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PubMed1995

"Strict" blood pressure control and progression of renal disease in hypertensive nephrosclerosis.

Hypertensive nephrosclerosis is a progressive renal disease and the leading cause of end-stage renal disease (ESRD) in blacks in the United States. It is generally believed that hypertensive renal injury is responsible for progressive renal failure; however, it is not known whether pharmacologic lowering of blood pressure to any level prevents progression of renal disease. Accordingly, we performed a long-term prospective randomized trial to determine whether "strict" [diastolic blood pressure (DBP) 65 to 80 mm Hg] versus "conventional" (DBP 85 to 95 mm Hg) blood pressure control is associated with a slower rate of decline in glomerular filtration rate. Eighty-seven non-diabetic patients (age 25 to 73; 68 black, 58 male) with long-standing hypertension (DBP > or = 95 mm Hg), chronic renal insufficiency (GFR < or = 70 m/min/1.73 m2) and a normal urine sediment were studied. DBP was pharmacologically lowered to < or = 80 mm Hg (3 of 4 consecutive measurements at 1 to 4 weeks intervals) after which patients were randomized. DBP and GFR (renal clearance of 125I-iothalamate) were measured at baseline, at three months and every six months post-randomization. The rate of decline in GFR (GFR slope, in ml/min/1.73 m2/year), estimated by the method of maximum likelihood in a mixed effects model, was the primary outcome variable. In a secondary analysis, 50% reduction in GFR (or a doubling of serum creatinine) from baseline, ESRD and death were combined.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

Change in vascular adhesion protein-1 and metabolic phenotypes after vertical banded gastroplasty for morbid obesity.

OBJECTIVE: The association between circulating vascular adhesion protein-1 (VAP-1) and metabolic phenotypes has been shown to be inconsistent. The current study explored whether the changes in serum VAP-1 levels correlate with the changes in metabolic phenotypes after weight reduction surgery. RESEARCH METHODS AND PROCEDURES: Clinical characteristics and serum VAP-1 levels in 20 morbidly obese subjects (mean BMI 38.84 kg/m(2)) were measured before and after vertical banded gastroplasty. RESULTS: Before surgery, serum VAP-1 levels correlated positively with fasting plasma glucose (gamma = 0.56, p = 0.01) and negatively with insulin levels (gamma = -0.51, p = 0.021). After surgery, the changes in serum VAP-1 levels were negatively correlated with the changes in waist circumference (gamma = -0.57, p = 0.011), diastolic blood pressure (DBP) (gamma = -0.56, p = 0.015), and mean arterial pressure (gamma = -0.46, p = 0.055). In multivariate regression, serum VAP-1 levels were negatively correlated with waist circumference (beta = -2.36, p = 0.014) and DBP (beta = -3.02, p = 0.017) after adjusting for age and gender. The change in DBP was negatively correlated with the change in VAP-1 levels after adjusting for age, gender, and steady-state plasma glucose. DISCUSSION: The results suggest that VAP-1 levels are correlated with fasting glucose and insulin levels in morbidly obese subjects. After surgery, the changes in VAP-1 levels were associated with changes in visceral adiposity and DBP. Serum VAP-1 might modulate DBP independently from the changes in insulin resistance in morbidly obese people.

Adolescent↗
PubMed1998

Significance of blood pressure levels achieved with felodipine anti-hypertensive treatment on cardiovascular structure and function changes.

One of the targets of anti-hypertensive treatment is cardiovascular structural and functional improvements, while the level of blood pressure (BP) under treatment is related to patient morbidity and mortality. The aim of this study was to evaluate the relation of BP achieved after felodipine monotherapy to the degree of cardiovascular changes. Six hundred patients with essential hypertension were studied and grouped according to diastolic BP (DBP) levels after 6 months of therapy: 90-94 (n = 86), 85-89 (n = 186), 80-84 (n = 180) and < 80 mm Hg (n = 148). Overall BP fell from 175/103 to 137/83 mm Hg with a concomitant moderate reflex tachycardia (3.3%). Left ventricular (LV) dimensions decreased to a degree (-0.4 and -0.8%, P < 0.0001), with the greatest decrease in patients with lower DBP levels under treatment (P < 0.0001). LV systolic function improved to a modest degree (0.8%, P < 0.0001), depending on DBP fall (P < 0.0001), as did cardiac output (2.4%, P < 0.0001). LV systolic wall stress and total peripheral resistance fell (-18% and -14%, P < 0.0001) in relation to DBP drop (P < 0.0001), as did aortic root distensibility (55%, P < 0.0001). It is concluded that the degree of cardiovascular structure and function improvements are directly related to the DBP levels achieved under felodipine anti-hypertensive therapy.

