Increased Inflammatory Markers Are Associated with Obesity and Not with Target Organ Damage in Newly Diagnosed Untreated Essential Hypertensive Patients

The aim of this study was to investigate whether inflammatory markers are associated with hypertensive end organ damage or obesity in patients with hypertension. Seventy newly diagnosed essential hypertensive patients (29 men and 41 women aged 49.6 ± 9.5 y) and 25 age–sex-matched normotensive subjects (12 men and 13 women aged 45.8 ± 7.3 y) were asked about their family history of hypertension and smoking habits, and body mass index (BMI) was recorded and blood samples were taken to measure fibrinogen, C-reactive protein (CRP), and homocysteine levels. In hypertensive patients, creatinine clearance, urinary albumin extraction, and left ventricular mass index were determined. Hypertensive patients had significantly higher BMIs and inflammatory markers when compared with normotensive healthy controls. The CRP was positively associated with BMI (P < .05), diastolic blood pressure (P < .05), fibrinogen (P < .01), urinary albumin extraction (P < .01), and left ventricular mass index (P < .05). The BMI and serum fibrinogen level were independently associated with CRP. The effect of inflammation on the development of hypertensive end organ damage may be associated with obesity, so that control of obesity may eliminate the inflammatory state in hypertensive patients and also hypertensive end organ damage.     

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.     

Association between salt sensitivity and target organ damage in essential hypertension

Cardiovascular events occur more frequently in sodium-sensitive patients with essential hypertension; recently, sodium sensitivity was shown to be a cardiovascular risk factor independently of other classic factors such as blood pressure and cigarette smoking This study examined the relationship between salt sensitivity status and target organ damage in hypertensive patients. Ninety-six patients (35 men, 61 women) with moderate essential hypertension were studied for salt sensitivity status and the presence of target organ damage, including hypertensive retinopathy, serum creatinine, creatinine clearance, and urinary albumin excretion (UAE). Four different patterns of left ventricular anatomic adaptation were identified by categorizing patients according to the values of left ventricular mass index and relative wall thickness by the means of echocardiography. Forty-five (47%) patients were shown to be salt-sensitive, in contrast to 51 (53%) salt-resistant subjects. Serum creatinine and UAE were significantly higher in the group of salt-sensitive hypertensives (P < .05 and P < .001, respectively). Left ventricular mass index (LVMI), relative wall thickness (RWT), and left atrial index (LAI) were all significantly higher in the group of salt-sensitive hypertensive patients. Concentric hypertrophy was significantly more prevalent in the salt-sensitive group (37.8% v 11.8%; P < .01). The prevalence of hypertensive retinopathy in the salt-sensitive group was 84.4%, in contrast to 59.6% in the salt-resistant group (P < .01). Multivariate regression analysis revealed salt sensitivity as a significant predictor of LVMI, RWT, and UAE, independently of age, body mass index, and mean blood pressure. In conclusion, salt-sensitive hypertensive patients are more prone to develop severe hypertensive target organ damage that may enhance their risk of renal and cardiovascular morbidity.     

Association of body mass index, body fat, and weight gain with inflammation markers among rural residents in Japan.

Because obesity is thought to play a key role in atherosclerosis through the low-grade chronic inflammation, the present study was designed to investigate associations of body mass index (BMI), body fat, and weight gain with optimized inflammation markers in 1,053 residents who were 40 years of age and older from a rural community (total population = 3,940 in 2000) in Japan. People reporting having a cold and those who did not undergo blood examinations were excluded. C-reactive protein (CRP), fibrinogen, serum albumin, and white blood cell (WBC) count were used as the markers for inflammation, body fat was calculated by a conventional method, and weight change since the age of 20 was assessed. The BMI and body fat significantly increased with CRP quartile, and its correlation coefficients to BMI or body fat were relatively high. Similar associations were found for fibrinogen, serum albumin and WBC. Multivariate-adjusted analysis found a high concentration of CRP was significantly associated with obesity, but attenuated the association in other markers. In an analysis restricted to people aged 40-69 years, body fat levels were more strongly associated with CRP and fibrinogen than with BMI only. Furthermore, only CRP concentrations were significantly elevated according to weight gain. Strong associations of CRP concentration with BMI, body fat, and weight gain were found among elderly Japanese, but not with fibrinogen, serum albumin or WBC.     

