Received: 26 March 2023 Revised: 7 July 2023 Accepted: 16 July 2023

DOI: 10.1002/JPER.23-0209

ORIGINAL ARTICLE

Multiplicative effect of stress and poor sleep quality on

periodontitis: A university-based cross-sectional study

Crystal Marruganti1 Carlo Gaeta1 Mario Romandini2

Edoardo Ferrari Cagidiaco1 Stefano Parrini3 Nicola Discepoli1
Simone Grandini1

1 Unitof Periodontology, Endodontology

and Restorative Dentistry, Department of Abstract
Medical Biotechnologies, University of Background: The aim of this study was to evaluate the association of perceived
Siena, Siena, Italy
2 Department
stress and poor sleep quality with periodontitis in a university-based cohort of
of Periodontology, Faculty
of Dentistry, University of Oslo, Oslo, individuals.
Norway Methods: A total of 235 individuals were included in this cross-sectional study.
3 Unitof Oral Surgery, Department of Perceived stress and sleep quality were evaluated through validated question-
Medical Biotechnologies, University of
naires, while periodontitis was identified with a full-mouth periodontal exam-
Siena, Siena, Italy
ination protocol using both European Federation of Periodontology/American
Correspondence Academy of Periodontology (EFP/AAP) and Centers for Disease Control and
Crystal Marruganti, Department of
Medical Biotechnologies, University of
Prevention (CDC)/AAP case definitions. Simple and multiple linear and ordinal
Siena, Viale Mario Bracci 16, 53100 Siena, logistic regression analyses were performed to evaluate the association between
Italy. perceived stress and sleep quality with periodontitis prevalence and severity.
Email: [email protected]
Results: Stage III/IV periodontitis resulted associated with both moderate/high
perceived stress (odds ratio [OR] = 5.4; 95% confidence interval [CI]: 2.2–13.5;
p < 0.001) and poor sleep quality (OR = 3.0; 95% CI: 1.2–7.4; p < 0.05). The inter-
action between moderate/high perceived stress and poor sleep quality presented
a multiplicative association with stage III/IV periodontitis (EFP/AAP; OR = 5.8;
95% CI: 1.6–21.3; p < 0.001). Multiple linear regression analyses indicated a sim-
ilar trend of association also with linear periodontal parameters, that is, mean
clinical attachment level (CAL) and mean probing pocket depth (PPD).
Conclusions: The findings from the present study suggest that stress and poor
sleep quality may exert a multiplicative effect on periodontitis prevalence and
severity.

KEYWORDS
epidemiology, periodontal diseases, risk factors, sleep hygiene, stress, psychological

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the
original work is properly cited.
© 2023 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.

J Periodontol. 2024;95:125–134. wileyonlinelibrary.com/journal/jper 125

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126 MARRUGANTI et al.

1 INTRODUCTION 2 MATERIALS AND METHODS

Stress and lack of adequate rest are among the major 2.1 Study design
issues of the modern lifestyle.1 In particular, perceived
stress refers to a condition described by the afflicted The present study is reported according to the Strengthen-
subject as threatening or uncontrollable2 ; in 2020, it ing the Reporting of Observational studies in Epidemiol-
affected around 20% of Americans.3 Stress has a nega- ogy (STROBE) guidelines for cross-sectional studies.18 The
tive impact on general health, both as a consequence research protocol was approved by the local ethics commit-
of direct biological mechanisms (e.g., immune system tee (protocol number: 18993/2021), and it was registered on
impairment) or indirect consequent behavioral changes Clinicaltrials.gov (NCT04771949).
(e.g., reduced physical activity, comfort eating, alcohol
intake, smoking).4 With regard to rest, epidemiological
studies indicated how around 20% of the American 2.2 Setting and participants
population suffer from chronic sleep disorders.5 Similarly
to stress, poor sleep quality has a negative effect on All consecutive patients attending the Dentistry Depart-
systemic health, which has been explained through direct ment at the University Hospital of Siena were screened
mechanisms involving systemic inflammation, oxidative between January 2021 and August 2021. The following
stress, and immune system impairment, and indirect inclusion criteria were applied:
mechanisms related to the associated compensatory
behaviors.6 - Age between 18 and 70 years old;
Being that inflammation and oxidative stress are key - Presence of at least two remaining teeth;
components of periodontitis pathogenesis,7,8 previous epi- - Ability and willingness to give informed consent.
demiological studies have proposed high levels of per-
ceived stress and poor sleep quality as modifiable risk The exclusion criteria were:
indicators for periodontitis.9,10 However, evidence from
the medical field already highlighted that high stress and - Current pregnancy or lactation;
poor sleep quality exert a multiplicative effect on the - Periodontal therapy performed in the previous 12
mortality risk for cardiovascular disease (CVD) compared months;
to subjects with low stress and adequate sleep quality.11 - Administration of antibiotics within the previous 6
The rationale behind such multiplicative systemic effects months;
may reside on the reciprocal association found between - Inability to effectively communicate in Italian.
stress and sleep quality12 : the sleep-induced recovery pro-
cess helps the human body attenuate stress-related acute Individuals were enrolled in the study after they read
load reactions,13 resulting in a fine balance between the and signed the written informed consent, in accordance
two factors. Indeed, whenever stress levels are chroni- with the Declaration of Helsinki.
cally high and there is an incomplete recovery due to poor
sleep quality, chronic allostatic load reactions and the dis-
rupted immune/inflammatory responses are additionally 2.3 Assessment of study variables
triggered.14 Therefore, it can be hypothesized that the com-
bination of high stress and poor sleep quality may exert 2.3.1 Clinical periodontal parameters
a negative effect on the periodontium that is likely to be
of higher magnitude than the two factors alone. How- Details on the assessment of study variables are reported in
ever, studies analyzing the possible multiplicative effect a separate publication on the same study sample.19 Briefly,
of high perceived stress and poor sleep quality on the all included participants received a full-mouth periodon-
periodontium are still lacking. This information would tal examination by two previously calibrated examiners
be clinically relevant, being that stress and sleep quality (C.M., C.G.). Probing pocket depth (PPD), gingival reces-
are modifiable in nature and, thus, potential targets of sion (REC), plaque,20 and bleeding on probing (BoP)21
interventions in the context of the Step 1 of periodontal were recorded with a standardized periodontal probe*
therapy.15–17 at six sites per tooth, third molars excluded. Whenever
Therefore, the aim of the present cross-sectional study the cementum enamel junction was located subgingi-
was to evaluate the multiplicative effect of stress and poor vally, negative values were recorded for REC. Clinical
sleep quality on periodontitis prevalence and severity in a
university-based cohort of individuals. * UNC 15 probe, Hu-Friedy Group, Chicago, IL.
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MARRUGANTI et al. 127