Aged↗
PubMed1998

Postexercise decrease in arterial blood pressure, total peripheral resistance and in circulatory responses to brief hyperoxia in subjects with mild essential hypertension.

The objective of our study was: (1) to compare the influence of moderate exercise on circulatory after-response in mildly hypertensive (n = 8) and normotensive male subjects (n = 9); (2) to examine the circulatory response to 3-min hyperoxic inactivation of arterial chemoreceptors at rest and during postexercise period in both groups. Hypertensive men (HTS) with a systolic blood pressure (SBP) 148 +/- 5 mm Hg, diastolic blood pressure (DBP) 92.4 +/- 4 mm Hg; and normotensive men (NTS), with a SBP 126 +/- 3 mm Hg, DBP 75.6 +/- 1.3 mm Hg, were submitted to 20-min of moderate exercise on a cycloergometer (up to the level of 55% of each subject's resting heart rate reserve). Finger arterial BP was recorded continuously with Finapres, impedance reography was used for recording stroke volume, cardiac output and arm blood flow. In HTS a significant decrease in SBP by 14.5 +/- 3.4 mm Hg, DBP by 8.9 +/- 1.9 mm Hg, total peripheral resistance (TPR) by 0.45 +/- 0.05 TPR u. (33.7 +/- 2.7%), and in arm vascular resistance (AVR) by 11.0 +/- 2.7 PRU u. (35.6 +/- 7%), was observed over a 60-min postexercise period. NTS exhibited insignificant changes in SBP, DBP, AVR except a significant decrease in TPR limited only to 20-min postexercise period. Hyperoxia decreased SBP, DBP and TPR in HTS. This effect was significantly attenuated during the postexercise period. Long-lasting antihypertensive effect of a single dynamic exercise in HTS suggests that moderate exercise may be applied as an effective physiological procedure to reduce elevated arterial BP in mild hypertension. We suggest also that the attenuation of the sympathoexcitatory arterial chemoreceptor reflex may contribute to a postexercise decrease in arterial BP and in TPR in mildly hypertensive subjects.

Adult↗
PubMed2002

Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by beta-adrenergic blocking agents: a placebo-controlled, double-blind, randomised trial.

Sibutramine is a serotonin-noradrenaline reuptake inhibitor that is effective for long-term weight reduction and maintenance in obese patients when used as an adjunct to dietary and behavioural measures. Because the inhibition of noradrenaline reuptake may be expected to increase systolic and diastolic blood pressure (SBP and DBP) and pulse rate (PR), a 12-week multi-centre, placebo-controlled, double-blind study was designed to evaluate the efficacy and tolerability of sibutramine for weight loss in obese patients whose hypertension was well controlled (DBP < or = 95 mm Hg) by beta-adrenergic blocking agents (beta-blockers), with or without concomitant thiazide diuretics. Of the 61 patients randomised to sibutramine 20 mg once daily or placebo, 55 patients (90%) completed the study. After 12 weeks, sibutramine-treated patients lost significantly more weight than placebo-treated patients: mean weight reductions were 4.2 kg (4.5%) in the sibutramine group vs 0.3 kg (0.4%) in the placebo group (P<0.001). Greater weight reduction on sibutramine was accompanied by trends for greater mean reductions in serum triglycerides and very low density lipoprotein cholesterol. Sibutramine was well tolerated, and most adverse events were mild or moderate in severity. No sibutramine patient discontinued treatment because of an adverse event. Mean supine and standing DBP and SBP were not statistically significantly different between the sibutramine group and the placebo group at any post-baseline visit during the 12-week trial. At week 12, mean increases from baseline supine SBP and DBP, respectively, were 1.6 and 1.7 mm Hg for the sibutramine group vs increases of 0.4 and 1.3 mm Hg for the placebo group. At week 12, mean increases from baseline standing SBP and DBP, respectively, were 1.5 and 1.8 mm Hg for the sibutramine group vs an increase of 0.3 and a decrease of 0.8 mm Hg for the placebo group (P > 0.05 for treatment comparison). A statistically significant mean increase of 5.6 bpm (+/-8.25, s.d.) in supine PR from a baseline of 62 bpm was reported in sibutramine-treated patients at week 12, whereas placebo-treated patients had a mean supine PR decrease of 2.2 bpm (+/-6.43) (P < 0.001). In summary, sibutramine was well tolerated and effective in weight reduction. The addition of sibutramine did not result in an increase in BP in obese patients whose hypertension was well controlled by a beta-blocker. However, based on the potential for changes in BP and PR, obese patients being treated with sibutramine should be monitored periodically for changes in BP and PR and managed appropriately.

