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ABSTRACT: In view of the low sensitivity of Sokolow-Lyon voltage criteria in the assessment of electrocardiographic left ventricular hypertrophy (ECG LVH) in overweight subjects, we determined its clinical utility in 1840 lean and 3555 overweight subjects with hypertension. They were followed prospectively over an average of 11 years by the Department of Health and Social Security Hypertension Care Computer Project. LVH was determined at baseline using the Sokolow-Lyon criterion that is, the amplitude voltage SV1+(max RV5 or RV6) > or =3.5 mV. Overweight status was defined as body mass index (BMI) > or =25 kg m(-2). Prevalence of ECG LVH was 16% in lean and 12% in overweight women, 35 and 20% in lean and overweight men. For each 0.1 mV increase in ECG voltage as a continuous variable, the age and sex adjusted risk of stroke, coronary heart disease and cardiovascular disease (CVD) mortality increased significantly by 3.0, 1.5 and 1.8% in overweight subjects and by 2.8, 1.8 and 2.4% in lean subjects. After additional adjustments for smoking, blood glucose and serum cholesterol concentration in a subgroup of 654 lean and 1281 overweight subjects with complete information on these variables, an increasing voltage still significantly predicted stroke and CVD mortality in overweight subjects. The excess high risk of dying was evident especially in women with LVH in the highest BMI quartiles. When ECG detects LVH in overweight subjects, it is a good predictor of mortality despite the lower sensitivity in this group.
Journal of Human Hypertension 09/2008; 23(1):20-6. · 2.80 Impact Factor
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ABSTRACT: The clinical usefulness of the Sokolow-Lyon voltage criteria in the assessment of electrocardiographic left ventricular hypertrophy (ECG LVH) is addressed. We prospectively studied 3,338 women and 3,330 men referred with hypertension, with an average follow-up of 11.2 years. The voltage amplitude sum SV1+max (RV5 or RV6) was calculated and ECG LVH was defined as a sum >or=3.5 mV. We adjusted survival for age, treatment status before presentation and a previous myocardial infarction or cerebrovascular accident. The risk of stroke, coronary heart disease (CHD) and cardiovascular disease (CVD) mortality increased significantly for each quantitative 0.1 mV increase in baseline electrocardiogram (ECG) voltage, in women within the range of 1.6-3.9% and in men 1.4-3.0%. After further adjustments for race, body mass index, smoking and systolic blood pressure, increasing voltage independently predicted CVD mortality in both men and women. In women, both increasing voltage and the presence of left ventricular hypertrophy (LVH) were predictors of stroke mortality, whereas in men this risk was attenuated. In men, the adjusted association between increasing voltage and CHD mortality tended to be stronger than in women. The use of different thresholds for the two genders made little difference. For stroke and CHD mortality, the population attributable fractions associated with LVH were 15.2 and 5.4% in women and 12.8 and 8.5% in men, respectively. In conclusion, the greater the baseline ECG voltage sum, the greater the associated CVD mortality risk. Women tended to have a high risk of stroke mortality owing to LVH despite adjustments.
Journal of Human Hypertension 07/2006; 20(6):451-9. · 2.80 Impact Factor
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ABSTRACT: Left ventricular hypertrophy (LVH) measured by electrocardiography (ECG LVH) in hypertensive patients has been shown to be associated with an increased risk of cardiovascular sequelae. Analysis of the determinants predisposing to ECG LVH may be helpful in the prevention of LVH. The Department of Health and Social Security Hypertension Care Computer Project studied 2994 hypertensive patients in whom an electrocardiogram was recorded while not on treatment. LVH was determined as the voltage sum SV1+RV5 or RV6>or=35 mm using Sokolow-Lyon voltage criteria. The relations were determined between the presence of LVH or voltage sum and different variables. Untreated systolic (SBP) and diastolic (DBP) blood pressure and pulse pressure were positively related to the increasing ECG voltage, while body mass index (BMI) and serum cholesterol were inversely related. Blood glucose and age did not correlate significantly. Patients with the presence of ECG LVH were more often men, black people, smokers and users of alcohol. In multiple logistic regression analyses, SBP, DBP, male gender and black race were positively, whereas BMI was negatively related to the presence of LVH. The positive relation of smoking and negative relation of serum cholesterol concentration to the presence of ECG LVH were apparent in men but not in women. This study confirms the adverse association between ECG LVH and SBP and DBP, male gender, black race and decreased BMI. It also addresses the less well-known associations of blood glucose, cholesterol, smoking and alcohol consumption.
