In Normotesive Salt Sensitive Subjects, Insulin Resistance Is Associated to Future Hypertension. A 3 Year Follow-Up Study

Objective: Salt sensitive hypertension (SS) is associated to insulin resistance even in lean individuals. However, no data has been shown in normotensive offspring of hypertensive salt sensitive parents. In a 3 year follow-up, we evaluated in normotensive SS or salt resistant (SR) offspring of hypertensive parents (offSS-HT or offSR-HT, respectively), the frequency to develop hypertension. In addition, a complete metabolic panel was performed in both groups, as well as urinary albumin excretion and creatinine clearance was calculated, as markers of kidney function. Design and method: 43 offSS-HT (29±2 years; 20 female), and 36 offSR-HT (26±2 years; 16 female) were followed-up for 3 years. Both groups were considered lean with a BMI Higher than 25kg/m2 and a waist circumference Greater than 98 cm in males or <105 cm in females). Creatinine clearance (CrCl), 24h urinary albumin excretion, Glycemia and insulinemia before and after 60 and 120 min a glucose overload (75 g; OGTT) was measured at baseline. The area under the curve (AUC; mg/dl.min) and the HOMA index (fasting glucose (mg/dl) × fasting insulin (μU/ml)/405),were also calculated. Blood pressure (BP) and 24h urine sodium excretion were measured each year. Results: Blood pressure rose significantly, after 3 years in offSS-HT (11.5±4.27/9.5±3.3mmHg) compared to offSR-HT, (-0.3±2.8/-0.9±3.6; p<0.0001). In offSS-HT, UAE was significantly higher (53±3μ.min, p<0.01) than in offSR-HT.(12±4μ.min) At baseline fasting, 60 min and 120-min, glycemia and insulinemia post OGTT were higher in offSS-HT(140.1±18; 130±15 mg.dl and 31.8±11; 31.8±11 IU) than in offSR-HT (116.5±5: 6.5±3 mg.dl and 18.8±7; 21.3±4IU, p<0.01). Glycemia AUC was significantly higher (258.80±25mg/dl.min) in offSS-HT compared to offSR-HT (194.39±6mg/dl.min, p<0.0001). Similarly, HOMA-IR was higher in offSS-HT (3.26±1.36; p < 0.002) than in offSR-HT (1.52±0.27). In offSS-HT the CrCl was significantly higher (136±8 ml.min; p<0.05) than in offSR-HT (107±6 ml.min). Conclusions: In offSS-HT blood pressure rise was associated to insulin resistance and glomerular hyperfiltration suggesting a familiar aggregation and a higher cardiometabolic risk when compared with offSR-HT.