Salivary Biomarkers,Oral Inflammation,and Functional Status in Patients With Heart Failure

Abstract

Aims:

To describe correlations and agreement between salivary and serum B-type natriuretic peptide (BNP), C-reactive protein (CRP), interleukin (IL)-6, and IL-10 and determine which biomarkers predict worse functional class in patients with heart failure (HF).

Methods:

Serum and saliva were collected from 75 hospitalized patients with HF (57 ± 12 years, 43% female, New York Heart Association [NYHA] Classes I [4%], II [43%], and III [53%]). Oral inflammation was rated as good, fair, or poor. Spearman’s ρ and Bland–Altman were used to determine correlations and agreement of the salivary and serum forms of each biomarker. Logistic regressions were used to determine which biomarkers predicted worse NYHA functional class, controlling for depression, body mass index, smoking, and oral inflammation.

Results:

Median biomarker concentrations were as follows: BNP (serum 361 pg/ml, saliva 9 pg/ml), CRP (serum 13 ng/ml, saliva 25.6 ng/ml), IL-6 (serum 19.3 pg/ml, saliva 10.5 pg/ml), and IL-10 (serum 64.1 pg/ml, saliva 4.7 pg/ml). There was a moderate-to-strong correlation for serum–salivary CRP, weak correlation for serum–salivary IL-6, and no correlations for serum–salivary BNP and IL-10. The Bland–Altman test showed good salivary–serum agreement for all biomarkers, but as serum concentrations rose, salivary measures underestimated serum levels. Visible oral inflammation was the only predictor of worse NYHA class.

Keywords

cytokines inflammatory biomarkers B-type natriuretic peptide periodontal disease

Get full access to this article

View all access options for this article.

References

Ackermann

R. T.

Rosenman

M. B.

Downs

S. M.

Holmes

A. M.

Katz

B. P.

… Inui

T. S.

(2005). Telephonic case-finding of major depression in a Medicaid chronic disease management program for diabetes and heart failure. General Hospital Psychiatry, 27, 338–343.

Al Moharib

H. S.

Al Mubarak

Al Rowis

Geevarghese

Preethanath

R. S.

Anil

(2014). Oral fluid based biomarkers in periodontal disease: Part 1. Saliva. Journal of International Oral Health, 6, 95–103.

American Academy of Periodontology. (n.d.). Periodontal disease fact sheet. Retrieved from http://www.perio.org/newsroom/periodontal-disease-fact-sheet.

Beck

Garcia

Heiss

Vokonas

P. S.

Offenbacher

(1996). Periodontal disease and cardiovascular disease. Journal of Periodontology, 67, 1123–1137.

Bland

J. M.

Altman

D. G.

(1986). Statistical methods for assessing agreement between two methods of clinical measurement. Lancet, 1, 307–310.

Bland

J. M.

Altman

D. G.

(1999). Measuring agreement in method comparison studies. Statistical Methods in Medical Research, 8, 135–160.

Bozkurt

Mann

D. L.

Deswal

(2010). Biomarkers of inflammation in heart failure. Heart Failure Reviews, 15, 331–341.

Burke

F. J.

Busby

McHugh

Delargy

Mullins

Matthews

(2003). Evaluation of an oral health scoring system by dentists in general dental practice. British Dental Journal, 194, 215–218.

Charlson

M. E.

Pompei

Ales

K. L.

MacKenzie

C. R.

(1987). A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. Journal of Chronic Diseases, 40, 373–383.

10.

Christodoulides

Mohanty

Miller

C. S.

Langub

M. C.

Floriano

P. N.

Dharshan

… Anslyn

(2005). Application of microchip assay system for the measurement of C-reactive protein in human saliva. Lab on a Chip, 5, 261–269.

11.

DeStefano

Anda

R. F.

Kahn

H. S.

Williamson

D. F.

Russell

C. M.

(1993). Dental disease and risk of coronary heart disease and mortality. British Medical Journal, 306, 688–691.

12.

Foo

J. Y.

Wan

Kostner

Arivalagan

Atherton

Cooper-White

… Punyadeera

(2012). NT-ProBNP levels in saliva and its clinical relevance to heart failure. PLoS ONE, 7, 31.

13.

Holmlund

Holm

Lind

(2010). Number of teeth as a predictor of cardiovascular mortality in a cohort of 7,674 subjects followed for 12 years. Journal of Periodontology, 81, 870–876.

14.

