Genes Complicate the Association Between Birth Weight and Cardiovascular Disease

From the Department of Medicine, University of California San Diego, La Jolla.

Correspondence to Wulf Palinski, UCSD, Department of Medicine 0682, 9500 Gilman Dr, La Jolla, CA 92093-0682. E-mail wpalinski@ucsd.edu

The risk factors of cardiovascular disease (CVD) are thought to be well known, but the  relative importance of nature versus nurture continues to be debated. Although sex, family history, and genetic susceptibility are recognized as playing a major role, most attention has focused on lifestyle risk factors because of the substantial clinical benefits achievable—and achieved—by preventing or treating hypercholesterolemia, diabetes mellitus, hypertension, obesity, and smoking. In addition to genetically determined and postnatal risk factors, during the past 2 decades, developmental programming has emerged as a potential determinant of CVD. The concept that adult CVD is influenced by the conditions encountered by the developing fetus in utero originated largely from the observation by Barker and colleagues 1 that low birth weight was associated with increased CVD. This prompted a flurry of epidemiological studies, the majority of which supported the association of birth weight with CVD and hypertension,2,3whereas the association with type 2 diabetes mellitus remains more controversial.4–6 Later studies highlighted the need to differentiate low birth weight resulting from premature birth from true intrauterine growth restriction and established that the CVD risk is in fact associated with birth weight adjusted for gestational length.7/.../