Adrenergic beta-Antagonists↗
PubMed2002

Comparison of trough effect of telmisartan vs perindopril using self blood pressure measurement: EVERESTE study.

This multicentre study was aimed at comparing the trough effect of telmisartan and perindopril on diastolic blood pressure (DBP), using self blood pressure measurement (SBPM). A second objective was to compare the data obtained from SBPM with those provided by automatic office BP measurement. A total of 441 mild-to-moderate hypertensive patients were randomised to receive either telmisartan 40 mg or perindopril 4 mg for a period of 12 weeks. Patients whose clinic DBP remained higher than or equal to 90 mmHg at the end of the 6th week (W6) were given a double-dose regimen. Office BP and SBPM were performed at baseline (W0), at W6 and at week 12 (W12), both with the same automatic device. A greater diminution of trough DBP was obtained with telmisartan (-6.6+/-6.7 mmHg) than with perindopril (-5.1+/-7.0 mmHg; P=0.018). Regarding clinic BP, the same results were observed. Doubling dose was significantly less frequent with telmisartan (41%; n=85) than with perindopril (55%; n=115, P=0.005). Mean values of SBPM were lower than office BP values, with a difference of a greater importance at W0 than at W12: 6.6 vs 4.7 mmHg for systolic blood pressure (P<0.005) and 3.2 vs 1.4 mmHg for DBP (P<0.0001). At W12, isolated office hypertension was found in 9% of the patients (n=37), while there were 14% of the patients (n=55) with isolated home hypertension. In conclusion, the trough effect on DBP was statistically higher with telmisartan than with perindopril. SBPM values were lower than office BP values, with greater differences before than after treatment. About a quarter of the patients were found to be controlled with a method but not with the other one.

Adult↗
PubMed2003

Diastolic blood pressure is an important determinant of augmentation index and pulse wave velocity in young, healthy males.

Pulse wave velocity (PWV) and augmentation index are widely used measures of arterial stiffness. The purpose of this study was to evaluate the role of blood pressure as a determinant of both indices independent of potentially confounding factors including gender, age and cardiovascular disorders. A total of 77 young, healthy subjects were investigated under resting conditions. Augmentation index was derived by pulse wave analysis using carotid applanation tonometry. PWV was determined from pressure tracing over the carotid and femoral artery. The relations between stiffness markers and haemodynamic parameters were analysed by simple (r) and multiple (beta) regression analysis. Using simple regression analysis, augmentation index was correlated to age (r=0.292, P=0.0105), diastolic blood pressure (DBP, r=0.483, P<0.0001), mean arterial blood pressure (MAP, r=0.381, P=0.0007), pulse pressure (r=-0.414, P=0.0002) and total peripheral resistance (r=0.266, P=0.0204). After multiple regression analysis, augmentation index remained significantly correlated only to DBP (beta=0.347, P=0.0051). Using simple regression analysis, PWV was correlated to age (r=0.304, P=0.0067), systolic blood pressure (r=0.280, P=0.0129). DBP (r=0.455, P<0.0001), MAP (r=0.446, P&<0.0001) and heart rate (r=0.348, P=0.0018). After multiple regression analysis, PWV remained correlated only to age (beta=0.218, P=0.0422) and DBP (beta=0.4105, P=0.0316). In summary, DBP is an important determinant of augmentation index and PWV in young, healthy males. Further studies are needed to characterize the impact of blood pressure on arterial stiffness in other populations including females and older subjects.

Adult↗
PubMed2003

Telmisartan vs losartan plus hydrochlorothiazide in the treatment of mild-to-moderate essential hypertension--a randomised ABPM study.