Associations between nondipping of nocturnal blood pressure decrease and cardiovascular target organ damage in strictly selected community-dwelling normotensives

BACKGROUND: In hypertensives, nondippers are more likely than dippers to suffer silent, as well as overt, hypertensive target organ damage. In this study, we investigated whether a nondipper status was associated with target organ damage in normotensives. METHODS: We performed ambulatory blood pressure (BP) monitoring, echocardiography, and carotid ultrasonography and measured natriuretic peptides and urinary albumin (UAE) in 74 normotensive subjects with the following criteria: 1) clinical BP <140/90 mm Hg; 2) average 24-h ambulatory BP <125/80 mm Hg. RESULTS: The left ventricular mass index (LVMI) and the relative wall thickness (RWT) measured by echocardiography were greater in nondippers than dippers (LVMI: 103 +/- 26 v 118 +/- 34 g/m(2), P <.05; RWT: 0.38 +/- 0.07 v 0.43 +/- 0.09, P <.01). Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were higher in nondippers than dippers (ANP: 14 +/- 10 v 36 +/- 63 pg/mL, P <.01; BNP: 16 +/- 12 v 62 +/- 153 pg/mL, P <.05). There were no significant differences in UAE and intima-media thickness measured by carotid ultrasonography. CONCLUSIONS: Normotensive nondipping may not reflect renal damage, but may have a predominant effect on cardiac damage. Nondipping of nocturnal BP seems to be a determinant of cardiac hypertrophy and remodeling, and may result in a cardiovascular risk independent of ambulatory BP levels in normotensives.     

Markers of inflammation and fibrosis are related to cardiovascular damage in hypertensive patients with metabolic syndrome

BACKGROUND: Previous studies have shown that metabolic syndrome (MS) is associated with an increased susceptibility to develop cardiovascular damage (CD). Experimental evidence indicates that inflammation and fibrosis could play a critical role in the development of CD in hypertension. This issue has not been clarified yet in patients with MS. The aim of our study was to investigate the relationship between markers of inflammation and fibrosis with CD in hypertensive patients with and without MS. METHODS: One hundred twenty-eight essential hypertensive patients were included in the study: 51 with MS and 77 without MS. Clinical, biochemical parameters, 24-h urinary albumin excretion rate (UAER), levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and procollagen type 1 carboxy-terminal propeptide (PICP) were measured. All patients underwent an echocardiographic examination with transmitral Doppler and tissue Doppler imaging (TDI). RESULTS: Left ventricular mass indexed by height(2.7) (LVM/h(2.7)) (P < .001), early diastolic peak flow velocity/early myocardial diastolic velocity ratio (E/Em ratio), a TDI index of diastolic function (P < .001), and 24-h UAER (P < .05) were significantly higher in the group with MS, whereas peak myocardial systolic velocity (Sm), a TDI index of systolic function (P < .001), was lower. Serum levels of CRP (P < .001), TNF-alpha (P < .05), TGF-beta (P < .01), and PICP (P < .001) were significantly increased in MS. These markers were significantly related to higher LVMI(2.7), higher E/Em ratio, and increased 24-h UAER and a lower Sm in the whole population, with a further significant enhancement in MS. CONCLUSIONS: Cardiovascular damage is more frequent in hypertensives with MS than in hypertensives without MS, and this is significantly related to the increased levels of inflammation and fibrosis found in hypertensives with MS.     

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.     

Family history of essential hypertension versus obesity as risk factors for hypertension in adolescents

