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Risk factors for periodontal disease

2.4 Alcohol use and periodontal disease

2.4.3 Risk factors for periodontal disease

The multi-factorial nature of periodontal disease makes it important to identify the risk factors for the disease. These risk factors can be categorized as modifiable, non-modifiable, and risk characteristics of individuals (Figure 4).

Some of these risk factors are common to both periodontal disease and major chronic NCDs such as cardiovascular disease, diabetes, chronic respiratory disease, and cancer. Based on this, researchers have advocated the common risk factor approach (CRFA) as a more effective way of tackling these chronic NCDs, as well as oral diseases like periodontal disease (Sheiham & Watt, 2000).

Source: Based on previous literature (Genco, Borgnakke, 2013; Reynolds, 2014; Borgnakke, 2016;

AlJehani, 2014)

Both cross-sectional studies (Sakki et al., 1995; Kongstad et al., 2008; Park et al., 2014; Kim et al., 2014; Merchant et al., 2017) and longitudinal studies have reported conflicting results. To date, only a very limited number of studies have examined the effects of alcohol use on periodontal disease development in periodontally healthy individuals (incidence) (Pitiphat et al., 2003; Okamoto et al., 2006), while others have focused on the progression of the disease (Ogawa et al., 2002; Jansson, 2008; Nishida et al., 2010; Hach et al., 2015; Wagner et al., 2017). Recent meta-analysis based on observational studies reported a dose-dependent effect, although the authors emphasized the need for more longitudinal studies and further studies investigating the effects of different alcoholic beverages on periodontal health (Wang et al., 2016).

Animal studies have explored the association between alcohol and periodontal disease, of which some studies reported a positive association between alcohol use and periodontal disease (Irie et al., 2008; Maia Dantas et al., 2012; Surkin et al., 2014;

de Souza et al., 2017), while another study showed no such association (Liberman et al., 2011).

Previous studies have shown that the effects of alcohol use on the periodontium differ by age, gender, or even SEP. With regard to age, studies conducted among older adults have reported alcohol use to be associated with poor periodontal condition (Sakki et al., 1995), while others reported no association (Torrungruang et al., 2005), except in cases of alcohol intoxication (Akpata et al., 2016). Regarding gender, some reports suggest that harmful effects can be observed only in men (Pitiphat et al., 2003; Park et al., 2014; Wagner et al., 2017), whereas others reported no harmful effects in men (Okamoto et al., 2006), while some studies found harmful effects in women (Wu et al., 2013; Susin et al., 2015). Currently, there is not enough data to compare the effects between different age groups or between men and women.

A limited number of earlier studies have explored whether the effects of alcohol use on periodontal health differs by SEP. However, these studies have been conducted among specific occupational groups. A study among male healthcare professionals (Pitiphat et al., 2003) and other studies among Japanese factory workers (Shizukuishi et al., 1998; Nishida et al., 2004; Nishida et al., 2010) reported an association between alcohol use and periodontal disease. There are no studies so far where the association is studied in different socio-economic groups in the same study population.

2.4.5 Plausible mechanisms linking alcohol use with periodontal disease outcomes

Although periodontal disease is a multi-factorial disease, pathogenic bacteria in dental plaque is the main etiological factor. One study suggested higher levels of pathogenic species in the sub-gingival microbiota among alcoholics compared to non-alcoholics (Amaral et al., 2011). Findings among alcohol-dependent individuals have also suggested an increased sub-gingival bacterial load, which eventually alters

the microbiological and immunological periodontal parameters (Lages et al., 2015).

It has been suggested that heavy alcohol use could reduce the host immune responses by altering the innate and adaptive immune responses. These altered responses could lead to an increased level of inflammatory cytokines; impaired functioning of neutrophils, macrophages, and T cells; and increased susceptibility to infections (Szabo & Mandrekar, 2009; Szabo, 1999).