Journal of Human Hypertension 03/2003; 17(3):159-64. · 2.80 Impact Factor
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ABSTRACT: Early survival of patients with intracerebral hemorrhage in general is known to be most strongly dependent on the Glasgow Coma Scale score on admission. The aim of this study was to examine the factors determining functional outcome and in-hospital mortality of patients admitted with an intracerebral hemorrhage related to oral anticoagulant (OAC) use.
Correlation studies and multiple logistic regression analyses were performed on data from a retrospective series of 42 patients admitted with OAC-related intracerebral hemorrhages over a 6-year period to a tertiary care center in the north of Scotland.
The functional outcome after an OAC-related intracerebral hemorrhage was dependent on maximum diameter of hematoma on CT scan (R:=-0.72, P:<0. 001) and international normalized ratio (INR) (R:=-0.35, P:=0.024). Hematoma diameter and INR were not themselves strongly correlated (R:=0.31, P:=0.099). In-hospital mortality can be predicted by the Glasgow Coma Scale score alone (R:(2)=0.36, overall predictive accuracy 68%) but more accurately by a logistic regression model including hematoma diameter and CT signs of cerebrovascular disease (R:(2)=0.70, predictive accuracy 83%).
Neither functional outcome nor in-hospital mortality appears to be strongly dependent on INR measured on admission. CT scan, however, provides essential information and allows accurate predictions about the short-term outcome of OAC-related intracerebral hemorrhages.
Stroke 11/2000; 31(11):2558-62. · 5.73 Impact Factor
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ABSTRACT: The aim of this study has been twofold: 1--to examine the impact of oral anticoagulant (OAC) use on a possible recent rise in the admission rate of intracerebral haemorrhages to Aberdeen Royal Infirmary (ARI), and 2--to estimate the absolute risk of intracranial haemorrhage for outpatients followed up in the OAC Clinic at ARI. The number of patients admitted to ARI with intracerebral bleedings increased by 60% between 1993 and 1998. A corresponding increase in the proportion of patients with concurrent OAC use (4.7% vs 15.7%, p = 0.055) cannot sufficiently explain the increase in the total number of intracerebral haemorrhages. The average annual incidence of intracranial haemorrhages for the OAC Clinic at ARI is found to be acceptably low at 0.33% per year. Further audit of the large number of patients receiving warfarin outwith the supervision of the clinic is urgently required.
Scottish medical journal 09/2000; 45(4):101-4. · 0.40 Impact Factor
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ABSTRACT: The aim of this study was to compare the clinical course and radiological features of oral anticoagulant (OAC)-related intracranial haemorrhages with those of haemorrhages unrelated to OAC use admitted over the last six years to a tertiary care centre in the North of Scotland. We furthermore wished to determine the measures taken for reversal of OAC therapy and the resulting short-term outcome. Sixty-eight patients had been treated with OACs at the time of intracranial haemorrhage (32% subdural, 62% intracerebral). Patients admitted with OAC-related and unrelated haemorrhages did not differ significantly in any of the clinical features considered. On CT scan, there was no significant difference according to OAC use in the mean size of subdural (depth 15 +/- 5 vs. 18 +/- 8 mm, p = 0.36), or intracerebral haematomas (max. diameter 40 +/- 21 vs. 41 +/- 20 mm, p = 0.73). No reversal measures were taken in 38% of OAC-treated patients. In-hospital mortality was significantly higher for OAC-related haemorrhages compared to unrelated haemorrhages (38% vs. 18%, p = 0.001). To further elucidate the effects of anticoagulant reversal on the outcome of OAC-related intracranial haemorrhages, a large-scale prospective study is warranted.