attachment levels (CAL) were computed as the sum 2.3.3 Perceived stress
between PPD and REC values. Furthermore, mean PPD
and mean CAL, as well as the proportion (%) of sites The Italian version of a validated 10-item questionnaire to
with PPD ≥4 mm and PPD ≥6 mm were calculated from measure patients’ level of perceived stress (IPSS-10) was
PPD/CAL measurements. administered by the clinical examiners, who asked struc-
Examiners’ calibration was performed for both PPD tured questions and gave the explanations provided by the
and REC on two non-study subjects suffering from peri- questionnaire itself.25 The instrument had 10 questions
odontitis, and it was considered satisfactory only when an with response options ranging between 0 (never) and 4
agreement in at least 95% of measurements (with a maxi- (very often). All questions were negatively stated (from 4
mum of 2 mm difference) was recorded between the two to 0), except for four questions that were positively stated
examiners. Intra-class correlation coefficients (ICCs) were (from 0 to 4; items 4, 5, 7, and 8). The sum scores were
computed using site-level measurements and not con- calculated after reversing the positive items’ scores and
sidering sites clustering at teeth/participant-level. Inter- then summing up all scores. Total scores ranged between
examiner agreement resulted in ICC = 0.98 (p < 0.001) 0 and 40; the higher the score, the higher the level of per-
for PPD and in ICC = 0.96 (p < 0.001) for REC. For ceived stress. Finally, the IPSS-10 score was categorized
the first examiner, intra-examiner agreement resulted in according to the guidelines in order to stratify participants
ICC = 0.89 (p = 0.002) for PPD and in ICC = 0.92 into two subgroups: moderate/high (IPSS-10 >13) and low
(p = 0.001) for REC; for the second one, intra-examiner perceived stress (IPSS-10 ≤13).26,27
agreement resulted in ICC = 0.94 (p < 0.001) for PPD and
in ICC = 0.98 (p < 0.001) for REC.
2.3.4 Sleep quality

