Microalbuminuria,a parameter independent of metabolic influences in hypertensive men

OBJECTIVE: To evaluate the relationship of albuminuria and microalbuminuria (overnight urine albumin > or = 15 micro g/min) with insulin resistance and related metabolic abnormalities in patients with essential hypertension. DESIGN: Cross-sectional evaluation of 271 (age range, 19-77 years) never-treated, non-diabetic, uncomplicated hypertensive men. MAIN OUTCOME MEASURES: Triplicate overnight urine albumin determination and homeostasis model assessment (HOMA) of insulin resistance as a surrogate measure of insulin sensitivity. Additional parameters were fasting and post-load circulating glucose and insulin, lipids, body mass index, blood pressure and echocardiographic left ventricular mass. RESULTS: HOMA, fasting and post-challenge glucose and insulin, percentages of glucose-intolerant patients, triglycerides and high-density lipoprotein cholesterol levels did not differ across ascending urine albumin quartiles. Body mass index, blood pressure and ventricular mass were significantly greater in the upper quartiles, and the prevalence of obesity fivefold more frequent in the top as compared with the bottom urine albumin fourth. The statistical trend was unchanged after adjustment for HOMA, while accounting for systolic blood pressure and left ventricular mass by co-variance analysis abolished it. Eighty-eight patients bearing the phenotypic traits of the metabolic syndrome and a striking degree of insulin resistance and hyperinsulinemia showed urine albumin rates and prevalence of microalbuminuria comparable with the 183 patients who were not affected by that syndrome. CONCLUSIONS: Albuminuria is independent of insulin resistance and other phenotypic components of the metabolic syndrome in never-treated, non-diabetic essential hypertensive men. Microalbuminuria is more frequent in obese hypertensives but this association is explained by higher blood pressure more than insulin resistance.     

Dissociation between microalbuminuria and common carotid thickness in essential hypertensive men

BACKGROUND: The reasons why microalbuminuria (albuminuria > or = 15 microg/min), an expression of a renal microcirculatory abnormality, predicts cardiovascular disease in essential hypertension are unsettled. To test the hypothesis that microalbuminuria represents a marker of subclinical atherosclerosis, we evaluated its association with common carotid artery (CCA) intima media thickness (IMT), a measure of preclinical atherosclerosis and an independent predictor of cardiac and cerebrovascular events, in uncomplicated essential hypertensive individuals. MATERIALS AND METHODS: Albuminuria, ultrasonographic CCA IMT (the mean of six bilateral far wall measurements within 1.5 cm proximally to the flow divider), brachial blood pressure (BP), smoking habits and lipids were evaluated in 136 stage 1-3 untreated essential hypertensive men free of cardiovascular disease. RESULTS: CCA IMT did not differ between normo- (n = 99) and microalbuminuric (n = 37) patients. The correlation between CCA IMT and albuminuria was not significant, and the prevalence of microalbuminuria across IMT quartiles was not different. Microalbuminuric patients showed higher systolic BP and that parameter was the only independent correlate in a multivariate logistic regression model including also age, CCA IMT, diastolic BP, lipids and smoking habits as independent variables and microalbuminuria as the dependent one. CONCLUSION: This cross-sectional study in hypertensive subjects free of cardiovascular disease has shown a dissociation between microalbuminuria and CCA IMT, a surrogate measure of subclinical atherosclerosis, and a parameter linearly related to cardiovascular events. The data do not support the theory of microalbuminuria as a surrogate measure of subclinical atherosclerosis, while confirming the importance of systolic BP levels as an independent correlate of increased albuminuria in essential hypertension. Journal of Human Hypertension (2000) 14, 831-835     

Microalbuminuria,insulin sensitivity and haemostatic factors in non-diabetic treated hypertensive men