Jaedicke

K. M.

Preshaw

P. M.

Taylor

(2000). Salivary cytokines as biomarkers of periodontal diseases. Periodontology, 70, 164–183.

15.

Jones

Reynolds

Gray

Hughes

Rolf

Davies

(1994). Salivary PAF in acute myocardial infarction and angina: Changes during hospital treatment and relationship to cardiac enzymes. Thrombosis Research, 75, 503–511.

16.

Jug

Salobir

B. G.

Vene

Sebestjen

Sabovic

Keber

(2009). Interleukin-6 is a stronger prognostic predictor than high-sensitive C-reactive protein in patients with chronic stable heart failure. Heart and Vessels, 24, 271–276.

17.

Katz

J. N.

Chang

L. C.

Sangha

Fossel

A. H.

Bates

D. W.

(1996). Can comorbidity be measured by questionnaire rather than medical record review? Medical Care, 34, 73–84.

18.

Kroenke

Spitzer

R. L.

Williams

J. B.

(2001). The PHQ-9: Validity of a brief depression severity measure. Journal of General Internal Medicine, 16, 606–613.

19.

Mattila

K. J.

Nieminen

M. S.

Valtonen

V. V.

Rasi

V. P.

Kesaniemi

Y. A.

Syrjala

… Jokinen

M. J.

(1989). Association between dental health and acute myocardial infarction. British Medical Journal, 306, 688–691.

20.

Miller

C. S.

Foley

J. D.

Campell

C. L.

Christodoulides

Bhagwandin

Redding

S. W.

(2010). Current developments in salivary diagnostics. Biomarkers in Medicine, 4, 171–189.

21.

Miller

C. S.

Foley

J. D.

3rd Floriano

P. N.

Christodoulides

Ebersole

J. L.

Campbell

… Kryscio

R. J

. (2014). Utility of salivary biomarkers for demonstrating acute myocardial infarction. Journal of Dental Research, 93, 72S–79S.

22.

Mills

R. M.

Jr Haught

W. H.

(1996). Evaluation of heart failure patients: Objective parameters to assess functional capacity. Clinical Cardiology, 19, 455–460.

23.

Mirzaii-Dizgah

Jafari-Sabet

(2011). Unstimulated whole saliva creatine phosphokinase in acute myocardial infarction. Oral Diseases, 17, 597–600.

24.

Mohamed

Campbell

J.-L.

Cooper-White

Dimeski

Punyadeera

(2012). The impact of saliva collection and processing methods on CRP, IgE, and myoglobin immunoassays. Clinical and Translational Medicine, 1, 19.

25.

Navazesh

(1993). Methods for collecting saliva. Annals of the New York Academy of Sciences, 694, 72–77.

26.

Nayer

Aggarwal

Galwankar

(2014). Utility of point-of-care testing of natriuretic peptids (brain natriuretic peptide and n-terminal pro-brain natriuretic peptide) in the emergency department. International Journal of Critical Illness and Injury Science, 4, 209–215.

27.

Offenbacher

Beck

J. D.

(2014). Commentary: Changing paradigms in the oral disease–systemic disease relationship. Journal of Periodontology, 85, 761–764.

28.

Pfaffe

(2011). Diagnostic potential of saliva: Current state and future applications. Clinical Chemistry, 57, 675–687.

29.

Punyadeera

(2011). One-step homogeneous C-reactive protein assay for saliva. Journal of Immunological Methods, 373, 19–25.

30.

Sachdeva

Horwich

T. B.

Fonarow

G. C.

(2010). Comparison of usefulness of each of five predictors of mortality and urgent transplantation in patients with advanced heart failure. American Journal of Cardiology, 106, 830–835.

31.

Tang

W. H.

Shrestha

Van Lente

Troughton

R. W.

Martin

M. G.

Borowski

A. G.

… Klein

A. L.

(2008). Usefulness of C-reactive protein and left ventricular diastolic performance for prognosis in patients with left ventricular systolic heart failure. American Journal of Cardiology, 101, 370–373.

32.

Wood

Johnson

R. B.

(2004). The relationship between tomato intake and congestive heart failure risk in periodontitis subjects. Journal of Clinical Periodontology, 31, 574–580.

33.

Yamaoka

Yamaguchi

Okuyama

Tomoike

(1999). Anti-inflammatory cytokine profile in human heart failure: Behavior of interleukin-10 in association with tumor necrosis factor-alpha. Japanese Circulation Journal, 63, 951–956.