Pathogenesis of Essential Hypertension: New Insights from a Five Year Follow-Up Study of Offspring of Essential Hypertensive Parents

The difficulty in distinguishing between genetic and environmental effects on blood pressure regulation is obvious. Comparative analyses of offspring of essential hypertensive parents (OHyp), who are at genetic risk to develop hypertension, and offspring of normotensive families (ONorm) may provide some insight. As long as OHyp are lean, their blood pressure (BP) usually remains within normal limits. The mechanism(s) transforming this «genetically dysregulated normotension» into hypertension has been unclear. To further address these questions, the course of, and interrelations among body weight, fat distribution and BP in young male OHyp as compared with ONorm were investigated prospectively at an initially lean normotensive stage and after 5 years of follow-up. Left ventricular (LV) mass and diastolic function were also assessed. Initially lean normotensive OHyp have a disparate long term course of central body fat as compared to ONorm. Thus, OHyp are not only genetically prone to develop hypertension, but they also have a particular propensity to accumulate central body fat, even before a distinct rise in resting BP occurs. Conversely, after 5 years, the OHyp had an exaggerated BP response to exercise. This represents another marker that confers them a greater risk of developing future hypertension. Over the 5-year follow-up, compared to matched ONorm, young, initially lean, normotensive male OHyp developed Doppler echocardiographic signs of diastolic dysfunction without a significant increase in LV mass. Signs of diastolic dysfunction were more prominent in the 5 subjects who developed mild hypertension during the 5-year follow-up, suggesting a possible association between higher BP per se, or perhaps a parallel effect of whatever mechanisms are causing BP to rise and diastolic (dys)function.