Family history of hypertension and obesity are both risk factors for hypertension. Hypertension and obesity share several physiopathologic abnormalities and are frequently associated. However, not all obese people are hypertensive. Renal handling of sodium has been proposed as a physiopathogenic mechanism of essential hypertension and obesity. This study was conducted in obese adolescents to evaluate the role of a family history of hypertension versus obesity in the renal handling of sodium. Fractional excretion of lithium (FELi) and uric acid (FEUA) were measured in 46 obese adolescent offspring of hypertensive parents (OH: body mass index [BMI], 29.5 +/- 0.6 kg/m2, age 14.2 +/- 0.3 years, 22 males); eight obese offspring of normotensive parents (ON: BMI, 30.7 +/- 1.7 kg/m2, 14.8 +/- 0.8 years, four males), and in 34 lean adolescent offspring of hypertensive parents (LH: BMI, 20.5 +/- 0.5 kg/m2, 14.3 +/- 0.3 years, 24 males). FELi in OH was 16.5% +/- 1.3%, in ON it was 22.4% +/- 2.3%, and in LH it was 14.4% +/- 1.2% (P < .05). FEUA in OH was 8.5% +/- 0.8%, in ON it was 14.8% +/- 3.6%, and in LH it was 7.9% +/- 0.8% (P < .01). Plasma renin activity (PRA) and aldosterone (PA) were measured in OH and LH; PRA was 5.3 +/- 0.4 and 4.5 +/- 0.4 ng/mL/h, respectively (P = NS), and PA was 366 +/- 36 and 242 +/- 32 pg/mL, respectively (P < .05). In summary, adolescents with a family history of hypertension, regardless of their body mass, have a diminished FELi and FEUA. Obese adolescents also have higher plasma levels of aldosterone than lean ones. In conclusion, the family history of hypertension would be related to the increased renal proximal sodium reabsorption whereas obesity would be related to increased distal sodium reabsorption mechanisms, such as aldosterone. Both mechanisms could explain the higher prevalence of hypertension in obese offspring of hypertensive parents.     

Enhanced vascular activity of endogenous endothelin-1 in obese hypertensive patients

Hypertensive patients have increased endothelin-1-dependent vasoconstrictor tone. This abnormality, however, might not be uniformly present in all forms of hypertension, as suggested by experimental studies showing that endothelin-1 activity is enhanced predominantly in low-renin, high-volume models and in insulin-resistant states. Because hypertension in obesity is commonly associated with both expanded plasma volume and insulin resistance, this study sought to determine whether increased body mass index (BMI) in hypertensive patients relates to activation of the endothelin-1 system. Forearm blood flow (FBF) responses (plethysmography) to intra-arterial infusion of an ETA receptor blocker (BQ-123) were analyzed in hypertensive patients and normotensive control subjects according to BMI. The vasodilator response to BQ-123 was significantly higher in hypertensive patients than in control subjects (P<0.001). During BQ-123, a significant increase in FBF from baseline was observed in obese (BMI > or =30 kg/m2; P<0.001) and overweight (BMI, 27 to 29.9 kg/m2; P=0.04) but not in lean (BMI <27 kg/m2; P=0.83) hypertensive patients. In contrast, no significant change in FBF was observed during BQ-123 either in obese (P=0.53), overweight (P=0.76), or lean (P=0.93) normotensive subjects. Moreover, a significant correlation between BMI and the vasodilator response to ETA blockade was observed in hypertensive subjects (R=0.53; P=0.005) but not in control subjects (R=0.11; P=0.58). In human hypertension, increased BMI is associated with enhanced ETA-dependent vasoconstrictor activity, suggesting that this abnormality may play a role in the pathophysiology of obesity-related hypertension and that targeting the endothelin-1 system may be useful in the treatment of these patients.     

Gender-specific correlates of leptin with hypertension-related phenotypes in African Americans

Leptin may be a link in the relationship of obesity with hypertension. We evaluated associations of leptin with blood pressure (BP) in 54 normotensive and 114 hypertensive African American individuals. Plasma leptin was higher (P <.03) in hypertensive women than in normotensive women, although body mass index did not differ (30.5 +/- 0.5 v 30.2 +/- 0.8 kg/m(2)). After adjusting for obesity and insulin resistance, there were no significant relationships between leptin and BP; however, leptin independently predicted 28% of the variability of heart rate in hypertensive men (P <.01) and 18% of the variability of lithium clearance in hypertensive women (P <.01). Thus, in these obese hypertensive African American women, there is no direct or independent association of leptin with BP. However, leptin may contribute to hypertension in these women by increasing renal tubular sodium reabsorption.     

