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Psychosocial job factors (PJF) have been implicated in the development of cardiovascular disease. The paucity of data from developing economies including Mexico hampers the development of worksite intervention efforts in those regions.This cross-sectional study of 2,330 Mexican workers assessed PJF (job strain [JS], social support [SS], and job insecurity [JI]) and biological cardiovascular disease risk factors [CVDRF] by questionnaire and on-site physical examinations. Alternative formulations of the JS scales were developed based on factor analysis and literature review. Associations between both traditional and alternative job factor scales with CVDRF were examined in multiple regression models, adjusting for physical workload, and socio-demographic factors.Alternative formulations of the job demand and control scales resulted in substantial changes in effect sizes or statistical significance when compared with the original scales. JS and JI showed hypothesized associations with most CVDRF, but they were inversely associated with diastolic blood pressure and some adiposity measures. SS was mainly protective against CVDRF.Among Mexican workers, alternative PJF scales predicted health outcomes better than traditional scales, and psychosocial stressors were associated with most CVDRF. Am. J. Ind. Med. 58:331–351, 2015. © 2015 Wiley Periodicals, Inc.