A neurobiological mechanism linking transportation noise to cardiovascular disease in humans

Abstract

Aims: Chronic noise exposure associates with increased cardiovascular disease (CVD) risk; however, the role of confounders and the underlying mechanism remain incompletely defined. The amygdala, a limbic centre involved in stress perception, participates in the response to noise. Higher amygdalar metabolic activity (AmygA) associates with increased CVD risk through a mechanism involving heightened arterial inflammation (ArtI). Accordingly, in this retrospective study, we tested whether greater noise exposure associates with higher: (i) AmygA, (ii) ArtI, and (iii) risk for major adverse cardiovascular disease events (MACE).

Methods and results: Adults (N = 498) without CVD or active cancer underwent clinical 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Amygdalar metabolic activity and ArtI were measured, and MACE within 5 years was adjudicated. Average 24-h transportation noise and potential confounders were estimated at each individual's home address. Over a median 4.06 years, 40 individuals experienced MACE. Higher noise exposure (per 5 dBA increase) predicted MACE [hazard ratio (95% confidence interval, CI) 1.341 (1.147-1.567), P < 0.001] and remained robust to multivariable adjustments. Higher noise exposure associated with increased AmygA [standardized β (95% CI) 0.112 (0.051-0.174), P < 0.001] and ArtI [0.045 (0.001-0.090), P = 0.047]. Mediation analysis suggested that higher noise exposure associates with MACE via a serial mechanism involving heightened AmygA and ArtI that accounts for 12-26% of this relationship.

Conclusion: Our findings suggest that noise exposure associates with MACE via a mechanism that begins with increased stress-associated limbic (amygdalar) activity and includes heightened arterial inflammation. This potential neurobiological mechanism linking noise to CVD merits further evaluation in a prospective population.

Keywords: 18F-FDG-PET/CT; Amygdalar activity; Arterial inflammation; Cardiovascular disease; Chronic noise exposure.

Figure 1

Study cohort.

Figure 2

Noise exposure and tissue ¹⁸F-fluorodeoxyglucose uptake. (A) Amygdalar metabolic activity by noise exposure (quartiles), adjusted for age and sex. Error bars represent standard error of the mean. (B) Amygdalar and arterial ¹⁸F-fluorodeoxyglucose uptake (arrows) from subjects with and without heightened noise exposure (>45 dBA vs. less) and subsequent major adverse cardiovascular disease events. Amygdalar (upper) and aortic (lower) ¹⁸F-fluorodeoxyglucose uptake were increased in a patient with increased noise exposure with subsequent major adverse cardiovascular disease event (right) vs. an individual with lower noise exposure without major adverse cardiovascular disease event (left).

Figure 3

Major adverse cardiovascular disease event-free survival by noise exposure. Major adverse cardiovascular disease event-free survival for individuals with noise exposure ≤ (blue) vs. > (red): (A) 45 dBA (upper tertile), (B) 50 dBA (upper quartile), and (C) 55 dBA (WHO cut-off). Log-rank P-values are shown.

Figure 4

Mediation analysis for the hypothesized pathway from noise exposure to major adverse cardiovascular disease events. Mediation analysis estimated the effect of a serial two-mediator path: ↑noise exposure (>45 dBA)→↑AmygA→↑ArtI→↑MACE. The proposed indirect path (red arrows) was significant [standardized log odds ratio (95% confidence interval) 0.11 (0.02–0.30)], suggesting that amygdalar metabolic activity and arterial inflammation serially mediate the association between increased noise exposure and major adverse cardiovascular disease events (accounting for ∼26% of the total effect) after adjustment for age, sex, and cardiovascular disease risk factors. c’, residual direct effect of noise on major adverse cardiovascular disease events (independent of mediated effects).

Take home figure

Hypothesized mechanism linking noise exposure to major adverse cardiovascular disease events through up-regulated amygdalar metabolic activity and arterial inflammation.