Scottish medical journal 09/2000; 45(4):105-9. · 0.40 Impact Factor
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R H Fagard,
J A Staessen,
L Thijs,
J Gasowski,
C J Bulpitt,
D Clement,
P W de Leeuw,
J Dobovisek,
M Jääskivi,
G Leonetti,
E O'Brien,
P Palatini,
G Parati,
J L Rodicio,
H Vanhanen, J Webster
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ABSTRACT: The goal of the present study was to assess the effect of antihypertensive therapy on clinic (CBP) and ambulatory (ABP) blood pressures, on ECG voltages, and on the incidence of stroke and cardiovascular events in older patients with sustained and nonsustained systolic hypertension.
Patients who were >/=60 years old, with systolic CBP of 160 to 219 mm Hg and diastolic CBP of <95 mm Hg, were randomized into the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial. Treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both. Patients enrolled in the Ambulatory Blood Pressure Monitoring Side Project were classified according to daytime systolic ABP into 1 of 3 subgroups: nonsustained hypertension (<140 mm Hg), mild sustained hypertension (140 to 159 mm Hg), and moderate sustained hypertension (>/=160 mm Hg). At baseline, patients with nonsustained hypertension had smaller ECG voltages (P<0.001) and, during follow-up, a lower incidence of stroke (P<0.05) and of cardiovascular complications (P=0.01) than other groups. Active treatment reduced ABP and CBP in patients with sustained hypertension but only CBP in patients with nonsustained hypertension (P<0.001). The influence of active treatment on ECG voltages (P<0.05) and on the incidence of stroke (P<0.05) and cardiovascular events (P=0.06) was more favorable than that of placebo only in patients with moderate sustained hypertension.
Patients with sustained hypertension had higher ECG voltages and rates of cardiovascular complications than did patients with nonsustained hypertension. The favorable effects of active treatment on these outcomes were only statistically significant in patients with moderate sustained hypertension.
Circulation 09/2000; 102(10):1139-44. · 14.74 Impact Factor
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ABSTRACT: Recent studies have shown inconsistent results on the risk of cancer in hypertensive patients using calcium channel blockers (CCBs) and angiotensin-converting enzyme (ACE) inhibitors. We investigated a large number of patients from the Department of Health Hypertension Care Computing Project (DHCCP) observational database treated with these drugs for hypertension to see whether the use of CCBs for hypertension is associated with an increased risk of cancer mortality and the use of ACE inhibitors with a reduction.
Matched case-control study and a longitudinal study of survival from 1 year after presentation.
A total of 11663 patients treated for hypertension from 1971 through 1987. They were recruited on presentation to one of the hospital hypertension clinics or general practices involved.
Death with any mention of cancer on the death certificate in patients treated with an Index drug group; CCBs, ACE inhibitors, beta adrenergic blocking drugs (BBs), or receiving a diuretic. The treatment groups were mutually exclusive.
A total of 391 cases of cancer were matched with 1050 controls. In this case-control study the adjusted relative risk estimate in comparison to diuretic treatment for CCBs was 0.79 (95% CI 0.37 to 1.69), and for CCBs plus a diuretic, 1.05 (0.65 to 1.69). Non-significant results were also observed for ACE inhibitors (1.48 (0.43 to 5.1), and 1.40 (0.56 to 3.50) with a diuretic), and also for the BB and methyldopa groups. In the longitudinal survival study, the adjusted relative risk estimate for CCBs was 1.1 (0.60 to 1.94) and 1.0 (0.53 to 1.86) for CCBs plus a diuretic, and for ACE inhibitors 1.33 (0.37 to 4.76) and 1.47 (0.67 to 3.23), respectively.
In this population there was no increased cancer mortality with the use of CCBs and a relative risk greater than 1.7 to 2.0 was excluded with 95% confidence. The suggestion that ACE inhibitors reduce cancer mortality was not supported with best estimates of relative risk of 1.3 to 1.5 and exclusion of values less than 0.4 to 0.7.
Journal of Human Hypertension 06/2000; 14(5):299-304. · 2.80 Impact Factor
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J A Staessen,
L Thijs,
R Fagard,
E T O'Brien,
D Clement,
P W de Leeuw,
G Mancia,
C Nachev,
P Palatini,
G Parati,
J Tuomilehto, J Webster
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ABSTRACT: The clinical use of ambulatory blood pressure (BP) monitoring requires further validation in prospective outcome studies.
