However, in patients with established HF, their contributory roles to clinical outcomes are para- doxical; that is, patients with HF with diabetes mellitus, obesity, and hypertension usually are associated with better outcomes than patients without those comorbidities individually, making their management targets and treatment reasons quite challenging. Participants in clinical trials receive maximally sup- portive and evidence-based interventions, yet adher- ence to standard guideline-directed HF therapy in real-world patients may be limited by the coexis- tence of chronic HF and comorbid conditions. Self-care strategies are limited by HF itself and these competing comorbidities and usually require coordination and different care models.249,341 Treatment options of these chronic comorbidities in HF are limited and usually without large-scale or definitive clinical trial evidence of improved out- comes in patients with HF. Treatment of these comorbidities may be associ- ated with adverse outcomes resulting from over- treatment or side effects of treatment modalities. It should be kept in mind that even modest changes in the prevention of comorbidities and risk factors for HF can greatly affect the development of and outcomes in HF. These underline the importance of prevention strategies, which probably are the most effective approaches to reduce the burden of HF. Furthermore, in recent years, focus has moved from control of a single risk factor to reducing overall car- Greater benefit may be realized by combining a healthy lifestyle with BP lowering; prevention of diabetes mellitus, insulin resistance, obesity, and ischemic events; and avoidance of cardiotoxic exposure (alcohol, cardiotoxic drugs, and chemotherapy) rather than any single approach Although this approach is likely to be valid, it requires evaluation in well-designed trials. 