Developmental Origins of Hypertension: Biology Meets Statistics

[摘要] The concept that environmental factors during development—both in utero and in early childhood—can permanently alter the adult phenotype derives from the seminal epidemiologic observations of Professor David Barker (1). He and his colleagues showed in the early 1990s that low birthweight predicted increased risk of cardiovascular diseases, including insulin resistance/diabetes (2–4), obesity (5), coronary disease (6), and, importantly, systolic hypertension (3,7,8). Birthweight was used as a readily available, albeit crude, surrogate for adequacy of fetal growth. While these early observations have now been confirmed in studies around the globe (9,10), the link between birthweight (BirthWt) and systolic BP (SysBP)—both its presence and its significance—has continued to generate controversy (11,12). The typical finding in adults has been an inverse relationship between BirthWt and SysBP (9) that is independent of—but enhanced by—accelerated childhood growth (7). The existence of this relationship in white adults, not always apparent in studies with limited maternal information (12), was recently confirmed in 31-yr-old subjects from a large prospective and broadly annotated North Finland birth cohort (13). While the differences in average SysBP across the birthweight range are typically small, their cardiovascular impact is predicted to be large based on modern hypertension treatment trials (e.g., [14]) and based on a similar inverse relationship of BirthWt and prevalence of clinical hypertension (15). The mechanisms linking BirthWt and adult SysBP are not known, but reduced nephron number (16), fetally programmed activation of the postnatal tissue renin/angiotensin II (AngII) system (17), and enhanced vascular reactivity to pressors (18) and stress (19) have each been implicated.

[学科分类] 泌尿医学

[关键词] Bone marrow necrosis;Sickle cell disease;Hyperhemolysis syndrome