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. 2022 Oct;10(10):731-741.
doi: 10.1016/j.jchf.2022.05.008. Epub 2022 Jul 6.

Periodontal Status, C-Reactive Protein, NT-proBNP, and Incident Heart Failure: The ARIC Study

Rebecca L Molinsky  1 , Melana Yuzefpolskaya  2 , Faye L Norby  3 , Bing Yu  4 , Amil M Shah  5 , James S Pankow  1 , Chiadi E Ndumele  6 , Pamela L Lutsey  1 , Panos N Papapanou  7 , James D Beck  8 , Paolo C Colombo  2 , Ryan T Demmer  9
Affiliations

Periodontal Status, C-Reactive Protein, NT-proBNP, and Incident Heart Failure: The ARIC Study

Rebecca L Molinsky et al. JACC Heart Fail. 2022 Oct.

Abstract

Background: Periodontal disease (PD), resulting from inflammatory host response to dysbiotic subgingival microbiota, has been linked to cardiovascular disease; however, its relationship to heart failure (HF) and its subtypes (heart failure with reduced ejection fraction [HFrEF] and heart failure with preserved ejection fraction [HFpEF]) is unexplored.

Objectives: The authors hypothesize that the presence of PD is associated with increased risk of incident HF, HFpEF, and HFrEF.

Methods: A total of 6,707 participants (mean age 63 ± 6 years) of the ARIC (Atherosclerosis Risk In Communities) study with full-mouth periodontal examination at visit 4 (1996-1998) and longitudinal follow-up for any incident HF (visit 4 to 2018), or incident HFpEF and HFrEF (2005-2018) were included. Periodontal status was classified as follows: healthy, PD (as per Periodontal Profile Classification [PPC]), or edentulous. Multivariable-adjusted Cox proportional hazards models were used to calculate HRs and 95% CIs for the association between PPC levels and incident HF, HFpEF, or HFrEF. Additionally, biomarkers of inflammation (C-reactive protein [CRP]) and congestion (N-terminal brain natriuretic peptide [NT-proBNP]) were assessed.

Results: In total, 1,178 incident HF cases occurred (350 HFpEF, 319 HFrEF, and 509 HF of unknown type) over a median of 13 years. Of these cases, 59% had PD, whereas 18% were edentulous. PD was associated with an increased risk for HFpEF (HR: 1.35 [95% CI: 0.98-1.86]) and significantly increased risk for HFrEF (HR: 1.69 [95% CI: 1.18-2.43]), as was edentulism: HFpEF (HR: 2.00 [95% CI: 1.37-2.93]), HFrEF (HR: 2.19 [95% CI: 1.43-3.36]). Edentulism was associated with unfavorable change in CRP and NT-proBNP, whereas PD was associated only with CRP.

Conclusions: Periodontal status was associated with incident HF, HFpEF, and HFrEF, as well as unfavorable changes in CRP and NT-proBNP.

Keywords: C-reactive protein (CRP); N-terminal brain natriuretic peptide (NT-proBNP); heart failure (HF); heart failure with preserved ejection fraction (HFpEF)/ heart failure with reduced ejection fraction (HFrEF); periodontal disease.

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Conflict of interest statement

Funding Support and Author Disclosures The ARIC study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract numbers (75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004, 75N92022D00005). Ms Molinsky was supported by institutional training grant T32HL007779 from the National Institutes of Health, and Dr Lutsey was supported by K24 HL 159246. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

Figure 1.
Figure 1.. Flow chart.
Participant flowchart for the three main analyses performed: incidence HFpEF and HFrEF; HF; and longitudinal NT-proBNP and CRP.
Figure 2.
Figure 2.. Association Between Baseline Periodontal Status (1996–1998) and Follow-up CRP (2011–2013) Among N=3,621 Participants in the ARIC Study.
Results presented as adjusted mean values of CRP±SE. Inverse probability weights were included for all models. Model 1: adjusts for baseline age, gender, race/center, education, insurance. Model 2: adjusts for model 1 + cigarette status, physical activity, BMI, LDL, hypertension medication, CHD, diabetes, SBP. Model 3: adjusts for model 2 + baseline CRP p-values are 2 d.f. type 3 F-tests were significant for all models (p-value = <.0001, 0.0003, 0.0003 respectively.) *p-value <0.05 for comparison with healthy participants.
Figure 3.
Figure 3.. Association Between Baseline Periodontal Status (1996–1998) and Follow-Up Mean NT-proBNP (2011–2013) Among N=3,979 Participants in the ARIC Study.
Values are presented as adjusted geometric mean transformed NT-proBNP and 95% confidence intervals. Inverse probability weights were included for all models. Model 1: adjusts for age, gender, race/center, education, insurance. Model 2: adjusts for model 1 + cigarette status, physical activity, BMI, LDL, hypertension medication, CHD, diabetes, SBP. Model 3: adjusts for model 2 + baseline NT-proBNP. p-values are 2 d.f. type 3 F-tests were significant for all models 1 and 2 (p-value = <0.0001, 0.001, 0.06 respectively.) *p-value <0.05 for comparison with healthy participants.
Central Illustration:
Central Illustration:. Periodontal status and incident heart failure among HFpEF and HFrEF participants in ARIC.
Cox regression of time to first HFpEF or HFrEF according to periodontal status. Follow-up time began in 2005, when HF adjudication allowed for the distinction between HFpEF and HFrEF.
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