Insulin response to oral glucose load is associated with coronary artery disease in subjects with normal glucose tolerance

AIM: The critical role of hyperinsulinemia, independent of hyperglycemia, in the pathogenesis of atherosclerosis has not been fully determined. We investigated the association between secretion patterns of insulin after oral glucose load and the severity of coronary artery disease (CAD) in patients with normal glucose tolerance (NGT). METHODS: We enrolled 116 subjects with NGT from 243 patients who had undergone coronary angiography and a standard 75-g oral glucose tolerance test. The patients were divided into 0-vessel, single-vessel and multi-vessel disease groups on the basis of the severity of CAD. RESULTS: The 2-h insulin levels in the multi-vessel disease group (p=0.005) and the single-vessel disease group (p<0.05) were significantly higher than those in the 0-vessel disease group. Multivariate analysis revealed that the levels of 2-h insulin were an independent variable for the presence of CAD (p=0.02) after adjustment for gender and the presence of each criterion of metabolic syndrome using the definition of the International Diabetes Federation. CONCLUSION: A slight but significant increase in prolonged insulin secretion, which is associated with the early stage of insulin resistance, in subjects with NGT, may play an important role in the pathogenesis of atherosclerosis.     

Salt loading affects cortisol metabolism in normotensive subjects: relationships with salt sensitivity

We studied cortisol metabolism together with insulin sensitivity [homeostatic model assessment (HOMA)] and renal hemodynamics in 19 salt-resistant (sr) and nine salt-sensitive (ss) normotensive subjects after a low- and high-salt diet. Results are described as high- vs. low-salt diet. Sum of urinary cortisol metabolite excretion (sum(metabolites)) increased in sr subjects (3.8 +/- 1.6 vs. 3.1 +/- 1.1 microg/min per square meter, P < 0.05) and decreased in ss subjects (2.3 +/- 1.0 vs. 2.9 +/- 1.1 microg/min per square meter, P < 0.05). Plasma 0830 h cortisol decreased in sr subjects but did not change significantly in ss subjects. In all subjects, the absolute blood pressure change correlated negatively with the percentage change in sum(metabolites) (P < 0.05) and positively with the percentage change in renal vascular resistance (P < 0.05). Sum(metabolites) during high-salt diet correlated negatively with the percentage changes in plasma 0830 h cortisol (P < 0.05) and renal vascular resistance (P = 0.05). HOMA did not change in either group, but the percentage change in HOMA correlated positively with the percentage change in plasma cortisol (P = 0.001) and negatively with the percentage change in sum(metabolites) (P < 0.01). Parameters of 11 beta-hydroxysteroid dehydrogenase activity were not different between groups and did not change. In conclusion, these data suggest that cortisol elimination is affected differently after salt loading in sr and ss subjects. Changes in circulating cortisol might contribute to individual sodium-induced alterations in insulin sensitivity.     

Insulin sensitivity and calcium homeostasis in young, lean, normotensive male subjects.

Insulin resistance is known to be closely related to essential hypertension. It has been hypothesized that abnormal calcium homeostasis both at the cellular level and in the whole body plays a substantial role in hypertension associated with insulin resistance. We attempted to determine the relationships among insulin sensitivity, blood pressure (BP), body mass index (BMI), and calcium-related parameters in young, lean, normotensive male subjects with extreme susceptibilities to hypertension, and to investigate the effects of euglycemic hyperinsulinemia on calcium-related parameters. Seven young, lean, normotensive male subjects with family histories of essential hypertension and 10 age-matched controls without any parental cardiovascular events were enrolled. Insulin sensitivity measurement by the euglycemic hyperinsulinemic clamp technique and a 75-g oral glucose tolerance test were performed. Calcium-related parameters, including intracellular Ca2+ levels in platelets, were measured simultaneously. Diastolic BP was inversely correlated with insulin sensitivity in vivo (M-value). Insulin sensitivity was inversely correlated with BMI and with intracellular Ca2+ in platelets. In the multivariate stepwise regression analysis using both diastolic BP and insulin sensitivity as dependent variables, BMI was found to be a determinant independent variable. Euglycemic hyperinsulinemia decreased intact parathyroid hormone levels and increased fractional excretion of calcium. In conclusion, BMI rather than a family history of hypertension plays a determinant role on the regulation of diastolic BP and insulin sensitivity even in young, lean, normotensive male subjects with extreme predispositions for the development of hypertension. Hyperinsulinemia decreased intact parathyroid hormone levels and increased fractional excretion of calcium.     