2.3.2 Periodontitis case definitions Sleep quality was assessed using the validated Ital-
ian version of Pittsburgh Sleep Quality Index (PSQI)
Periodontitis was diagnosed using both the European questionnaire.2 The PSQI was administered by the clini-
Federation of Periodontology/American Academy of Peri- cal examiners, who asked structured questions and gave
odontology (EFP/AAP)22 and the Centers for Disease the explanations provided by the questionnaire. The ques-
Control and Prevention (CDC)/AAP criteria.23 According tionnaire included seven domains (subjective sleep quality,
to EFP/AAP criteria, periodontitis cases were identified sleep latency, sleep duration, habitual sleep efficiency,
whenever interdental CAL was detectable at ≥2 non- sleep disturbances, use of sleeping medications, daytime
adjacent teeth, or whenever buccal or oral CAL ≥3 mm dysfunction), each one assessed with a 0 to 3 scoring
with pocketing (PPD >3 mm) was detectable at ≥2 teeth.24 system; the final scores ranged between 0 and 21, with
Cases were classified according to their stage and extent. higher values indicating worse sleep quality. Participants
Periodontitis stage was identified using severity (i.e., inter- with a total score of 5 or higher were classified as having
dental CAL at site of greatest loss, number of missing teeth “poor sleep quality,” vice versa for those with lower scores
due to periodontitis) and complexity factors (i.e., sites with (classified as having “good sleep quality”).28
PPD ≥6 mm, furcation involvement, number of opposing
pairs). The number of missing teeth due to periodonti-
tis was drawn from clinical records whenever available, 2.3.5 Covariates
otherwise it was self-reported by the patient; the number
of opposing pairs was clinically assessed. For each stage, Self-reported socio-demographic characteristics, including
extent was described as either localized (<30% of teeth age, sex, weight, height, smoking and oral hygiene habits,
involved) or generalized. According to the CDC/AAP cri- occupation, and education level, were registered. More-
teria, periodontitis was categorized as being either mild, over, self-reported information regarding the presence of
moderate, or severe. Severe periodontitis was defined as any comorbidity possibly affecting susceptibility to peri-
having ≥2 interproximal sites with CAL ≥6 mm and ≥1 odontitis was collected (i.e., diabetes, rheumatoid arthritis,
interproximal site with PPD ≥5 mm. Moderate periodonti- osteoporosis, and cardiovascular and inflammatory bowel
tis was defined as having ≥2 interproximal sites with CAL diseases); in case participants self-reported one of the men-
≥4 mm and ≥2 interproximal sites with PPD ≥5 mm, while tioned comorbidities, the medical reports were checked
mild periodontitis was defined as the presence of ≥2 inter- for verification. The body mass index (BMI) was com-
proximal sites with CAL ≥3 mm and ≥2 interproximal sites puted as weight (kg)/height (m2 ). The detailed assessment
with PPD ≥4 mm.23 methods of socio-demographic characteristics are reported
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128 MARRUGANTI et al.

in the Supplementary Appendix in the online Journal of 3 RESULTS

Periodontology.
3.1 Participant characteristics

2.4 Sample size calculation A total of 235 participants were included in the present
study. Table 1 provides the descriptive statistics of the study
The sample size calculation was based on the null hypoth- population. The mean age was 53.9 years, and most of
esis that the prevalence of periodontitis in the present the included participants were females (57.9%) and never
sample was the same as previously reported (37.3%).29 For smokers (45.5%). The prevalence of periodontitis according
a 10% threshold in prevalence difference (with α = 0.05), to the EFP/AAP classification was 85.5%, while the preva-
a sample of 185 participants would have resulted in 80% lence according to the CDC/AAP classification was 64.7%.
power to reject the null hypothesis. Due to the broader Approximately 52% of subjects were in the moderate/high-
scope of the present work, this number was inflated of 20%; stress subgroup, and 48% were in the poor sleep quality
therefore, the inclusion of 235 participants was planned. subgroup.

2.5 Statistical analyses 3.2 Perceived stress and periodontitis

Statistical analyses were performed through an ad hoc Participants with moderate/high perceived stress pre-
software† , a priori setting the level of significance at 5%. sented a significantly higher periodontitis severity (stag-
Continuous variables were reported as mean and standard ing) (p = 0.00). Other periodontal parameters (i.e., mean
deviation (SD); categorical data were expressed as number CAL and mean PPD, number of bleeding pockets, full-
of observations (percentage-%). mouth bleeding score (FMBS), teeth lost for periodontal
After verification of data distribution, the unpaired Stu- causes) were significantly worse in subjects with high com-
dent’s t test and the Chi2 test were used to compare pared to low perceived stress. Conversely, FMPS as well as
patients’ characteristics according to the categories of domiciliary plaque control habits were comparable across
perceived stress and sleep quality. subgroups of perceived stress (p = 0.56) (Table 1).
Simple and multiple ordinal logistic regression analy- Ordinal logistic regression analyses indicated how mod-
ses were then performed to study the association between erate/high perceived stress was significantly associated
perceived stress/sleep quality (binary variables) and their with stage I and III periodontitis with increasing estimates
interaction with periodontitis (EFP/AAP and CDC/AAP of association from stage I to stage III (Table 2; see Tables
criteria). Simple and multiple logistic regression anal- S1–S4 in online Journal of Periodontology), while the esti-
yses were also performed using perceived stress/sleep mates were attenuated when considering the CDC/AAP
quality (continuous variables) as exposure. Furthermore, criteria (see Tables S5–S7 in online Journal of Periodon-
after assumptions verification, multiple linear regression tology). Moreover, an increase in the PSS (continuous) was
models were built to evaluate the association between per- associated with significantly higher odds of severe peri-
ceived stress and sleep quality with additional periodontal odontitis (CDC/AAP; OR = 2.4) (see Table S5 in online
variables, that is, mean CAL, and mean PPD. The multiple Journal of Periodontology). Furthermore, simple and mul-
models were adjusted for age,30,31 body mass index,32 sex,33 tiple linear regression analyses demonstrated a significant
smoking,34 education,35,36 toothbrushing frequency,37 and association between moderate/high perceived stress and
comorbidities (binary variable defined as the presence of other measures of periodontitis, that is, mean CAL and
at least one comorbidity among those mentioned above), a mean PPD (Table 3).
priori selected according previous evidence of their associ-
ation with the exposure, the outcome, or both.38 Results
from regression analyses were expressed as odds ratios 3.3 Sleep quality and periodontitis
(ORs) or beta coefficient (β) with 95% CI. Sensitivity anal-
yses by age (≤40 vs. >40 years) and number of teeth (≤20 Poor sleep quality presented a significantly higher peri-
vs. >20 teeth) were also performed. odontitis severity (staging) (p = 0.03). Other periodontal
parameters (i.e., mean PPD, %PPD ≥4 mm, %PPD ≥6 mm,
number of bleeding pockets, teeth lost for periodontal
causes) were significantly worse in subjects with poor
† StataCorp. 2021, Stata Statistical Software: Release 17, StataCorp LLC, compared to good sleep quality. Conversely, domiciliary
College Station, TX. plaque control habits were comparable across subgroups
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MARRUGANTI et al. 129