Some of these mechanisms were proposed in previous epidemiological studies to explain the detrimental effect of alcohol on periodontal health (Tezal et al., 2001;

Pitiphat et al., 2003). These explanations are further supported by findings where it was reported that alcohol dependence could impair neutrophil function (Khocht 2013). Experimental research suggests that alcohol use can also affect bone metabolism by inhibiting osteoblastic activity and thus reducing bone formation, eventually contributing to periodontal tissue damage (Dyer, Buckendahl & Sampson, 1998; Turner et al., 2001). Studies have also reported that ethanol intake could increase alveolar bone loss (Souza et al., 2009). Conversely, other studies suggest that poor oral hygiene and poor dental care, rather than alcohol intake, contribute to a high risk of periodontal disease (Movin, 1981; Novacek et al., 1995).

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able 1. Existing literature on alcohol use and periodontal disease association. Author (Year)Gender Age (years) Sample size

Alcohol use (Exposure) Periodontal parameter (Outcome)Confounders Main findings RR (95% CI) in the highest category Longitudinal studies: Incidence Pitiphat et al. (2003)Male 40–75 n=39,461 Questionnaire: alcohol use (g/day), type of beverage

Self-reported: one question about periodontal diseaseAge, smoking, BMI, physical activity, diabetes, total calories ≥30 g/day: 1.27(1.08−1.49) No effect of beverages Okamoto et al. (2006)Male 43.5 n=1,332

Questionnaire: alcohol use (g/day) 0; <20; >20

CPI scores: based on PPDAge, smoking No association ≥20 g/day: 1.05(0.73−1.51) Longitudinal studies: Progression Ogawa et al. (2002)Male and female 70 n= 436

Alcohol drinking habits: daily vs not dailyCAL < 6 mm; CAL > 6mmGender, smoking, missing teeth, visit dentist regularly, need for treatment, recent visit to dentist in a year, use of floss, use of interdental brush, brushing frequency, blood pressure levels, liver agents, immunoglobulins, lip factors, nutritional factors

No significant correlation Jansson (2008)Male and female 18–65 n=477

Questionnaire: alcohol use (cl/day): ≤5; >5 Longitudinal bone Loss; Bleeding index; Plaque index; Calculus index Age, gender, smoking, decayed teeth, dental visits, education level, diabetes, coronary heart disease

No association Nishida et al. (2010)Male and female 1863 n=224

Questionnaire: alcohol use (g/day): <33; ≥33. Percentage of teeth with a PPD 3.5 mm: above or below the upper 20th percentile of the percentage, as periodontitis or non- periodontitis Age, gender, BMI, smoking habit, and frequency of toothbrushing 33 g/day: 3.43(1.57 7.48) 33 g/day and ALDH2*1/*2 genotype: 4.28(1.20–15.3) Table 1. Continues

aire: alcohol /week) 814; >14 0−3; 47; >7

≥3 teeth with CAL ≥3 mmAge, gender, smoking Heavy drinkers: 2.24(0.58−8.58) aire: se /week; >1 k and 1 >1 glass/day.

≥2 teeth with proximal (clinical AL) progression3 mm over 5 years

Age, gender, smoking, socioeconomic status, BMI >1 glass/day: 1.30(1.07−1.58) aire: se eeks:

PPD3 mmGender, dietary habits, alcohol consumption, smoking, toothbrushing frequency

≥7 drinks/2 weeks: 2.52(1.44.54) aire: se eek): 0

CAL 0–1 mm; 1.1–2 mm; 2.1–3 mm; 3.1–4 mm; >4mm Age, education, income, smoking, plaque, gender, race, diabetes, allergy ≥10 drinks/week: 1.44(1.04–2.00) aire: alcohol /week): 20

CAL < 1.5 mm; CAL >1.5mmAge, smoking, gender, race, education, income, diabetes, diet, remaining teeth, gingival bleeding

20 drinks/week: 1.67(1.25–2.23) aire: alcohol ; 0.1–14.9; 15–

None: no teeth with PPD 4 mm; no teeth with CAL 5 mm. Low: 0.1–19.9% teeth with PPD 4 mm; 0.1–9.9% teeth with CAL 5 mm. Mild: 20–34.9% teeth with PPD 4 mm; 10–21.9% teeth with CAL 5 mm. High:35% teeth with PPD 4 mm; ≥22% teeth with CAL 5 mm.

