Plasma tumor necrosis factor alpha levels and insulin sensitivity in hypertensive subjects

Recent studies have shown that tumor necrosis factor-alpha (TNFalpha), secreted by macrophage, adipocyte and muscle cells, are associated with insulin resistance syndrome i.e., hyperinsulinemia, hypertriglyceridemia and decreased high density lipoprotein (HDL) cholesterol levels. However, it is unclear whether plasma TNFalpha levels relate to insulin resistance syndrome in subjects with essential hypertension who are also characterized by an insulin resistance state. We recruited 85 nondiabetic subjects (45 men and 40 women) with essential hypertension and 85 nondiabetic subjects who were matched for age, sex and body mass index (BMI) to determine their fasting plasma glucose, insulin and lipoprotein concentrations, their glucose and insulin responses to an oral glucose challenge, and their degrees of insulin resistance. Fasting plasma leptin and TNFalpha levels were measured by radioimmunoassay and chemiluminescent enzyme immunometric assay respectively. Total body fat mass was assessed by the bioelectrical impedance method. The results showed that fasting plasma leptin levels were similar between hypertensive and normotensive subjects (7.9 +/- 0.6 vs 7.4 +/- 0.7 ng/ml, p=0.190). Fasting plasma TNFalpha concentrations were not different between subjects with hypertension and normotension (10.5 +/- 0.5 vs 9.8 +/- 0.4 pg/ml, p=0.360). Fasting plasma TNFalpha concentrations were not different across three subgroups of the insulin resistance both in hypertensive patients (8.4 +/- 0.4 vs. 10.9 +/- 1.6 vs. 9.9 +/- 1.0 pg/ml, p=0.297) and normotensive subjects (9.2 +/- 0.7 vs. 9.3 +/- 0.9 vs. 9.7 +/- 0.9 pg/ml, p=0.875). Fasting plasma TNFalpha values showed significantly positive correlations with triglyceride concentrations (p<0.03) but negative correlation with HDL cholesterol concentrations (p<0.04) in normotensive but not in hypertensive individuals. These relations persisted even after adjustment for BMI and total fat mass. In conclusion, our data indicated that circulating levels of TNFalpha did not differ between hypertensive subjects and normotensive controls. Plasma TNFalpha concentrations correlated positively with fasting plasma triglyceride levels and negatively with HDL cholesterol concentrations in normotensive but not in hypertensive subjects. The influence of TNFalpha on carbohydrate and lipoprotein metabolism in hypertensive patients deserves further investigations.     

Plasma homocysteine concentrations and insulin sensitivity in hypertensive subjects

Hyperhomocysteinemia is associated with several cardiovascular disease risk factors including endothelial dysfunction and abnormalities of clotting functions, which are also common features of insulin resistance syndrome observed in hypertensive patients. Recent study has shown that acute hyperinsulinemia can lower plasma homocysteine concentrations in nondiabetic but not in type 2 diabetic individuals, indicating that insulin may regulate homocysteine metabolism. To investigate the relationships between plasma homocysteine concentration and insulin sensitivity, we studied 90 Chinese hypertensive patients and a group of control subjects (n = 86) matched for age, gender, and body mass index. Fasting plasma homocysteine levels, plasma lipoprotein concentrations, plasma glucose, and insulin responses to oral glucose tolerance tests (OGTT) were determined. The results showed that fasting plasma homocysteine concentrations were significantly higher in subjects with hypertension than in those with normotension (mean ± SEM, 8.1 ± 0.6 v 6.8 ± 0.2 μmol/L; P < .05). Fasting plasma homocysteine levels correlated significantly with insulin secretion in response to OGTT even after adjustment for body mass index (P < .05) in hypertensive patients but not in normotensive individuals. However, fasting plasma homocysteine concentrations showed no correlations with steady-state plasma glucose concentration, a measurement of insulin sensitivity, during an insulin suppression test in groups of hypertensive (n = 42) and normotensive (n = 37) subjects. When the steady-state plasma glucose concentrations were divided into three tertiles, fasting plasma homocysteine concentrations showed no difference across these three groups in either hypertensive patients (8.6 ± 0.5 v 7.2 ± 0.5 v 8.4 ± 0.6 μmol/L; P = .148) or normotensive subjects (6.3 ± 0.4 v 8.0 ± 0.8 v 7.0 ± 0.8 μmol/L; P = .199). In conclusion, hypertensive Chinese subjects had higher fasting plasma homocysteine concentrations and a higher degree of insulin resistance when compared to a group of age-, gender-, and body mass index-matched normotensive individuals. Fasting plasma homocysteine levels were associated with insulin response to OGTT in hypertensives but not in normotensives. No correlation was observed between the degree of insulin resistance and plasma homocysteine levels in either the hypertensive or the normotensive group. The role of insulin in homocysteine metabolism deserves further investigation.     

