The pace of present-day change is dizzying; rapid evolutions in technology, lifestyle and demographics, burgeoning information, and challenges to our planet surround us. Never before has humankind experienced such immense societal shifts. In the face of so much change, one theme remains constant: the primacy of cardiovascular disease as the number one killer, of both men and women, around the globe. > Plus ca change plus c’est la meme chose This unfortunate reality is not for lack of assiduous effort, and robust success, at taming the acutely lethal manifestations of cardiovascular disease. Indeed, age-adjusted mortality from heart disease has declined a remarkable 75% over the past 50 years.1 This astonishing progress is the result of innumerable advances in our understanding of disease pathogenesis and intervention, culminating in a vast array of advances in prevention, diagnosis, and therapy. Given this degree of success, how is it that heart disease remains the No. 1 killer, still leading in this deadly race? Several developments contribute. For one, we have succeeded in many instances in transforming heart disease from an acutely lethal condition (eg, myocardial infarction–induced sudden death) to a chronic disorder that can be managed for years (eg, heart failure). Furthermore, people are living longer, allowing for lifelong accretion of the insults of cardiovascular stress (eg, hypertension, hypercholesterolemia, diabetes mellitus) and consequent progressive impact on the heart. Finally, spectacular deteriorations in lifestyle, especially the worldwide pandemic of “diabesity”, are an important contributor. Thus, just as society has benefited from significant gains in treating and preventing the acutely lethal effects of atherothrombotic heart disease, the rules of the game have changed, and cardiovascular disease has emerged with new challenges. Never before has there been a time of greater challenge in cardiovascular science and medicine. Never before have we been equipped with such an …