Heredity and obesity-associated hypertension: impact of hormonal characteristics and left ventricular mass.

OBJECTIVES: To investigate the influence of heredity on obesity-associated hypertension, we evaluated casual and 24-h blood pressure, left ventricular mass and some metabolic and hormonal measurements in normotensive obese subjects. DESIGN: Healthy, normotensive obese subjects (n = 81) with positive or negative family history of hypertension were studied. Both groups were also subdivided according to a positive or a negative family history of obesity. Accordingly, 45 obese subjects had a positive family history of hypertension, 25 of these having a positive (subgroup A) and 20 having a negative family history of obesity (subgroup B). The other 36 obese subjects had a negative family history of hypertension, 19 of these having a positive (subgroup C) and 17 having a negative family history of obesity (subgroup D). METHODS: Casual and 24-h systolic (SBP), diastolic (DBP) and mean blood pressure (MBP) were evaluated. Serum fasting blood sugar, total cholesterol and triglycerides levels, urinary excretion of sodium, immunoreactive fasting insulin, plasma ANF levels, plasma renin activity (PRA), plasma aldosterone level, plasma adrenaline and noradrenaline levels and echocardiographic total left ventricular mass (LVM) and LVM:height ratio were also calculated. RESULTS: Twenty-four-hour DBP, 24-h MBP, LVM, LVM:height ratio, total cholesterol and PRA values were significantly higher in normotensive obese offspring of hypertensive parents than in obese offspring of normotensive parents. Twenty-four-hour DBP and MBP, LVM, LVM:height ratio, insulin level, insulin:glucose ratio and PRA were significantly higher in subgroup A than in subgroup B. Fasting blood sugar level, 24-h DBP and MBP, insulin level, insulin:glucose ratio, PRA, noradrenaline, adrenaline and plasma aldosterone levels were significantly higher in subgroup C than in subgroup D. Multivariate analysis also indicated that 24-h MBP and PRA levels were significantly influenced by the association between a positive family history of hypertension and obesity. CONCLUSIONS: The present results suggest that a family history of obesity might increase the risk of developing hypertension in obese subjects. An elevated PRA may precede the development of hypertension in obese subjects who are at risk for developing hypertension.

Central obesity and hypertension. Relationship between fasting serum insulin, plasma renin activity, and diastolic blood pressure in young obese subjects.

This study was designed to evaluate the role of fasting serum insulin and plasma renin activity in obesity-induced hypertension. In view of this, plasma catecholamines, fasting serum insulin (IRI), urinary sodium excretion (NaU), plasma renin activity (PRA), and plasma aldosterone (PA) levels were assessed in young (age less than 40 years) normotensive (n = 27) and hypertensive (n = 14) subjects with central obesity and in lean normotensives (n = 20). Central obesity was evaluated by waist-to-hip ratio (WHR) according to the indication of the Italian Consensus Conference of Obesity. PRA, PA, IRI, and plasma norepinephrine levels were significantly (P < .05) higher in both obese groups than in lean normotensives. PRA was significantly (P < .05) higher and NaU was significantly (P < .05) lower in obese hypertensives than in obese normotensives. Diastolic blood pressure correlated directly with WHR and PRA in normotensive and hypertensive obese subjects and with IRI but only in normotensive obese subjects. Multiple regression analysis indicated that diastolic blood pressure values increased with WHR (P < .05), IRI (P < .005), and PRA (P < .002), but not with body mass index, NaU, and norepinephrine levels. Our results indicated that increased PRA could play an important role in the development of hypertension in subjects with central obesity.

Hemostatic function in young subjects with central obesity: relationship with left ventricular function.