Age, gender, smoking, number of teeth, mean plaque index, glucose tolerance

30 g/day: 2.5(1.1−5.7) Table 1. Continues

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Table 1. Continued Torrungruang et al. (2005)Male and female 5073 n=2,005 Questionnaire: alcohol use: non-drinkers; former; current drinkers Mild: CAL <2.5 mm, moderate: CAL 2.5−3.9 mm high: CAL ≥4 mm Age, gender, education, income, plaque, smoking, diabetes, BMI, waist circumference

No association Bouchard et al. (2006)Male and female 35–65 n=2,132

Questionnaire: alcohol use: non-drinkers, occasional drinkers, regular drinkers CAL: Mild:1–2mm; moderate :3–5 mm; high: >5mm Age, gender, height, BMI, socioeconomic status, decayed teeth, dental visits, smoking, blood pressure, glucose tolerance, hypertensive, cholesterol

1.4(1.1−1.8) Kongstad et al. (2008)

Male and female 2095 n=1,521

Questionnaire: alcohol use (drinks/ week) - <1, (1–6: women, 1–13: men); (7–13: women, 14–20: men); (14–20: women, 21–34: men); (≥21: women, ≥35: men). Type-specific alcohol drinks/ week: <1, 1–5, 6– 10 and >10 in women and <1, 1–6, 7–14 and >14 in men for beer, wine and spirits, respectively.

Mean CAL: based on 75 percentiles (<3mm and3 mm), BOP score: <25% and ≥25%.

Age, smoking status: amount, type of tobacco smoked, daily consumption, pack years; education, income, physical activity, BMI, diabetes, number of teeth, plaque score

Men consuming 35+ drinks/week: 0.3(0.2–0.8) Lages et al. (2012)Male and female 35–55 n=542

AUDIT and CAGE Questionnaires: alcohol use: non-drinker, 2–4 drinks/month, 2–3 drinks/week,4 drinks/month Periodontitis: four or more teeth with one or more sites CAL ≥3 mm and PPD 4 mm at same time Age, gender, education level, family income, smoking, co-habitation status, BMI, last dental visit, diabetes

≥4 drinks/month: 4.72 (2.73−7.92) Table 1. Continues

se (g/day): 0, oderate drinker eavy drinker DIT score (0–7; 9;20). drinking (g/day): en; >40 g/day CPI score: >1 site had a >3.5 mm pocket in the index teeth

Age, education, income, smoking, BMI, exercise, white blood cell count, diabetes, hypertension, metabolic syndrome, toothbrushing frequency per day

Heavy drinkers: 1.27(1.03−1.57) for men; 1.44(0.91−2.28) for women AUDIT levels of20: 1.57(1.28−1.91) for men res: 8 or Higher CPI: at least one site had a>3.5 mm (code 4:>5.5 mm) probing pocket depth.

Age, gender, household income, educational level, daily frequency of toothbrushing, use of dental floss or interdental brush, the number of decayed teeth, current smoking status, diabetes and obesity

Higher CPI: 1.16(0.97−1.38); 1.28(1.03−1.60) for men; 1.29(1.06−1.57) for non- smokers. aire; se: non-drinker; week; <1 day

30% teeth with CAL 5 mmAge, gender, socioeconomic status, race, dental care, BMI, diabetes, smoking

>1 glass/day: 1.48(0.88−2.48) : drinks/week: <8;8 Mild: ≥2 interproximal sites with CAL 3 mm / PPD4 mm or 1 site with PPD5 mm. Moderate:2 interproximal sites with CAL 3 mm / PPD5 mm. Severe:2 interproximal sites with CAL 3 mm and1 site with PPD5 mm.

Age, gender, education, income-to- poverty ratio, race/ethnicity, cigarette use, overall health,glycated hemoglobin level

≥8 drinks/week with severe periodontitis: 1.9(1.2−3.0) t loss, PPD: probing pocket depth, CPI: Community Periodontal Index; AUDIT: Alcohol Use Disorders Identification ticism, Guilty Feeling, and Eye-Opener.

