>> The interaction of genetic susceptibility, learned health-relevant behavior, formative life events and external circumstances such as noise or emissions influence the risk of many diseases. The increasing availability of data from large cohort studies and registries describing the genome, specific organ functions and potentially modifiable behaviors will allow more precise and individualized risk assessment for the development of common diseases in the near future. In addition to individualized treatment of patients, the analyzes also enable stratification of preventive measures (1, 2). Particularly for slowly and chronically developing cardiovascular “common diseases” – such as coronary heart disease, heart failure or atrial fibrillation – stratified prevention offers the chance of significantly reducing the number of those affected.
The basis for stratified prevention are well-known principles
Truths: Behaviors for a healthy life have been described since the Middle Ages, which - supplemented by nicotine abstinence - have been scientifically recognized for many years and based on numerous studies (text box) (3).
The discussion about the legal framework in which these behavioral recommendations should be implemented focuses on information, e.g. B. in the form of warnings or so-called health traffic lights on food (4). The legal questions become more difficult when the legislature tries to encourage people to take preventive measures without using regulatory law and often without making those affected aware of it (“nudging”) (5), for example through legal requirements, sweets and alcohol in supermarkets to avoid purchasing. Exaggerations that violate the rule of law would be subliminal advertising or other manipulative measures by the public sector for a healthier life and - from a regulatory perspective - Gottfried Wilhelm Leibniz's “health confession” (6, 7).
The “preventive self”
Above all, the improvement of nutrition and hygiene, the development of antibiotics and the introduction of vaccination programs in the 19th and 20th centuries led to a significant increase in life expectancy and a change in the spectrum of diseases (“epidemiological transition”) and the causes of death (8th century). ). Cancer and cardiovascular diseases are the leading causes of death in industrialized countries. At the same time, maintaining one's own health plays a greater role: society develops and demands a “preventive self” (9). Although the social consequences of this trend await further analysis, the goal is a longer and healthier life and thus also a right to knowledge to support potential threats. However, the normative conclusion that individuals must implement this knowledge into prevention practices cannot be derived from this knowledge.
Health and illness are to be understood in a continuum, within which boundaries are often easiest to define at the extremes - certainly healthy or sick - but difficult to define in transition. This is illustrated by over 40 years of salutogenesis research, which includes: was initiated by the WHO's broad definition of health. The reality of the disease is shaped by the biological etiology of the disease and the quantifiable consequences of the disease, but also by the subjective experience of the disease and the social perception of the disease. The general behavioral recommendations (text box) already show the importance of protective factors on the one hand and risk factors on the other. They target behaviors that help maintain or improve health status. Findings that enable more accurate descriptions of disease risk further transform the classic but difficult-to-maintain dichotomy of “healthy” and “sick” into a fluid scale on which people are assigned a predictably low or high risk of physical or psychological harm . Knowledge of one's own risk or that of others opens up new approaches to targeted disease prevention, but can also have negative consequences if fear and uncertainty, even damage to health and unequal treatment arise.
Information as central
Prevention tool
The concern of prevention and the sensible general behavioral measures are recognized (text box), but their implementation is associated with numerous difficulties. The reasons for this often lie in a lack of motivation to change behavior, a lack of education, predetermined or learned behavior patterns and habits, the family living situation, the wider social environment or the peer group, which can maintain or reinforce health-endangering behavior (10). In addition, there is an information environment that is not influenced by health interests, for example through advertising communication via mass media and increasingly via digital “social media”. Accordingly, a right to correct information and knowledge about prevention must be emphasized if a free, individual decision regarding prevention based on knowledge and will is to be made possible. Is the resulting information mandate currently being fulfilled? Effective and continuous information about the essential options for maintaining one's own health, combined with a social consensus that everyone bears responsibility for one's own health, could help here. Experience to date suggests that suppressing (mis)information (e.g. by restricting advertising) is less effective.
The Conference of Ministers of Education passed a recommendation on “Health Education in Schools” in 1979 and further developed this into the “Recommendation on Health Promotion and Prevention in Schools” in 2012. However, the responsibility does not only lie with school education, as the reality of life and behavior are strongly influenced in the extracurricular area and health promotion is a lifelong process. What should be emphasized here is that digital technologies (Internet, smartphones, social media, the digital “measurement of the self”) are firmly anchored in modern everyday life and have the potential to reach target groups that are more remote from prevention. Context-dependent assistance could be provided and the effectiveness of information measures could also be monitored and optimized. Quality assurance and a multi-channel communication architecture with individualized preparation are important for the credibility and success of such information. It is also conceivable to use biofeedback based on e.g. B. to integrate smartphone data or fitness trackers (11). It is also advisable to continually improve information campaigns based on evidence (12).