Abstract. Objective . To examine whether microalbuminuria in non-diabetic, treated hypertensive men is associated with insulin resistance and measures of endothelial function, thrombogenesis and fibrinolysis. Design . Cross-sectional study. Setting . Outpatient clinic in city hospital. Patients . Ninety-two treated hypertensive men, aged 57–77 years, either with a serum cholesterol of ≥ 6.5 mmol L^?1 or smokers, or both. Patients with diabetes mellitus or overnight urinary albumin excretion of > 100 mg 12 h^?1 were excluded. Main outcome measures . Overnight urinary albumin excretion, insulin-mediated glucose disposal (hyper-insulinaemic euglycaemic clamp), blood glucose and plasma insulin during oral glucose tolerance test, fibrinogen, von Willebrand factor and plasminogen activator inhibitor activity. Results . Microalbuminuric patients had increased blood glucose concentrations during the oral glucose tolerance test and higher plasma fibrinogen levels compared with the normoalbuminuric patients. In a randomly selected subgroup (n = 36), insulin-mediated glucose disposal was lower in microalbuminuric than in normoalbuminuric patients, and an inverse relationship between insulin sensitivity and albuminuria (r = –0.37; P = 0.028) was found. This relationship was not significant after adjustment for body-mass index (P = 0.098). In the univariate analyses including all patients, albuminuria was associated with blood glucose, serum creatinine, body-mass index, systolic blood pressure, fibrinogen, von Willebrand factor and cholesterol (negatively). In a multiple regression analysis, only the body-mass index was independently related to urinary albumin excretion. Conclusions . Microalbuminuria was associated with insulin resistance but obesity was a confounding factor. Relationships between microalbuminuria and fibrinogen as well as von Willebrand factor were found, but only in univariate analysis.     

Microalbuminuria is associated with the insulin resistance syndrome independent of hypertension and type 2 diabetes in the Korean population

To investigate whether microalbuminuria is associated with the insulin resistance syndrome independent of hypertension and type 2 diabetes, we studied the association between microalbuminuria and features of insulin resistance syndrome in Korean general population. We selected 1006 subjects by a random cluster sampling among residents aged >40 years living in the Chung-Up district, a rural area of South Korea. Subjects were stratified by oral glucose tolerance status [normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus], and by the presence or absence of hypertension. Urinary albumin excretion rate (UAER) was determined using timed overnight urine collection. Various cardiovascular risk factors including anthropometric indices, serum lipid, true insulin and proinsulin concentrations were also measured. The prevalence of microalbuminuria (UAER between 20 and 200 microg/min) increased as the glucose tolerance worsened (6.0% in NGT, 11.8% in IGT, and 21.8% in diabetes; chi(2) trend=25.9, P<0.001). Subjects with microalbuminuria had a higher body mass index (BMI), waist-to-hip circumference ratio (WHR), systolic and diastolic blood pressure (BP), fasting and 2 h plasma glucose, fasting plasma insulin and proinsulin levels, and lower HDL-cholesterol level than subjects without microalbuminuria. In multiple regression analysis, BMI, diastolic BP, 2 h plasma glucose, and fasting plasma insulin levels were found to be independent factors associated with UAER. Multiple logistic regression analysis showed that not only diabetes mellitus and hypertension, but also fasting hyperinsulinemia and waist-to-hip ratio were independent factors associated with the presence of microalbuminuria. When the normotensive, non-diabetic subjects were analyzed separately, fasting hyperinsulinemia and impaired glucose tolerance remained independent variables associated with the presence of microalbuminuria. These results show that microalbuminuria in the Korean general population is associated with hyperinsulinemia and central obesity, and suggest that microalbuminuria is a feature of the insulin resistance syndrome independent of hypertension or type 2 diabetes.     

