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Background: The aim was to investigate the relationship between self-rated health (SRH) in healthy midlife, mortality, and frailty in old age.Methods: In 1974, male volunteers for a primary prevention trial in the Helsinki Businessmen Study (mean age 47 years, n = 1,753) reported SRH using a five-step scale (1 = "very good," n = 124; 2 = "fairly good," n = 862; 3 = "average," n = 706; 4 = "fairly poor," or 5 = "very poor"; in the analyses, 4 and 5 were combined as "poor", n = 61). In 2000 (mean age 73 years), the survivors were assessed using a questionnaire including the RAND-36/SF-36 health-related quality of life instrument. Simplified self-reported criteria were used to define phenotypic prefrailty and frailty. Mortality was retrieved from national registers.Results: During the 26-year follow-up, 410 men had died. Frailty status was assessed in 81.0% (n = 1,088) of survivors: 434 (39.9%), 552 (50.7%), and 102 (9.4%) were classified as not frail, prefrail, and frail, respectively. With fairly good SRH as reference, and adjusted for cardiovascular risk in midlife and comorbidity in old age, midlife SRH was related to mortality in a J-shaped fashion: significant increase with both very good and poor SRH. In similar analyses, average SRH in midlife (n = 425) was related to prefrailty (odds ratio: 1.52, 95% confidence interval: 1.14-2.04) and poor SRH (n = 31) both to prefrailty (odds ratio: 3.56, 95% confidence interval: 1.16-10.9) and frailty (odds ratio: 8.38, 95% confidence interval: 2.32-30.3) in old age.Conclusions: SRH in clinically healthy midlife among volunteers of a primary prevention trial was related to the development of both prefrailty and frailty in old age, independent of baseline cardiovascular risk and later comorbidity. [ABSTRACT FROM AUTHOR]