Stratified cardiovascular medicine
The prevention and treatment of cardiovascular diseases have improved significantly in recent decades. Cardiovascular mortality has decreased measurably across the population. Progress has also been made in describing disease mechanisms and developing and validating therapies targeted to these mechanisms in controlled clinical trials. This is one of the reasons why life expectancy in Germany has continuously increased (13). Half of this increase in lifespan is attributed to prevention, and about the other half to better treatment of patients with cardiovascular diseases, with smooth transitions between prevention and therapy. However, these successes have triggered an “evidence spiral” (14): ever larger studies are required to demonstrate the additional benefit of new measures and new treatments. But these slow down and make the development of new drugs and interventions more expensive. The effort involved in approving new forms of treatment, which is justified by greater patient safety, is already sometimes leading to cardiovascular research programs being reduced or canceled (15). In addition, there is an almost paradoxical incentive to test and approve new stratified treatments for patients, even though the newly chosen therapy does not appear to be ideal - one of the reasons for "late phase failures" in the development of cardiovascular drugs (15). Given the significant cardiovascular morbidity and mortality in Europe, these developments should be criticized. Different pathomechanisms also cause similar chronic cardiovascular diseases, such as heart failure or atrial fibrillation. This pathophysiological heterogeneity has led to the demand for a new disease taxonomy, e.g. B. is based more on disease mechanisms than on their clinical manifestation (for atrial fibrillation exemplified in (16)). The causes of disease, which can be described by genomic and biomedical differences as well as the social context, enable targeted prevention measures. Therefore, agility in the thinking and actions of academic cardiology, cardiovascular industry partners and research funders is required. The European Medicines Agency (EMA) and the Food and Drug Administration (FDA) have already begun to adapt the requirements for the approval of new drugs to these concepts. However, the classic scientific approach to gaining knowledge - evidence of association of characteristics with disease manifestations, identification of disease mechanisms and subsequent controlled intervention studies - can also be applied to stratified treatment and prevention concepts. Possible risks must be taken into account.
Institutional framework for prevention
Medical prevention occurs in the area of tension between self-determination and external determination, between freedom and the obligation to take precautions. In a free, constitutional state, this tension is resolved primarily through fundamental rights. The individual's decision as to whether and how to participate in prevention is protected by civil liberties. State coercion for prevention is fundamentally contrary to fundamental rights and therefore unconstitutional. Private coercion, such as that imposed by insurance companies or an employer, must generally be prevented by the state. The public sector is obliged to protect the individual's right to self-determination. But that by no means means that the state should not or should not promote prevention. Health is a valuable asset. It develops a transcendental meaning because it is a prerequisite for a self-determined life. In addition to the requirement to respect the space for free self-determination, there is also the constitutional mandate to promote and protect the health of the individual through information, education and immediate assistance. These and comparable measures sometimes enable the free individual to take responsibility for prevention or to decide against it.
In the German health system, which is characterized by its federal diversity, various actors with their specific responsibilities seek to fulfill the broad educational and information mandate, which is also emphasized in constitutional law, such as the Federal Center for Health Education (a specialist authority within the scope of the Federal Ministry of Health) and the Public Health Service , general practitioners and specialists, associations and initiatives as well as the providers of statutory health, nursing care, accident and pension insurance. The Prevention Act ( PrävG ) obliges the social insurance providers in the area of health care, above all the health insurance companies, to develop a “national prevention strategy” in which numerous bodies at the federal, state and local level participate. In 2016, the National Prevention Conference adopted nationwide cross-agency federal framework recommendations for health promotion in living environments and companies for the first time. The health insurance companies' recently launched innovation fund also enables the implementation and evaluation of novel prevention approaches. Even if the state and health insurance companies in particular are promoting this development, it is unclear whether better prevention of chronic diseases will reduce or increase costs and expenses in the health system (14). In any case, these measures are justified primarily by the benefits for the population, not by the economy.
In response to the development of stratified medicine and - sometimes unconsciously - also the prevention specified in this sense, the legal system then emphasizes the existing need for research when preventive model projects are planned. In addition to general health promotion, primary prevention, secondary prevention and tertiary prevention measures are legally recognized. With a few exceptions such as B. Apart from vaccinations, the content of “[primary prevention and health promotion” (as the heading to Section 20 SGB V) is not legally defined. The individual health insurance company determines which specific measures are meant (see Section 20 Paragraph 1 Sentence 1 SGB V). Model projects (§ 20g SGB V) will often generate the knowledge that is currently missing in the area of primary prevention. For the first time, the Innovation Fund is introducing an application and evaluation process for the implementation of such projects by individual health insurance companies. It should be noted critically that the current model projects are not sufficiently scientifically evaluated. Overall, the current forms of general information and education are not sufficient to ensure truly precise prevention.