Increased human urotensin II levels are correlated with carotid atherosclerosis in essential hypertension

BACKGROUND: Circulating blood levels of human urotensin II (U-II), the most potent vasoconstrictor peptide identified to date, are increased in patients with essential hypertension. Our previous studies showed that U-II accelerates human macrophage foam cell formation and vascular smooth muscle cell proliferation, suggesting development of atherosclerotic plaque. In this study, we demonstrated a correlation between plasma U-II level and progression of atherosclerosis in hypertensive patients. METHODS: The intima-media thickness (IMT) and plaque score in the carotid artery, blood pressure (BP), plasma levels of U-II, and atherosclerotic parameters were determined in 50 hypertensive patients and 31 normotensive controls. RESULTS: Plasma U-II level, maximum IMT, plaque score, systolic BP, and homeostasis model assessment for insulin resistance (HOMA-IR) were significantly greater in hypertensive patients than normotensive controls. Age, gender, body mass index, and serum levels of high-sensitive C-reactive protein (CRP), HDL and LDL cholesterols, small dense LDL, triglycerides, lipoprotein(a), insulin, and fasting plasma glucose level were not significantly different between the two groups. In all subjects, plasma U-II level showed significant positive correlations with systolic BP, maximum IMT, plaque score, and HOMA-IR. Multiple logistic regression analysis indicated that the contribution of plasma U-II levels to carotid plaque formation (plaque score >/=1.1) was significantly still greater with a 60% increase than those of established risk factors, such as age, systolic BP, high-sensitive CRP, small dense LDL, and HOMA-IR. CONCLUSIONS: Our results suggest that increased levels of U-II may play a crucial role in the development of carotid atherosclerosis in hypertensive patients.     

Hypertension in Pregnancy Is a Risk Factor for Microalbuminuria Later in Life

The authors aimed to compare renal function by estimated glomerular filtration rate and albuminuria in 3 groups of women: nulliparous women, women with a history of normotensive pregnancies, and women with a history of at least one hypertensive pregnancy. Women who participated in the second Family Blood Pressure Program Study visit (2000–2004) and had serum creatinine and urine albumin measurements (n=3015) were categorized as having had no pregnancy lasting >6 months (n=341), having had only normotensive pregnancies (n=2199), or having had at least 1 pregnancy with hypertension (n=475) based on a standardized questionnaire. Women who reported having had at least one pregnancy with hypertension were significantly more likely to be hypertensive (75.6% vs 59.4%, P<.001), diabetic (34.2% vs 27.3%, P≤.001), and have higher body mass index (32.8 vs 30.5, P<.001) than those who reported normotensive pregnancies. There was a significantly greater risk of microalbuminuria (urine albumin‐creatinine ratio >25 mg/g) in those who reported at least one pregnancy with hypertension (odds ratio, 1.37; confidence interval, 1.02–1.85; P=.04) than in those with normotensive pregnancies, after adjusting for risk factors for chronic kidney and cardiovascular disease. Hypertension in pregnancy is associated with an increased risk of future microalbuminuria.     

Metabolic risk factors and markers of cardiovascular and renal damage in overweight subjects

BACKGROUND: The prevalence of overweight and obesity in the United States has dramatically increased. Obesity clusters with a variety of hemodynamic and metabolic disturbances that increase the risk of cardiovascular disease. In this study we evaluated whether overweight subjects with hypertension also manifest hemodynamic and metabolic abnormalities compared with individuals of normal weight. METHODS: In a cohort of 129 patients with essential hypertension we measured the relationship between body mass index (BMI), blood pressure (BP), insulin sensitivity, lipid profile, and markers of organ damage including thickness of the carotid artery (IMT) and urine albumin excretion (UAE). A total of 41 normotensive, age-matched, healthy individuals served as control subjects. RESULTS: Hypertensive individuals showed higher levels of serum triglycerides, insulin area-under-the-curve (AUC), UAE, and greater IMT than normotensive subjects. Overweight hypertensive subjects showed higher levels of serum triglycerides, LDL cholesterol, glucose AUC, insulin AUC, UAE, and IMT than hypertensive subjects with normal body weight (BMI <25). Night-time systolic BP was higher and night-time fall in BP was lower among overweight than among normal-weight hypertensive patients. Simple regression analysis showed that BMI was correlated with age, UAE, BP, insulin and glucose AUC, serum triglycerides, cholesterol, and IMT in hypertensive subjects. However multiple regression analyses showed that BMI significantly correlated only with UAE. CONCLUSIONS: The study results show that increased body weight clusters with a variety of hemodynamic and metabolic abnormalities in hypertensive subjects. However multiple regression analyses showed a significant correlation only between BMI and UAE, a marker and predictor of cardiovascular and renal disease.     

