Pooled adjusted mean differences for both the EA-ratio and the deceleration time are shown. Model 2 is displayed, which is adjusted for age-specific, age2-specific, sex-specific, cohort-specific covariates, APOE-ε4 carriership, smoking, body mass index, ethnicity, systolic blood pressure, diastolic blood pressure, use of blood pressure–lowering medication, total cholesterol, high-density lipoprotein-cholesterol, use of lipid-lowering medication, diabetes, and history of coronary heart disease. Categorical associations (systolic and diastolic function) are displayed in eFigure 5A…

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  Figure 5. Age-Stratified Analysis of Systolic and Diastolic Function and Its Neuroimaging Correlates Age-stratified analysis of LVEF (systolic function) and deceleration time (diastolic function) with brain volumes (A, B) and cerebral small vessel disease (C, D). Results are displayed as pooled adjusted mean differences and corresponding 95% CIs (DerSimonian and Laird method) from AGES, ARIC, FHS, RS, SHIP-START, and SHIP-TREND for LVEF, and AGES, ARIC, RS, SHIP-START, and SHIP-TREND for deceleration time. The number of participants in each age category is mentioned in the legend. All echocardiographic and neuroimaging markers were standardized (displayed per 1 SD) to facilitate comparison. Model 2 is displayed, which is adjusted for age-specific, age2-specific, sex-specific, cohort-specific covariates, APOE-ε4 carriership, smoking, body mass index, ethnicity, systolic blood pressure, diastolic blood pressure, use of blood pressure–lowering medication, total cholesterol, high-density lipoprotein-cholesterol, use of lipid-lowering medication, diabetes, and history of coronary heart disease. AGES = Age, Gene/Environment Susceptibility Study; ARIC = Atherosclerosis Risk in Communities Study;…