TA B L E 1 Patients’ characteristics by perceived stress and sleep quality level

Perceived stress Sleep Quality
Overall Moderate/high Low Poor Good
Variable n = 235 n = 122 n = 113 p-Value* n = 113 n = 122 p-Value*
Age, years 53.9 ± 14.7 55.8 ± 12.9 51.8 ± 16.2 0.07 57.5 ± 12.6 50.5 ± 15.7 <0.001
BMI, kg/m2 25.5 ± 4.8 25.3 ± 4.2 25.7 ± 5.4 0.93 25.9 ± 5.1 25.1 ± 4.5 0.22
Sex, females 136 (57.9) 73 (59.8) 63 (55.8) 0.31 72 (63.7) 64 (52.5) 0.08
Occupation
Unemployed 42 (17.9) 25 (20.7) 17 (15.1) 0.41 18 (15.9) 24 (19.8) 0.24
Employed 133 (56.8) 64 (52.9) 69 (61.1) 61 (53.9) 72 (59.5)
Retired 59 (25.2) 32 (26.5) 27 (23.9) 34 (30.1) 25 (20.7)
Education
Elementary/middle school 69 (29.5) 44 (36.1) 25 (22.3) 0.02 36 (31.9) 33 (27.3) 0.45
High school 107 (45.7) 55 (45.1) 52 (46.4) 53 (46.9) 54 (44.6)
College or more 58 (24.8) 23 (18.8) 35 (31.3) 24 (21.3) 34 (28.1)
Smoking
Never 107 (45.5) 53 (43.4) 54 (47.8) 0.77 51 (45.1) 56 (45.9) 0.99
Former 67 (28.5) 37 (30.3) 30 (26.5) 32 (28.3) 35 (28.7)
Smoker 61 (25.9) 32 (26.2) 29 (25.7) 30 (26.6) 31 (25.4)
Familiarity for periodontitis, yes 87 (37.1) 53 (43.4) 34 (30.1) 0.02 43 (38.1) 44 (36.1) 0.79
a
Comorbidities , yes 43 (18.3) 21 (17.2) 22 (19.5) 0.69 27 (23.9) 16 (13.1) 0.09
Oral health status
Periodontitis stagingb
(EFP/AAP)
Healthy/gingivitis 34 (14.5) 7 (5.7) 27 (23.9) <0.001 8 (7.1) 26 (21.3) 0.03
Stage 1 27 (11.5) 13 (10.7) 14 (12.4) 9 (7.9) 18 (14.8)
Stage 2 56 (23.8) 27 (22.1) 29 (25.7) 25 (22.1) 31 (25.4)
Stage 3 94 (40.0) 58 (47.5) 36 (31.9) 56 (49.6) 38 (31.2)
Stage 4 24 (10.2) 17 (13.9) 7 (6.2) 15 (13.3) 9 (7.4)
Periodontitisc (CDC/AAP)
No periodontitis 83 (35.3) 21 (17.2) 62 (54.9) <0.001 26 (23.0) 57 (46.7) <0.001
Mild 29 (12.3) 20 (16.4) 10 (8.8) 16 (14.2) 13 (10.7)
Moderate 70 (29.8) 57 (46.7) 13 (11.5) 41 (36.3) 29 (23.8)
Severe 53 (22.6) 15 (12.3) 38 (33.6) 30 (26.6) 23 (18.9)
No. of teeth 24.2 ± 5.4 23.7 ± 5.3 24.7 ± 5.6 0.06 23.7 ± 5.3 24.6 ± 5.5 0.08
Mean CAL, mm 2.8 ± 1.1 2.9 ± 1.1 2.4 ± 1.1 <0.001 2.9 ± 1.0 2.4 ± 1.1 <0.001
Mean PPD, mm 2.5 ± 0.7 2.6 ± 0.7 2.4 ± 0.6 0.02 2.6 ± 0.7 2.4 ± 0.6 0.03
% PPD≥4 mm 9.3 ± 11.6 11.0 ± 12.7 7.4 ± 9.9 <0.001 11.6 ± 12.8 7.2 ± 9.9 <0.001
% PPD≥6 mm 5.8 ± 9.4 6.4 ± 4.8 3.2 ± 3.9 0.001 7.5 ± 4.2 3.6 ± 3.0 <0.001
No. of bleeding pocketsd 7.3 ± 10.4 8.9 ± 12.1 5.5 ± 7.8 <0.001 9.1 ± 10.9 5.7 ± 9.5 <0.001
FMPS 50.6 ± 24.3 51.3 ± 23.9 49.8 ± 24.6 0.69 50.6 ± 24.8 50.5 ± 23.8 0.98
FMBS 28.5 ± 17.8 30.1 ± 15.6 26.7 ± 19.8 0.02 29.7 ± 17.9 27.3 ± 17.7 0.25
Teeth lost for periodontitis, yes 76 (32.3) 51 (41.8) 25 (22.1) <0.001 49 (43.4) 27 (22.1) <0.001
Domiciliary plaque control
Brushing frequency
Not performed 4 (1.7) 2 (1.6) 2 (1.8) 0.37 1 (0.9) 3 (2.5) 0.22
Occasionally 46 (19.6) 28 (22.9) 18 (15.9) 27 (23.9) 19 (15.6)
Every day 185 (78.7) 92 (75.4) 93 (82.3) 85 (75.2) 100 (81.9)
(Continues)
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130 MARRUGANTI et al.