Further evidence that insulin metabolism is a major determinant of peripheral insulin response to oral glucose in subjects with mild glucose intolerance

In mild glucose intolerance plasma concentration of C-peptide seems to give an estimate of pancreatic B cell secretion more reliable than plasma insulin itself. In the present study we measured the plasma levels of insulin and C-peptide after oral glucose load in 100 mildly glucose intolerant subjects, focusing our attention on high and low insulin responders. According to an insulin incremental area after oral glucose higher or lower than the mean +/- SD of the mean, 16 subjects were classified as "high insulin responders", and 17 as "low insulin responders". The two groups were similar for sex, age and bw. Mean insulin incremental area was almost 9-fold greater in high insulin responders than in low insulin responders (0.88 +/- 0.03 vs 0.10 +/- 0.01 pmol/ml min, p less than 0.001). Also mean C-peptide incremental area was significantly greater in high insulin responders than in low insulin responders, but the differences between the two groups were smaller. Indeed, mean C-peptide area was approximately 2.5-fold greater in high insulin responders than in low insulin responders (1.58 +/- 0.12 vs 0.66 +/- 0.07 pmol/ml min, p less than 0.001). These results give further support to the concept that in mild glucose intolerance insulin metabolism is a major determinant of peripheral insulin response to oral glucose load.     

Hyperproinsulinaemia in impaired glucose tolerance is associated with a delayed insulin response to glucose

Summary In subjects with impaired glucose tolerance hyperproinsulinaemia has been shown to be predictive for progression to Type II (non-insulin-dependent) diabetes mellitus. These findings are often interpreted as early indicators of an impaired beta-cell function. The aim of our study was to assess the potential determinants of hyperproinsulinaemia in subjects with impaired glucose tolerance. The study group consisted of 110 subjects, 45–74 years of age with mean 2 h plasma glucose concentrations between 8.6 and 11.1 mmol/l following two oral glucose tolerance tests. Subsequently, the hyperglycaemic clamp technique (10 mmol/l, with a priming infusion of 20 % glucose solution, 150 mg/kg) was used to assess the beta-cell function (time needed to reach the insulin peak) and insulin sensitivity (M/I value: glucose metabolised divided by insulin response, 150–180 min). Results showed that the intact-proinsulin:insulin ratio increased with increasing time needed to reach the insulin peak (0.065, 0.079 and 0.101; time needed to reach the insulin peak ≤ 5 min, 5 to 15 min, > 15 min; p < 0.05). The split-proinsulin:insulin ratio showed a similar association with the time needed to reach the insulin peak. These associations were independent of age, sex, body mass index and waist:hip ratio. In conclusion, this study shows that relative hyperproinsulinaemia is associated with an impaired beta-cell function in a study group of subjects with impaired glucose tolerance selected after two oral glucose tolerance tests. [Diabetologia (1999) 42: 177–180] Received: 5 June 1998 and in final revised form: 5 October 1998     