3 AIMS OF THE STUDY

The general hypothesis of the study was that alcohol use is a risk for periodontal disease. The main aim was to investigate the association of alcohol use with periodontal conditions measured by periodontal pockets.

More specific hypotheses and aims of this dissertation were:

1. Hypothesis 1 for this study was that the effects of alcohol use on the periodontium are dependent on age, gender, or SEP. The aims of this study were to examine (i) the association of alcohol use (amount, frequency, and use over the risk limit) with the number of teeth with deepened (≥4 mm) periodontal pockets, and (ii) the role of age, gender, and SEP in the association of alcohol use with the number of teeth with deepened periodontal pockets (study I).

2. Hypothesis 2 for this study was that the effects of spirit intake are more harmful to periodontal health than beer or wine. The aims of this study were to examine (i) the association between the use of different alcoholic beverages (amount and frequency)/GGT and the number of teeth with deepened (≥4 mm) periodontal pockets, and (ii) the role of SEP in the association of the use of different alcoholic beverages with the number of teeth with deepened periodontal pockets (study II).

3. Hypothesis 3 for this study was that alcohol use (higher, frequent, or use over the risk limit) increases the incidence of periodontal pocket development over a period of four years. The aim of this study was to investigate whether alcohol use (amount, frequency, and use over the risk limit) predicts the incidence of deepened periodontal pockets during the four-year follow-up period (study III).

4. Hypothesis 4 for this study was that alcohol use (higher or frequent) increases the incidence of periodontal pocket development over a period of 11 years. The aim of this study was to investigate whether alcohol use (amount, frequency, and type of beverage) predicts the incidence of deepened periodontal pockets during the 11-year follow-up period (study IV).

4 MATERIALS AND METHODS

4.1 STUDY POPULATION

4.1.1 The Health 2000 Survey

This dissertation was based on the nationally representative Health 2000 Survey, which was conducted in Finland in 2000−2001 by the THL (formerly the National Public Health Institute of Finland, KTL). The aim of this survey was to provide information about the health and functional capacity of the Finnish adult population.

The survey had a two-stage, stratified cluster sampling design with initial stratification performed according to five university hospital regions (stratum). This was followed by a first stage of sampling of sixteen health center districts in each hospital region, resulting in 80 health center districts (clusters), and then the second stage of sampling included sampling of individual persons from these health districts (primary sampling units). The main sample included 8,028 adults aged 30 years or older living in continental Finland. Of these, 6,986 (87%) subjects participated in home or institutional interviews, 6,354 subjects participated in the health examination, and 6,335 (79%) subjects participated in the clinical oral health examination (Aromaa & Koskinen (eds.) 2004).

The survey included a home-visit interview, questionnaires (questionnaire 1 [basic questionnaire], questionnaire 2 [infection questionnaire], questionnaire 3 [complementary questionnaire], and a dietary questionnaire), and clinical health examinations with an oral health examination, functional capacity tests, and laboratory measurements. Further information about the Health 2000 Survey is available from the methodology report by Heistaro (2008).

4.1.2 The Follow-up Study on Finnish Adults’ Oral Health

After the implementation of the dental healthcare reform in Finland in 2001 and 2002, the THL collaborated with the Social Insurance Institution of Finland (KELA) to investigate the effects of this reform. For this purpose, they conducted a series of

units, which included fewer than 15 participants, were excluded, which resulted in a final sample of 1,248 subjects. These subjects were invited to a follow-up clinical oral health examination in 2004, similar to the one conducted in the Health 2000 Survey.

Of those, 1,049 (84%) agreed to participate.