To compare the prognostic significance of conventional and ambulatory BP measurement in older patients with isolated systolic hypertension.
Substudy to the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial, started in October 1988 with follow up to February 1999. The conventional BP at randomization was the mean of 6 readings (2 measurements in the sitting position at 3 visits 1 month apart). The baseline ambulatory BP was recorded with a noninvasive intermittent technique.
Family practices and outpatient clinics at primary and secondary referral hospitals.
A total of 808 older (aged > or =60 years) patients whose untreated BP level on conventional measurement at baseline was 160 to 219 mm Hg systolic and less than 95 mm Hg diastolic.
For the overall study, patients were randomized to nitrendipine (n = 415; 10-40 mg/d) with the possible addition of enalapril (5-20 mg/d) and/or hydrochlorothiazide (12.5-25.0 mg/d) or to matching placebos (n = 393).
Total and cardiovascular mortality, all cardiovascular end points, fatal and nonfatal stroke, and fatal and nonfatal cardiac end points.
After adjusting for sex, age, previous cardiovascular complications, smoking, and residence in western Europe, a 10-mm Hg higher conventional systolic BP at randomization was not associated with a worse prognosis, whereas in the placebo group, a 10-mm Hg higher 24-hour BP was associated with an increased relative hazard rate (HR) of most outcome measures (eg, HR, 1.23 [95% confidence interval [CI], 1.00-1.50] for total mortality and 1.34 [95% CI, 1.03-1.75] for cardiovascular mortality). In the placebo group, the nighttime systolic BP (12 AM-6 AM) more accurately predicted end points than the daytime level. Cardiovascular risk increased with a higher night-to-day ratio of systolic BP independent of the 24-hour BP (10% increase in night-to-day ratio; HR for all cardiovascular end points, 1.41; 95% CI, 1.03-1.94). At randomization, the cardiovascular risk conferred by a conventional systolic BP of 160 mm Hg was similar to that associated with a 24-hour daytime or nighttime systolic BP of 142 mm Hg (95% CI, 128-156 mm Hg), 145 mm Hg (95% CI, 126-164 mm Hg) or 132 mm Hg (95% CI, 120-145 mm Hg), respectively. In the active treatment group, systolic BP at randomization did not significantly predict cardiovascular risk, regardless of the technique of BP measurement.
In untreated older patients with isolated systolic hypertension, ambulatory systolic BP was a significant predictor of cardiovascular risk over and above conventional BP.
JAMA The Journal of the American Medical Association 09/1999; 282(6):539-46. · 30.03 Impact Factor
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J Gasowski,
J A Staessen,
H Celis,
R H Fagard,
L Thijs,
W H Birkenhäger,
C J Bulpitt,
A E Fletcher,
G G Arabidze,
P de Leeuw, [......],
K Kawecka-Jaszcz,
G Leonetti,
C Nachev,
M Safar,
J L Rodico,
J Rosenfeld,
M L Seux,
J Tuomilehto, J Webster,
Y Yodfat
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ABSTRACT: The Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (> or = 60 years) patients with isolated systolic hypertension (systolic BP > or = 160 mm Hg and diastolic BP < 95 mm Hg). After the completion of the Syst-Eur trial on 14 February 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the Syst-Eur trial. This open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine. To lower the sitting systolic BP below 150 mm Hg (target BP), the first-line agent nitrendipine (10-40 mg/day) may be associated with enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), both add-on study drugs, or if required any other antihypertensive agent. On 1 November 1998, 3248 patients were still being followed, 86 patients had proceeded to non-supervised follow-up, and 43 had died. The median follow-up in Syst-Eur 2 was 14.3 months. At the last available visit, systolic/diastolic BP in the patients formerly randomised to placebo (n = 1682) or active treatment (n = 1824), had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg, respectively, so that the between-group BP difference was 1.7 mm Hg systolic (95% Ci: 0.8 to 2.6 mm Hg; P < 0.001) and 0.9 mm Hg diastolic (95% Cl: 0.4 to 1.5 mm mm Hg; P < 0.001). At the beginning of Syst-Eur 2, the goal BP was reached by 25.4% and 50.6% of the former placebo and active-treatment groups; at the last visit these proportions were 55.9% and 63.1%, respectively. At that moment, 45.9% of the patients were on monotherapy with nitrendipine, 29.3% took nitrendipine in combination with other study drugs. Until the end of 2001, BP control of the Syst-Eur 2 patients will be further improved. Cardiovascular complications and adverse events, such as cancer or gastro-intestinal bleeding, will be monitored and validated by blinded experts.