The objective of this prospective, randomised, open-label, blinded-end point parallel-group, multicentre study was to show that telmisartan 80 mg is not inferior to a fixed-dose combination of losartan 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg in patients with mild-to-moderate hypertension. The criterion for noninferiority was a treatment difference of < or =3.0 mmHg in the reduction of 24-h mean ambulatory diastolic blood pressure (DBP) from the end of the 4-week placebo washout period to the end of the 6-week active treatment period. In the intent-to-treat analysis, the mean reduction in 24-h DBP was 8.3+/-6.7 mmHg among telmisartan-treated patients (n=332) and 10.3+/-6.3 mmHg among losartan/HCTZ-treated patients (n=350). The mean adjusted difference in 24-h DBP between the two treatment groups was 1.9 mmHg, allowing rejection of the a priori null hypothesis of a treatment difference of >3 mmHg. The reduction in mean 24-h systolic blood pressure was 13.2+/-10.2 mmHg with telmisartan and 17.1+/-10.3 mmHg with losartan/HCTZ. Both drugs provided effective control over the 24-h dosing interval. Analyses of morning (0600-1159) ambulatory blood pressure monitoring DBP means and trough cuff DBP confirmed the noninferiority hypothesis of the protocol for telmisartan 80 mg vs losartan 50 mg/HCTZ 12.5 mg. The reductions in office blood pressures measured at trough in patients treated with telmisartan were -16.3/-9.6 and -18.5/-11.1 mmHg in the patients treated with losartan/HCTZ (difference -2.4/-1.2 mmHg). There were no differences between the side-effect profiles of the two treatments.

Aged↗
PubMed2003

Associations of blood pressure with carotid intima-media thickness in elderly Finns with diabetes mellitus or impaired glucose tolerance.

The aim of the present study was to evaluate the associations of ultrasonographic manifestations of carotid atherosclerosis with systolic (SBP) and diastolic blood pressure (DBP) and pulse pressure (PP) in 65-year-old Finns drawn from a population-based cohort. Carotid ultrasonographic measurements were performed on 54 diabetic subjects, 97 subjects with impaired glucose tolerance (IGT) and 57 normoglycaemic subjects (NGT). The subjects were classified into four quartiles of SBP, DBP and PP. SBP, DBP, PP and the use of antihypertensive drugs increased along with the deterioration of glucose status. The maximal intima-media thickness (IMT) of the common carotid artery (CCA) from the lowest to the highest quartiles of SBP was 0.98+/-0.34, 1.00+/-0.35, 1.03+/-0.29, 1.18+/- 0.52 mm (P=0.038), respectively. SBP was higher (161+/-22 mmHg) in the subjects with severe intima-media thickening (maximal IMT CCA > or =1.2 mm) than in those with maximal IMT CCA of <1.2 mm (153+/- 20 mmHg) (P=0.030). DBP and PP tended to be higher in the former than the latter group (DBP: 89+/-9 mmHg vs 86+/-9 mmHg, P=0.055 and PP: 72+/-18 mmHg vs 67+/-17 mmHg, P=0.159). The prevalence of severe intima-media thickening was 39% in the subjects in the highest SBP quartile (> or =170 mmHg) and 20% in the subjects with lower SBP (P=0.008). In multiple regression analysis, the adjusted OR for severe intima-media thickening was 2.9 (95% CI 1.1-7.9) in the subjects in the highest SBP quartile compared to the subjects with lower SBP. In the present study, high SBP was associated with severe carotid intima-media thickening. We suggest that the results can be generalized to apply to elderly Finnish subjects with DM and IGT, but not to normoglycaemic subjects, on the basis of this study.

Aged↗
PubMed2003

Blood pressure levels in 7 to 14-year-old Belgrade children.

The objective of the work was to study blood pressure and some anthropometric characteristics in children. The study design included the prevalence study at Belgrade, Serbia and Montenegro. The study comprised 1651 subjects (809 boys and 842 girls) aged 7-14 years, that is, 2.6% of all relevant population. The average levels of systolic and diastolic blood pressures (SBP and DBP) were 113.4/70.3 mmHg in boys and 114.6/71.1 mmHg in girls. High SBP was present in 4.7% of boys and in 5.3% of girls. High DBP was found in 5.6% of boys and in 4.8% of girls. According to multivariate regression analysis, in boys SBP and DBP were significantly associated with age, body mass index (BMI) and subscapular skinfold, SBP was also associated with body weight, and DBP with triceps skinfold. In girls, SBP was significantly related to BMI, suprailiac skinfold and body height, and DBP was significantly associated with BMI, suprailiac and subscapular skinfolds. The results of the present study support the opinion that BMI is a significant predictor of blood pressure in children and point out to suprailiac skinfold in girls as a possible predictor of blood pressure.

