Mediating effect of subclinical inflammation on the process of morning hypertension leading to atrial fibrillation in community-based older adults

ABSTRACT

Background

The impacts and mechanisms of morning hypertension (MHT) on the risk of new-onset atrial fibrillation (AF) in the elderly have not been clarified. We aimed to investigate an association between MHT and new-onset AF and explore a mediating effect of subclinical inflammation on this association.

Methods

From 2008 to 2010, 1789 older adults aged ≥60 years were recruited in Shandong area, China. Morning blood pressure (BP) was assessed using 24-hour ambulatory BP monitoring. MHT was defined as BP ≥ 135/85 mm Hg during the period from wake time to 0900 a.m. Subclinical inflammation was assessed by hypersensitive C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-α), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and galectin-3. New-onset AF was rated during the follow-up period.

Results

Over an average 129.0 [standard deviation (SD): 21.58] months of follow-up, the hazard ratio of new-onset AF in MHT patients was 1.39 (95% confidence interval: 1.01 to 1.91) compared with non-MHT participants (P_adjusted = 0.027). The risk of new-onset AF was 1.17-fold with one-SD increment of morning systolic BP. Subclinical inflammation was significantly associated with new-onset AF. The hazard ratios of new-onset AF were 2.29, 2.04, 2.08, 2.08, 2.03, and 3.25 for one-SD increment in hsCRP, TNF-α, SII, NLR, PLR, and galectin-3, respectively (P_adjusted < 0.001). The analysis showed that hsCRP, TNF-α, SII, NLR, PLR, and galectin-3 separately mediated the process of MHT inducing new-onset AF (P_adjusted < 0.05).

Conclusions

MHT is associated with an increased risk of new-onset AF. The subclinical inflammation might play a mediating role in this association.

KEYWORDS:

• Hypertension
• circadian rhythm
• atrial fibrillation
• inflammation
• mediating effect

Abbreviations

AF, atrial fibrillation; BP, blood pressure; SBP, systolic blood pressure; MHT, morning hypertension; HBPM, home blood pressure monitoring; ABPM, ambulatory blood pressure monitoring; MS, morning surge; SNMH, sustained nocturnal and morning hypertension; SII, systemic immune-inflammation index; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; hsCRP, hypersensitive C-reactive protein; TNF-α, tumor necrosis factor-alpha; Gal-3, Galectin-3; FPG, fasting plasma glucose; TCHO, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; CCA-IMT, common carotid artery intima-media thickness; SD, standard deviation; IQR, interquartile range; HR, hazard ratio; CI, confidence interval.

Acknowledgments

We would like to thank all participants, general practitioners, and nurses who provided assistance in this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Study conception and design: YG, WL, ZL. Acquisition of data, analysis and interpretation of data: JL, ZH, LH, PL, RY, YD, HZ, YG, WL, ZL. Drafting the article: JL, ZH, LH. Final approval of the version of the article to be published: all authors, and all authors agree to be accountable for all aspects of the work.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/10641963.2023.2253381.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China grants number 81973139; Shandong Provincial Natural Science Foundation of China grants number ZR2022MH179; College Students’ innovation and entrepreneurship training program grants number 2022104391161.