High plasma leptin concentrations in hypertensive men but not in hypertensive women.

OBJECTIVE: Previous studies on humans have reported higher leptin levels in women than in men, independent of body fat, and leptin has been correlated with insulin resistance in men but not in women. Since insulin resistance is thought to play a role in raising blood pressure, we investigated sex differences in leptin concentrations between hypertensive and normotensive individuals. METHODS: Ninety-two nondiabetic hypertensive patients (48 men and 44 women) and 92 age, body mass index (BMI)-matched normotensive control individuals were studied. Fasting plasma glucose, insulin, leptin and lipoprotein concentrations, glucose and insulin responses to 75 g oral glucose tolerance test (OGTT) and insulin suppression tests were determined. RESULTS: Fasting plasma leptin concentrations were higher in hypertensive men than in normotensive men (5.1 +/- 0.5 versus 3.9 +/- 0.4 ng/ml, P = 0.015). However, fasting plasma leptin concentrations were not significantly different between hypertensive and normotensive women (11.8 +/- 1.0 versus 10.9 +/- 1.0 ng/ml, P = 0.440). Fasting plasma leptin concentrations showed good correlation with BMI, body fat, fasting plasma insulin concentrations, and insulin area to OGTT in both men and women (all P < 0.001). However, fasting plasma leptin concentrations were related to steady-state plasma glucose (SSPG) concentrations, a measure of insulin sensitivity by insulin suppression test, in men only (P < 0.001). After adjustment for body fat amount, age and duration of hypertension, fasting plasma leptin levels still correlated significantly with SSPG concentrations in men. These four variables together accounted for a 67.9% variation in fasting plasma leptin levels in men. In women, body fat amount was the only significant determinant for plasma leptin levels. These four variables accounted for a 78.2% variation in plasma leptin levels in women. CONCLUSIONS: Our study confirmed a sex difference in leptin levels both in hypertensive and normotensive subjects. Higher plasma leptin concentrations in hypertensive men but not in hypertensive women when compared with normotensive control individuals was also demonstrated. These observations are consistent with the findings that plasma leptin is correlated with insulin sensitivity in men but not in women. Further studies are needed to understand the causes and consequences of sex effects on leptin in blood pressure regulation.     

Elevated insulin, norepinephrine, and neuropeptide Y in hypertension

To investigate the relationship between insulin and sympathetic activity, plasma norepinephrine, neuropeptide Y, serum glucose and insulin concentrations were measured in ten age-, weight-, and sex-matched normotensive and untreated hypertensive subjects at fasting and 2 h following ingestion of a 75 g oral glucose dose. Hypertensives had higher fasting serum insulin (27 +/- 6 v 12 +/- 2 microU/mL; P = .02) and plasma norepinephrine (356 +/- 38 v 235 +/- 35 pg/mL; P = .03) concentrations than normotensives. Glucose load increased serum insulin (P less than .001) and plasma norepinephrine concentrations (P = .001) in both groups and hypertensives had still higher postglucose insulin (P = .003) and norepinephrine levels (P = .003) than normotensives. Fasting neuropeptide Y was higher in hypertensives than in normotensives (P = .03) and correlated with age in both groups (r = 0.7; r = 0.77). Postglucose serum insulin correlated positively with plasma norepinephrine (r = 0.75; P = .013) in normotensives, but these parameters correlated negatively in hypertensives (r = -0.7; P = .036). We hypothesize that elevated plasma norepinephrine and neuropeptide Y levels reflect an increased level of sympathetic nervous activity in hypertensives, which in turn may be responsible for the abnormal relationship between plasma NE and insulin levels.     

