Almost 30 years ago, a series of epidemiological studies popularized the early programming theory that had resulted from observed associations between low birthweight and increased cardiovascular morbidity and mortality later in life. Since then, several clinical and experimental models have been created to understand the principles and mechanisms of this fascinating phenomenon and describe its relevance to the pathophysiology of cardiovascular and many other chronic diseases. Despite the growing body of published evidence, the specific mechanisms mediating early programming effects are still elusive. Moreover, many controversial issues have arisen regarding the characteristics of the most commonly used clinical and experimental models, the existence of potential windows of susceptibility for different organs, and the presence of sex differences in its pathophysiology. Therefore, this review synthesizes some of the antecedents behind the early programming theory and discusses some of the controversial issues surrounding it. Early programming has been extensively linked to several chronic diseases; however, for the purposes of this review we have concentrated on the potential role of this entity in the pathophysiology of chronic cardiovascular diseases.
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