4.1.3 The Health 2011 Survey

In 2011, a follow-up to the Health 2000 Survey, namely the Health 2011 survey, was conducted in Finland. The follow-up survey was quite similar to the baseline survey. All the participants of the Health 2000 Survey who were residents of Finland and had given their consent to participate in follow-up studies were invited in this follow-up survey. Of the sample of 7,964 adults who were 30 years or older in 2000, 5,806 (73%) subjects participated in at least one part of the survey, and 4,218 (53%) subjects participated in the health examination. However, a clinical oral health examination was conducted in only two of the five hospital districts of the Health 2000 Survey due to limited resources. Hence, 3,689 subjects were invited for clinical oral examinations, and 1,496 (41%) subjects participated. More information on this follow-up survey is available in the Health 2011 methodology report (Lundqvist &

Mäki-Opas, 2016).

4.1.4 Study samples (Studies I‒IV)

This dissertation includes four studies: two cross-sectional and two longitudinal.

The two cross-sectional studies were based on the Health 2000 Survey (studies I−II).

One of the longitudinal studies was based on the data from the Health 2000 Survey and the Follow-up Study on Finnish Adults’ Oral Health (study III). The other longitudinal study included data from the Health 2000 Survey and the Health 2011 Survey (study IV). Table 2 shows the details of studies I−IV. Figure 5 shows the origin of the datasets for all the studies (I‒IV). The basic characteristics of the study population are presented in Table 3.

Participants who took part in clinical oral examination in the Health 2000 Survey (n=6,335)

icipants aged ≥30 years invited to health examination in the Health 2000 Survey (n=8,028) Participated in clinical oral examination in the Health 2011 Survey (n=1,496) Periodontal health: Participants with at most two adjacent teeth with deepened (≥4 mm) periodontal pockets in 2000 (n=540)

Periodontal health: Participants with no teeth with deepened (≥4 mm) periodontal pockets in 2000 (n=383) years, etic, dition ed

Participated in clinical oral examination in the Follow-up Study on Finnish Adults' Oral Health 2004 (n=1,049) Periodontal health: Participants with no teeth with deepened (≥4 mm) periodontal pockets in 2000 (n=365)

Periodontal health: Participants with at most two adjacent teeth with deepened (≥4 mm) periodontal pockets in 2000 (n=519) Exclusions: diabetes or rheumatoid arthritis in 2000, missing pocket data at follow-up Study III: Dataset I (Outcome variable as count) (n=307) Study III: Dataset II (Outcome variable as dichotomous) (n=432) Exclusions: diabetes or rheumatoid arthritis in 2000, age >65 years in 2000, and missing alcohol data in 2000/2011 Study IV: Dataset I (Outcome variable as count) (n=362) Study IV: Dataset II (Outcome variable as dichotomous) (n=507)

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. Characteristics of the studies (I–IV). dy Study participants ExposureOutcome Covariates and Regression models ectional A subsample of the Health 2000 Survey, consisted of dentate, non-smoking Finnish adults aged 30−65 years whounderwent periodontal examination duringthe Health 2000 Survey (n=3,059). Supplementary analyses were performed with identical restrictions except inclusion of both smokers and non- smokers (n=4,319).

Amount (g/week) (continuous) Amount (g/week) (categorical): 0; 0.1−23.8; 23.9−79.4; 79.51303.5 Frequency: Never; Seldom; Often Alcohol use over the risk limit: No; Yes.

Number of teeth with deepened(≥4 mm) periodontal pockets (count)

Age(continuousand categorical), gender, level of education, presence ofdentalplaque, toothbrushing frequency,dentalattendance pattern,BMI (continuous),use of lipid-lowering drugs and NSAIDs, diabetes and total number of teeth (log form). Zero-inflated negative binomial regression model. ectional A subsample of the Health 2000 Survey, consisted of dentate, non-diabetic Finnish adults aged 3065 years whounderwent periodontal examination duringthe Health 2000 Survey (n=4,294)

Average wine intake during the last month: Not at all; < 1 glass (8–12 cl) a week; 14 glasses a week; 0.53 bottles a week; 35 bottles a week; >5 whole bottles a week. Average spirit intake during the last month: Not at all; < 1 glass (4 cl) a week; 16 glasses a week; half a bottle 2 half-liter bottles; 2 half-liter bottles to 4 half-liter bottles; 4 half- liter bottles or more Average beer/cider/long drinks intake g/week during the last month (continuous) Average beer/cider/long drinks intake g/week during the last month: 0; 23.8; >23.8 Frequency of intake of each beverage during the last 12 months wine; spirits; beer/cider/long drinks: Never; about once a month to once/twice a year; a couple of times a month to once a week; 2–3 times a week; 4–7 times a week Serum gamma-glutamyltransferase level (continuous) Number of teeth with deepened(≥4 mm) periodontal pockets (count)