PLASMA TUMOR NECROSIS FACTOR α LEVELS AND INSULIN SENSITIVITY IN HYPERTENSIVE SUBJECTS

Recent studies have shown that tumor necrosis factor-alpha (TNFα), secreted by macrophage, adipocyte and muscle cells, are associated with insulin resistance syndrome i.e., hyperinsulinemia, hypertriglyceridemia and decreased high density lipoprotein (HDL) cholesterol levels. However, it is unclear whether plasma TNFα levels relate to insulin resistance syndrome in subjects with essential hypertension who are also characterized by an insulin resistance state. We recruited 85 nondiabetic subjects (45 men and 40 women) with essential hypertension and 85 nondiabetic subjects who were matched for age, sex and body mass index (BMI) to determine their fasting plasma glucose, insulin and lipoprotein concentrations, their glucose and insulin responses to an oral glucose challenge, and their degrees of insulin resistance. Fasting plasma leptin and TNFα levels were measured by radioimmunoassay and chemiluminescent enzyme immunometric assay respectively. Total body fat mass was assessed by the bioelectrical impedance method. The results showed that fasting plasma leptin levels were similar between hypertensive and normotensive subjects (7.9±0.6 vs 7.4±0.7 ng/ml, p=0.190). Fasting plasma TNFα concentrations were not different between subjects with hypertension and normotension (10.5±0.5 vs 9.8±0.4 pg/ml, p=0.360). Fasting plasma TNFα concentrations were not different across three subgroups of the insulin resistance both in hypertensive patients (8.4±0.4 vs. 10.9±1.6 vs. 9.9±1.0 pg/ml, p=0.297) and normotensive subjects (9.2±0.7 vs. 9.3±0.9 vs. 9.7±0.9 pg/ml, p=0.875). Fasting plasma TNFα values showed significantly positive correlations with triglyceride concentrations (p<0.03) but negative correlation with HDL cholesterol concentrations (p<0.04) in normotensive but not in hypertensive individuals. These relations persisted even after adjustment for BMI and total fat mass. In conclusion, our data indicated that circulating levels of TNFα did not differ between hypertensive subjects and normotensive controls. Plasma TNFα concentrations correlated positively with fasting plasma triglyceride levels and negatively with HDL cholesterol concentrations in normotensive but not in hypertensive subjects. The influence of TNFα on carbohydrate and lipoprotein metabolism in hypertensive patients deserves further investigations.     

Differential blood pressure effects of oral glucose and intravenous L-arginine in healthy lean normotensive and obese hypertensive subjects

We investigated the role of insulin and glucose in the pathophysiology of hypertension associated with obesity. The comparative effects of an oral glucose load and of an L-arginine infusion on plasma glucose, plasma insulin and blood pressures (BP) were assessed in lean normotensive and in obese hypertensive males. Oral glucose (75 g in 1-2 min) induced a small but significant lowering of BP in lean normotensives, but failed to modify BP in obese hypertensives. L-arginine infusion (30 min, 500 mg/kg total dose) reduced BP; significantly greater reductions in systolic and diastolic BP were observed in obese hypertensives than in the control group. Both oral glucose and L-arginine induced greater increases in plasma insulin in obese hypertensives than in lean normotensives. Endothelial dysfunction which accompanies the insulin resistant state of obesity, glucose intolerance and hypertension, may account for the different BP effects induced by glucose and L-arginine in obese hypertensives and lean normotensives.     

Hyperinsulinemia,family history of hypertension,and essential hypertension

The aim of this study was the evaluation of the relationships among hyperinsulinemia, a family history of hypertension, and essential hypertension. Insulin and C-peptide responses to an oral glucose load were studied in 175 lean normotensives (N) and untreated hypertensives (H) with (F+) and without (F−) a family history of hypertension: 30 NF-, 30 NF+, 45 HF-, and 70 HF+. The groups were comparable for age, sex, body mass index, and blood pressure. The following parameters were evaluated: plasma glucose (G), serum insulin (I), and C-peptide (Cp) before and 30, 60, 90, and 120 min after the glucose load, fasting glucose/insulin ratio (ISI), fasting insulin/C-peptide ratio (I/Cp), and 24-h ambulatory blood pressure monitoring. Plasma glucose was measured, fasting and during the test, and it and I/Cp were similar in the four groups. Serum insulin and Cp, both fasting and stimulated, were significantly higher and ISI lower in normotensives and hypertensives with hypertensive parents. Grouping the subjects first on the basis of blood pressure and then on the basis of family history, no differences were found between normotensives and hypertensives, whereas I and Cp, fasting and stimulated, were significantly higher and ISI lower in subjects with positive as compared to negative family history. The closest correlations between insulin and ambulatory blood pressure were found in normotensives with hypertensive parents; in hypertensives with hypertensive parents we only found a direct correlation between fasting Cp and nocturnal blood pressure fall; in hypertensives with normotensive parents insulin inversely correlated with nocturnal blood pressure fall. Insulin resistance seems to have a familial basis, independently of the presence of hypertension. Instead of showing a causal relationship between insulin resistance and hypertension, our results indicate that the two are partly independent components of a common familial pattern.     