Journal of Human Hypertension 03/1999; 13(2):135-45. · 2.80 Impact Factor
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F Forette,
M L Seux,
J A Staessen,
L Thijs,
W H Birkenhäger,
M R Babarskiene,
S Babeanu,
A Bossini,
B Gil-Extremera,
X Girerd,
T Laks,
E Lilov,
V Moisseyev,
J Tuomilehto,
H Vanhanen, J Webster,
Y Yodfat,
R Fagard
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ABSTRACT: Systolic hypertension increases the risk of dementia in elderly people. The vascular dementia project, set up in the framework of the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial, investigated whether antihypertensive drug treatment could reduce the incidence of dementia.
Eligible patients had no dementia, were at least 60 years old, and had a blood pressure when seated of 160-219 mm Hg systolic and below 95 mm Hg diastolic. Active treatment consisted of nitrendipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), or both drugs, titrated or combined to reduce the systolic blood pressure by at least 20 mm Hg to reach a value below 150 mm Hg. Cognitive function was assessed by the mini mental state examination (MMSE). If the MMSE score was 23 or less, diagnostic tests for dementia were done (DSM-III-R criteria). The cause of dementia was established by the modified ischaemic score with brain imaging or the Hachinski score.
Median follow-up by intention to treat was 2.0 years. Compared with placebo (n=1180), active treatment (n=1238) reduced the incidence of dementia by 50% from 7.7 to 3.8 cases per 1000 patient-years (21 vs 11 patients, p=0.05). The median MMSE score at randomisation was 29 in both treatment groups. At the last available assessment, systolic and diastolic blood pressure were, respectively, 8.3 mm Hg and 3.8 mm Hg lower (p<0.001) in the active-treatment group, but on average the MMSE scores did not change in either group. In the control patients, however, the MMSE decreased (p=0.04) with decreasing diastolic blood pressure, whereas in the active-treatment group MMSE scores improved slightly (p=0.01) with greater reduction in diastolic blood pressure (p=0.002 for between-group difference).
In elderly people with isolated systolic hypertension, antihypertensive treatment was associated with a lower incidence of dementia. If 1000 hypertensive patients were treated with antihypertensive drugs for 5 years 19 cases of dementia might be prevented.
The Lancet 10/1998; 352(9137):1347-51. · 38.28 Impact Factor
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J A Staessen,
L Thijs,
R H Fagard,
W H Birkenhäger,
G Arabidze,
S Babeanu,
B Gil-Extremera,
C J Bulpitt,
C Davidson,
P W de Leeuw, [......],
A E Fletcher,
R Fogari,
M Jääskivi,
K Kawecka-Jaszcz,
C Nachev,
J C Petrie,
M L Seux,
J Tuomilehto, J Webster,
Y Yodfat
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ABSTRACT: In the double-blind Systolic Hypertension in Europe (Syst-Eur) Trial, active treatment was initiated with nitrendipine (10 to 40 mg/d) with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d) titrated or combined to reduce sitting systolic blood pressure by at least 20 mm Hg to <150 mm Hg. In the control group, matching placebos were used similarly. In view of persistent concerns about the use of calcium channel blockers as first-line antihypertensive drugs, this report explored to what extent nitrendipine, administered alone, prevented cardiovascular complications. Age at randomization averaged 70.2 years and systolic/diastolic blood pressure 173.8/85.5 mm Hg. Of 2398 actively treated patients, 1327 took only nitrendipine (average dose, 23.4 mg/d), and 1042 progressed to other treatments including nitrendipine (n=757; 35.7 mg/d), enalapril (n=783; 13.4 mg/d), and/or hydrochlorothiazide (n=294; 21.0 mg/d). Compared with the whole placebo group (n=2297), patients receiving monotherapy with nitrendipine had 25% (P=0.05) fewer cardiovascular end points, and those progressing to other active treatments showed decreases (P</=0. 01) in total mortality (40%), stroke (59%), and all cardiovascular end points (39%). Among the control patients, 863 used only the first-line placebo. Compared with this subgroup, patients receiving monotherapy with nitrendipine showed a nearly 50% (P</=0.004) reduction of all types of end points, including total and cardiovascular mortality. The full relative benefit from nitrendipine was seen as early as 6 months after randomization. To ascertain that the benefit conferred by the dihydropyridine was not due to selection bias, the 1327 patients remaining on monotherapy with nitrendipine were matched by gender, age, previous cardiovascular complications, and systolic blood pressure at entry with an equal number of placebo patients. In this analysis, nitrendipine reduced (P</=0.05) cardiovascular mortality by 41%, all cardiovascular end points by 33%, and fatal and nonfatal cardiac end points by 33%. Despite the limitations inherent in post hoc analyses, the present findings suggest that the calcium channel blocker nitrendipine, given as a single antihypertensive medication, prevents cardiovascular complications in older patients with isolated systolic hypertension.