Salt sensitivity in humans is associated with abnormal acid-base regulation

Metabolic acidosis has recently been observed in rat models of salt-sensitive genetic hypertension. To test the hypothesis that salt sensitivity in humans may be associated with abnormal acid-base homeostasis, we performed arterial blood gas analyses in young (20-31 years old) normotensive subjects (n = 40) who were placed on a low salt diet (20 mmol NaCl/day) for 2 weeks with either 200 mmol sodium chloride or placebo added to the low salt diet for 1 week each in a randomized, single-blind crossover order. Furthermore, a subset of the subjects (seven salt-sensitive and eight salt-resistant) received 200 mmol sodium/day as the citrate salt as a supplement to the low salt diet for a third week. During each regimen, blood pressure as well as arterial pH and bicarbonate levels were measured. Salt sensitivity was defined as a significant drop in mean arterial pressure greater than 3 mm Hg (mean of 30 readings taken during each diet, p less than 0.05) while the subject was on the low salt diet. According to this definition, 16 subjects were salt-sensitive and 24 salt-resistant. During the high sodium chloride regimen, arterial pH and bicarbonate levels were significantly lower in the salt-sensitive than in the salt-resistant group (p less than 0.0001). The increase in blood pressure caused by sodium chloride correlated inversely to the arterial pH (r = -0.57, p = 0.0002) and bicarbonate levels (r = -0.52, p = 0.0007) during the high salt diet. Sodium chloride increased mean arterial blood pressure in the salt-sensitive subjects; sodium citrate did not. Sodium citrate led to an increase in pH and bicarbonate levels in both groups. Our finding that a sodium chloride-induced rise in blood pressure is associated with lower arterial plasma pH and bicarbonate levels points to an abnormality in renal acid-base regulation in salt-sensitive subjects.     

不同体重者下丘脑对葡萄糖耐量试验的反应

目的应用功能核磁共振观察不同体重者下丘脑对口服葡萄糖耐量试验的反应，揭示不同体重者下丘脑中枢糖代谢调节的敏感性与代谢紊乱发生的关系。方法分别采集10名正常体重者与10名肥胖者口服75克葡萄糖后的下丘脑功能磁共振图像数据以及腹部解剖结构图像数据；同时测定受试者的空腹血糖、游离脂肪酸及相应激素水平。应用自行建立的灰度平均值方法进行图像分析处理；同时进行受试者脑功能信号参数与血生化指标水平、相应激素水平及腹部脂肪含量的相关分析。结果不同体重者口服葡萄糖后在下丘脑部位均出现一过性的抑制反应。但肥胖者此抑制反应出现的时间较正常体重者明显延迟；抑制反应强度明显低于正常体重者；抑制反应恢复时间也明显迟于正常体重者。受试者的空腹血浆胰岛素及其瘦素水平与其下丘脑抑制信号恢复到基线的时间有关联；受试者的腹部脂肪含量与其下丘脑抑制信号恢复到基线的时间亦有关联。而受试者空腹血浆葡萄糖、游离脂肪酸水平与其下丘脑功能磁共振采集信号各项参数间没有关联。结论不同体重者下丘脑对糖负荷的中枢反应有所不同，肥胖者下丘脑对糖刺激反应的敏感性有所降低。功能核磁共振是确定脑特定区域功能的一个有效手段。     

Insulin resistance in obese subjects with impaired glucose tolerance. Studies with hyperinsulinemic euglycemic clamp technique

Insulin resistance is a key factor in the pathogenesis of impaired glucose tolerance (IGT) and type 2 diabetes and is also associated with greater risk for cardiovascular disease. Insulin resistance is more common in obese individuals and is considered to be the link between obesity and IGT and diabetes. The aim of the present study was to assess insulin resistance in obese subjects with IGT. We examined 57 subjects with marked overweight or obesity (BMI > > 27.8 kg x m-2), 27 with IGT and 30 with normal glucose tolerance (NGT), assessed by an oral glucose tolerance test, according to WHO criteria. Thirty lean (BMI < 25 kg x m-2) healthy subjects served as a control group. Anthropometric and biochemical parameters were measured. Insulin sensitivity was evaluated with hyperinsulinemic euglycemic clamp technique. Subjects with IGT had higher levels of glucose, insulin, non-esterified fatty acids and glycated hemoglobin than obese with NGT, all those parameters were also higher in both obese groups in comparison to controls. We showed significant differences in insulin sensitivity between the studied groups, an index of the whole-body glucose uptake was decreased in both obese groups in comparison to controls, and it was also lower in IGT than in obese NGT group. We observed marked negative correlations between insulin sensitivity and estimated anthropometric and biochemical parameters. Our study indicates that insulin resistance is an important factor determining a deterioration of glucose tolerance in subjects with overweight and obesity.     