This study was designed to evaluate coagulation and fibrinolysis activity and their relationship with left ventricular function in young obese subjects with central fat distribution. We assessed coagulation and fibrinolysis activity by evaluation of factor VII activity, fibrinogen and plasminogen, plasminogen activator inhibitor (PAI), and tissue plasminogen activator antigen basally (tPA1) and after venous occlusion (tPA2). These measures were evaluated in young (< 40 years) obese subjects with central fat distribution (n = 19) and in comparable lean subjects (n = 20). Blood glucose, triglycerides, total and high-density lipoprotein (HDL) cholesterol, apolipoprotein (apo) A1 and apo B, fasting immunoreactive insulin, and lipoprotein(a) levels were also measured by current methods. Left ventricular ejection fraction (LVEF) and peak filling rate (PFR) determined by radionuclide angiocardiography and left ventricular mass (LVM) and LVM indexed for body height (LVM/H) determined by echocardiographic study were calculated. Central obesity was evaluated by the waist to hip ratio (WHR) according to the criteria of the Italian Consensus Conference of Obesity. Factor VII (P < .001), fibrinogen (P < .001), plasminogen (P < .001), PAI activity (P < .001), tPA1 (P < .02), fasting blood glucose (P < .01), apo B (P < .02), and immunoreactive insulin (P < .01) were significantly higher in obese than in lean subjects. In contrast, HDL cholesterol (P < .01), tPA2 (P < .01), LVEF (P < .001), and PFR (P < .02) were significantly lower in obese than in lean subjects. In all subjects, WHR correlated directly with fibrinogen and inversely with tPA2; LVEF correlated inversely with tPA1, PAI, and fibrinogen; and PFR correlated inversely with factor VII activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of obesity and ischaemic heart disease in hypertensive subjects.

In the present study the prevalence of obesity and its association with ischemic heart disease, recognized according to clinical criteria (chest pain or previous infarction) and/or instrumental data, were described in 8,847 normotensive subjects and in 867 hypertensive subjects, hospitalized during a ten years period (1983-1992), through a cross-sectional study. In view of this all the subjects were considered as lean or obese according to their body mass index (BMI) and to sex specific cut-off values reported in the Italian Consensus Conference on Obesity. In particular, according to BMI values, the subjects were grouped as lean, overweight, moderate and severe obese subjects. Our results indicated that 3,982 normotensive subjects (45%) could be considered lean, whereas 2,654 of them (30%) were overweight, 1,769 of them (20%) were moderate obese and 442 of them (5%) were severe obese. On the contrary only 206 hypertensives (23.7%) might be considered lean, whereas 313 (36.1%) were overweight, 302 (34.8%) were moderate obese and 46 (5.3%) were severe obese. According to age subgrouping (lower than or equal to 65 years or higher than 65 years) the distribution of hypertensives within the lean, overweight, moderate and severe obese groups did not change significantly, but, according to sex subgrouping, the distribution of hypertensives within the BMI groups was significantly different (chi 2, p < 0.001). When we considered the degree of hypertension, distribution of hypertensives was significantly different according to c2 test (p < 0.004), suggesting that the percentage of the subjects with severe hypertension increased only in subjects with severe obesity. Concomitant ischaemic heart disease (IHD) was also documented in 350 normotensives (4%) and in 119 hypertensives (13.8%). The prevalence of IHD was not significantly different in lean, overweight, moderate and severe obese hypertensives, also when sex and smoking habits were considered. Our data indicated a strong association between obesity and hypertension. In addition they may be consistent with the suggestion that obese hypertensives were not characterized by a lower risk of ischaemic heart disease (IHD), than lean hypertensives.

Effect of obesity on left ventricular function studied by radionuclide angiocardiography.