血小板游离Ca~(2+)、胰岛素抗性与原发性高血压

为探讨原发性高血压胰岛素抗性与细胞钙代谢障碍的关系,我们测定了18例非肥胖性原发性高血压患者静息和凝血酶激发下血小板游离Ca~(2+)、空腹及口服75g葡萄糖负荷后血糖和血清胰岛素水平,并与13例正常血压者对照。原发性高血压患者静息和凝血酶激发下血小板Ca~(2+)均高于正常对照组,葡萄糖负荷后,血糖和血清胰岛素也高于正常对照组,静息血小板Ca~(2+)与血压及胰岛素反应曲线下面积正相关。结果提示,细胞钙代谢障碍和胰岛素抗性可能相互影响,共同参与高血压病的发病机制。     

Altered circadian blood pressure profile in patients with active acromegaly. Relationship with left ventricular mass and hormonal values

To determine the relationships between the circadian blood pressure profile and left ventricular mass, hormonal pattern and insulin sensitivity indices in patients with active acromegaly, ambulatory 24-h blood pressure monitoring (ABPM) was recorded in 25 subjects (47.0 +/- 15.1 years, range 23-72). Serum growth hormone (GH) and insulin-like growth factor-1, fasting and mean plasma glucose and insulin during oral glucose tolerance test (OGTT), insulinogenic index, the sum of the plasma insulin levels and the homeostasis model insulin resistance index (Homa's index) were determined. Left ventricular mass index (LVMI) was calculated from two-dimensional guided M-mode echocardiogram. The prevalence of hypertension was 56% (n = 14) and 40% (n = 10) according to sphygmomanometric measurements and ABPM, respectively. Non-dipping profile was observed in six of 10 hypertensives and in six of 15 normotensives. Serum growth hormone, fasting glucose, the area under the serum insulin curve and LVMI were higher for acromegalics with non-dipping profile than for dippers (all of them, P < 0.05). In non-dippers daytime heart rate was higher than night time (P < 0.001). In conclusion, the main observations in the present study suggested that both normotensive and hypertensive acromegalics had a highly prevalent non-dipping profile with a preserved circadian pattern of heart rate, that was associated with higher levels of serum GH. The disturbance in nocturnal blood fall in normotensives was associated with a decreased insulin sensitivity. The role of GH in blood pressure circadian rhythm regulation in essential hypertension deserves further studies.     

Plasma immunoreactive endothelin in essential hypertension

PURPOSE: Endothelin plays a role in the regulation of vascular tonus. Therefore, it has been hypothesized that increased production or release of endothelin or both may contribute to the pathogenesis of hypertension. To assess any changes in the plasma endothelin concentration in essential hypertension, plasma immunoreactive endothelin concentrations were measured in patients with essential hypertension. PATIENTS AND METHODS: We measured plasma immunoreactive endothelin concentrations in 42 subjects with essential hypertension, 12 subjects with borderline hypertension, and 25 normotensive control subjects. RESULTS: The concentrations were higher in hypertensive patients than in borderline hypertensive patients and normotensive subjects (both p less than 0.05), although values in normotensives and hypertensives overlapped. Reverse-phase high-performance liquid chromatography (HPLC) and radioimmuno-assay showed two components of plasma endothelin, one corresponding to synthetic endothelin-1 (1-21) and the other corresponding to synthetic big endothelin (human, 1-38). The HPLC profile of plasma endothelin of hypertensive patients was the same as that of normotensive subjects. Hypertensives with reduced glomerular filtration rates or increased serum creatinine levels had higher plasma endothelin concentrations than hypertensive patients as a whole (p less than 0.05). Mean blood pressure and serum creatinine levels were correlated to plasma endothelin in the hypertensives. Correlation was negative between glomerular filtration rate and the endothelin level in the hypertensives. CONCLUSION: Plasma endothelin was elevated in many hypertensive patients with severe hypertension or renal involvement. Its major components were endothelin-1 and big endothelin.     