老年2型糖尿病患者尿白蛋白排泄率与胰岛素抵抗的相关性研究

目的探讨老年2型糖尿病患者不同尿白蛋白分期与胰岛素抵抗的关系,为糖尿病肾病的预防与控制提供有益的参考。方法将152例老年2型糖尿病患者根据24小时尿微量白蛋白,分为正常白蛋白尿、微量白蛋白尿和大量白蛋白尿3组,分别测定体质指数、血压、空腹血糖、空腹胰岛素、糖化血红蛋白、血脂、血尿酸、24小时尿白蛋白定量等,并计算胰岛素抵抗指数(HOMA-IR)及估算的肾小球滤过率(eGFR)。结果与正常白蛋白尿组比较,微量白蛋白尿组患者的年龄、高血压合并率、HOMA-IR均明显升高,而eGFR明显下降(P<0.05);大量白蛋白尿组患者的高血压合并率、血压、空腹血糖、空腹胰岛素、总胆固醇、HOMA-IR亦均明显升高,而eGFR明显下降(P<0.05)。与微量白蛋白尿组比较,大量白蛋白尿组患者舒张压、空腹血糖、空腹胰岛素、总胆固醇均明显增高(P<0.05)。多因素逐步回归分析显示HOMA-IR是影响老年2型糖尿病患者尿白蛋白排泄率的独立危险因素。结论老年2型糖尿病患者尿白蛋白增多与胰岛素抵抗有关。     

Relation of microalbuminuria to adiponectin and augmented C-reactive protein levels in men with essential hypertension

Microalbuminuria, and recently, hypoadiponectinemia, have been associated with progression of atherosclerotic disease and increased cardiovascular risk. We examined the possible associations of urinary albumin excretion, expressed as the ratio of albumin to creatinine (ACR), with plasma adiponectin and high-sensitivity C-reactive protein (hs-CRP) levels in men who had essential hypertension. The study population consisted of 108 men who did not have diabetes and were newly diagnosed with stage I to II essential hypertension (age 44.6 years, office blood pressure 148/95 mm Hg) and 110 men matched according to age and body mass index as controls. According to ACR values, which were determined as the average of 2 nonconsecutive overnight spot urine samples, subjects who had hypertension were categorized into 2 groups: those who had microalbuminuria (n = 28; mean ACR 30 to 300 mg/g) and those who had normal albuminuria (n = 80; mean ACR <30 mg/g). Subjects who had hypertension compared with controls exhibited higher ACR and log hs-CRP levels and a trend toward lower log adiponectin values (p = 0.062), whereas those who had normal albuminuria compared with controls had similar log adiponectin levels but significantly higher levels of ACR and log hs-CRP. Moreover, subjects who had hypertension and microalbuminuria compared with those who had hypertension and normal albuminuria had higher log hs-CRP and lower log adiponectin concentrations independently of confounding factors. Among those who had hypertension, ACR exhibited an independent positive correlation with log hs-CRP and a negative correlation with log adiponectin. Multiple linear regression analysis showed that age, body mass index, systolic blood pressure, log hs-CRP, and log adiponectin were significant independent predictors of the ACR. In conclusion, microalbuminuria is accompanied by decreased adiponectin and increased hs-CRP levels in the setting of essential hypertension, reflecting a rather diffuse atherosclerotic process.     

Mortality and morbidity in relation to changes in albuminuria,glucose status and systolic blood pressure: an analysis of the ONTARGET and TRANSCEND studies

Aims/hypothesis

Urinary albumin excretion is a strong predictor of cardiovascular disease. It is uncertain whether improvement from microalbuminuria or deterioration from normoalbuminuria over time in patients with differing changes in glucose and BP change their cardiovascular risk.