TA B L E 1 (Continued)
Perceived stress Sleep Quality
Overall Moderate/high Low Poor Good
Variable n = 235 n = 122 n = 113 p-Value* n = 113 n = 122 p-Value*
Toothbrush type, powered 122 (51.9) 60 (49.2) 62 (54.9) 0.23 55 (48.7) 67 (54.9) 0.20
Interdental cleaning (IC)
Not performed 75 (31.9) 41 (33.6) 35 (30.9) 0.78 37 (32.7) 38 (31.9) 0.98
Interdental floss 51 (21.7) 27 (22.1) 24 (21.2) 25 (22.1) 26 (21.3)
Interproximal brushes 109 (45.9) 54 (44.3) 54 (47.8) 51 (45.1) 57 (46.7)
Frequency of IC
Not performed 75 (31.9) 42 (34.4) 33 (29.2) 0.56 37 (32.7) 38 (31.2) 0.99
Occasionally 48 (20.4) 26 (21.3) 22 (19.5) 23 (20.4) 25 (20.5)
Every day 112 (47.7) 54 (44.3) 58 (51.3) 53 (46.9) 59 (48.4)
Notes: Data are presented as mean ± standard deviation or numbers (percentages). Comparisons across subgroups of stress/sleep were performed using the
unpaired Student’s t test for continuous variables, and the Chi2 test for categorical variables.
Abbreviations: AAP, American Academy of Periodontology; BMI, body mass index; CAL, clinical attachment level; CDC, Centers for Disease Control and Pre-
vention; EFP, European Federation of Periodontology; FMBS, full-mouth bleeding score; FMPS, full-mouth plaque score; IC, interdental cleaning; PPD, probing
pocket depth.
a
Defined as the presence of at least one comorbidity among diabetes, rheumatoid arthritis, osteoporosis, cardiovascular, and inflammatory bowel diseases.
b
According to the 2018 EFP/AAP classification.
c
According to the CDC/AAP classification.
d
Defined as the number of sites with probing depth≥5 mm and positive to bleeding on probing.
*p < 0.05 is considered statistically significant. * p < 0.05; ** p < 0.01; *** p < 0.001.