Adolescent↗
PubMed2004

Comparison of the antihypertensive effects of the fixed dose combination enalapril 10 mg/nitrendipine 20 mg vs losartan 50 mg/hydrochlorothiazide 12.5 mg, assessed by 24-h ambulatory blood pressure monitoring, in essential hypertensive patients.

Fixed combinations of calcium channel blockers and angiotensin converting enzyme inhibitors represent an alternative to diuretic-based combination therapy. The aim of the present study was to compare the antihypertensive efficacy of the combination enalapril 10 mg/nitrendipine 20 mg (E/N) vs losartan 50 mg/hydrochlorothiazide 12.5 mg (L/H), assessed by 24-h ambulatory blood pressure monitoring. This multicentre, double-blind, parallel study included 97 hypertensive patients (office diastolic blood pressure (DBP) 90-109 mmHg and daytime DBP > 85 mmHg). After a 2- to 3-week period of single-blind placebo, they were randomized to receive double-blind treatment with E/N (n = 48) or L/H (n = 49) for a 4-week period. The primary outcome measure was the difference in 24-h DBP reduction between treatments from randomization to the end of the double-blind period. Secondary efficacy variables included differences in 24-h systolic (S) BP reduction, daytime, night-time and office SBP and DBP reduction, proportion of responders and controlled patients, trough-to-peak ratio and smoothness indexes. Safety was assessed by the proportion of patients with adverse events and the detection of laboratory abnormalities. No significant differences were observed in the primary outcome measure. The group receiving E/N tended to show greater reductions in most measures (24 h, daytime and office SBP and DBP) and higher BP control rates, but only the difference in the rate of office SBP control (< 140 mmHg) reached statistical significance (42.2 vs 22.4%; P = 0.048). The trough-to-peak ratios and smoothness indexes were similar in both groups. The incidence of adverse events related to the treatment was 27.1% (95% CI 14.5-39.6%) in E/N-treated patients and 14.3% (95% CI 4.5-45.8%) in the L/H group, but differences were not significant. The kind of event more frequently observed were flushing and headache in E/N, and dizziness and asthenia in L/H; all observed adverse events were mild. We conclude that E/N and L/H have a similar antihypertensive efficacy, assessed by office or ambulatory blood pressure monitoring. E/N achieved a significantly higher office SBP control rate, but this was accompanied by an apparently higher proportion of mild adverse events.

Antihypertensive Agents↗
PubMed2005

Effects of low-dose aspirin on blood pressure and endothelial function of treated hypertensive hypercholesterolaemic subjects.

The main objective of this study was to assess whether aspirin 100 mg QD can improve blood pressure (BP) control and endothelial function in subjects with arterial hypertension (AH) and hypercholesterolaemia. In total, 21 patients of both sexes (52.1+/-11.5 years) with treated AH and hypercholesterolaemia on antihypertensive and statin therapy were included in the treatment group. In the control group, 20 matched patients of both sexes (51.3+/-12.7 years), but without statin therapy, were recruited. Treatment group subjects received aspirin (100 mg QD) for a duration of 12 weeks at randomization (Treatment phase-1), followed by single blind matching placebo for 12 weeks (Placebo phase) and then again received aspirin (100 mg QD) for an additional 12 weeks (Treatment phase-2). The control group participated in Treatment phase-1, but did not continue Placebo phase and Treatment phase-2. At randomization and at the end of each study phase, mean 24-h systolic BP (SBP) and diastolic BP (DBP) were assessed by 24-h ambulatory blood pressure monitoring (ABPM) and endothelium-dependent (flow mediated, FMD) and -independent (nitroglycerin induced, NTG) vasodilatations of brachial artery were measured using high-resolution ultrasound. In Treatment phase-1, reduction of SBP and DBP (DeltaSBP 5.7+/-2.6 mmHg, P=0.008; DeltaDBP 3.8+/-1.7 mmHg, P=0.014) and improvement of FMD (4.1+/-0.6%, P=0.019), in Placebo phase an elevation of SBP and DBP (DeltaSBP -6.2+/-2.9 mmHg, P=0.002; DeltaDBP -4.2+/-1.9 mmHg, P=0.031) and worsening of FMD (-3.8+/-0.9%, P=0.027), and in Treatment phase-2 reduction of SBP and DBP (DeltaSBP 4.9+/-2.3 mmHg, P=0.005; DeltaDBP 4.1+/-1.3 mmHg, P=0.024) and improvement of FMD (4.5+/-1.3%, P=0.009) were observed in the treatment Group but not in the control group. Addition of low-dose aspirin to antihypertensive medications and statins in hypertensive and hypercholesterolaemic subjects can reduce both SBP and DBP by improvement of endothelial function.