Methods

Data on mortality, cardiovascular and renal outcomes were analysed in 22,984 patients from two large parallel randomised clinical trials followed for 56 months. A central laboratory analysed first morning spot urine samples at baseline and after 24 months, and events were recorded over the subsequent 32 months. Patients were stratified by changes in albuminuria, glucose status and mean systolic BP over 2 years.

Results

There was a strong association between albuminuria status and all-cause and cardiovascular mortality and combined cardiovascular and renal endpoints (all p?p?=?0.0004).

Conclusions/interpretation

Patients who showed improvement to normoalbuminuria over 2 years were at lower risk of all-cause and cardiovascular mortality and of cardiovascular and renal events than those who deteriorated to microalbuminuria over time. Albuminuria over time was significantly better than glucose status and BP control in predicting mortality and both cardiovascular and renal outcomes in patients at a high cardiovascular risk.     

Hyperinsulinemia for the development of hypertension: data from the Hawaii-Los Angeles-Hiroshima Study.

The present study was to assess the association of metabolic factors including hyperinsulinemia, with the development of hypertension in Japanese-Americans. One hundred forty normotensive (<140/90 mmHg) subjects aged 40 to 69 years old from the Hawaii-Los Angeles-Hiroshima study were followed for 15 years. Patients with cardiovascular disease were excluded. Body mass index (BMI), blood pressure (BP), serum total cholesterol (TC), triglycerides (TG), uric acid (UA), and glucose and insulin responses at baseline, 1 h, and 2 h after a glucose load were analyzed. Seventeen subjects became hypertensive (systolic BP > or = 160 mmHg, diastolic BP > or = 95 mmHg, or received drug treatment) during follow-up. Age- and sex-adjusted BMI, BP, serum UA, TG, insulin, and changes in fasting glucose during follow-up were higher in subjects who later became hypertensive than in those who did not. There was no difference in the change in BMI. Age- and sex-adjusted relative risks for the development of hypertension by quartiles of BMI, serum UA, TG, and the sum of insulin values (sigmainsulin) during a glucose load were highest in highest quartile of the distribution. When age, sex, systolic BP, BMI, serum UA, TC, TG, fasting glucose, sigmainsulin, and the change in BMI were used in a proportional hazard analysis, hyperinsulinemia, hyperuricemia, and systolic BP were found to be significant risk factors for hypertension. In conclusion, hyperinsulinemia, as well as obesity, hyperuricemia, and hypertriglyceridemia were associated with hypertension in Japanese-Americans. Hyperinsulinemia and hyperuricemia were independent predictors of the development of hypertension.     

Postprandial hypotension in the elderly with and without hypertension]

To clarify the mechanism of postprandial hypotension in the elderly, blood pressure and humoral factors were measured before and after meal, water, and glucose ingestion in 20 healthy elderly. The elderly patients were divided into 10 normotensive and 10 hypertensive cases. A reduction in systolic BP after meals in the hypertensive group was significantly larger than that in the normotensive group (-12.0 +/- 4.1 vs. 4.0 +/- 3.2 mmHg, p < 0.05). Systolic BP in hypertensive group significantly decreased at 30, 45 and 60 minutes after meals compared to the value before meals. However, no significant reduction in systolic BP was observed in the normotensive group. A change in systolic BP after meal significantly correlated with that after glucose, but not with that after water ingestion, suggesting that glucose intake mainly contributes to the postprandial hypotension in the elderly. An increase in plasma renin activity and plasma catecholamine were observed after meals in the normotensive group, but not in the hypertensive group. An increase in systolic BP significantly correlated with an increase in PRA. It was suggested that an impairment of the sympathetic nervous system in the elderly with hypertension was involved in the mechanism of postprandial hypotension.     