T A B L E 2 Effect estimates from ordinal logistic regression models for the association between perceived stress, sleep quality, and their
interaction with periodontitis (EFP/AAP classification)
Stage Ia Stage IIa Stage III/IVa
OR (95% CI) OR (95% CI) OR (95% CI)
Exposure variables Crude Adjustedb Crude Adjustedb Crude Adjustedb
PSQI (continuous) 3.2 (0.9, 7.2) 2.5 (0.7, 5.1) 2.9 (0.9, 6.2) 2.3 (0.8, 5.3) 5.5 (0.9, 9.7) 2.5 (0.2, 5.2)
PSS (continuous) 3.6 (0.9, 7.9) 2.2 (0.4, 5.0) 2.3 (0.4, 5.9) 2.1 (0.7, 6.2) 3.2 (0.9, 6.1) 2.9 (0.6, 4.9)
Poor sleep quality (vs. good sleep quality) 1.4 (0.5, 4.0) 1.2 (0.4, 3.8) 2.0 (0.8, 4.9) 1.7 (0.7, 4.4) 4.0 (1.8, 8.7)* 3.0 (1.2, 7.4)*
Moderate/high perceived stress (vs. low 2.3 (0.8, 6.4) 2.2 (1.0, 8.8)* 2.3 (0.9, 5.7) 2.6 (1.1, 6.6)* 4.6 (2.1, 10.1)* 5.4 (2.2, 13.5)*
perceived stress)
Interaction between sleep quality and
perceived stress
Poor sleep quality (vs. good sleep quality) 2.4 (0.7, 9.0) 3.2 (0.7, 15.0) 1.3 (0.4, 3.3) 1.2 (0.3, 4.9) 3.4 (1.3, 9.0)* 2.5 (1.1, 8.2)*
Moderate/high perceived stress (vs. low 3.5 (0.7, 12.0) 5.5 (1.1, 26.3)* 1.4 (0.4, 4.5) 2.0 (0.9, 7.7) 3.9 (1.4, 10.9)* 4.0 (1.0, 15.6)*
perceived stress)
Moderate/high stress # poor sleep qualityc 3.7 (0.5, 12.9) 1.0 (0.1, 7.1) 2.7 (1.1, 17.9)* 2.7 (0.7, 9.9) 6.4 (2.1, 19.1)* 5.8 (1.6, 21.3)*
Abbreviations: CI, confidence interval; OR, odds ratio; PSQI, Pittsburgh Sleep Quality Index; PSS, Perceived Stress Scale.
a
vs. healthy or gingivitis.
b
Adjusted for age, sex, smoking, body mass index, education, brushing frequency, and comorbidities (defined as the presence of at least one comorbidity among
diabetes, rheumatoid arthritis, osteoporosis, cardiovascular and inflammatory bowel diseases).
c
The interaction term equaled 1 whenever the participant had moderate/high stress and poor sleep quality, otherwise it equaled 0 (i.e., reference category).
*p < 0.05 is considered statistically significant. * p < 0.05; ** p < 0.01; *** p < 0.001.

of sleep quality (p = 0.99) (Table 1). Ordinal logistic (continuous) as exposure, only a non-statistically signifi-
regression analyses indicated how poor sleep quality was cant tendency in the same direction was noted (Tables 2
significantly associated with stage III/IV periodontitis and 3; see Tables S1–S7 in online Journal of Periodontology).
(EFP/AAP; OR = 3.0), as well as with severe periodon- Moreover, multiple linear regression analyses indicated
titis (CDC/AAP; OR = 2.5) (Table 2; see Table S5 in a significant association between poor sleep quality and
online Journal of Periodontology). When considering PSQI mean CAL, but not mean PPD (Table 3).
 19433670, 2024, 2, Downloaded from https://aap.onlinelibrary.wiley.com/doi/10.1002/JPER.23-0209 by Nat Prov Indonesia, Wiley Online Library on [07/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
MARRUGANTI et al. 131

T A B L E 3 Effect estimates from linear regression models for the association between perceived stress, sleep quality, and their interaction
with mean CAL and mean PPD
Mean CAL (mm) Mean PPD (mm)
β (95% CI) β (95% CI)
Exposure variables Crude Adjusteda Crude Adjusteda
PSQI (continuous) 0.7 (0.3, 1.1)* 0.4 (0.1, 0.8)* 0.9 (0.3, 1.6)* 0.2 (0.02, 1.0)*
PSS (continuous) 0.7 (0.4, 1.2)* 0.5 (0.2, 1.9)* 0.4 (0.04, 1.2)* 0.2 (−0.1, 1.3)
Poor sleep quality (vs. good sleep quality) 0.1 (0.04, 0.2)* 0.3 (0.05, 0.6)* 0.1 (0.02, 0.2)* 0.1 (−0.03, 0.3)
Moderate/high perceived stress (vs. low perceived 0.1 (0.06, 0.2)* 0.4 (0.1, 0.6)* 0.1 (0.03, 0.2)* 0.2 (0.004, 0.3)*
stress)
Interaction between sleep quality and perceived stress
Poor sleep quality (vs. good sleep quality) 0.1 (0.01, 0.3)* 0.2 (0.001, 0.5)* 0.2 (0.06, 0.4) 0.1 (−0.1, 0.4)
Moderate/high perceived stress (vs. low perceived 0.1 (−0.003, 0.2) 0.3 (0.01, 0.6)* 0.2 (0.03, 0.4)* 0.2 (0.001, 0.4)*
stress)
Moderate/high stress # poor sleep qualityb 0.7 (0.4, 0.9)* 0.5 (0.2, 0.7)* 0.2 (0.04, 0.4)* 0.2 (−0.02, 0.3)
Abbreviations: CAL, clinical attachment level; CI, confidence interval; PPD, probing pocket depth; PSQI, Pittsburgh Sleep Quality Index; PSS, Perceived Stress
Scale.
a
Adjusted for age, sex, smoking, body mass index, education, brushing frequency, and comorbidities (defined as the presence of at least one comorbidity among
diabetes, rheumatoid arthritis, osteoporosis, and cardiovascular and inflammatory bowel diseases).
b
The interaction term equaled 1 whenever the participant had moderate/high stress and poor sleep quality, otherwise it equaled 0 (i.e., reference category).
* p < 0.05 is considered statistically significant. * p < 0.05; ** p < 0.01; *** p < 0.001.