A close association between insulin resistance and dehydroepiandrosterone sulfate in subjects with essential hypertension

To examine the serum levels of dehydroepiandrosterone sulfate (DHEAS) and its relation with insulin resistance and the other risk factors in essential hypertension, serum DHEAS and insulin sensitivity were assessed in 35 male hypertensive and 17 male healthy control subjects aged 50-59 years. Fasting plasma insulin and the area under curve of plasma insulin were determined during a 75 g oral glucose tolerance test. Insulin sensitivity was measured by the steady state plasma glucose method. Fasting plasma insulin and the area under curve of plasma insulin were significantly higher in the hypertensive group than in control group. Steady state plasma glucose was significantly higher in hypertensive subjects indicating insulin resistance compared with control subjects. On the other hand, fasting serum DHEAS levels were significantly lower in the hypertensive group than in the control group. Fasting serum DHEAS levels were inversely correlated with steady state plasma glucose significantly (p=0.0008), indicating a close association between DHEAS levels and insulin resistance. Fasting serum DHEAS was inversely correlated with systolic blood pressure and fasting plasma insulin. In multiple regression analysis of hypertensive subjects, steady state plasma glucose was the strongest determinant of the fasting serum level of DHEAS, followed by systolic blood pressure and fasting plasma insulin. These 3 factors accounted for 51.6% of the variation in DHEAS. In nonobese and nondiabetic essential hypertension, serum DHEAS was lower and insulin resistance was the most significant independent determinant of reduced serum DHEAS, followed by systolic blood pressure and fasting plasma insulin.     

-308 Nco I polymorphism of tumour necrosis factor alpha in overweight Caucasians

We investigated whether a polymorphism in the promoter region of the TNFalpha gene (-308 A/G) is associated with reduced weight loss in obese Australian subjects on an energy restricted diet. 189 healthy subjects and 91 subjects with type II diabetes were genotyped for the -308 Nco I polymorphism using PCR-RFLP techniques. A subset of these subjects (211 females and 45 males), were placed on a 30% energy restricted diet (6200 kJ) for 12 weeks. Subjects were assessed every 2 weeks and changes in body weight, waist circumference and BMI were used as determinants of weight loss. Fasting plasma was analysed for glucose, insulin, lipids and free fatty acids. 64% of subjects were GG homozygotes, 31% were AG heterozygotes and 5% were AA homozygotes. There was no significant difference between the allele frequency in healthy subjects (0.21) and type 2 diabetic patients (0.24). The presence of the -308 A/G polymorphism did not significantly influence initial BMI, the amount of weight lost (GG, 8.1+/-0.65 kg, AG, 6.9+/-0.77 kg, AA, 7.6+/-0.12 kg), waist circumference or any metabolic variable. The AA variant at position -308 in the promoter region of the TNFalpha gene does not influence the amount of weight lost in overweight and obese men and women on a 30% energy restricted diet.     

卡托普利对高血压高胰岛素血症的干预

通过对42例原发性高血压患者（EH）、26例正常人测定口服葡萄糖耐量试验（OGTT）前后血糖（GS）、血胰岛素（IS）及其反应曲线下面积，发现EH组空腹GS与对照组之间无统计学差异；空腹IS和服糖后EH组GS、IS及其曲线下面积显著高于对照组，提示EH患者存在糖耐量降低、IS抵抗（IR）。EH组中21例患者单纯接受卡托普利有效降压4～8周后，OGTT显示糖负荷1h、2h的IS和GS水平均显著低于治疗前水平，结果提示卡托普利可以改善EH患者IR。     

Hyperinsulinemia and dyslipidemia in non-obese, normotensive offspring of hypertensive parents in northern India.