Adult↗
PubMed2003

Photophysical behaviour of an opp-dibenzoporphyrin (2,12-diethyl-3,13-dimethyldibenzo[g,q]porphyrin) in micelles and organic solvents.

Photophysical parameters relevant to photodynamic therapy have been studied for a novel lipophilic opp-dibenzoporphyrin (DBP), 2,12-diethyl-3,13-dimethyldibenzo[g,q]porphyrin, in N,N-dimethylformamide and TX-100 micelles. The structure of DBP is intermediate between a porphyrin and a phthalocyanine and is associated with higher molar extinction coefficients in the red Q-bands than those found in the haematoporphyrin derivative currently used for photodynamic therapy. The ultrafast measurements on DBP in DMF revealed a fast (ps) lifetime for the second excited singlet state. Observed lifetimes of the first excited singlet state were found to be similar in DMF and TX-100 (12.2 and 14.7 ns), but excited triplet lifetimes were different in the two solvents (0.46 and 2.86 micros). The fluorescent quantum yields of DBP in DMF and TX-100 were twice that of free-base tetraphenylporphyrin and the singlet oxygen quantum yield in DMF and TX-100 was high (0.56-0.65). The combination of stable chemical structure, stronger red-absorption, high singlet oxygen quantum yields, and high fluorescent quantum yields suggests that DBP is an potential chromophore for applications in photodynamic therapy.

Journal Article↗
PubMed1985

Chromatofocusing in the purification and separation of apo- and holo-(vitamin D-binding protein).

Chromatofocusing was used to purify the vitamin D-binding protein (DBP) from pig plasma in a procedure that consisted of an initial DEAE-cellulose chromatography followed by DEAE-Sephadex chromatography, with final purification by chromatofocusing. The protein was purified 184-fold over its concentration in plasma. When the plasma was labelled with a tracer concentration of [3H]calcidiol, it was apparent that holo- and apo-DBP did not co-chromatograph on chromatofocusing. The separation of these two forms of DBP on chromatofocusing was verified by using purified apo-DBP mixed with either a tracer or a saturating concentration of calcidiol. This separation was consistent with differences observed in their isoelectric points. The ability to separate apo and holo forms of DBP should permit the study of their specific interactions with other binding proteins and help determine the physiological relevance of these interactions.

25-Hydroxyvitamin D 2↗
PubMed2000

Does the age of onset of growth hormone deficiency affect cardiac performance? A radionuclide angiography study.