C-reactive protein in young, apparently healthy men: associations with serum leptin, QTc interval, and high-density lipoprotein-cholesterol

To determine which anthropometric, biochemical, and cardiovascular variables are associated with serum levels of C-reactive protein (CRP) in young, apparently healthy men, a cross-sectional study of 179 male college students aged 18 to 22 years was performed. Multiple regression analysis was used to derive models for serum CRP concentrations in terms of the other variables measured. Although CRP was positively correlated with body mass index (BMI), percent fat mass, and serum leptin, correlations with BMI (r = 0.15, P =.05) and percent body fat (r = 0.16, P =.003) were not as strong as the correlation with leptin (r = 0.28, P =.0002). CRP was also associated with resting heart rate (r = 0.14, P =.05), heart-rate corrected QT (QTc) interval (r = 0.22, P =.003) and several components of the insulin resistance (IR) syndrome. CRP showed a strong and negative association with high-density lipoprotein (HDL)-cholesterol (r = -0.26, P =.0005) and a marginal and positive association with triglyceride (r = 0.14, P =.05). Although CRP was associated with fasting insulin (r = 0.15, P =.04), it was not related to serum adiponectin or IR index estimated using homeostasis model assessment (HOMA). Multiple regression analysis indicated that serum CRP was positively related to serum leptin (P =.003) and QTc interval (P =.01), and negatively correlated with HDL-cholesterol (P =.01, R(2) = 0.15). In young, apparently healthy men, serum leptin but not BMI was independently associated with serum CRP, suggesting that amount of body fat may be the most significant predictor of CRP. Although low-grade inflammation was associated with long QTc interval and low HDL-cholesterol, the mechanism underlying these associations is an important question to be addressed.     

Elevated blood pressure,cardiometabolic risk and target organ damage in youth with overweight and obesity

Background and aimTo compare cardiometabolic risk profile and preclinical signs of target organ damage in youth with normal and elevated blood pressure (BP), according to the American Academy of Pediatrics (AAP) guidelines.Methods and resultsThis cross-sectional multicenter study included 2739 youth (5-17 year-old; 170 normal-weight, 610 overweight and 1959 with obesity) defined non hypertensive by the AAP guidelines. Anthropometric, biochemical and liver ultrasound data were available in the whole population; carotid artery ultrasound and echocardiographic assessments were available respectively in 427 and 264 youth. Elevated BP was defined as BP ≥ 90th to <95th percentile for age, gender and height in children or BP ≥ 120/80 to <130/80 in adolescents. The overall prevalence of elevated BP was 18.3%, and significantly increased from normal-weight to obese youth. Young people with elevated BP showed higher levels of body mass index (BMI), insulin resistance and a higher prevalence of liver steatosis (45% vs 36%, p < 0.0001) than normotensive youth, whilst they did not differ for the other cardiometabolic risk factors, neither for carotid intima media thickness or left ventricular mass. Compared with normotensive youth, individuals with elevated BP had an odds ratio (95%Cl) of 3.60 (2.00–6.46) for overweight/obesity, 1.46 (1.19–1.78) for insulin-resistance and 1.45 (1.19–1.77) for liver steatosis, controlling for centers, age and prepubertal stage. The odds for insulin resistance and liver steatosis persisted elevated after correction for BMI-SDS.ConclusionCompared to normotensive youth, elevated BP is associated with increased BMI, insulin resistance and liver steatosis, without significant target organ damage.     

Cytosolic calcium and insulin resistance in elderly patients with essential hypertension.

We evaluated insulin sensitivity in normotensive (blood pressure, BP, less than 135/85 mm Hg) and hypertensive (BP greater than 160/90 mm Hg) elderly subjects over 65 years old who were stratified as normal weight (body mass index, BMI, less than 27) and obese (BMI greater than 27). Obese hypertensive individuals demonstrated marked hyperinsulinemia (P less than .01) and significantly reduced (P less than .05) submaximally stimulated adipocyte 2-deoxyglucose (2-DOG) uptake (abdominal wall fat biopsy). Normal weight hypertensive subjects also demonstrated higher levels of insulinemia and lower insulin-stimulated 2-DOG uptake than nonobese controls. Adipocyte [Ca2+]i levels were elevated in all elderly subjects compared to young individuals (P less than .01). Basal and maximally stimulated 2-DOG uptake were similar in all groups. One month of therapy with a calcium channel blocker, 10 mg nitrendipine twice daily, reduced blood pressure in the hypertensive subjects, reduced plasma insulin to control values during an oral glucose tolerance test in obese hypertensive individuals (P less than .01), and restored adipocyte 2-DOG uptake at submaximally effective insulin concentration to control values in normal weight and obese hypertensive subjects. In summary, older hypertensive, and particularly older obese hypertensive, patients manifest significant insulin resistance accompanied by elevated levels of [Ca2+]i in their adipocytes.     