Flow associated (endothelium dependent) vasodilation and TSH-levels in young normotensive and normoglycemic subjects.

BACKGROUND: Endothelial dysfunction (ED) is regarded as an early step in the development of atherosclerosis. Recent experimental data showed a crosstalk between endothelial NO-synthase activity and thyrotropin production. Therefore we studied whether basal TSH can predict flow associated vasodilation (FAD) in a cohort of healthy young subjects with normal TSH levels. PATIENTS AND METHODS: FAD was evaluated in 60 normotensive and normoglycemic subjects (mean age 34 years; range 18-50). The mean thyrotropin level was 1.43 +/- 0.11 microU/ml (range 0.18-3.52 microU/ml). RESULTS: Comparing subjects in the upper, middle and lower tertile of TSH (2.38 +/- 0.14 microU/ml, 1.23 +/- 0.04 microU/ml and 0.65 +/- 0.06 microU/ml respectively) there was no difference in terms of the classical cardiovascular risk factor profiles (24 h blood pressure, HDL- and LDL-cholesterol, triglycerides, oral glucose load and body fat content). Regarding the vascular parameters, we could neither find an independent association with FAD (7.0 +/- 1.1%, 6.4 +/- 1.0% and 5.8 +/- 1.1% respectively) nor with endothelial independent vasodilation (after application of glycerol trinitrate GTN, 17.3 +/- 1.9%, 18.4 +/- 1.7% bzw. 17.5 +/- 1.6% respectively) between the groups. Furthermore, we could not find a significant association between free thyroid hormones (fT3/fT4) and FAD or GTN-induced vasodilation. CONCLUSION: TSH has no predictive value towards endothelial dysfunction in subjects with thyrotropin levels within the normal range.     

Correlation of sodium-related factors with insulin sensitivity in young, lean, male offspring of hypertensive and normotensive subjects.

Pioneer studies have proposed that multiple metabolic abnormalities, such as insulin resistance, increased Na(+)-H(+) exchanger activity and abnormal intracellular calcium homeostasis, are frequently associated with a subset of essential hypertensive patients with low plasma renin activity (PRA). However, it is unclear whether insulin resistance is related to the low renin status in the very early phase of genetical hypertension. Besides, there is controversy on the subject of the in vivo effect of acute hyperinsulinaemia on sodium-related factors. We investigated the relationship between sodium-related parameters and insulin sensitivity, and the effects of euglycaemic hyperinsulinaemia on cyclic guanosine monophosphate (cGMP) and atrial natriuretic peptide (ANP) levels in 17 young, lean, normotensive male subjects, who displayed extreme predispositions for the development of hypertension. PRA was significantly lower in the positive than in the negative family history group (P < 0.05). Insulin sensitivity (M-value) was correlated with PRA before euglycaemic hyperinsulinaemic clamping (r = 0.577, P < 0.05), and was also inversely correlated with fractional excretion of sodium (FE(Na)) before clamping (r = -0.51, P < 0.05). Euglycaemic hyperinsulinaemia significantly decreased PRA (P < 0.0001) and increased cGMP (P < 0.05) and ANP levels (P < 0.01). In conclusion, insulin sensitivity may be partially determined by PRA levels and FE(Na) before clamping in young, lean, normotensive male subjects. Acute euglycaemic hyperinsulinaemia decreases PRA, and increases cGMP and ANP levels from the fasting condition.     

Deletion polymorphism of ACE gene is associated with higher blood pressure after hospitalization in normotensive subjects.

