Search

Objective: We tested whether men and women in the European Society of Hypertension (ESH) high normal and normal blood pressure (BP) categories, all included in the the Seventh Joint National Committee (JNC 7) prehypertension group, share similar metabolic characteristics and whether they differ from men and women with optimal BP (<120/80 mmHg)., Methods: BP (multiple measurements with a standardized automatic device), insulin sensitivity (euglycaemic clamp), oral glucose tolerance test (OGTT), carotid intima-media-thickness (IMT, echo), family history (questionnaire), physical activity (accelerometer), and anthropometrics (bioimpedance) were evaluated in the 1384 healthy European individuals ranging from 30-60 years participating in the multicentre study Relationship between Insulin Sensitivity and Cardiovascular disease (RISC)., Results: BMI and waist-to-hip ratio were higher (both P < 0.05 adjusted for age and recruiting centre) in men and women with high normal (but not normal) BP with respect to optimal BP. Similarly, in women (after adjustment for study centre, age, physical activity, and waist), serum triglycerides and carotid IMT were higher in those with high normal (but not normal) BP; moreover, in this group there was a higher prevalence of glucose-intolerance (21.8 versus 9.7%, P = 0.02) and insulin sensitivity tended to be lower (P = 0.07). Insulin sensitivity and diastolic blood pressure were weakly related variables displaying a nonlinear association with a threshold below the normal BP values and no interaction with family history of hypertension., Conclusion: The JNC 7 category prehypertension identifies a dishomogeneous group of individuals whereas the ESH classification, particularly in women, was more accurate in identifying both the predisease and the healthy phenotype. Insulin resistance is not a major characteristic of the condition of prehypertension.

Background: Retinol-binding protein-4 (RBP4) is a novel adipokine able to modulate the action of insulin in several tissues. A variable degree of insulin resistance characterizes the vast majority of hypertensive (HYP) patients. The aim of this study was to evaluate the relationship between RBP4 and essential hypertension, exploring potential links between RBP4 and other adipokines with some proxies of early vascular damage in female naive HYP patients., Methods: Serum RBP4, leptin, adiponectin, and resistin levels were determined in 35 HYP and 35 normotensive lean women with normal glucose tolerance paired by age and body mass index (BMI) served as controls (CTL); carotid intima-media thickness (IMT) was also measured., Results: A striking difference was observed in RBP4 levels between HYP and CTL with significantly higher levels in the former than in the latter. No relationship was observed between glomerular filtration rate (GFR) and RBP4. Adiponectin levels were slightly but significantly lower in HYP than in CTL, whereas no differences were observed in resistin and leptin concentrations between the two groups of women. In the whole study group, a strong linear relationship was observed between IMT value and both RBP4 (rho = 0.321, P = 0.0076) and resistin (rho = 0.340, P = 0.0048); these two adipocytokines, together with cholesterol, were the only variables independently related to IMT (r(2) = 0.24; P = 0.004) by a stepwise analysis., Conclusions: RBP4 levels are increased in naive HYP women and correlated with the degree of IMT suggesting a participation of this adipocytokine in the modulation of the atherosclerotic process exerted by the adipose tissue as endocrine organ.

Mild-to-moderate hypertension is often associated with insulin resistance and visceral adiposity. Whether these metabolic abnormalities have an independent impact on regional cardiac function is not known. The goal of this study was to investigate the effects of increased blood pressure, insulin resistance, and ectopic fat accumulation on the changes in peak systolic circumferential strain. Thirty-five male subjects (age: 47+/-1 years; body mass index: 28.4+/-0.6 kg m(-2); mean+/-SEM) included 13 with normal blood pressure (BP: 113+/-5/67+/-2 mm Hg), 13 with prehypertension (BP: 130+/-1/76+/-2 mm Hg), and 9 newly diagnosed with essential hypertension (BP: 150+/-2/94+/-2 mm Hg) who underwent cardiac magnetic resonance tissue tagging (MRI) and MRI quantitation of abdominal visceral and epicardial fat. Glucose tolerance, on oral glucose tolerance test, and insulin resistance were assessed along with the serum lipid profile. All of the subjects had normal glucose tolerance, left- and right-ventricular volumes, and ejection fraction. Across the BP groups, left ventricular mass tended to increase, and circumferential shortening was progressively reduced at basal, midheart, and apical segments (on average, from -17.0+/-0.5% in normal blood pressure to -15.2+/-0.7% in prehypertension to -13.6+/-0.8% in those newly diagnosed with essential hypertension; P=0.004). Reduced circumferential strain was significantly associated with raised BP independent of age (r=0.41; P=0.01) and with epicardial and visceral fat, serum triglycerides, and insulin resistance independent of age and BP. In conclusion, regional left ventricular function is already reduced at the early stages of hypertension despite the normal global cardiac function. Insulin resistance, dyslipidemia, and ectopic fat accumulation are associated with reduced regional systolic function.