Insulin resistance contributes to initiation and acceleration of hypertension and atherosclerosis. This study attempted to detect occurrence of pre-hypertensive metabolic abnormalities, including hyperinsulinemia, in the offspring of hypertensive patients. Thirty-eight healthy offspring of hypertensive parents (group I, mean age 23.6+/-3.7 years) and 18 control offspring of normotensive parents (group II, mean age 24.2+/-2.8 years) were clinically examined, subjected to oral glucose tolerance test (OGTT), and the samples were analysed for blood glucose, insulin and lipid profile. Subjects in group I with fasting serum insulin <90 nmol/L constituted group Ia (n = 23, 62%) and those with >90 nmol/L constituted group Ib (n = 15, 38%). Both groups consisted of non-obese and normotensive subjects matched for body mass index and waist-hip ratio. There were no statistically significant differences in blood glucose levels between groups Ia, Ib and II during OGTT. Serum insulin levels during OGTT in group I were significantly higher than in group II (p<0.05), except at 30 min. Fasting insulin and 2 h post-OGTT insulin in group Ib were significantly higher than the other groups. Serum triglyceride levels, though within normal range, were higher in group I than group II (p<0.01). Similarly, high-density lipoprotein cholesterol levels in groups Ia and Ib were lower than those observed in group II (p<0.01). In conclusion, non-obese, normotensive offspring of hypertensive parents were observed to be hyperinsulinemic and dyslipidemic at an early age. These metabolic abnormalities may be associated with hypertension, glucose intolerance and accelerated atherosclerosis in adulthood.     

A genetic approach to the geography of hypertension : examination of Na+ - K+ cotransport in Ivory Coast Africans

Outward Na+ - K+ cotransport in erythrocytes from essential hypertensive Caucasian subjects was found to be excessively low (Co -) compared to normotensives (Co +) carefully selected for their negative family history of hypertension. Since the frequency of essential hypertension varies widely among different populations and is particularly high in certain coloured peoples, we compared erythrocyte Na+ - K+ cotransport in normotensive and hypertensive subjects in Paris (France) and in Abidjan (Ivory Coast) to seen whether defective cotransport was related to high blood pressure in the African group as well. Of the 66 French unselected normotensives investigated, 26 (39%) were Co - whereas 14 of the 18 Ivory Coast unselected normotensives (79%) were Co -. 64 (80%) of the 80 essential hypertensives examined in France were Co -, but the proportion of Co - subjects among the Ivory Coast hypertensives was even higher. In addition, both hypertensives and normotensives in the African groups often had undetectable outward Na+ effluxes, a rare finding in the French subjects. We suggest that the high incidence of abnormal Na+ - K+ cotransport in the Ivory Coast series may reflect a genetic propensity to hypertension in this population, and that consequently, Na+ - K+ erythrocyte cotransport measurements might prove useful in defining geographic variations in hypertension.     

Insulin resistance and hypertension in postmenopausal women

The aim of the study was to elucidate the role of hyperinsulinaemia/insulin resistance in hypertension of lean postmenopausal women. Twenty-four women with essential hypertension (systolic/diastolic > or =140/90 mm Hg) and a body mass index (BMI) less than 26 kg/m(2) not receiving antihypertensive treatment or who had been without treatment for a 4-week washout period, and 10 normotensive postmenopausal weight- and aged-matched controls were compared. Both groups were not receiving hormone replacement therapy. Hip and waist circumferences were measured and waist/hip ratios were calculated. Casual blood pressure was measured in triplicate. Neither the fasting plasma glucose nor serum insulin levels in hypertensive women and normotensives differed significantly. During 2 h oral glucose (75 g)-tolerance test the mean plasma glucose levels after 30 min (172.5 +/- 40.24 mg/dl vs. 143.67 +/- 20.16 mg/dl), 60 min (134.88 +/- 38.78 mg/dl vs. 112.33 +/- 5.44 mg/dl) and 120 min (116.08 +/- 26.65 mg/dl vs. 95.56 +/- 20.17 mg/dl) were significantly higher in hypertensives than that for normotensives (P < 0.05 for all three comparisons). The mean serum insulin levels of hypertensive women were significantly higher than that in normotensives after 15 min (92.04 +/- 59.90 microU/ml vs. 54.89 +/- 33.67 microU/ml) and 120 min (49.63 +/- 44.45 microU/ml vs. 19.22 +/- 24.10 microU/ml; P< 0.05 for both comparisons). The mean serum insulin: plasma glucose ratio for hypertensive women was significantly higher than that for normotensives after 15 min (0.596 +/- 0.46 vs. 0.359 +/- 0.20 microU/mg), 60 min (0.406 +/- 0.30 vs. 0.329 +/- 0.25 microU/mg) and 120 min (0.436 +/- 0.35 vs. 0.205 +/- 0.26 microU/mg) (P < 0.05 for all three comparisons). Significant correlations were observed between the daytime period and 24-h average ambulatory systolic blood pressure and the area under the serum insulin curve (r = 0.41 and 0.36, respectively). For non-dippers we found higher fasting insulinaemias but the AUC(insulin) did not differ. Plasma glucose levels did not differ either during fasting or during OGTT (AUC(glucose)). Insulinogenic index was higher in dippers than in non-dippers. We conclude that in lean, postmenopausal hypertensive women insulin resistance is increased compared with age- and weight-matched normotensive women. Also, hyperinsulinaemia correlates with ambulatory systolic blood pressure. Thus, insulin resistance may possibly be involved as a pathogenetic factor in lean, postmenopausal hypertensive women.     