Age (continuous),gender, level of education,presenceofdental plaque, toothbrushing frequency, dentalattendancepattern,BMI (continuous),use oflipid-lowering drugs and NSAIDs,smoking,C- reactive protein, and total number of teeth (log form). Zero-inflated negative binomial regression model. Table 2. Continues

clinical oralhealth Survey and the Follow- l Health, , did not have diabetes e periodontally healthy m) periodontal pockets d (≥4 mm) periodontal e than one tooth or two 2) Amount (g/week) in 2000 (continuous) Amount (g/week) in 2000 (categorical): 0; 0.1−30.8; 30.9−105.3;105.4 Frequency of alcohol use in 2000: Never; Seldom; Often Alcohol use over the risk limit in 2000: No; Yes.

Dataset I Number ofteeth with deepened(≥4 mm) periodontal pockets (count) DatasetII Deepened (≥4 mm) periodontal pocket in atleast two non- adjacentteeth (dichotomous)

Baseline (2000)covariates:Age (continuous),gender, level of education,presenceofdental plaque, toothbrushing frequency, dentalattendancepattern,BMI (continuous),use oflipid-lowering drugs, smoking, and total number of teeth (log form). Dataset I: Negative binomial regression model Dataset II: Poissonregression model with robust variance estimator clinical oralhealth Survey and the Health s or older, did not have , and were periodontally m) periodontal pockets d (≥4 mm) periodontal than one tooth, or two 7)

Amount of alcohol use (g/week) in 2000, (continuous) Amount of alcohol use (g/week) in 2000: 0; 0.1–18.9; 19.0–76.8; >76.8 Frequency of alcohol use in 2000: Never; about once a month to once/twice a year; a couple of times a month to once a week; 2–3 times a week; 4–7 times a week Frequency of use of each beverage during the last 12 months in 2000 wine; spirits; beer/cider/long drinks: Never; about once a month to once/twice a year; a couple of times a month to once a week; 2–7 times a week Dataset I Number ofteeth with deepened(≥4 mm) periodontal pockets (count) DatasetII Deepened (≥4 mm) periodontal pocket in atleast two non- adjacentteeth (dichotomous)

Age in 2000 (continuous), gender, level of education in 2000, presence ofplaquein2000and 2011, toothbrushing frequency in 2000 and 2011, dentalattendancepattern bothyears,bodymass index (continuous) in 2000 and change in BMI from 2000 to 2011, use of lipid- lowering drugs in 2011, smoking in 2011, and log formofnumber of teeth in 2011 (offset variable). Dataset I: Negative binomial regression model Dataset II: Poissonregression model with robust variance estimator matory drugs.

4.2 VARIABLES

4.2.1 The assessment of periodontal condition

Trained and calibrated dentists, with the assistance of a dental nurse, conducted almost similar clinical oral examinations during the Health 2000 survey, the Follow-up Study on Finnish Adults’ Oral Health, and the Health 2011 Survey. The clinical examination was performed using a fibre-optic light (Novar), a fibre-optic headlamp (Tekmala), a mouth mirror, and a WHO periodontal probe (Plandent, nro. 19577) with a probing force of 20 g (calibrated using a letter scale) in a portable dental treatment unit (Dentronic Mini-Dent®, Planmeca) with a portable chair. The total number of teeth was checked and recorded during the clinical oral health examinations. If the subjects had at least one natural tooth observed during the clinical oral examination, they were considered dentate.