The gain in knowledge that enables stratified prevention is accompanied by justified concern about the “transparent person” whose behavior becomes predictable and manipulable (4, 5, 6). Further potential threats to individual freedom and integrity include cumulative restrictions if preventative measures are not taken, the lack of recognition or implementation of a health-promoting right not to know, and the unwanted danger from misdiagnosis and overdiagnosis, which is particularly important in low-risk areas are. Precise insights into individual performance and specific health risks must be reconciled with the constitutional right to equal rights and obligations for all citizens. In extreme cases, the state may be required to maintain equality. The legal starting point and the overall guiding principle is the self-responsible, informed citizen.
Legally limited possibility of consent to research projects
Better information, the model projects under social insurance law, the prevention strategy of the new Prevention Act and overall knowledge of the opportunities and risks of stratified prevention underline the broad interdisciplinary research mandate. The legal framework for the necessary research should be improved through research consent or authorization. The subject's consent to participate in a research project is a central expression of his or her self-determination, which is often guaranteed at the fundamental and human rights level (Art. 2 and Art. 1 GG, Art. 3 Para. 2 EuGRC, Art. 5 Council of Europe Convention on human rights and biomedicine). In contrast to consent to a therapeutic medical measure, the health benefit for the test subject in a research project is uncertain. The essence of research is not knowing in advance what results will be obtained. In addition, new scientific findings may make it necessary to access existing data again for a research purpose other than that originally planned. As research progresses, it may therefore appear sensible to re-examine existing data sets or to change the originally planned course of research, including the methods considered. This is particularly true given the rapid developments in the field of stratified medicine. However, such additions or deviations from the original research plan are not covered by consent to a scientific study and would often require further information and consent from the patient or test subject - which is difficult to do, especially with large amounts of data. There is therefore a need for a new general declaration of consent that enables the person concerned to consent to research as a process, including the re-evaluation and re-examination of the data provided to the researchers: understandable, targeted and graduated. The gradation aims to enable general or only partial approval of the research plans according to a predetermined scheme that can provide for exclusion points. This general consent trusts the researchers and the institutions involved in the research. Participants in a research study are particularly worthy of protection, as individual health benefits often cannot compensate for participation in the trial. The protection of the test subject and the openness of the results of the intended research goal must be reflected in the declaration of consent. The general research regulation (Good Clinical Practice - GCP, International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use - ICH) remains intact. That means,
• that the test subject can generally consent to participation in a research project with only a limited foreseeable research goal that can be determined in the study protocol,
• that consent to the further use of your individual data by third parties requires special consent, which can be obtained in advance
• and that third-party information (genetic analyses) may only be passed on taking into account the interests of those affected (and with the consent of all those involved).

Due to the general consent to participate in the study and the measures associated with it, oral and written information must be limited to the essential circumstances of the study, such as: B. the research objectives, the process, the foreseeable risks and the handling of the data obtained. The declaration of consent must – following this information and, if necessary, a predetermined scheme with exclusion points – enable the person concerned to understand and agree to the process. Unnecessary and overly detailed information sheets and declarations of consent should also be avoided here.
“Governance” of stratified
Research projects and biobanks
The indeterminacy of the approach and results of research requires a defined “governance” of research projects that regulates how research is carried out and how results are treated and communicated. This need for control particularly affects epidemiological data and biobanks. The regulation of biobanks must, on the one hand, protect citizens in their personal rights (Art. 1 Para. 1 in conjunction with Art. Para. 1 GG, Art. 7 f. EuGRC, Art. 8 ECHR) and against genetic discrimination (Art. 3 Para. 1 GG, Art. 21 EuGRC) and, on the other hand, protect biomedical research (Art. 5 Para. 3 Sentence 1 GG, Art. 13 EuGRC) especially with a view to individual and public health (Art. 2 Para. 2 Sentence 1 GG, Art. 35 EuGRC). The starting point for the regulation of biobanks in the Federal Republic is data protection law (Section 2 Paragraph 2 No. 1
GenDG). However, the primary data protection “governance” does not meet the requirements of a differentiated research infrastructure: on the one hand, due to the altruistic donations of many thousands of citizens; on the other hand, with regard to their function to promote individual and public health. This suggests a comprehensive regulatory approach that effectively protects the self-determination of donors, guarantees biobank secrecy, regulates the establishment and operation, access rights and monitoring of biobanks, and provides for rights to refuse to testify in criminal proceedings (17).
