Review: The placenta is a programming agent for cardiovascular disease

Abstract

Cardiovascular disease remains the number one killer in western nations in spite of declines in death rates following improvements in clinical care. It has been 20 years since David Barker and colleagues showed that slow rates of prenatal growth predict mortality from ischemic heart disease. Thus, fetal undergrowth and its associated cardiovascular diseases must be due, in part, to placental inadequacies. This conclusion is supported by a number of studies linking placental characteristics with various adult diseases. A "U" shaped relationship between placental-to-fetal weight ratio and heart disease provides powerful evidence that placental growth-regulating processes initiate vulnerabilities for later heart disease in offspring. Recent evidence from Finland indicates that placental morphological characteristics predict risks for coronary artery disease, heart failure, hypertension and several cancers. The level of risk imparted by placental shape is sex dependent. Further, maternal diet and body composition strongly influence placental growth, levels of inflammation, nutrient transport capacity and oxidative stress, with subsequent effects on offspring health. Several animal models have demonstrated the placental roots of vulnerability for heart disease. These include findings that abnormal endothelial development in the placenta is associated with undergrown myocardial walls in the embryo, and that placental insufficiency leads to depressed maturation and proliferation of working cardiomyocytes in the fetal heart. Together these models suggest that the ultimate fitness of the heart is determined by hemodynamic, growth factor, and oxygen/nutrient cues before birth, all of which are influenced, if not regulated by the placenta.

Figure 1

Hypertension in offspring of short and tall mothers as a function of placental area. Incidence of hypertension according to placental area is divided based upon maternal height (black bars: <160 cm; white bars: >160 cm). Individual bars represent placental area categories. There was a significant relationship between hypertension and placental area in offspring of short mothers (p<0.002) but not tall mothers (p=0.72). Data from Barker et al. [8].

Figure 2

Standardized mortality ratios (SMR) for coronary heart disease for adult offspring of short women (<158 cm) according to maternal BMI at term. Data from Forsen et al. [6].