Insulin resistance and endogenous digoxin-like factor in obese hypertensive patients with glucose intolerance

Hypertensive obese subjects with glucose intolerance have hyperinsulinaemia, insulin resistance and intracellular cation imbalance resulting in increased sodium content. The aim of our study was to assess in these patients plasma levels of endogenous digoxin-like factor (EDLF), an inhibitor of the sodium-pump mechanism. We studied 14 hypertensive and 12 normotensive subjects with obesity and glucose intolerance for fasting blood glucose, and plasma insulin, C-peptide and EDLF levels: the two groups were matched for age and BMI and were studied after a 2-week wash-out period from hypotensive drugs. Compared with normotensives, hypertensive subjects had higher plasma insulin levels, a greater immunoreactive insulin/C-peptide ratio, a lower glucose/insulin ratio and higher plasma EDLF levels. Our results confirm that among obese people with glucose intolerance, hypertensives are more hyperinsulinaemic and insulin-resistant than normotensives and indicate that the intracellular cation imbalance in these patients may be attributable, at least in part, to EDLF.Presented in part at the XII Congress of the European Society of Cardiology, Stockholm, 16–20 September 1990     

White-coat hypertension and sex

OBJECTIVES: To compare, by sex, selected behavioral and biologic characteristics among normotensive, white-coat hypertensive, and essential hypertensive patients, and to assess the similarities and differences in these characteristics between men and women diagnosed as having white-coat hypertension. METHODS: The subjects of this study were 764 men (80 normotensives, 112 white-coat hypertensives, and 572 essential hypertensives) and 442 women (53 normotensives, 81 white-coat hypertensives and 308 essential hypertensives) who were a nonrandom subset of a larger cohort of patients being assessed to determine the prognostic significance of ambulatory blood pressure measurements. Physician-measured technician-measured and ambulatory (average awake and asleep) blood pressures, daytime blood pressure variability, the difference between awake and sleeping blood pressures, cholesterol levels, plasma renin activity (PRA) and anthropometric and demographic characteristics were compared across the patient classifications within each sex group and between male and female white-coat hypertensives using one-way analysis of variance. Student's t tests and chi squared analysis. RESULTS: Among men, cholesterol levels of normotensives were significantly lower than those of either white-coat or essential hypertensives (P < 0.05 and P < 0.01, respectively). White-coat hypertensives were significantly younger than the essential hypertensives. The ambulatory and technician-measured blood pressures of the white-coat hypertensives were similar to those of the normotensives, as were most measures of variability of blood pressure. Among women, there were no differences in cholesterol level; however, white-coat hypertensives had lower PRA than did the essential hypertensives (P < 0.01) In contrast to the men, women with white-coat hypertension were similar in age to those with essential hypertension, and 10 years older than normotensives (P < 0.01). The ambulatory blood pressures of white-coat hypertensives were similar to those of normotensives, but their technician-measured blood pressures were intermediate between those of the normotensive and essential hypertensive groups. The daily variability of diastolic blood pressure among the white-coat-hypertensive women was greater than that of the normotensive women and similar to that of the essential hypertensive women. For all other measures of variability, data for white-coat-hypertensive women were similar to those for the normotensive women. There was no anthropometric or demographic difference among the patients either for men or for women. White-coat-hypertensive women were older than white-coat-hypertensive men and had higher systolic blood pressures and variabilities of blood pressure (P < 0.05). They also had lower PRA. CONCLUSIONS: These results are consistent with the ideas that the phenomenon of white-coat hypertension is similar for the two sexes, women may exhibit white-coat hypertension at a greater age than do men, and women with white-coat hypertension may further exhibit a broader white-coat effect, reflected in blood pressures measured by other medical personnel.     

