IJOMEH 2010;23(3) 293 REVIEW PAPERS International Journal of Occupational Medicine and Environmental Health 2010;23(3):293 – 312 DOI 10.2478/v10001-010-0035-2 DESCRIPTION OF A LARGE-SCALE STUDY DESIGN TO ASSESS WORK-STRESS-DISEASE ASSOCIATIONS FOR CARDIOvASCULAR DISEASE ROBERT KARASEK 1,2 , SEAN COLLINS 3 , ELS CLAYS 4 , ALICJA BORTKIEWICZ 5 , and MARCO FERRARIO 6 1 University of Massachusetts Lowell, Lowell, MA, USA Department of Work Environment 2 Copenhagen University, Copenhagen, Denmark Department of Psychology 3 University of Massachusetts Lowell, Lowell, MA, USA Department of Physical Therapy 4 University Hospital, Ghent, Belgium Department of Public Health 5 Nofer Institute of Occupational Medicine, Łódź, Poland Department of Work Physiology and Ergonomics 6 University of Insubria, Insubria, Varese, Italy Department of Experimental and Clinical Biomedical Sciences Abstract We claim that a new level of studies is needed to answer a series of important questions about the expanding global chronic disease burden for cardiovascular disease (CVD) and for related conditions such as diabetes, metabolic syndrome, and obesity. These require a new study design structure, related to a new level of theory that goes beyond the current single-factor, a-theoretic epidemiological studies. This new platform for the design of large-scale Work/Stress/Disease studies would assess CVD-related disease mechanisms in a more general and dynamic form, based on the use of new tools for measuring autonomic functions in an occupational stress context and a new theory of disease causation. A sample outline is presented for such a study, based on Stress- Disequilibrium Theory (SDT) hypotheses, building on analytic tools developed for the assessment of stress-related exhaustion ef- fects and chronic disease risks from Heart Rate Variability (HRV) research studies. The goal is to assess the associations between social organizational risks, particularly at work, and hypertension, metabolic syndrome, and diabetes II. The study design is multi- stage, spanning across several levels of disease-related de-regulation, and addressing co-morbidity of the conditions themselves. The study design is meant to span across a broad social population at all levels and would probably be multi-site, involving several countries, to yield the larger sample increased power for finding associations for work — physiological effects. Key words: Stress, Cardiovascular disease, Low control, Growth and regeneration, Large-scale study design Address reprint request to R. Karasek, Department of Work Environment, University of Massachusetts Lowell, Kitson Hall, One University Avenue, Lowell, MA, USA (e-mail: Robert_Karasek@uml.edu), or Department of Psychology, Copenhagen University, Øster Farinagsgade 2A, DK-1353 Copenhagen K, Denmark. SECTION I. JUSTIFICATION FOR A LARGE STUDY IDEA BASED ON MAJOR UNRESOLVED QUESTIONS There is increasing evidence around the world of a growing chronic disease problem: for example: cardiovascular dis- eases (CVD) are the leading cause of death in the US [1,2] and other industrialized countries, and are fast becoming the major cause of mortality in rapidly industrializing so- cieties such as China. In the US CVD risk factors and re- lated conditions for persons over age 20 are estimated to have prevalence of 34%, 33%, and 34% for hypertension,