Background: Acute cardiac and cerebrovascular accidents are more frequent in hypertensive subjects with a family history of acute vascular accidents. The mechanisms underlying the susceptibility to vascular disease in these subjects are unknown. We investigated whether a parental history of premature heart attack or stroke in hypertensive subjects is associated with abnormalities of sodium handling.
Methods and results: Patients with mild, uncomplicated essential hypertension were divided into two subgroups according to family history: a subgroup with a parental history of premature heart attack or stroke (FV+, n = 18) and a subgroup with a family history completely negative for vascular accidents (FV-, n = 14). The two subgroups were comparable with respect to age, weight, sex distribution, blood pressure, duration of hypertension, cardiovascular risk factors, renal function, and organ damage. Baseline plasma renin activity (PRA), concentrations of aldosterone (PA), atrial natriuretic factor (ANF), and norepinephrine, and urinary electrolyte excretion were also comparable in the two subgroups. Despite these similarities, the responses to an acute saline load, measured under controlled metabolic and experimental conditions, were different in the two subgroups. In the FV+ subgroup at 60 minutes of saline load, PRA fell by 1.0 +/- 0.2 ng/ml/hr and PA concentration by 89.4 +/- 26 pg/ml and ANF concentration increased by 38 +/- 9 pg/ml, whereas in the FV- subgroup the corresponding responses were -2.3 +/- 0.3 ng/ml/hr (p less than 0.005), -190 +/- 43 pg/ml (p less than 0.05), and 80 +/- 13 pg/ml (p less than 0.005), respectively. Urinary sodium excretion was delayed in the FV+ subgroup (270 +/- 67 mu eq/min at 60 minutes) compared with the FV- subgroup (555 +/- 157 mu eq/min at 60 minutes, p less than 0.05). At 120 minutes of saline load, significant (p less than 0.005) differences in PRA and ANF concentration were still observed. In a control group of eight normal subjects the responses to a saline load were comparable to those in the FV- subgroup but greater than those in the FV+ subgroup at 60 minutes.
Conclusions: These results provide evidence that the hormonal and renal adjustments to an acute salt load are impaired in hypertensive patients with a parental history of vascular accidents. We speculate that abnormalities of sodium handling may represent markers of a more rapid development of vascular injury in human hypertension.