Association of high sensitivity C-reactive protein with coronary heart disease prediction, but not with carotid atherosclerosis, in patients with hypertension.

BACKGROUND: Inflammation is believed to predict coronary heart disease (CHD) in healthy subjects and in patients with atherosclerosis. We investigated the association of high sensitivity C-reactive protein (HS-CRP) and other inflammatory markers on cardiovascular outcome, and carotid atherosclerosis in hypertensive patients. METHODS AND RESULTS: We conducted a cross-sectional study of 122 hypertensive patients and compared them with 64 normotensive volunteers. We measured circulating levels of HS-CRP, white blood cells (WBC), albumin, fibrinogen, erythrocyte sedimentation rate, and interleukin-6, and examined the associations with traditional risk factors of CHD, carotid atherosclerosis, and a 10-year risk of CHD, based on the risk prediction algorithm of the Framingham model. The mean of blood pressure (BP) of the hypertensive patients was 163/102 mmHg (normotensives; 118/79 mmHg). The 10-year risk of CHD was higher in the hypertensive patients (9.3 +/- 7.3%) compared with the normotensive volunteers (4.3 +/- 4.2%). Albumin and HS-CRP were significantly higher in the hypertensive patients. Multivariate analysis showed that among markers, only HS-CRP was associated with 10-year risk of CHD (beta=0.13, p=0.03). The BP, body mass index, high-density lipoprotein, WBC count, fibrinogen, and cardiac hypertrophy increased across quartiles of HS-CRP. There was no association between HS-CRP and carotid atherosclerosis in subjects with hypertension and normotension. CONCLUSION: A higher HS-CRP level was associated with a higher risk score of CHD, but not with carotid atherosclerosis, in patients with hypertension.     

Effect of obesity on endothelium-dependent, nitric oxide-mediated vasodilation in normotensive individuals and patients with essential hypertension.

The purpose of this study was to determine the interdependent and independent effects of hypertension and obesity on endothelial function in humans. We evaluated the forearm blood flow (FBF) response to acetylcholine, an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, in 16 lean and 12 obese normotensive individuals and the 18 lean and 15 obese hypertensive patients with no history of smoking, hypercholesterolemia, diabetes mellitus, or renal dysfunction. The FBF was measured using a mercury-filled Silastic strain-gauge plethysmograph. The systolic and diastolic blood pressures (BP) and forearm vascular resistance were significantly greater in hypertensive patients than in the normotensive individuals. Insulin resistance, determined by a homeostatic model assessment (HOMA), was significantly greater in the obese group than in the lean group (3.59 +/- 1.68 v 1.91 +/- 1.12, P < .01). There was no significant difference in the HOMA index between normotensive and hypertensive subjects regardless of weight. The response of FBF to acetylcholine was greatest in lean normotensive individuals and least in obese hypertensive patients (40.5 +/- 8.5 and 10.4 +/- 2.8 mL/min/100 mL of tissue, P < .001 v other groups). The FBF response was similar in obese normotensive individuals and lean hypertensive patients (24.1 +/- 7.9 and 19.3 +/- 3.2 mL/min/100 mL of tissue). The vasodilatory effect of ISDN was similar in all four groups. Multiple regression analysis revealed that the maximal FBF response to acetylcholine correlated independently with age (P = .043), obesity (P = .012), HOMA index (P = .002), and mean BP (P < .001). These findings suggest that obesity and hypertension are independently involved in abnormal endothelium-dependent vasodilation by attenuated nitric oxide production.     