Hypertension 10/1998; 32(3):410-6. · 6.21 Impact Factor
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ABSTRACT: To determine the actual use of 'statin' therapy for primary and secondary prevention and the potential effect of using the Sheffield Table for primary prevention of coronary heart disease upon 'statin' use in a consultant-run Hypertension and Cardiovascular Risk Clinic.
Prospective audit of the current use of cholesterol-lowering therapy and the effect of implementing the criteria used in the Sheffield Table and the Scandinavian Simvastatin Study for cholesterol lowering in 'at risk' patients upon statin use in a consultant-led cardiovascular risk clinic.
The Aberdeen Hypertension Clinic.
A total of 1500 patients were reviewed of which 416 (27.7%) had experienced at least one clinical manifestation of atherosclerotic cardiovascular disease (CVD) and 392 (94%) of these had a total cholesterol measured of whom 298 (76%) had a total cholesterol >5.5 mmol/l. Only 11.2% of eligible patients were actually receiving lipid-lowering treatment for secondary prevention. A total of 1084 patients with no prior cardiovascular disease were identified, 97 (8.9%) were excluded because of age. Using the Sheffield Table, 92 (9.4%) of these patients were eligible for statin therapy and only six of the 92 patients were actually receiving treatment.
The results of this study reveal that even in a consultant-led cardiovascular prevention clinic there is a significant discrepancy between optimal evidence-based management and the actual delivery of clinical care. Seventy-two per cent and 9.3% of patients attending the clinic were eligible for statin treatment for secondary and primary prevention, respectively. However, only 11.2% of patients suitable for secondary prevention and 6.5% of patients suitable for primary prevention were actually receiving appropriate lipid-lowering therapy. Considering the proven benefit of this form of medical intervention the results of this study are of real importance to practising clinicians and patients alike.
Journal of Human Hypertension 07/1998; 12(7):469-71. · 2.80 Impact Factor
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ABSTRACT: To assess the effect of trandolapril (2 mg once daily) and indomethacin (25 mg three times daily), alone and in combination, on renal function and renal functional reserve in hypertensive patients (DBP 95-115 mmHg) requiring regular non-steroidal anti-inflammatory drugs (NSAIDs).
Randomized, double-blind, placebo-controlled, four way crossover design. After 3 weeks treatment renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured using the p-aminohippurate (PAH) and inulin methods. Renal functional reserve was estimated by measuring RPF and GFR at the end of an intravenous infusion of dopamine 2 microg kg(-1) and 10% amino acid solution.