Several studies have shown a significant association of obesity with cardiovascular morbidity and mortality. The present study was carried out to investigate central and systemic haemodynamics in overweight and moderate obese, but otherwise healthy subjects, and in a lean control group to determine whether obesity can influence left ventricular performance per se. In this study an attempt has been made to eliminate misleading factors, such as diabetes, lipid abnormalities and hypertension. A total of 67 subjects, 44 with overweight or moderate obesity and 23 lean healthy subjects, were included. Patients were divided into three groups according to BMI levels and Garrow's criteria as follows: lean control group (BMI less than 25 kg/m2); overweight (BMI from 25 to 30 kg/m2); moderate obese (BMI greater than 30 less than 40 kg/m2). Overweight and moderate obese subjects were further subgrouped according to duration of obesity (DO) in subgroup A (DO less than 98 months) and in subgroup B (DO greater than 98 months). Haemodynamic assessment was performed using first pass radionuclide angiocardiography. When compared with lean subjects, overweight and moderate obese subjects were characterized by a significant increase in cardiac output (CO), stroke volume (SV), end diastolic volume (EDV), end systolic volume (ESV), total blood volume (TBV) and total plasma volume (TPV) and by a significant decrease in left ventricular ejection fraction (EF); some of these changes appeared to be related to the degree of obesity. In overweight and moderate obese subjects, total peripheral resistance (TPR) was lower than in lean controls, but this difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of amlodipine on renal haemodynamics in mild to moderate hypertensive patients. A randomized controlled study versus placebo.

In this study the efficacy and safety of short-term amlodipine administration on renal haemodynamics were evaluated in mild to moderate hypertensive subjects. Our final goal was to evaluate whether the reduced blood pressure induced by treatment was associated with maintenance of renal function. After a run-in period with placebo, 30 hypertensive patients without cardiac or renal diseases were randomly allocated to a double-blind 4 weeks controlled study with amlodipine 10 mg once a day (15 patients) or placebo (15 patients). Renal haemodynamic measurements included effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) by radionuclide study using 131I-hippuran and 99mTc, with methods described by Schlegel and Gates, respectively. In addition, effective renal blood flow [ERBF = ERPF/(1-Ht)], filtration fraction (FF = GFR/ERPF) and renal vascular resistance (RVR = MBP x 80/ERBF) were calculated. Plasma renin activity (PRA), serum aldosterone (ALD) and urinary excretion of sodium (NaU) were evaluated. At the end of amlodipine administration a significant decrease (P < 0.001) in SBP, DBP and MBP from baseline values was observed. A significant decrease (P < 0.01) in RVR and significant increases (P < 0.05) in ERPF, ERBF and in NaU were also found, without relevant changes in GFR, FF, PRA and ALD. No significant variation in clinical and renal measurements was observed in the placebo group. No relevant side effects were observed in either group. In conclusion, amlodipine was effective in lowering blood pressure in mild to moderate hypertension and exerted favourable effects on renal haemodynamics and function.

Antihypertensive efficacy and effects of nitrendipine on cardiac and renal hemodynamics in mild to moderate hypertensive patients: randomized controlled trial versus hydrochlorothiazide.

In this study antihypertensive efficacy, safety, and the effects of short-term nitrendipine administration on central and renal hemodynamics were evaluated in mild to moderate hypertensives. Our final goal was to ascertain whether the reduction in blood pressure induced by nitrendipine treatment was associated with maintained renal function. After a run-in period with placebo, 26 hypertensives without cardiac or renal disease were randomly assigned to a double-blind 8-week controlled trial with nitrendipine (N) 20 mg once a day (13 pts) or hydrochlorothiazide (HCT) 25 mg once a day (13 pts). Renal hemodynamic measurements included effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) by radionuclide study using I-131 hippuran and Tc-99m, according to the methods described by Schlegel and Gates, respectively. Effective renal blood flow [ERBF = ERPF/(1-Ht)], filtration fraction (FF = GFR/ERPF), and renal vascular resistance (RVR = MBP x 80/ERBF) were also calculated. Other hemodynamic measurements included cardiac index (CI), left ventricular (LV) ejection fraction (EF), and total peripheral resistance (TPR) measured by the first-pass radionuclide angiography technique. At the end of N or HCT administration significant decreases (p less than 0.001) in SBP, DBP, and MBP vs. baseline values were observed in both hypertensive groups. In the N group a significant decrease (p less than 0.01) in TPR and RVR, and significant increases (p less than 0.05) in CI, ERPF, and ERBF were observed. In the HCT group a significant decrease (p less than 0.05) in RVR was found without significant changes in other hemodynamic parameters. No important side effects were observed with either therapy. In conclusion, nitrendipine was effective in reducting blood pressure in mild to moderate hypertensive patients and exerted favorable effects on cardiac and renal function.

