Psychosocial and work stress, socioeconomic status, and environmental health directly impact the onset and progression of cardiovascular diseases, irrespective of sex or conventional cardiovascular risk factors (cCRFs). On the other hand, the impact of cCRFs on health-related quality of life (HRQoL) is not well known, and the psychological socioeconomic environmental somatic health interaction is often neglected. Accordingly, we aimed to: (i) compare the self-reported HRQoL using the WHOQOL-BREF questionnaire between healthy subjects and those with cCRFs; and (ii) evaluate the interplay between HRQoL, cCRFs, and cardiovascular treatment adherence. We prospectively included 90 working adults (46 healthy and 44 with cCRFs age- and sex-matched adults) evaluated by clinical examination, 12-leads electrocardiography, and transthoracic echocardiography as part of a cardiovascular diseases screening program, that also filled in the WHOQOL-BREF questionnaire. Subjects with CRFs were less satisfied with their own individual health. The presence and the number of CRFs, as well as the need for cardiovascular treatment and the number of drugs taken correlated with reduced scores at the majority of HRQoL domains. The results in the social relationships domain were the best predictor of cardiovascular treatment adherence. Finally, the results of all HRQoL domains were strongly correlated to each other demonstrating the psychological socioeconomic environmental somatic health interaction.