Blood pressure has been shown to decrease in response to hospital admission. Several parameters including the decline of sympathetic nervous activity and negative sodium balance have been shown to be involved in this phenomenon. We investigated genetic influence on office BP and BP after hospitalization. One hundred and sixty-three men from the general population, free from antihypertensive medication, were enrolled in the present study. They stayed at the hospital for general medical check-up. BP was measured on the day of admission, and again the following day. Mean systolic blood pressure was significantly decreased after hospitalization from 117.3 +/- 9.9 mmHg to 115.3 +/- 12.8 mmHg (p=0.042). Subjects with DD+ID genotype showed a significantly higher systolic blood pressure after hospitalization than that of subjects with genotype II. There were no genotype specific differences in diastolic blood pressure or changes in blood pressure by the administration. In summary, systolic blood pressure after hospitalization was significantly higher in normotensive male subjects who possessed the D allele of ACE I/D polymorphism.     

An exaggerated blood pressure response to exercise is associated with the dietary sodium,potassium, and antioxidant vitamin intake in normotensive subjects

Aim: This study was designed to examine the associations between an exaggerated systolic blood pressure (SBP) response to exercise and the nutrient intake in normotensive subjects.

Methods: The subjects consisted of 302 normotensive subjects (64 males and 238 females; age, 48.4 ± 11.3 years) without a history of cardiovascular disease or stroke who were not taking any medications. Each subject performed a multistage graded submaximal exercise stress test using an electric bicycle ergometer, and their blood pressure was measured at rest and during the last minute of each stage. The nutrient intake was assessed using a self-administered food frequency questionnaire. An exaggerated SBP response to exercise was defined according to the criteria of the Framingham Study (peak SBP ≥210 mmHg in males, or ≥190 mmHg in females).

Results: An exaggerated SBP response to exercise was observed in 85 subjects. A multiple logistic regression analysis revealed that the dietary sodium-to-potassium (Na/K) ratio (odds ratio [OR]: 5.75, 95% confidence interval [CI]: 2.37–13.75, p = 0.001) and vitamin E intake (OR: 0.67, 95% CI: 0.51–0.93, p = 0.012) were significantly associated with an exaggerated SBP response to exercise. Furthermore, the percent change in SBP during exercise was found to be significantly associated with an increase in the dietary Na/K ratio (p for trend = 0.0005) and a decrease in the vitamin E intake (p for trend = 0.018).

Conclusions: These results suggest that an exaggerated SBP response to exercise was associated with the dietary sodium, potassium, and antioxidant vitamin intake in normotensive subjects.     

A decrease in glucose production is associated with an increase in plasma citrulline response to oral arginine in normal volunteers

Acute arginine administration (30 g) increases insulin secretion and reduces glucose production (GP). A slower administration of L-arginine may have direct effect on the liver without increasing C-peptide or insulin secretion. We tested the direct effect of oral L-arginine on fasting GP in 15 normal-weight volunteers and compared these to a group of L-alanine-treated controls (placebo). Volunteers were admitted to the General Clinical Research Center for a 3-day stay. Three grams of freebase arginine or alanine was ingested hourly between 4 am and 2 pm. Neither arginine nor alanine had an effect on C-peptide or insulin concentration. Oral arginine, but not alanine, increased plasma arginine, citrulline, and ornithine concentrations. Arginine-treated volunteers had a greater fall in GP as compared to the alanine-treated group (16.2% +/- 1.9% v 9.7% +/- 3.6%, respectively; P<.05). Five volunteers treated with arginine had less than a 30% increase in citrulline concentration (26 +/- 2 to 32 +/- 2 micromol/L, mean +/- SEM) and 10 volunteers had equal to or greater than a 30% increase in plasma citrulline concentration (29 +/- 2 to 49 +/- 4 micromol/L, P<.05). Since citrulline is generated in the conversion of arginine to nitric oxide (NO), the failure of oral arginine to increase citrulline concentration suggests that NO generation may be varied in different individuals. The increased plasma citrulline group reduced GP by 18.2% +/- 1.9% over the final 4 hours of arginine administration (2.00 +/- 0.08 to 1.64 +/- 0.07 mg/kg/min; P<.01). In contrast, GP only decreased by 12.4% +/- 3.9% (1.97 +/- 0.13 to 1.73 +/- 0.13 mg/kg/min; not significant [NS]) in those who had little to no increase in plasma citrulline concentration. The 12% decrease in GP in the hyporesponders was similar to the 10% decrease seen in the alanine-treated normal volunteers (9.7% +/- 3.6%). Individuals may have a variable NO response from an oral arginine administration. GP is suppressed in those who have a greater increase in plasma citrulline concentration.     