Central obesity and hypertension: pathophysiologic role of renal haemodynamics and function.

OBJECTIVE: To investigate the role of alterations in renal haemodynamics and function and in plasma renin activity on obesity-induced hypertension. DESIGN: Renal haemodynamics and function, salt-regulating hormones and structural cardiac parameters were evaluated in 20 lean normotensives and in 64 obese subjects with central or peripheral fat distribution, 43 of them were normotensives and 21 of them were hypertensives. Obesity and central fat distribution were defined according to sex-specific 85th percentile respectively of Body Mass Index (BMI) and Waist to Hip Ratio (WHR). MEASUREMENTS: Serum immunoreactive insulin (IRI), plasma renin activity (PRA), plasma aldosterone (PA), microalbuminuria (UAE) and 24h urinary excretion of sodium (NaU) were evaluated by current methods. Renal haemodynamics was evaluated by radionuclide study according to Schlegel's and Gate's methods. By radionuclide study, effective renal plasma flow (ERPF), effective renal blood flow (ERBF), glomerular filtration rate (GFR), filtration fraction (FF) and renal vascular resistances (RVR) were measured. Left ventricular mass (LVM) and indexed for body height (LVM/H), cardiac output (CO) and total peripheral resistances (TPR) by ecocardiography were also calculated. RESULTS: CO, LVM and LVM/H were significantly (P < 0.05) higher in all the obese groups than lean controls. In addition, LVM and LVM/H were significantly (P < 0.05) higher in obese hypertensives than obese normotensives either with central fat distribution. TPR values were significantly (P < 0.05) higher in central obese hypertensives than peripheral obese hypertensives and than central obese normotensives. Moreover, IRI levels were significantly (P < 0.05) higher in central normotensive and hypertensive obese subjects than lean subjects. ERBF and ERPF were significantly (P < 0.05) lower and PRA levels were significantly higher only in central obese than lean subjects. On the contrary RVR were significantly (P < 0.05) higher in both obese hypertensive groups and in central obese normotensives than lean subjects. Comparisons between peripheral and central obese groups indicated that PRA, RVR and UAE were significantly (P < 0.05) higher and ERBF and ERPF values were significantly (P < 0.05) lower in both central obese groups than comparable subjects with peripheral obesity. Multiple regression analysis indicated that RVR increased significantly (P < 0.05) with WHR and PRA but not with CO and IRI. CONCLUSIONS: Our results indicate that obesity with body fat distribution of central type, more than obesity of peripheral type, is associated to abnormalities in renal haemodynamics and function. These data are consistent with the indication that change in renal haemodynamics take place at an early stage in the obesity-induced hypertension.

Effects of cilazapril on renal haemodynamics and function in hypertensive patients: a randomised controlled study versus hydrochlorothiazide.