The need for more extensive regulation can be illustrated using the example of the donor's right to self-determination: In principle, according to the current understanding, a donation to a biobank must be earmarked for specific research projects as precisely as possible. However, this disproportionately restricts research opportunities with regard to future scientific questions that were not foreseeable at the time of consent. A biobank only fulfills its function as a research infrastructure for the common good if donations “for science” as a whole are also possible. It is not helpful to ban generalized consent with reference to data protection law. Many participants in biobanks are driven by a general desire to “help research.” The general consent corresponding to this will must be legally contained through formal procedures and material standards (“governance”). Through legislation that supports current research developments, citizens can develop the legally justified trust that their generalized consent will be handled responsibly. An effective, research-friendly “research governance” that safeguards fundamental rights must be developed in cooperation between research institutions, ethics commissions and state supervisory and data protection authorities.
Interdisciplinary research assignment
Sufficient exercise and sleep, a balanced diet, little alcohol, avoiding nicotine and dealing with stress appropriately protect your health. This “prevention sextet” has long been recognized. Nevertheless, there is still a need to better follow the guidelines, especially in socially and otherwise defined “areas that are not preventable”. The law relies primarily on information so that the balancing act that characterizes prevention is successful: the space for self-responsible people must be protected and at the same time the health of every person must be protected and promoted. The school mission of health education is rightly emphasized and improved. Extracurricular information campaigns should be increasingly included in the spirit of lifelong learning. In this area too, digital technology allows perhaps a decisive step towards easily accessible, stratified, context-dependent and then evaluated health information that could also reach population groups “remote to prevention”.
The general behavioral recommendations of the “prevention sextet” already blur the already difficult line between illness and health when people who are not “sick” are supposed to change their behavior to maintain health and are classified on a health risk scale. These uncertainties are intensified by stratified prevention: the evaluation of, in particular, broad studies, large biomedical data sets and physiological measurements will in the near future make it possible to better predict individual health risks and draw more precise prevention strategies. This development offers immense opportunities to enable more targeted and better health promotion. However, the premise that medical measures must be tested in large studies with many test subjects to ensure patient safety must be questioned. Because the point of stratified prevention lies in the individualization, which blocks the way to broad studies. Clinical pictures and other findings that lead to medical actions must therefore be defined more narrowly. In response to the development of stratified medicine and - sometimes unconsciously - also of more precise prevention, the legal system rightly emphasizes the general information mandate, but also the need for interdisciplinary research when preventive model projects are planned.
Research is necessarily open, not knowing what results will be achieved. This is particularly true given the rapid developments in the field of stratified medicine. There is therefore a need – as explained – for a new general declaration of consent that enables the person concerned to agree to developing research, including a re-evaluation of data and a change in methods. The current approach to biodatabases, which is primarily characterized by data protection, does not do justice to dynamic science. Here too, general consent should remove barriers to access, but should be legally contained through procedures and material standards. There is a need for effective, research-friendly “research governance” that safeguards fundamental rights.
Stratified prevention offers immense opportunities to prevent diseases in a more targeted, effective and less risky manner. The necessary interdisciplinary research must address these elementary goals, but also the dangers when warnings are rightly given of a “transparent person”, of difficult questions of equal opportunities or of measures that are generally useful medically but in individual cases endanger health. The goal is to develop ethical, effective, evidence-based and fundamental rights-compliant stratified prevention and make it generally accessible. It is uncertain whether such a development will reduce or increase costs in the healthcare system. However, the precise prevention does not primarily pursue economic goals, but rather aims to sustainably serve the health of those affected. <<

Adequate physical activity
Balanced nutrition
Adequate sleep
Moderate alcohol consumption or abstinence from alcohol
Avoiding or balancing stress
Avoiding nicotine

*Prevention working group

include: Gregor Kirchhof, Josef Franz Lindner, Stephan Achenbach, Klaus Berger, Stefan Blankenberg, Heiner Fangerau, Henner Gimpel, Ulrich M. Gassner, Jens Kersten, Dorothea Magnus, Herbert Rebscher, Heribert Schunkert, Stephan Rixen, Paulus Kirchhof. The three members named in the header are the corresponding authors. For the present text, see Dt. Ärzteblatt 2018 Feb. 115 (8): A324 - A327 and Clin. Res. Cardiol. 2018 Mar. 107 (3): 193-200.