C-reactive protein and target organ damage in untreated patients with primary hypertension

High sensitivity C-reactive protein (hs-CRP) has been recognized as a risk factor for cardiovascular disease. Asymptomatic organ damage is known to precede cardiovascular events in hypertension. The aim of the present study was to investigate the relationship between hs-CRP and signs of organ damage, namely left ventricular mass index (LVMI), albuminuria, and carotid atherosclerosis in a group of hypertensive patients. One hundred and eighty-two untreated patients with primary hypertension were studied. HS-CRP was measured by immunonephelometry. LVMI was assessed by echocardiography, albuminuria was measured as albumin to creatinine ratio, and carotid atherosclerosis by ultrasonography. Patient stratification according to quartiles of hs-CRP showed a significant trend toward higher age, prevalence of left ventricular hypertrophy, and carotid plaques. Moreover, there was a significant correlation among hs-CRP quartiles and left ventricular mass index, carotid cross-sectional area, carotid plaques, and albuminuria. Multiple regression analysis showed that, after adjusting for established cardiovascular risk factors (ie, age, duration of hypertension, smoking habit, body mass index (BMI), 24-hour systolic and diastolic blood pressures, glucose, creatinine, uric acid, triglycerides, total and low-density lipoprotein cholesterol), hs-CRP remained a strong correlate of target organ damage. These results support the importance of chronic microinflammation in the development of atherosclerotic disease in hypertension.     

The relationship between obesity and transforming growth factor beta on renal damage in essential hypertension

The aim of this study was to evaluate the effect of obesity on renal functions and the possible relationship between TGF-beta1 and obesity in hypertensive patients. Seventy newly diagnosed, hypertensive patients (male/female 36/34, aged 45.0 +/- 8.0 years) and 30 (male/female 17/13, aged 41.8 +/- 7.7 years) normotensive controls were included. Patients in both groups were analyzed for serum levels of glucose, creatinine, uric acid, lipids, and TGF-beta1. A 24-hour urine sample was also obtained; creatinine clearance rate and urinary albumin excretion (UEA) were investigated. TGF-beta1 levels were significantly higher (40.7 +/- 13.6 versus 34.2 +/- 12.1 pg/mL, P = 0.02), and creatinine clearance was significantly lower in patients compared with controls (98.9 +/- 25.5 versus 124.5 +/- 23.1 mL/min. per. 1.73 m(2), P = 0.001). Serum TGF-beta1 levels (45.2 +/- 14 versis 38.0 +/- 12.8 pg/mL, P = 0.03), creatinine clearance rates (109.8 29.9 versus 93.0 +/- 20.8 mL/min. per. 1.73 m(2), P = 0.001), and urinary albumin excretion (55.7 +/- 62.0 versus 12.7 +/- 12.6 mg/24 h, P = 0.002) were higher in obese hypertensive patients than in nonobese patients. In hypertensive patients, TGF-beta1 levels correlated with body mass index (r = 0.296, P = 0.01) and creatinine clearance (r = 0.238, P = 0.04). The results suggest that increased body mass index is associated with increased creatinine clearance, urinary albumin excretion, and TGF-beta1 levels in essential hypertension. In addition, TGF-beta1 is positively correlated with body mass index and creatinine clearance in patients with essential hypertension.     

The chest radiograph. A useful investigation in the evaluation of hypertensive patients

BACKGROUND: The assessment of target organ damage is important in the evaluation of a hypertensive patient as it provides information on the severity of the hypertension and the cardiovascular risk assessment. The aim of our study was to determine the usefulness of the chest radiograph in the assessment of target organ damage in hypertensive patients. METHODS: Unselected patients attending an academic hypertension clinic were studied. The cardiothoracic ratio and the aortic knob width were measured and compared to other markers of target organ damage. The aortic width was measured in age- and sex-matched controls. RESULTS: Seventy-two hypertensive and 77 age- and sex-matched normotensives were evaluated. There was a highly significant difference the aortic knob width between the normotensive and hypertensive patients (3.28 cm v 3.69 cm, P <.0001). The aortic knob width was significantly correlated with age in normotensive and hypertensive patients, systolic and diastolic blood pressure (BP), and all markers of target organ damage except the electrocardiogram (ECG) voltage. The cardiothoracic ratio was also significantly correlated with age and other markers of target organ damage, but not clinic BP. Multiple regression analysis revealed that only the cardiothoracic ratio (r = 0.34, P <.02) and the ECG voltage (r = 0.58, P <.00005) were independently correlated with left ventricular mass. CONCLUSIONS: The chest radiograph provides important predictive information of associated target organ damage in hypertensive patients.     