In this study the efficacy and safety of short-term cilazapril administration on renal haemodynamics were evaluated in mild to moderate hypertensive subjects. Our final goal was to evaluate whether the reduction in blood pressure achieved by treatment was associated with maintained renal function. After a run-in period with placebo, 40 hypertensive subjects without renal or cardiac diseases were randomly allocated to a double-blind 4 week controlled trial with cilazapril 5 mg once a day (20 patients) or hydrochlorothiazide 25 mg once a day (20 patients). Renal haemodynamics measurements included effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) by radionuclide study using 131I-hippuran and 99mTc, according to the methods described by Schlegel and Gates, respectively. Effective renal blood flow [ERBF = ERPF/(1-Ht)], filtration fraction (FF = GFR/ERPF) and renal vascular resistance (RVR = MBP x 80/ERBF) were calculated. At the end of cilazapril and hydrochlorothiazide administration significant decreases (p < 0.001) in SBP, DBP and MBP vs baseline values were observed. In the cilazapril group a significant decrease (p < 0.001) in RVR and FF and a significant increase (p < 0.001) in ERPF and ERBF were also found. In the hydrochlorothiazide group a significant decrease (p < 0.001) in RVR was found. No important side effects were observed with either treatment. In conclusion our data indicate that both cilazapril and hydrochlorothiazide reduced blood pressure equally well but only cilazapril improved renal blood flow and reduced filtration fraction.

Lymphocyte beta-adrenergic receptors in young subjects with peripheral or central obesity: relationship with central haemodynamics and left ventricular function.

This study was designed to evaluate total (t) and surface (s) beta-adrenergic receptor (BAR) density and their relationship with central haemodynamics and left ventricular function in young subjects with central or peripheral obesity. A total of 31 obese subjects (BMI > or = 30.5 kg.m-2 for males and > or = 27.3 kg.m-2 for females) aged less than 40 years and without other risk factors for cardiovascular diseases (smoking, hypertension, diabetes and lipid abnormalities) were studied. Nine had peripheral obesity and 22 central obesity according to WHR values; there were 20 lean controls (BMI < 25 kg.m-2 for males and < 24.7 kg.m-2 for females). Casual (c) and 24 h ambulatory mean blood pressures (MBP-24 h) were determined. BAR density was evaluated according to Böyum and De Blasi methods. Plasma catecholamines by high perfusion liquid chromatography and fasting immunoreactive plasma insulin (IRI) were also measured by RIA. Radionuclide angiocardiography was used to determine central haemodynamics and both systolic and diastolic left ventricular function. Total peripheral resistances (TPR) and intravascular volumes were also determined. Echocardiographic study was used to measure LVM, LVM.h-1, LVDD and IVS. Left ventricular ejection fraction (LVEF), peak filling rate (PFR), BARt and BARs were significantly lower (P < 0.05) and cardiac output, cardiac volumes, LVM, LVM. h-1 and time to PFR significantly higher (P < 0.05) in both obese groups than in lean controls. Plasma IRI was significantly (P < 0.05) higher in both obese groups whereas plasma norepinephrine was higher only in central obese.(ABSTRACT TRUNCATED AT 250 WORDS)

Association between reduced lymphocyte beta-adrenergic receptors and left ventricular dysfunction in young obese subjects.

This study was designed to evaluate total (t) and surface (s) beta-adrenergic receptors (BAR) density and their relationships with left ventricular function in young obese subjects. BAR density, plasma insulin, catecholamines and left ventricular function were evaluated in 27 young obese subjects (BMI > 30.5 kg/m2 for males and > 27.3 kg/m2 for females) without other risk factors for cardiovascular diseases (smoking, hypertension, diabetes and lipid abnormalities) and in 20 lean controls (BMI < 25 kg/m2 for males and < 24.7 kg/m2 for females). Both groups were matched for gender, age and body height. BAR density was evaluated according to Böyum and De Blasi methods. Plasma catecholamines by high perfusion liquid chromatography and fasting immunoreactive plasma insulin (IRI) levels by RIA were also measured. Casual (c) and 24 h ambulatory mean blood pressure (MBP/24h) were determined. Radionuclide angiocardiography was used to measure left ventricular ejection fraction (LVEF), peak filling rate (PFR), time to PFR (tPFR), cardiac output (CO) and stroke volume (SV). Total left ventricular mass (LVM), indexed for height (LVM/H), left ventricular diastolic dimension (LVDD) and interventricular septal (IVS) thickness by echocardio-graphic study were calculated. LVEF, PFR, BARt, BARs were significantly lower (P < 0.0001) and plasma IRI, CO, SV (P < 0.0001), LVM (P < 0.003), LVM/H (P < 0.004), LVDD (P < 0.02) and tPFR (P < 0.02) were significantly higher in obese subjects than in lean controls. BARt and BARs correlated inversely with BMI, SV and LVDD.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular diastolic and systolic function in normotensive obese subjects: influence of degree and duration of obesity.