Arterial response to venous occlusion in normotensive and hypertensive subjects

Plethysmographic blood flow records made shortly after venous occlusion of the forearm showed a biphasic response, first vasodilator then vasoconstrictor, in both normotensive and hypertensive subjects. The vasodilator component of this response was significantly lower in hypertensive than in normotensive subjects, whereas the vasoconstrictor component was identical. The decreased vasodilator capacity of the forearm resistance vessels in hypertension may indicate structural adaptation of these vessels, while the unaltered vasoconstrictor response is against any increased myogenic activity in the vascular smooth muscle in hypertensive subjects.     

Shape of the glucose response curve during an oral glucose tolerance test is associated with insulin clearance and muscle insulin sensitivity in healthy non‐obese men

Individuals with a monophasic glucose response curve (GRC) during a 75‐g oral glucose tolerance test have a higher risk for type 2 diabetes than those with a biphasic GRC. However, no studies have addressed the association between GRC type and insulin clearance. Thus, we studied 49 healthy non‐obese Japanese men. We divided study participants into the monophasic or biphasic group based on the shape of their GRC. We evaluated tissue‐specific insulin sensitivity and insulin clearance using a two‐step hyperinsulinemic‐euglycemic clamp. The monophasic group had more visceral fat, lower insulin clearance and lower muscle insulin sensitivity than the biphasic group, whereas liver and adipose tissue insulin sensitivity, and insulin secretion were comparable. In conclusion, healthy non‐obese men with a monophasic GRC have lower insulin clearance and muscle insulin sensitivity.     

Endothelium-dependent vasodilation in normotensive subjects with a familial history of essential hypertension and in young subjects with borderline hypertension

OBJECTIVE: To investigate if young normotensive subjects with a familial history of essential hypertension (FHH) or young borderline-hypertensive (BHT) subjects have a defect endothelial function. METHODS: Fifteen young (26 +/- 4 years) healthy normotensive (115 +/- 8/71 +/- 6 mmHg) subjects with a FHH, 31 matched healthy normotensive subjects without FHH and seven BHT (143 +/- 12/92 +/- 2 mmHg), otherwise healthy, young males underwent evaluation of endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation (EIDV), by means of local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium nitroprusside (SNP, evaluating EIDV) in the forearm. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. RESULTS: Although there was no significant difference between normotensive subjects with and without a FHH regarding FBF during vasodilation induced by MCh or SNP, the subjects with a FHH presented a significantly suppressed endothelial function index, calculated as the ratio between EDV and EIDV, when compared to subjects without FHH (1.04 +/- 0.15 vs. 1.24 +/- 0.23, p < 0.01). Also in the group of BHT subjects, the endothelial function index was suppressed (1.01 +/- 0.18, p < 0.01), in this case due to a significantly attenuated EDV (p < 0.05), when compared to male subjects without a FHH. CONCLUSION: The present findings suggest an early occurrence of endothelial dysfunction in the development of essential hypertension.     

