Scientific Concept of the National Cohort (status ... - Nationale Kohorte

A.2 Scientific background and rationale for study elements
Periodontal disease is one of the most prevalent infectious disorders in adults. A probing
depth of >4 mm, indicating a current periodontal infection, was found in 76.9% of German
adults aged 35–44, and an attachment loss of >3 mm (a consequence of previous infection)
in 95% of the subjects, with 69% of teeth being affected. Applying the Center for Disease
Control (CDC) definition, the prevalence in this age group was 70.9% and 87.4% in adults
aged 65–74 144 . Indeed, dental treatment costs due to this condition amount to 16 billion Euros,
i.e., ~6% of the total expenditures of the German statutory health insurance funds 35 .
Periodontitis, an opportunistic bacterial infectious disease, causes chronic inflammation of
the periodontium, ultimately causing tooth loss (as a clinical disease endpoint). The onset,
severity, and distinct clinical phenotype of periodontitis are mainly influenced by individual
susceptibility and heritability. Besides age and low SES, major risk factors are male gender,
oral hygiene behavior, smoking, obesity, and a genetic predisposition. In addition to tooth loss
as its clinical endpoint, periodontitis is associated with systemic diseases such as diabetes,
CVD, metabolic syndrome, and arthritis 145-153 . Therefore, periodontitis should be understood
as a chronic infectious disease with considerable impact on overall health.
Assessment of periodontal disease:
Examinations and questionnaires (at baseline and during reassessment)
Level 1: Questionnaire (periodontitis)
Tooth count
Collection of saliva samples
Level 2: Oral examination
A.2.3 Intermediate (preclinical) phenotypes and function measurements
As outlined above, most of the aforementioned major chronic diseases can be considered
as distinct clinical endpoints of a disease continuum that begins earlier in life and advances
during a person’s life in conjunction with subclinical alterations. These subclinical alterations
represent intermediate states in the time sequence and biological model of the development
of disease. It is important to assess these intermediate states in a large study such as the
National Cohort for several reasons: First, such an assessment may help to better predict
hard clinical endpoints, and, thus, to identify persons at risk for major disease outcomes, and
some of these factors, particularly those that are downstream on the disease pathway, may
also be taken as symptoms for early disease. Secondly, it is likely that the effect of nongenetic
and genetic risk factors on future disease outcomes may depend on a person’s existing
phenotype (effect modification). Here, again, proper assessment of intermediate phenotypes
may improve risk prediction towards more personalized prevention. Thirdly, by measuring
these intermediate phenotypes repeatedly – as it is planned in the National Cohort – we can
study the nature of subclinical disease progression as well as its predictors and its impact on
major diseases.
A.2.3.1 Cardiovascular functions and preclinical phenotypes
Subclinical atherosclerosis: Evidence indicates that atherosclerosis begins already at an
early age with the accumulation of lipid in the intima of arteries to form fatty streaks 154 . This
atherosclerotic process results rapidly in (subclinical) changes in the structure and function
of the arteries 155 . Noninvasive measurements of subclinical atherosclerotic disease increasingly
are being used for detection disease at an early stage, thereby allowing early stage
treatment and prevention of target-organ damage. Thus, the National Cohort will assess
subclinical atherosclerosis and its precursors by measuring arterial stiffness, ankle–brachial
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