The present study was carried out to evaluate systolic and diastolic parameters in overweight and moderately obese, but otherwise healthy subjects, and in a lean control group, to determine whether degree and duration of obesity can influence left ventricular function. A total of 27 subjects, 17 overweight or with moderate obesity and 10 lean, healthy subjects were included. Patients were divided into three groups according to their body mass index (BMI) and to Garrow's criteria as follows: lean control group (BMI less than 25 kg.m-2); overweight subjects (BMI from 25 to 30 kg.m-2); moderately obese subjects (BMI greater than 30 less than 40 kg.m-2). Systolic and diastolic parameters were measured using blood pool gated radionuclide angiography. Left ventricular (LV) ejection fraction (EF), peak ejection rate (PER), time to PER (tPER), peak filling rate (PFR) and time to PFR (tPFR) were evaluated. PER and PFR values were normalized for end-diastolic volume (EDV). EF and PFR were significantly lower (P less than 0.05) both in moderately obese and in overweight subjects and tPFR was significantly (P less than 0.05) prolonged in both groups in comparison to lean controls. Only in moderately obese subjects was PER significantly (P less than 0.05) decreased and tPER significantly (P less than 0.05) prolonged in comparison to lean controls. As compared to overweight individuals, moderately obese subjects were characterized by a significant decrease (P less than 0.05) in LVEF and PER and by a significant increase (P less than 0.05) in tPER, without relevant change in PFR and in tPFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Micro-albuminuria in obese subjects: relationship among body fat distribution, blood pressure and left ventricular structure and function.

OBJECTIVE: To evaluate the relationships among micro-albuminuria, blood pressure and measurements of left ventricular structure and function in centrally and peripherally obese subjects compared with members of a lean control group. METHODS: Centrally obese subjects were subdivided according to whether they had levels of micro-albuminuria higher than 30 mg/24 h (micro-albuminuric group) or lower than or equal to 30 mg/24 h (normo-albuminuric group). For all the subjects we measured heart rate, casual mean blood pressure (MBP), 24 h MBP, total cholesterol level, high-density lipoprotein cholesterol, lipoprotein (a) level, fasting immunoreactive insulin level, plasma renin activity, plasma aldosterone level and micro-albminuria (UAE) by current methods. Left ventricular mass indexed for body height, left ventricular diastolic and systolic diameters, interventricular septal thickness and left ventricular ejection fraction were measured by echocardiography. Peak filling rate was also calculated by radionuclide study. Family history of cardiovascular disease was evaluated for all the obese subjects.RESULTS: Lipoprotein (a) level, total cholesterol level, 24 h MBP and interventricular septal thickness were significantly (P < 0.05) greater for micro-albuminuric than they were for normo-albuminuric centrally obese subjects, whereas high-density lipoprotein cholesterol level and left ventricular ejection fraction were significantly (P < 0.05 lower. In addition, UAE levels of centrally obese subjects were significantly (P < 0.05) higher than those of peripherally obese subjects. UAE of all the centrally obese subjects was correlated directly to lipoprotein (a) level (r = 0.33, P < 0.009), 24 h MBP (r = 0.41, P < 0.002), interventricular septal thickness (= 0.36, P < 0.005) and family history of cardiovascular disease (r = 0.33, P < 0.007). Multiple regression analysis indicated that UAE was independently related to 24 h MBP and family history of cardiovascular disease. CONCLUSION: Our data indicated that measurement of micro-albuminuria is useful for evaluating cardiovascular risk profiles of obese subjects with a central fat distribution.