3.4 Interaction between perceived poor/good sleep quality, suggesting that these associations
stress and sleep quality are not due to this factor.
Results of the current investigation on the association
When considering the interaction between perceived stress between perceived stress and periodontitis are consistent
and sleep quality, ordinal logistic regressions indicated with those obtained by a previous report conducted on
how the subgroup with combined “moderate/high stress, 621 Brazilian individuals,9 where a significant association
poor sleep quality” (OR = 5.8) resulted associated with was also found. Nonetheless, the magnitude of associa-
stage III/IV periodontitis (EFP/AAP) with around a double tion was weaker than the one found in the present study,
magnitude than either poor sleep quality or moderate/high possibly due to the different periodontitis case defini-
perceived stress alone (Table 2); these results remained tions employed.22,23 Indeed, the present study underlined
consistent also for severe periodontitis (CDC/AAP) (see similar, but more attenuated results for the CDC/AAP
Table S5 in online Journal of Periodontology). Multiple compared to the EFP/AAP criteria, consistent with those
linear regression analyses indicated a similar trend of asso- findings reporting discrepancies in the identification of
ciation also with other additional periodontal parameters, periodontitis cases between the two case definitions.40 The
that is, mean CAL and mean PPD (Table 3). association between stress and periodontitis may be boiled
down to mainly two pathways: a direct biological nega-
tive impact on the immune and endocrine system, and
4 DISCUSSION behavioral adaptive changes (including smoking).1 As for
the direct biological impact, stress triggers an increase in
The present cross-sectional study indicated that mod- neuroendocrine hormones, such as glucocorticoids and
erate/high perceived stress and poor sleep quality are catecholamines which, in turn, exert suppressive effects
associated with severe forms of periodontitis (defined on the immune system, by reducing lymphocyte prolifera-
with both the EFP/AAP and the CDC/AAP criteria). The tion, antibody production, and natural killer cell activity.41
estimates of association were found to be multiplicative Consequently, subjects with chronic stress tend to be more
for subjects reporting moderate/high perceived stress and prone to infections.
poor sleep quality, irrespective of the disease classifica- With regard to sleep quality, results from the present
tion employed, subgroups of age, and participant’s total research are consistent with those from a previous study,
number of teeth. Furthermore, moderate/high perceived which reported a significant association between staging
stress and poor sleep quality also showed a linear relation- and grading of periodontitis and PSQI.10 A proper com-
ship with additional periodontal parameters, such as mean parison of the magnitude of association with the present
CAL and mean PPD. Plaque control was comparable across study could not be performed, due to the differences in
stressed/non-stressed subjects and among those reporting the outcome assessment methods and in the employed
 19433670, 2024, 2, Downloaded from https://aap.onlinelibrary.wiley.com/doi/10.1002/JPER.23-0209 by Nat Prov Indonesia, Wiley Online Library on [07/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
132 MARRUGANTI et al.