Determinants of endothelial cell damage in the elderly hypertension: assessment by plasma von Willebrand factor

To investigate the determinants of endothelial cell damage in hypertensive elderly patients, we measured the plasma von Willebrand factor (vWF) levels by a recently developed enzyme-linked immunosorbent assay using monoclonal antibody for the functional epitope. Plasma vWF level was markedly increased in the elderly normotensive subjects (n = 42) than in younger normotensive subjects (n = 39) (127 vs 88%, p < .0001), and was further increased in elderly hypertensive subjects (n = 68) (148%, p < .05 vs elderly normotensives). The vWF level was positively correlated with body mass index in younger normotensive subjects (r = 0.41, p < .01), with systolic blood pressure (BP) in elderly normotensive subjects (r = 0.41, p < .01), and with age (r = 0.44, p < .001) and fibrinogen level (r = 0.37, p < .01) in elderly hypertensive subjects. In elderly hypertensive subjects (n = 150), vWF level had a stronger positive correlation with 24-hr systolic BP measured (r = 0.41, p < .0001) by ambulatory BP monitoring than with clinic systolic BP (r = 0.33, p < .0001). In conclusion, in hypertensive elderly patients, endothelial cell damage increases with systolic BP and fibrinogen levels, indicating a prethrombotic condition.     

Risk variables of insulin resistance syndrome in African-American and Caucasian young adults with microalbuminuria: the Bogalusa heart study

Microalbuminuria is a strong predictor of cardiovascular disease. Previous studies are inconsistent regarding the relationship between microalbuminuria and insulin resistance syndrome. Therefore, we examined this relationship in 1031 young adults (61% Caucasian, 39% African-American) aged 19 to 32 years. Individuals with either urinary albumin to creatinine ratio at or above the 90th percentile (age, race, and gender specific) or urinary albumin level at or above 30 mg/L were considered as having slightly elevated albumin excretion (microalbuminuria). The multiple risk variables of insulin resistant syndrome measured include body mass index, waist circumference, blood pressure (BP), triglycerides, high-density lipoprotein (HDL) cholesterol, glucose, insulin, insulin resistance index (calculated from a homeostasis model assessment equation), and uric acid. After controlling for age and gender, African-Americans with microalbuminuria by either measure had higher mean systolic (P < .001) and diastolic (P < .05) BP, prevalence of hypertension (P < .05), and, contrary to expectations, HDL cholesterol (P < .05) than those without this condition. On the other hand, Caucasians showed no such associations. In African-Americans, the above differences in BP levels persisted when hypertensive subjects were excluded. None of the other risk variables displayed any relation to microalbuminuria in both races. These results suggest that microalbuminuria is not necessarily an intrinsic component of the insulin resistance syndrome, at least in the young adult age. Furthermore, the observed association between hypertension and microalbuminuria among young African-Americans may reflect early evidence of renal dysfunction due to the burden of elevated BP in this group.     

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.     

Urinary albumin excretion in lean, overweight and obese glucose tolerant individuals: its relationship with dyslipidaemia, hyperinsulinaemia and blood pressure.