BACKGROUND: GH and IGF-I seem to play a relevant role in cardiac development and performance. Long-standing GH deficiency (GHD) causes several abnormalities in cardiac structure and performance which ultimately determine an increased cardiovascular morbidity and mortality. OBJECTIVE: To investigate whether the age of onset of GHD plays a role in determining the negative effects on the heart. DESIGN: Open cross-sectional PATIENTS: 55 patients with adulthood-onset GHD and 36 healthy sex- and age-matched controls. Patients and controls were divided into 2 groups in line with age: 32 patients and 16 controls, were aged </= 35 years (young); while 23 patients and 20 controls were aged between 36 and 60 years (middle-aged). The estimated disease duration was similar in young (6.7 +/- 0.5 years) and middle-aged patients (8.1 +/- 1.2 years, P = 0.2). STUDY PROTOCOL: All subjects underwent ECG, blood pressure and heart rate measurement, plasma IGF-I level assay, and equilibrium radionuclide angiography. RESULTS: Plasma IGF-I levels were significantly lower in patients than in controls (P < 0.0001). When considered as a whole, no difference in systolic (SBP) and diastolic blood pressure (DBP) at peak exercise was found between patients and controls. However, a significant decrease of SBP at rest was found in young patients as compared to age-matched controls (P = 0.009), while a significant increase of DBP at rest was found in middle-aged patients as compared to age-matched controls (P = 0.03). In addition, in young patients, both resting (P = 0.02) and exercise heart rate (P = 0.01) were significantly lower than in controls. Diastolic filling when measured as end-diastolic volume (EVD/sec), was significantly reduced in middle-aged patients (P = 0.04). An impaired peak filling rate (PFR) (< 2.5 EDV/sec) was found in 30 patients (54.5%) and 10 controls (27.7%, chi2 = 5.3, P = 0.02): 17 young (53.1%) and 13 middle-aged patients (56.5%). A significant decrease of left ventricular (LV) ejection fraction (EF) at peak exercise was found in both patients groups (P < 0.0001) while LVEF at rest was lower only in middle-aged patients (P = 0.004). An impaired LVEF at rest (< 50%) was found in 13 patients (23.6%) and in none of controls (chi2 = 8.1, P = 0.004). The exercise induced changes in LVEF (DeltaEF) were significantly lower in both patients groups than in age-matched controls (P < 0.0001). Impaired LVEF response to exercise (< 5% increase vs. basal value) was found in 36 patients (65.4%) and in 5 controls (13.8%, chi2 = 21.3, P < 0.000): 21 young (65.6%) and 15 middle-aged patients (65.2%). The peak ejection rate (PER) was also significantly lower in young GHD patients than in controls (P < 0.001). Exercise duration and capacity were significantly reduced in both groups of GHD patients. In the patient group, age was significantly correlated with SBP and DBP levels both at rest (r = 0.612, and r = 0.516, respectively, P < 0.001) and at peak exercise (r = 0.4, P < 0.005 and r = 0.34, P < 0. 01, respectively), with exercise duration (r = - 0.383, P < 0.005) and capacity (r = - 0.355, P = 0.005). Disease duration was also correlated with IGF-I levels (r = - 0.319, P < 0.01), SBP levels at peak exercise (r = 0.352, P = 0.005), and LVEF at rest (r = - 0.254, P < 0.05). Finally, a significant correlation was found between IGF-I levels and DBP at peak exercise (r = 0.3, P < 0.05) and between GH peak at ARG + GHRH test and LVEF at rest (r = 0.232, P < 0.05). Exercise-induced changes in LVEF were significantly correlated with SBP levels at peak exercise (r = - 0.401, P < 0.005), PFR expressed as EDV/sec (r = - 0.306, P < 0.05) and SV/sec (r = - 0.292, P < 0.05). At multiple regression analysis in the patient group, age was the strongest predictor of SBP both at rest (t = 4.17, P < 0.0001) and at peak exercise (t = 2.32, P = 0.025), and capacity (t = - 2.84, P = 0.007). IGF-I levels were the strongest predictor of DBP at peak exercise (t = 2.2, P = 0.

Adult↗
PubMed2002

Predictors of antihypertensive response to a standard dose of hydrochlorothiazide for essential hypertension.

BACKGROUND: Determinants of inter-individual variation in blood pressure (BP) response to antihypertensive therapy remain largely unknown. Although differences in race, age and measures of the renin-angiotensin-aldosterone system (RAAS) have been associated with variation in blood pressure response to hydrochlorothiazide, whether these characteristics make additive contributions to predicting response has not been established. We conducted a comprehensive search for predictors of BP response to a standard dose of hydrochlorothiazide in a biracial sample to estimate how much inter-individual variation in BP response could be explained by all of the identified predictors. METHODS: After withdrawal of antihypertensive medications for at least four weeks (baseline) and stabilization on a diet approximating 150 mmol sodium per day, 225 African American and 280 Caucasian subjects with diagnosed essential hypertension were treated for four weeks with hydrochlorothiazide 25 mg per day. At baseline and the end of treatment, subjects were admitted to the General Clinical Research Center for measurement of activity of the RAAS and other regulators of BP. Characteristics measured at study enrollment, at baseline, and in response to drug treatment were incorporated stepwise into linear regression models in order to quantify their additive contributions to predicting BP responses to hydrochlorothiazide. RESULTS: Black race and female gender were both associated with significantly greater systolic (SBP) and diastolic (DBP) blood pressure responses to hydrochlorothiazide. Together the combined effects of race and gender accounted for 11% inter-individual variation in SBP response (P < 0.0001) and 4% of inter-individual variation in DBP response (P < 0.0001). Additional statistically significant predictors of greater systolic and diastolic responses to hydrochlorothiazide included, shorter duration of diagnosed or treated hypertension (P < 0.001), higher baseline BP level (P < 0.0001), lower baseline plasma renin activity (P < 0.05), lower baseline urinary aldosterone excretion (P < 0.002), and greater decrease in urinary sodium excretion (P < or = 0.004). Greater decrease in weight was an additional statistically significant predictor of SBP but not DBP response, and older age was a predictor of diastolic but not SBP response. The combined effects of all identified predictors accounted for 38% of inter-individual variation in SBP response (P < 0.0001) and 20% of inter-individual variation in DBP response (P < 0.0001). CONCLUSIONS: A systematic search reveals numerous predictors of BP response to a standard antihypertensive dose of hydrochlorothiazide. However, because the majority of inter-individual variation in SBP and DBP responses remains unexplained, there is considerable opportunity for future investigations to improve the ability to predict individual BP responses to antihypertensive drug therapy.

