Direct and indirect effects of adiposity on markers of autonomic nervous system activity in older adults

Abstract

Several cardiovascular disease (CVD) risk factors (e.g., hypertension, poor glycemic control) can affect and be affected by autonomic nervous system (ANS) activity. Since excess adiposity can influence CVD development through its effect on hypertension and diabetes mellitus, it is important to determine how adiposity and altered ANS activity are related. The present study employed structural equation modeling to investigate the relation between adiposity and ANS activity both directly and indirectly through biological variables typically associated with glycemic impairment and cardiac stress in older adults. Utilizing the Atherosclerosis Risk in Communities (ARIC) dataset, 1,145 non-smoking adults (74±4.8 yrs, 62.8% female) free from known CVD, hypertension, and diabetes and not currently taking beta-blockers were evaluated for fasting blood glucose (FBG), insulin, and HbA1c concentrations, waist circumference (WC), blood pressure (BP), and markers of ANS activity. WC was recorded just above the iliac crest and was used to reflect central adiposity. Resting 2-minute electrocardiograph recordings, pulse wave velocity, and ankle-brachial index data were used to assess the root mean square of successive differences in RR intervals (RMSSD) and the pre-ejection period (PEP), markers of parasympathetic and sympathetic activity, respectively. FBG, insulin, and HbA1c inferred a latent variable termed glycemic impairment (GI), whereas heart rate and diastolic BP inferred a latent variable termed cardiac stress (CS). The structural equation model fit was acceptable [root mean square error of approximation = 0.050 (90% CI = .036, .066), comparative fit index = .970, Tucker Lewis Index = 0.929], with adiposity having both significant direct (β = 0.208, p = 0.018) and indirect (β = -.217, p = .041) effects on PEP through GI. Adiposity displayed no significant direct effect on RMSSD. CS displayed a significant pathway (β = -0.524, p = 0.035) on RMSSD, but the indirect effect of WC on RMSSD through CS did not reach statistical significance (β = -0.094, p = 0.137). These results suggest that adiposity's relation to ANS activity is multifaceted, as increased central adiposity had opposing direct and indirect effects on markers of sympathetic activity in this population of older adults.

Fig 1. Proposed model.

A priori model including observed variables (squares) depicting the proposed pathways for the direct and indirect effects of waist circumference on markers of ANS activity. Construction of the latent variables (circles) Cardiac Stress (CS) and Glycemic Impairment (GI) are depicted. WC, Waist Circumference; HR, Heart Rate; DBP, Diastolic Blood Pressure; Hb_A1c, Glycosylated Hemoglobin; FBG, Fasting Blood Glucose; RMSSD, Root Mean Square of Successive Differences between normal-to-normal beats; PEP, Pre-Ejection Period.

Fig 2. Structual equation model.

Structual equation model including the standardized solutions for the direct and indirect effects of waist circumference on markers of RMSSD and PEP. Cardiac Stress, CS; Glycemic Impairment, GI; WC, Waist Circumference; HR, Heart Rate; DBP, Diastolic Blood Pressure; Hb_A1c, Glycosylated Hemoglobin; FBG, Fasting Blood Glucose; RMSSD, Root Mean Square of Successive Differences between normal-to-normal beats; PEP, Pre-Ejection Period. Note: SE, standard error; *p < .05; **p < .001.