Failure of fasting to influence the GIP response to oral glucose in non-obese human subjects

The plasma GIP response to an oral 50 g glucose tolerance test has been compared in eight non-obese human subjects after 12 and 36 h of fasting. Basal plasma GIP and basal plasma insulin concentrations were similar after 12 and 36 h of fasting. Basal blood glucose was lower after 36 h fasting than after 12 h fasting (p less than 0.0125). After 36 h fasting the oral glucose tolerance test stimulated higher blood glucose concentrations at 60, 90 and 120 min (p less than 0.0125) and higher plasma insulin concentrations at similar time points (p less than 0.05), but stimulated plasma GIP concentrations were similar after 12 and 36 h fasts. These findings show that the increased insulinotrophic effect of oral glucose after 36 h fasting in non-obese subjects is not due to an associated augmentation of the glucose-induced GIP response.     

Leg blood pressure measured in orthostatic posture is associated with left ventricular mass in normotensive subjects

BackgroundChanging from a supine to an orthostatic posture is associated with substantial increments in leg blood pressure (BP) levels, which could ultimately influence the hemodynamic burden imposed on the heart. This study investigated the relationship between brachial and leg BP measurements and the left cardiac chamber's structure and assessed the role of body posture changes in this regard.MethodsOne hundred and thirty normotensive, nondiabetic, nonsmoking, normolipemic subjects were evaluated by a clinical history, anthropometry, the analysis of metabolic parameters, echocardiography, and the measurement of BP in the arm and the calf in both supine and orthostatic positions.ResultsSignificant correlation coefficients between the leg BP measurements and the cardiac structure were detected, especially between the orthostatic pulse pressure (PP) and the left ventricular (LV) wall thickness (r = 0.38; P < 0.001), the orthostatic PP and the LV mass (r = 0.37; P < 0.001), and the orthostatic systolic BP (SBP) and the left atrial size (r = 0.35; P < 0.001). Stepwise and standard regression analysis adjusted for brachial BP and anthropometric and metabolic variables confirmed that the leg orthostatic PP was independently related to the LV wall thickness and mass. Moreover, the leg orthostatic SBP was associated with the left atrial dimension even after adding the LV mass to the statistical models. Finally, triglyceride levels and body surface area showed significant relationship with leg orthostatic PP and SBP, whereas brachial orthostatic PP and SBP were only associated with age and anthropometric variables.ConclusionsOrthostatic leg BP is independently associated with the cardiac structure in normotensive subjects.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.101.     

An exaggerated systolic blood pressure response to exercise is associated with cardiovascular remodeling in subjects with prehypertension.

BACKGROUND: Although many observers consider the cardiovascular risk associated with isolated prehypertension to be low and not worth pharmacological treating, the cardiovascular disease rate is increased among individuals within this blood pressure stratum. METHODS: We performed Doppler echocardiography and submaximal bicycle ergometry in 20 nonsmoking sedentary prehypertensive subjects and 20 age- and sex-matched nonsmoking sedentary normotensive subjects, and investigated the association between the systolic blood pressure response to exercise (SBPRE) and hypertensive target organ damage. An exaggerated SBPRE (E-SBPRE) and a normal SBPRE (N-SBPRE) were diagnosed using the mean +2 standard deviations of systolic blood pressure at 100 W in normotensives. RESULTS: Body mass index was similar in the two groups. Resting blood pressure and systemic vascular resistance were higher in prehypertensives. Almost half the latter had an E-SBPRE. There were no differences in age, gender, and body mass index between normotensives and prehypertensives with an E-SBPRE or a N-SBPRE. Resting blood pressure and systemic vascular resistance were similarly increased in prehypertensives with an E-SBPRE and a N-SBPRE vs normotensives. Compared with normotensives, prehypertensives with an E-SBPRE showed: (a) a significantly greater left ventricular relative wall thickness, mostly due to a smaller cavity, (b) a significantly longer left ventricular isovolumic relaxation time, and (c) a significantly greater global arterial stiffness, as estimated by the pulse pressure/left ventricular stroke volume ratio. CONCLUSIONS: Our findings suggest that an E-SBPRE is frequent among prehypertensive subjects and is associated with cardiovascular remodeling, which may herald cardiovascular disease.