Developmental Origins of Heart Disease

In 1989 David Barker showed that the risk of dying from ischemic heart disease was inversely related to birthweight in 15,000 English men and women born in Hertfordshire. Those data also showed an upward trend in risk for babies born larger than 9.5 pounds. The process by which prenatal nutritional stress leads to later cardiovascular disease is called “programming” or “the developmental origins of health and disease” and is driven by two mechanisms, structural changes in fetal organs and epigenetic modification of genes related to organ function. Programming begins at conception and continues through the first 1000 days. Poor growth in the womb is associated with detrimental changes in immune function, antioxidant systems and stem cell function. These are manifest as later risk factors including dyslipidemias, hypercoagulability, hypertension and endothelial dysfunction. Recent population data from Helsinki show that maternal body composition and maternal diet in combination with placental structure, predict coronary heart disease, heart failure and sudden death-- the three primary causes of cardiac death. The number of cardiomyocytes and coronary architectural arrangement in the adult heart are determined by oxygen, hormonal and hemodynamic conditions in the fetus. The maternofetal transport of nutrients related to cardiovascular development is sex specific and related to maternal weight gain in early pregnancy and maternal BMI. The sum of the intrauterine environmental conditions, including nutrient and cortisol levels, sets a trajectory for adult onset heart and blood vessel disease, including stroke as a cause of death in large numbers of people around the world.