Nocturnal blood pressure dipping as a marker of endothelial function and subclinical atherosclerosis in pediatric-onset systemic lupus erythematosus

Abstract

Background: Loss of the normal nocturnal decline in blood pressure (BP), known as non-dipping, is a potential measure of cardiovascular risk identified by ambulatory blood pressure monitoring (ABPM). We sought to determine whether non-dipping is a useful marker of abnormal vascular function and subclinical atherosclerosis in pediatric-onset systemic lupus erythematosus (pSLE).

Methods: Twenty subjects 9-19 years of age with pSLE underwent ABPM, peripheral endothelial function testing, carotid-femoral pulse wave velocity/analysis for aortic stiffness, and carotid intima-media thickness. We assessed the prevalence of non-dipping and other ABPM abnormalities. Pearson or Spearman rank correlation tests were used to evaluate relationships between nocturnal BP dipping, BP load (% of abnormally elevated BPs over 24-h), and vascular outcome measures.

Results: The majority (75%) of subjects had inactive disease, with mean disease duration of 3.2 years (± 2.1). The prevalence of non-dipping was 50%, which occurred even in the absence of nocturnal or daytime hypertension. Reduced diastolic BP dipping was associated with poorer endothelial function (r 0.5, p = 0.04). Intima-media thickness was significantly greater in subjects with non-dipping (mean standard deviation score of 3.0 vs 1.6, p = 0.02). In contrast, higher systolic and diastolic BP load were associated with increased aortic stiffness (ρ 0.6, p = 0.01 and ρ 0.7, p < 0.01, respectively), but not with endothelial function or intima-media thickness.

Conclusion: In a pSLE cohort with low disease activity, isolated nocturnal BP non-dipping is prevalent and associated with endothelial dysfunction and atherosclerotic changes. In addition to hypertension assessment, ABPM has a promising role in risk stratification and understanding heterogeneous mechanisms of cardiovascular disease in pSLE.

Keywords: Ambulatory blood pressure monitoring; Cardiovascular diagnostic techniques; Cardiovascular disease; Pediatric systemic lupus erythematosus; Systemic lupus erythematosus.

Fig. 1

Conceptual model of the continuum of subclinical atherosclerosis and available measures of vascular health. Inflammatory states downregulate endothelium-dependent nitric oxide production and increase expression of adhesion molecules, leading to the inability to regulate vascular tone, cellular adhesion, and thrombosis that characterizes endothelial dysfunction. Subsequent maladaptive cellular changes result in increased arterial stiffness and thickening of the intimal-medial layers. RHI, reactive hyperemia index measures nitric oxide-dependent vasodilatory responses; PWV, pulse wave velocity and analysis approximate arterial stiffness; IMT, intima-media thickness by carotid ultrasound measures structural remodeling, which precedes plaque formation