thresholds for the categorization of variables. Substantial tion of the medical conditions and medications that may
evidence supports the biological plausibility of the asso- have affected the periodontal status of the participants as
ciation between poor sleep quality and periodontitis, and well as the estimates of association between the exposure
this relationship seems to be bi-directional.42 Indeed, poor and the outcome. In addition, all the included partici-
sleep quality was found to be associated with higher mark- pants came from urban or suburban areas in the south-east
ers of systemic inflammation which may influence the part of a region in Central Italy (Tuscany), where most
development of periodontitis43 ; in turn, the presence of a adults are Caucasian; hence, any possible variability in
state of systemic inflammation, which can be triggered by the results related to ethnicity could not be investigated.
periodontitis,44 may negatively impact sleep quality.7 Moreover, given that the study population was selected
The combination of moderate/high perceived stress among patients coming to a public university hospital,
and poor sleep quality was associated with a higher the risk of selection bias could not be excluded. Overall,
prevalence of both periodontitis and severe periodonti- these two factors may also reduce the generalizability of
tis, and with worse periodontal parameters, irrespective the study findings. In addition, the reduced sample size
of socio-demographic characteristics and plaque control. resulted in wide confidence intervals for the multiplicative
Therefore, the results from the current study suggest the association of stress and sleep quality with periodonti-
presence of a multiplicative effect of poor sleep quality tis, which lead to insecurity towars the central estimates
and perceived stress on periodontitis occurrence and sever- and—consequently—on the reported concept of a multi-
ity, similar to what was observed for CVD.11 To the best plicative effect. Finally, no saliva or blood samples were
of the authors’ knowledge, no previous study evaluated collected, so assessments of inflammatory markers could
the combined effect of perceived stress and sleep quality not be performed. Nonetheless, to the best of the authors
on periodontal health. On the grounds of these consider- knowledge, this represents the first study investigating the
ations, it can be hypothesized that the pro-inflammatory multiplicative effect of perceived stress and sleep qual-
systemic action of stress and poor sleep quality and the sup- ity on periodontal health. Assessments of perceived stress
pressive action on the immune functions of moderate/high and sleep quality were performed using reliable and val-
perceived stress may exert a multiplicative effect on the idated tools for the selected sample, whose validity and
periodontium,45,17 which may be conducive to an increased reproducibility for the Italian population were previously
susceptibility to periodontitis onset and severity, as well as demonstrated.2,49
a worse response to periodontal therapy.17 In particular,
chronic psychological stress was shown to hyperacti-
vate the hypothalamic-pituitary axis (leading to increased
5 CONCLUSION
cortisol production and release) and the sympathetic ner-
The present study indicated a multiplicative association
vous system which, similarly to the systemic effects of
of perceived stress and sleep quality with periodontitis.
poor sleep quality, eventually leads to an increase in the
Specifically, individuals whose lifestyle is characterized by
markers of systemic inflammation, such as C-reactive pro-
both moderate/high perceived stress and poor sleep quality
teins and interleukin-6; in turn, systemic inflammation
have a from 5- to 6-times increased odds of suffering from
was demonstrated to have a detrimental impact on the
severe forms of periodontitis.
periodontium.12,14,43 This information may be relevant for
clinicians since stress and sleep quality may be poten- AU T H O R CO N T R I B U T I O N S
tial targets of interventions in the context of the Step 1 of Crystal Marruganti contributed to study conception, study
periodontal therapy,15 and for researchers since they may design, data analysis, and manuscript drafting. Carlo Gaeta
represent potential confounders to be taken into account contributed to data interpretation and manuscript draft-
in well-established associations between periodontitis and ing. Mario Romandini contributed to data analysis, data
systemic diseases.46–48 interpretation, and manuscript drafting. Edoardo Ferrari
Some limitations are worth mentioning when inter- Cagidiaco and Stefano Parrini contributed to data inter-
preting these findings, including the cross-sectional study pretation, and critically revised the manuscript. Nicola
design (which hampers the investigation of the temporal- Discepoli contributed to study design. Simone Gran-
ity of association and does not rule out the reverse causality dini contributed to study conception, study design, and
hypothesis), the risk of information bias for periodonti- manuscript drafting.
tis (e.g., due to the lack of radiographic information in
some non-periodontitis or incipient periodontitis cases) AC K N OW L E D G M E N T S
and stress/sleep quality (i.e., self-reported) assessments. This research received no specific grants from fund-
Furthermore, the risk of residual confounding cannot be ing agencies in the public, commercial, or not-for-profit
ruled out, also due to the lack of a detailed considera- sectors.
 19433670, 2024, 2, Downloaded from https://aap.onlinelibrary.wiley.com/doi/10.1002/JPER.23-0209 by Nat Prov Indonesia, Wiley Online Library on [07/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
MARRUGANTI et al. 133

C O N F L I C T O F I N T E R E S T S TAT E M E N T 15. Sanz M, Herrera D, Kebschull M, et al. Treatment of stage I–

The authors deny any conflict of interest related to this III periodontitis—The EFP S3 level clinical practice guideline. J
study. Clin Periodontol. 2020;47:4-60.
16. Marruganti C, Baima G, Grandini S, et al. Leisure-time and
occupational physical activity demonstrate divergent associ-
D A T A AVA I L A B I L I T Y S T A T E M E N T
ations with periodontitis: a population-based study. J Clin
The data that support the findings of this study are avail- Periodontol. 2023; 50:559-570. doi:10.1111/jcpe.13766. Published
able upon reasonable request from the corresponding online.
author. 17. Marruganti C, Romandini M, Gaeta C, et al. Healthy lifestyles
are associated with a better response to periodontal therapy: a
ORCID prospective cohort study. J Clin Periodontol. 2023;50:1089-110.
Crystal Marruganti https://orcid.org/0000-0003-1088- Published online.
18. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC,
2046
Vandenbroucke JP. The Strengthening the Reporting of Obser-
Mario Romandini https://orcid.org/0000-0001-5646- vational Studies in Epidemiology (STROBE) statement: guide-
083X lines for reporting observational studies. J Clin Epidemiol.
2008;61:344-349.
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