In normal subjects, insulin decreases the urinary excretion of sodium, potassium, and uric acid. We tested whether these renal effects of insulin are altered in insulin resistant hypertension. In 37 patients with essential hypertension, we measured the changes in urinary excretion of sodium, potassium, and uric acid in response to physiological euglycemic hyperinsulinemia (by using the insulin clamp technique at an insulin infusion rate of 6 pmol/min/kg). Glucose disposal rate averaged 26.6 +/- 1.5 mumol/min/kg, i.e., 20% lower than in normotensive controls (33.1 +/- 2.1 mumol/min/kg, P = .015) In the basal state, fasting plasma uric acid concentrations were higher in men than women (P < .001), were positively related to body mass index (r = 0.38, P = .02), waist/hip ratio (r = 0.35, P < .05), and serum triglyceride levels (r = 0.59, P = .0001), and negatively related to HDL cholesterol concentrations (r = -0.59, P = .0001) and glucose disposal rate (r = 0.42, P < .01). Uric acid clearance, on the other hand, was inversely related to body mass index (r = 0.41, P = .01), plasma uric acid (r = 0.65, P < .0001) and triglyceride concentrations (r = 0.39, P < .02), and directly related to HDL cholesterol levels (r = 0.52, P < .001). During insulin infusion, blood pressure, plasma uric acid and sodium concentration, and creatinine clearance did not change. In contrast, hyperinsulinemia caused a significant decrease in the urinary excretion of uric acid (2.67 +/- 0.12 to 1.86 +/- .14 mumol/min/1.73 m2, P = .0001), sodium (184 +/- 12 to 137 +/- 14 mumol/min/1.73 m2, P = .0001), and potassium (81 +/- 7 to 48 +/- 4 mumol/ min/1.73 m2, P = .0001). Both in absolute terms (clearance and fractional excretion rates) and percentagewise, these changes were similar to those found in normotensive subjects. Insulin-induced changes in urate excretion were coupled (r = 0.55, P < .0001) to the respective changes in sodium excretion. In hypertensive patients, higher uric acid levels and lower renal urate clearance rates cluster with insulin resistance and dyslipidemia. Despite insulin resistance of glucose metabolism, acute physiological hyperinsulinemia causes normal antinatriuresis, antikaliuresis, and antiuricosuria in these patients.

Microalbuminuria in patients with essential hypertension is a marker of incipient glomerular dysfunction and clusters with lipid and hemodynamic abnormalities. Recent evidence has shown that hypertensive patients with microalbuminuria have a hyperinsulinemic response to oral glucose, suggesting the presence of insulin resistance. To directly test this possibility we studied insulin action in two accurately matched groups (n = 10 each) of hypertensive patients with or without microalbuminuria (14 +/- 2 versus 52 +/- 7 mg/24 h-1, mean of three 24-hour collections). In response to glucose ingestion microalbuminuric patients showed slight hyperglycemia (area under the curve, 928 +/- 43 versus 784 +/-19 nmol/L-1/2h-1, P < .02) and a marked hyperinsulinemia (26.8 +/- 3.3 versus 49.8 +/- 3.7 nmol/L-1/2h-1, P < 0.01). Basal arterial blood pressure, heart rate, and forearm blood flow were similar in the two groups and did not change significantly during a 2-hour euglycemic insulin clamp. Insulin-stimulated wholebody glucose uptake was 25% lower in microalbuminuric patients (33.5 +/- 2.5 versus 25.2 +/- 2.1 mumol/min-1/kg-1, P < .02). This difference was entirely due to a 40% reduction in glycogen synthesis (12.9 +/- 1.8 versus 21.3 +/- 3.2 mumol/min-1/kg-1, P < .05) as glucose oxidation was similarly stimulated in the two groups. In contrast there was no difference in the ability of insulin to suppress hepatic glucose production (by approximately 100% at the end of the clamp), to decrease fractional sodium and potassium excretions (by 35%), to lower circulating free fatty acids (by 80%), and to reduce plasma potassium concentrations (by 10%).(ABSTRACT TRUNCATED AT 250 WORDS)