Adult↗
PubMed2002

Evidence for elevated pulse pressure in patients on chronic hemodialysis: a case-control study.

BACKGROUND: Few analyses have compared pulse pressure (PP) values in hemodialysis patients with healthy individuals, and they have provided only limited data. We retrospectively examined PP in a large cohort of hemodialysis patients and healthy control subjects. METHODS: The relationships of systolic blood pressure (SBP), diastolic blood pressure (DBP), and PP to mean arterial pressure (MAP) levels were investigated in 234 chronic hemodialysis patients and in 682 control subjects matched for age, sex, diabetes mellitus, and body mass index. RESULTS: In both control and patients, PP was positively correlated with MAP, and the two regression lines were parallel (beta of control subjects = 0.52; beta of hemodialysis patients = 0.57, P = 0.48). According to the regression line, at any MAP level, the PP in hemodialysis patients was significantly higher than that in control subjects: the mean PP difference between control and patients was 19.2 mm Hg (95% CI, 17.2 to 21.1 mm Hg, P < 0.0001). When the relationships between MAP and SBP and that between MAP and DBP were analyzed, the regression lines were also parallel. However, at any MAP level, SBP was higher and DBP was lower in hemodialysis patients than control subjects; the mean SBP difference was 12.8 mm Hg (95% CI, 11.5 to 14.1 mm Hg, P < 0.0001) and mean DBP difference was 6.4 mm Hg (95% CI, 5.7 to 7.0 mm Hg, P < 0.0001). CONCLUSIONS: At any MAP level, hemodialysis patients had a higher SBP, lower DBP, and higher PP values than those control subjects with a normal renal function who were matched for age, sex, diabetes mellitus, and body mass index. Further study is needed to determine whether preventing or reducing an elevated PP improves the prognosis for hemodialysis patients.

Adult↗
PubMed2002

Diastolic blood pressure-estimated left ventricular dp/dt.

BACKGROUND: Peak dp/dt is one of the best isovolumic phase indexes of the myocardial contractile state requiring invasive procedures or presence of mitral regurgitation severe enough to measure in clinical practice by Doppler echocardiography. In this study, we sought the correlation between two noninvasive methods of measurements for left ventricular dp/dt-diastolic blood pressure- (DBP) estimated and continuous-wave Doppler-derived dp/dt-min electrocardiographic/echocardiographic study to emphasize the clinical feasibility of the DBP-estimated method. METHOD: Thirty-six randomized patients (27 male, 9 female; 58 +/- 8 years) with mild mitral regurgitation were enrolled in this study. DBP-estimated dp/dt was calculated from DBP minus the left ventricular end-diastolic pressure (LVEDP) over the isovolumetric contraction time (IVCT). LVEDP was assumed to be 10 mmHg for all patients. Doppler-determined left ventricular dp/dt was derived from the continuous-wave Doppler spectrum of mitral regurgitation jet by dividing the magnitude of the left ventricular atrial pressure gradient rise between 1 mm/sec-3 mm/sec of mitral regurgitant velocity signal by the time taken for this change. RESULTS: Left ventricular dp/dt by Doppler was 1122 +/- 303 mmHg/sec and blood pressure-estimated dp/dt was 1063 +/- 294 mmHg/sec. There was a high correlation (r = 0.97, P < 0.001) of dp/dt between the two techniques. CONCLUSIONS: DBP and IVCT can generate left ventricular dp/dt without invasive procedures, even in the absence of mitral regurgitation in clinical practice.

Aged↗