The presence of microalbuminuria has become an important tool for therapeutic intervention. In this study we investigated whether the dysmetabolic syndrome of obesity was associated with or could occur in the absence of microalbuminuria. The study was conducted in 71 clinically healthy, glucose tolerant Hispanics (age: 43 +/- 1.4 years, body mass index (BMI): 28.7 +/- 0.6 kg/m(2), systolic blood pressure (SBP): 117 +/- 2 mm Hg, diastolic blood pressure (DBP): 77 +/- 1.3 mm Hg, urinary albumin excretion: 10.2 +/- 0.6 mg/24 h). Subjects were classified as lean (BMI <25), overweight (BMI >25 <30) and obese (BMI >30 kg/m(2)). Greater BMI was associated with higher body weight, waist-to-hip ratio (WHR), BP, fasting insulin, triglyceride, post glucose load insulin and glucose, and lower high-density lipoprotein (HDL) cholesterol levels. However, no significant differences in the urinary albumin excretion (mg/24 h) were found between lean (9.0 +/- 0.9; median: 9.1), overweight (11.3 +/- 1.2; median: 10.5) and obese (11.1 +/- 1.2; median: 9.7) subjects. In addition, microalbuminuria (urinary albumin excretion >30 mg/24 h) was not found in any of the study subjects. For all subjects combined, as well as for each of the groups separately, the urinary albumin excretion was unrelated to the BMI, WHR, body weight, triglyceride, cholesterol (total, LDL or HDL), fasting or post-load glucose and insulin plasma concentrations. Neither in females nor in males, abdominal fat accumulation was associated with an increase in the urinary albumin excretion. However, in the obese groups, urinary albumin excretion was strongly related to the level of SBP (r(2): 0.67; P < 0.0001) and DBP (r(2): 0.55; P < 0.0001). In summary, obesity, hyperinsulinaemia and dyslipidaemia per se are not determinants of increased albumin excretion. However, in the obese subjects, the BP, particularly the SBP, was a strong determinant of the level of albumin in the urine. Microalbuminuria may occur later in the course of the dysmetabolic syndrome, due to worsening of hypertension and development of hyperglycaemia.     

Low-grade inflammation and microalbuminuria in hypertension

Background- Albuminuria and C-reactive protein (CRP), a marker of systemic low-grade inflammation, are frequently elevated in essential hypertension and predict cardiovascular prognosis independent of conventional risk factors. However, in spite of their potentially important links, the interrelationships between the 2 parameters have not been explored in depth in hypertensive patients. METHODS AND RESULTS: Albuminuria (the mean of 3 overnight urine collections), high-sensitive CRP (hs-CRP), 24-hour blood pressure (BP), weight, lipids, poststimulative (75 g PO) plasma glucose, insulin, and insulin sensitivity by the homeostasis model assessment model were evaluated in 220 never treated, nondiabetic, uncomplicated essential hypertensive men. Albuminuria > or =15 microg/min was defined as microalbuminuria and hs-CRP values above and below median (2.3 mg/L) as high and low, respectively. Concentric left ventricular hypertrophy was diagnosed by echocardiography, and a full-blown metabolic syndrome was identified in presence of hypertension and at least 3 of following: obesity, subclinical hyperglycemia, low high-density lipoprotein (HDL) and high triglycerides. Microalbuminuria was present in 54 patients, 29 with high hs-CRP characterized by higher 24-hour systolic BP, postload glucose, body mass index, lower HDL cholesterol, more frequent metabolic syndrome, concentric LVH, and active smoking than those with either isolated microalbuminuria (n=27) or normoalbuminuria. CONCLUSIONS: Microalbuminuria accompanied by evidence of subclinical inflammation is a strong correlate of metabolic abnormalities in essential hypertension and identifies a patient subset at very high cardiovascular risk. In contrast, isolated microalbuminuria may represent a distinct pathophysiological condition characterized by a more benign profile and possibly a better prognosis.     

Microalbuminuria as a marker of preclinical diastolic dysfunction in never-treated essential hypertensives

Using 24-h ambulatory blood pressure (BP) monitoring and digitized M-mode echocardiography, we evaluated whether microalbuminuria is related to preclinical left ventricular (LV) diastolic dysfunction in hypertensive patients. We selected 87 never-treated hypertensive patients (mean 24-h BP > 140 and/or > 90 mm Hg); albuminuria was evaluated as mean value of 24-h urinary albumin excretion (UAE) from two 24-h urine collections. Microalbuminuria was found in 28 patients, classified as MA+ (UAE 30 to 300 mg/24 h); 59 patients had normal UAE (< 30 mg/24 h) and were classified as MA−. The MA+ and MA− groups did not differ with regard to age, sex, body mass index, or 24-h heart rate, whereas 24-h, daytime, and nighttime systolic and diastolic BP were significantly higher in MA+ than in MA−. The LV mass index was greater in MA+, as was the prevalence of LV hypertrophy; peak shortening rate of LV diameter, index of systolic function, was normal in all, but was lower in MA+. Peak lengthening rate of LV diameter and peak thinning rate of posterior wall, indices of diastolic function, were lower in MA+ and the prevalence of diastolic dysfunction was higher in MA+. UAE was inversely correlated with both indices of LV diastolic function, also after correction for age, 24-h heart rate, 24-h BP, and LV mass. In conclusion, in never-treated hypertensive patients, microalbuminuria is not only associated with greater myocardial mass, but is also related with preclinical impairment of LV diastolic function. This relation, independent from increased BP or LV mass, strengthens the role of microalbuminuria as an early and reliable marker of preclinical cardiac involvement.     