Concentration of the complement activation product, acylation-stimulating protein, is related to C-reactive protein in patients with type 2 diabetes

Type 2 diabetes is characterized by increased acute phase serum proteins. We wanted to study how these proteins are related to complement activation in type 2 diabetes and how improvement of glycemic control affects them or complement activation. A total of 29 type 2 diabetic patients (age, 55.2 +/- 1.8 years, glycosylated hemoglobin [HbA(1c)] 8.9% +/- 0.2%, body mass index [BMI] 30.9 +/- 0.8 kg/m(2), duration 5.9 +/- 1.3 years) participated in the study. They were previously treated either with diet alone or in combination with 1 oral antihyperglycemic medication. After a period of at least 4 weeks run-in on diet only, the patients were randomized to pioglitazone, glibenclamide, or placebo. Blood samples were taken before the treatments and at the end of the 6-month therapy. Basal C-reactive protein (CRP) level was related to acylation-stimulating protein (ASP) concentration (r =.55, P <.01), and many acute phase serum protein concentrations were associated with each other. The treatment reduced HbA(1c) level in the pioglitazone (from 9.1 +/- 0.3% to 8.0 +/- 0.5%, P <.05) and glibenclamide (from 8.9 % +/- 0.3% to 7.7% +/- 0.2%, P <.05) groups. Glibenclamide treatment was associated with a reduction in alpha-1-antitrypsin (P <.05), ceruloplasmin (P <.01), and complement C3 protein (C3) (P <.05). Although ASP did not change significantly in any of the treatment subgroups, in the whole patient population, the change in HbA(1c) during the treatments correlated positively with the change in ASP, (r =.43, P <.05). The changes in many acute phase serum proteins and ASP were related to each other. In conclusion, (1) inflammatory factors and complement activation are associated in patients with type 2 diabetes, and (2) changes in hyperglycemia are related to changes in the concentration of the complement activation product, ASP.     

Association of left ventricular hypertrophy with metabolic risk factors: the HyperGEN study

OBJECTIVE : To determine whether combinations of metabolic risk factors (obesity, diabetes and hypercholesterolemia) influence the magnitude of left ventricular (LV) mass and prevalence of LV hypertrophy. DESIGN : Cross-sectional, relational. METHODS : A total of 1627 hypertensive (85.9% treated, 1036 women, 1041 African Americans) and 342 normotensive (180 women, 183 African Americans) participants in the Hypertension Genetic Epidemiology Network (HyperGEN) Study, without prevalent cardiovascular disease, were studied. Echocardiographic LV mass, normalized by height(2.7) or fat-free mass or body surface area (BSA) and the ratio of stroke volume to pulse pressure as a percentage of predicted (as a crude estimate of arterial compliance) were analyzed in relation to obesity [by body mass index (BMI)], central fat distribution (by waist circumference), diabetes (by ADA criteria) and hypercholesterolemia. RESULTS : Obesity, hypercholesterolemia, and diabetes were more frequent among hypertensives than normotensives (all P < 0.001). After controlling for age, sex, race and type and combination of antihypertensive medication, LV mass/height(2.7), but not LV mass/fat-free mass and LV mass/BSA, increased with the number of metabolic risk factors, both in normotensive and hypertensive participants, also after further adjustment for blood pressure (all P < 0.001). Stroke volume/pulse pressure also decreased in hypertensive, but much less in normotensive subjects, with increasing number of metabolic risk factors, independently of relevant confounders (P < 0.0001). Prevalence of LV hypertrophy was predicted by older age, hypertension, central fat distribution, black race and independently increased with the number of associated metabolic risk factors (P < 0.0001). CONCLUSIONS : The progressive addition of metabolic risk factors including central obesity, diabetes and hypercholesterolemia is associated with higher LV mass normalized by height(2.7), independently of hypertension and other important biological covariates. Obesity played a major role in this association. This finding indicates that LV mass is a potentially useful bioassay of strategies of global cardiovascular prevention.