The effect of overweight/obesity on diastolic function in children and adolescents: A meta-analysis

Abstract

Left ventricular diastolic function (LVDF) is an important marker of early cardiovascular remodelling, which has not been well summarized in young people with overweight/obesity. Weighted, random-effects regression was used to determine the strength of associations of both body mass index (BMI) and homeostatic model assessment of insulin resistance (HOMA-IR) with LVDF measures, adjusting for age and sex. Six databases were searched after PROSPERO registration (CRD42020177470) from inception to July 2020 for studies that compared LVDF between overweight/obesity and control groups aged ≤24 years, yielding 70 studies (9983 individuals). Quality and risk of bias were assessed using NHLBI tools, with scores of good, fair, and poor for 6, 48, and 16 studies, respectively. Increased BMI was associated with worse LVDF in all measures except early mitral inflow deceleration time, with septal early diastolic tissue peak velocity to late diastolic tissue peak velocity ratio having the strongest association (n = 13 studies, 1824 individuals; r = -0.69; P < 0.001). Elevated HOMA-IR was also associated with worse LVDF. Although we could not determine the causality of reduced LVDF in young people, our findings should aid the development of paediatric guidelines for the assessment of LVDF and support further work to address the longitudinal consequences of childhood obesity and IR on LVDF.

Keywords: children; diastolic function; obesity.

FIGURE 1

Stages of diastole and echocardiography measures of diastolic function. Stage I—isovolumic relaxation (IVR) which occurs after aortic valve closure and before mitral valve opening, as left ventricle (LV) pressure falls rapidly until it reaches left atrial pressure, prompting mitral valve (MV) opening; Stage II—rapid filling, where the MV is open and blood is suctioned towards the apex of the LV from the left atrium (LA), which occurs as the myocardium lengthens during falling LV pressure; Stage III—diastasis, after initial filling where LA and LV pressures equalize and flow ceases; Stage IV—LA contraction, which generates an additional pressure gradient that drives more blood into the LV. A wave indicates late mitral inflow peak velocity; a′, late diastolic tissue peak velocity; DT, E wave deceleration time; E wave, early mitral inflow peak velocity; e′, early diastolic tissue peak velocity; IVRT, isovolumic relaxation time

FIGURE 2

Flow diagram of study identification, screening, eligibility and inclusion/exclusion. Echo indicates echocardiography; HOMA‐IR, Homeostatic Model Assessment of Insulin Resistance; n, number of studies; OB, obese; OW, overweight. ^aExclusion criteria and reasons can be found in the Supporting Information

FIGURE 3

Distribution of body mass index (BMI) in control (red) and overweight/obese (blue) groups included in the meta‐analysis. Groups were defined as per the definitions in individual studies. A normal distribution curve was generated using the reported sample size (N), mean BMI, and BMI standard deviation. Significant overlap of BMI distributions between groups and marked variability of distributions within groups highlights that it was not possible to perform traditional group‐based meta‐analysis reliably

FIGURE 4

Percentage of studies included in the qualitative analysis reporting increased (+), unchanged (=), or decreased (−) measures of left ventricle diastolic function (LVDF) in children/adolescents with OW/Ob compared to controls. Darker red squares indicate a greater percentage of studies. Measures are ranked by the strength of association (r) from strongest positive to strongest negative as identified in the meta‐analysis. The directionality of greater percentages from top left to bottom right supports the meta‐analysis results. A wave indicates late mitral inflow peak velocity; a′, late diastolic tissue peak velocity; DT, E wave deceleration time; E wave, early mitral inflow peak velocity; e′, early diastolic tissue peak velocity; E/A, E wave/A wave ratio; E/e′, E wave/e′ ratio; e′/a′, e′/a′ ratio; IVRT, isovolumic relaxation time