Persistent remodeling of resistance arteries in type 2 diabetic patients on antihypertensive treatment

We hypothesized that resistance arteries from diabetic patients with controlled hypertension have less remodeling than vessels from untreated hypertensive subjects. Eight normotensive subjects (aged 44+/-3 years, 3 men; values are mean+/-SEM), 19 untreated hypertensive subjects (46+/-2 years, 9 men), and 23 hypertensive subjects with type 2 diabetes mellitus under antihypertensive treatment (58+/-1 years, 15 men) were studied. Resistance arteries dissected from gluteal subcutaneous tissue were assessed on a pressurized myograph. Most diabetic patients (70%) were being treated with angiotensin-converting enzyme inhibitors. Although systolic blood pressure was still above the normotensive range in these patients (144+/-2 versus 150+/-3 mm Hg in hypertensive and 114+/-4 mm Hg in normotensive subjects), diastolic blood pressure was well controlled (83+/-2 mm Hg) and significantly lower compared with that in untreated hypertensives (100+/-1 mm Hg; P<0.001) but higher than in normotensives (76+/-3 mm Hg; P<0.05). Thus, pulse pressure was higher in diabetic patients (P<0.05). The media-to-lumen ratio of resistance arteries was greater in hypertensives (0.083+/-0.002) compared with normotensive controls (0.059+/-0.003; P<0.05) and was even higher in diabetic hypertensive subjects (0.105+/-0.004; P<0.001 versus normotensive controls). The medial cross-sectional area was greater in diabetic and hypertensive patients compared with normotensive controls (P<0.001). Acetylcholine-induced relaxation was impaired in vessels from hypertensive patients and from patients with both diabetes mellitus and hypertension (P<0.05 versus normotensive controls), whereas endothelium-independent vasorelaxation was similar in all groups. Despite effective antihypertensive treatment, resistance arteries from hypertensive diabetic patients showed marked remodeling, greater than that of vessels from untreated, nondiabetic, hypertensive subjects, in agreement with the high cardiovascular risk of subjects suffering from both diabetes and hypertension.     

Plasma N terminal pro-brain natriuretic peptide levels and its determinants in a multi-ethnic population

This study documents the determinants and plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) among hypertensive and normotensive subjects in a multi-ethnic population in the United Arab Emirates (UAE). We obtained demographic, anthropometric and clinical data, together with fasting NT-proBNP and biochemical indices from 128 hypertensive patients and 138 normotensive subjects matched for age, gender and ethnicity. Plasma NT-proBNP levels were significantly (P<0.001), and several-fold higher among hypertensives (median 5.92, inter quartile range (IQR): 1.79-18.48 pmol/l) than normotensives (median 1.78, IQR: 0.59-4.32 pmol/l) in the total study population, and the same was true for the ethnic groups separately. Similarly, plasma levels of glucose, blood urea nitrogen (BUN) and creatinine, but not insulin, were significantly (P<0.05) higher among hypertensives than normotensives. For all subjects combined, log NT-proBNP correlated positively and significantly with age (P<0.01), log glucose (P<0.05), systolic blood pressure (SBP, P<0.001), log BUN (P<0.001) and log creatinine (P<0.001). Multivariate regression analysis showed that NT-proBNP levels were independently and positively correlated with SBP, age, gender, log BUN, Emirati and South East Asian ethnic groups and inversely associated with current exercise. In conclusion, we found circulating levels of NT-proBNP to be significantly increased in hypertensive versus normotensive subjects in the UAE and independently related to SBP, age, gender, indices of renal function and possibly exercise. Our results further suggest a possible modulating effect of ethnicity on NT-proBNP levels.