© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Cardiac injuries, like heart attacks, drive the secondary pathology with advanced heart failure. In this process, non-resolving inflammation is a prime component of accelerated cardiovascular disease and subsequent fatal events associated with imbalanced diet, physical inactivity, disrupted circadian rhythms, neuro-hormonal stress, and poly- or co-medication. Laboratory rodents have established that splenic leukocyte–directed resolution mechanisms are essential for cardiac repair after injury. Here, we discuss the impact of three lifestyle-related factors that are prime causes of derailed cardiac healing, putative non-resolving inflammation-resolution mechanisms in cardiovascular diseases, and progressive heart failure after cardiac injury. The presented review resurfaces the lifestyle-related risks and future research directions required to understand the molecular and cellular mechanisms between the causes of cardiovascular disease and their related consequences of non-resolving inflammation.