Glomerular permeability defect in hypertension is dependent on renin angiotensin system activation

BACKGROUND: The aim of the present study was to compare glomerular permeability alterations associated with experimental hypertension models known to have different effects on the circulating renin-angiotensin system (RAS). METHODS: Five groups, 10 animals each, were studied. One group served as a nonhypertensive control. The other four groups of hypertensive animals were composed of spontaneously hypertensive rats, deoxycorticosterone acetate hypertensive rats, Goldblatt two-kidney, one-clip rats, and a group of Wistar rats infused with angiotensin II (200 ng/kg/min). Tail-cuff sphygmomanometric systolic blood pressure (BP), albumin permeability determined in isolated glomeruli exposed to oncotic gradients (P(alb)), glomerular filtration rate (GFR, iopamidol method), plasma renin activity (PRA), and albuminuria were evaluated. RESULTS: Alterations in P(alb) and albumin excretion rate were more evident in the experimental models with an activation of the RAS despite similar levels of systolic BP and GFR. A positive correlation was found between P(alb) and albuminuria (r = 0.51; P < .001) and between systolic BP and albuminuria (r = 0.37; P < .01). No relation was found between systolic BP and P(alb). CONCLUSIONS: The present study indicates that the activation of the RAS plays a significant role in the development of glomerular albumin permeability defects in hypertensive models and may contribute to the mechanisms that lead to target organ damage in hypertension.     

Serum Insulin Level Versus Blood Pressure: A Cross-sectional,Case-controlled Study in Non-obese,Middleaged Japanese Subjects with Normal Glucose Tolerance

To assess the relationship between blood pressure (BP) and serum insulin level in nonobese (body mass index (BMI) ≤ 27 kg m^?2), middle-aged (40–64 years of age) Japanese subjects with normal glucose tolerance, a three-phase study protocol was designed. First, the responses of plasma glucose and serum insulin to an oral glucose load were compared between 40 patients with untreated essential hypertension and 40 age-, sex- and BMI-matched normotensive control subjects. Second, the glucose and insulin responses to an i.v. glucose load were evaluated in 7 non-obese hypertensive, 7 non-obese normotensive and 7 obese hypertensive subjects. Third, BP and serum lipid profile were compared between 21 hyperinsulinaemic (serum insulin level (while fasting, after glucose loading, or both) > 2 SDs higher than the mean) and 21 age-, sex- and BMI-matched normoinsulinaemic subjects (serum insulin level within 1 SD of the mean). The glucose and insulin responses to the oral glucose load were comparable between the hypertensive and normotensive groups. Similarly, the glucose and insulin responses to the i.v. glucose load were comparable between the non-obese hypertensive and normotensive groups, whereas the mean AUC_insulin in the obese hypertensive group was significantly greater (p < 0.01) than that in either of the non-obese groups. The respective mean values for systolic and diastolic BPs did not differ between the hyperinsulinaemic and normoinsulinaemic groups. The mean serum triglyceride and HDL cholesterol concentrations were significantly higher (p < 0.01) and lower (p < 0.05), respectively, in the hyperinsuslinaemic than in the normoinsulinaemic group. The results suggest no association between serum insulin level and BP in non-obese, middle-aged, Japanese subjects with normal glucose tolerance.