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RESEARCH PRODUCT

Exercise as the master polypill of the 21st century for the prevention of cardiovascular disease

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To the Editor,The growing pandemic of cardiovascular diseases (CVD) has para-doxically paralleled advances in pharmacology, and CVD remains theleading cause of death worldwide. Therapeutic strategies aiming atcontrolling several CVD risk factors simultaneously in individualswithout evidence of CVD are expensive and difficult to implement.Thus, the development of fixed-dose drug combinations of antiplatelettogether with blood pressure (BP) and cholesterol-lowering drugs,i.e., polypills, is gaining attention to prevent CVD [1,2] and all-causemortality [3], even after an acute coronary syndrome [4]. Despite thepotential of polypills to increase adherence at a lower cost [5], peoplerandomized to this therapy are 20% more likely to report an adverseevent compared with those receiving placebo, single-drug therapy, orusual care [6]. Further, the association of polypills with lower all-causemortality or CVD events is still uncertain [5]. Yet the evidence that reg-ular exercise and one of its main consequences, high cardiorespiratoryfitness (CRF), are associated with reduced rates of all-cause and espe-cially CVD mortality is irrefutable [7].Exerciseis available atlow costand relatively freeof adverse events[8]. Exercise interventions, especially endurance activities (jogging,brisk walking), have drug-like effects on CVD risk factors, particularlyinreducingsystolicBPandLDL/totalcholesterol[8].Anadditionalexer-cise benefit that further decreases CVD risk (together with the risk ofother major diseases, particularly multiple cancer types) and cannotbe achieved by drug therapies is a significant decrease and increase inadiposity and CRF, respectively [8,9]. Rates of tolerability/adherenceseem to favor exercise interventions vs. most drugs, with an averagedropoutfromtheexerciseprogramsof10%[9].Further,exercisecande-crease CVD risk beyond traditional risk factors, notably by attenuatingaging autonomic dysfunction [8].Exercising muscles can produce several hundred secreted factors,collectively known as ‘myokines’. These molecules travel through thebloodstream to tissues where they exert beneficial drug-like effectsbut without adverse effects. For instance, secreted protein acidic andrich in cysteine (SPARC) can inhibit colon cancer proliferation, muscle-released interleukin-6 can promote a healthy anti-inflammatory milieuand improve glucose homeostasis or irisin can induce thermogenesisin adipocytes [8].Advances in cardiovascular medicine are welcome and in fact ur-gent. Ongoing research might hopefully show that polypills representa step forward in CVD prevention. But why not putting more emphasison exercise interventions? Starting from medical schools, physiciansshould be taught to prescribe exercise, that is, the right dosage foreach individual.Conflicts of interestsThe authors declare that no conflicts of interest exist.References