There was no significant difference in RPF between treatments: -22.79 ml min(-1) (95% CI -54.82, 9.24) for placebo and trandolapril, -10.37 ml min(-1) (95% CI -30.7, 9.96) for placebo and indomethacin, -14.78 ml min(-1) (95% CI -50.33, 20.77) for placebo and trandolapril with indomethacin. There was no significant difference in functional reserve RPF between treatments: -34.96 ml min(-1) (95% CI -119.8, 49.88) for placebo and trandolapril, 29.78 ml min(-1), -15.18, 74.74) for placebo and indomethacin, and -25.84 ml min(-1) (95% CI -87.62, 35.94) for placebo and trandolapril with indomethacin. There was no significant difference in GFR between treatments: -1.01 ml min(-1) (95% CI -7.45, 5.42) for placebo and trandolapril, -7.88 ml min(-1) (95% CI -15.08, -0.68) for placebo and indomethacin, and -0.36 ml min(-1) (95% CI -7.58, 6.86) for placebo and trandolapril with indomethacin. There was no significant difference in functional reserve GFR between treatments: 5.13 ml min(-1) (95% CI -4.97, 15.23) for placebo and trandolapril, 6.31 ml min(-1) (95% CI -1.88, 14.5) for placebo and indomethacin, 7.21 ml min(-1) (95% CI 1.26, 13.16) for placebo and trandolapril with indomethacin.
In hypertensives chronic treatment with NSAIDs or ACEI alone or in combination did not change RPF or GFR and did not change renal functional reserve capacity of RPF or GFR.
British Journal of Clinical Pharmacology 09/1997; 44(2):145-9. · 2.96 Impact Factor
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ABSTRACT: A case control study has reported a 60% higher risk of myocardial infarction in hypertensives treated with a calcium channel blocker (CCB). We examined the Department of Health Hypertension Care Computing Project (DHCCP) data to see if we could confirm or refute this suggestion.
Two case control studies, matched and unmatched, plus two longitudinal studies from 1 year of presentation, one for all subjects given a CCB for more than 1 year compared with those not given this drug, and the second comparing survival on the different drugs initially given between 3 and 12 months of follow-up.
A total of 9328 subjects were included in the analyses and 2154 died. Of these, 6406 received one or more of the following index drugs: 26% a calcium channel blocker (CCB); 84% a diuretic; 29% alpha methyldopa; 12% a beta-blocker (BB); and 11% an angiotensin-converting enzyme (ACE) inhibitor. The CCBs were nifedipine, diltiazem or verapamil.
In the case control studies a group given diuretics +/- other treatments (but not including one of the index drugs) provided a reference group with a relative risk (RR) of 1.0. In the matched case control study the adjusted RR for a CCB without a diuretic was 1.32 (95% CI 0.64-2.70) for IHD mortality and 1.05 (95% CI 0.60-1.84) for cardiovascular mortality. Similar results were observed for methyldopa, BBs and ACE inhibitors. The results in the unmatched case control analysis were also similar. The longitudinal study comparing all those treated for over 1 year with a CCB with all other treatments showed a RR for total mortality of 1.03 (95% CI 0.85-1.25). The longitudinal study of total mortality according to treatment initiated at 3-12 months found results of a similar magnitude for CCBs, methyldopa and BBs.
The reference diuretic group had less severe cardiovascular disease than other groups. Treatment with a CCB, BB or methyldopa was associated with an excess mortality in comparison with this reference group. The excess was similar in the different drug groups.
Journal of Human Hypertension 05/1997; 11(4):205-11. · 2.80 Impact Factor
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ABSTRACT: GR117289C is a non peptide, selective angiotensin (AT1) receptor antagonist. The purpose of this study was to determine whether this agent, given orally, could attenuate the vasoconstrictor effects of angiotensin II(AII) infused locally into the forearm circulation in man.
Eight healthy male subjects were studied on four occasions in a randomized, double-blind, placebo controlled, crossover study. Five hours (approximate time of peak dynamic effect) following dosing with GR117289C (300 mg, 100 mg, 10 mg or placebo), A II was infused in incremental doses (0, 0.1, 0.4, 1.6, 6.2, 25 and 100 pmol min-1) into the left brachial artery, each for 10 min. Forearm blood flow was measured using venous occlusion plethysmography.
GR117289C inhibits the vasoconstrictor effects of A II in a dose dependent manner. The active treatment: placebo ratios of forearm blood flow in the infused arm during the highest dose of AII (100 pmol min-1) were: GR117289C 10 mg, 1.12 (95% C.I. 0.81-1.55; P = 0.478), 100 mg, 1.43 (95% C.I. 1.01-2.01; P = 0.042) and 300 mg, 1.62 (95% C.I. 1.17-2.24; P = 0.006). There was no significant difference in blood pressure between each of the treatment groups and placebo.