The participants’ periodontal condition was assessed by measuring the periodontal pocket depth on four sites per tooth (distobuccal, midbuccal, midpalatal/lingual, mesiopalatal/lingual), except for third molars and tooth remnants. The deepest pocket depth for every tooth was recorded as follows: no pathologically deepened periodontal pocket; periodontal pocket with a depth of 4−5 mm; and periodontal pocket with a depth of ≥6 mm. In the analyses, the periodontal pocket depth of 4‒5 mm and ≥6 mm were combined in one category as periodontal pocket depth of ≥4 mm. In the Health 2000 Survey, the inter-examiner and intra-examiner reliability were assessed for pocket measurement, which showed a percentual agreement of 77% between examiners (k-value of 0.41), and repeatability showed a k-value of 0.83 (Vehkalahti, 2004).

For the cross-sectional studies (studies I−II), the number of teeth with deepened (≥4 mm) periodontal pockets (a count variable ranging from 0 to 28) was the outcome variable. For the longitudinal (incidence) studies (studies III−IV), participants were considered periodontally healthy if they had no teeth with deepened (≥4 mm) periodontal pockets (Dataset I); or alternatively, if they had ≤1 tooth with deepened (≥4 mm) periodontal pockets or two adjacent teeth with deepened (≥4 mm) periodontal pockets (Dataset II). At follow-up (2004 [study III] and 2011 [study IV]), outcome variables were defined as follows: a count variable—the number of teeth with deepened periodontal pockets at follow-up (Dataset I); and a dichotomous variable—the presence of deepened periodontal pockets in at least two non-adjacent teeth at follow-up (Dataset II).

4.2.2 Alcohol use measures

Information about participants’ alcohol use was collected through a self-report questionnaire during the Health 2000 Survey and the Health 2011 Survey. The questionnaire comprised items such as the amount of alcohol consumed, the frequency of alcohol intake, the maximum amount of alcohol consumed on one

occasion during the last 12 months, and the frequency and the amount of intake of different alcoholic beverages (for example, wine, spirits, and beer/cider/long drink).

The amount of alcohol use (g/week) in 2000 was calculated based on the participants’ responses about their last months’ average amount of the intake of different alcoholic beverages (wine, spirits, and beer/cider/long drink) per week.

These responses were pooled together after converting them to alcohol (g/week), assuming that wine contains 13%, spirits 44%, and beer 4.5% of alcohol. The alcohol use (g/week) variable was used as a continuous and a categorical variable in studies I, III and IV. In study I, the categories were as follows: 0; 0.1−23.8; 23.9−79.4; and 79.5−1303.5 g/week. Likewise, in study III, alcohol use was categorized into equal quartiles of alcohol consumed: 0; 0.1–30.8; 30.9–105.3; and ≥105.4 g/week. In study IV, alcohol use (g/week) was categorized as: 0; 0.1–18.9; 19.0–76.8; and >76.8 g/week. In addition to alcohol use (g/week) in 2000, alcohol use (g/year) in 2011 was used as a continuous variable in study IV.

Additionally, the average beverage-specific intake per week during the last month for each beverage was used as an explanatory variable in study II. The participants reported their intake, and this was converted into average g/week by the THL, according to the portion conversions used at the time of the survey. The average wine intake per week during the last month was recorded as: not at all; less than one glass (8‒12 cl); 1‒4 glasses; from 0.5‒3 bottles; 3‒5 bottles; and >5 whole bottles.

Answer options for spirit intake per week during the last month were as follows: not at all; < 1 glass (4 cl); 1‒6 glasses; half a bottle‒2 half-liter bottles; 2 half-liter bottles−4 half-liter bottles; and ≥4 half-liter bottles. The average weekly intake of beer/cider/long drinks during the last month was recorded in terms of the number of bottles: not at all; and the number of bottles. This variable was used as a continuous

Answer options for spirit intake per week during the last month were as follows: not at all; < 1 glass (4 cl); 1‒6 glasses; half a bottle‒2 half-liter bottles; 2 half-liter bottles−4 half-liter bottles; and ≥4 half-liter bottles. The average weekly intake of beer/cider/long drinks during the last month was recorded in terms of the number of bottles: not at all; and the number of bottles. This variable was used as a continuous