GR117289C is a pharmacologically active, oral A II antagonist in healthy men.
British Journal of Clinical Pharmacology 04/1997; 43(3):323-6. · 2.96 Impact Factor
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ABSTRACT: Different ACE inhibitors can be distinguished in vitro by their affinity for converting enzyme in vascular and other tissues. Quinapril appears to be amongst the more effective inhibitors of vascular tissue ACE in vitro. This study assesses the in vivo effect of single oral doses of quinapril and enalapril, in attenuating the vasoconstrictive action of angiotensin I (AI) (which we have previously shown depends on its conversion to angiotensin II (AII) by vascular ACE) in the forearm resistance vessels of man.
The design was of randomized, open, placebo controlled, two way crossover type, Forearm blood flow (FABF) was measured simultaneously in both forearms by mercury in silastic strain gauge plethysmography. AI infusion were via a fine bore cannula in the left brachial artery with the right arm serving as a control.
Mean plasma ACE on placebo was 34.3 U.l-1. Both quinapril and enalapril produced a similar degree of plasma ACE inhibition reducing concentrations to 2.8 U.l-1 and 2.6 U.l-1 respectively. Quinapril caused a significantly greater inhibition of AI induced vasoconstriction with a 30.0% reduction compared with 67.0% and 85.0% for enalapril and placebo respectively. Enalapril attenuated AI induced vasoconstriction to a greater degree than placebo but the difference was not significantly different.
These results indicate that when quinapril and enalapril are administered as single 20 mg doses, each of which produces the same degree of plasma ACE inhibition and blood pressure reduction- quinapril inhibits vascular ACE to a greater degree than both enalapril and placebo.
European Journal of Clinical Pharmacology 02/1997; 51(5):373-8. · 2.85 Impact Factor
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ABSTRACT: This is a randomised, double-blind, placebo-controlled, four-way crossover study to determine if indomethacin attenuates the hypotensive effect of trandolapril. Twenty-three hypertensive patients (diastolic blood pressure (DBP) 95-115) requiring NSAID were recruited. Seventeen completed the study. Three week treatment periods: trandolapril 2 mg od and indomethacin 25 mg tds, trandolapril 2 mg and placebo, indomethacin and placebo, placebo and placebo. Clinic and ambulatory BP after 3 weeks of each treatment. Study had 85% power to detect a 5 mm Hg difference in BP (s.d. 7 mm Hg). End of treatment clinic BPs were: 152.9/98 mm Hg (95% CI 147.2, 158.6/95.8, 101.4) with placebo and placebo; 150.4/94.9 mm Hg (95% CI 144.7, 156.1/92.1, 97.7) with trandolapril and indomethacin; 148.2/96.5 mm Hg (95% CI 142.5, 153.9/93.7, 99.3) with trandolapril and placebo; and 156.6/97.4 mm Hg (95% CI 150.9, 162.3/94.6, 100.2) with indomethacin and placebo. There were no significant interactions between trandolapril and indomethacin for clinic systolic BP (SBP) (P = 0.79) or clinic DBP (P = 0.87). When trandolapril treatments (placebo or with indomethacin) were compared to treatments without trandolapril (placebo or indomethacin), trandolapril lowered clinic SBP by 5.4 mm Hg (P = 0.047) and DBP by 2.3 mm Hg (P = 0.08). Mean ambulatory BP was: 140.6/88.2 mm Hg (trandolapril and placebo); 142.8/89.7 mm Hg (trandolapril and indomethacin); 149.6/95.0 mm Hg, (indomethacin and placebo); 147.7/94.0 mm Hg (placebo and placebo). Compared with placebo, trandolapril and placebo lowered BP by 6.5/7.5 mm Hg (P < 0.001, SBP; P < 0.001, DBP). Compared with indomethacin, trandolapril and indomethacin lowered BP by 5.0/5.5 mm Hg (P = 0.001, SBP; P < 0.001, DBP). In the present study trandolapril 2 mg lowered clinic SBP and ambulatory BP, but indomethacin did not attenuate this. Indomethacin had no significant effect on either clinic or ambulatory BP. The antihypertensive effects of trandolapril in this study were modest. Patient selection factors may have contributed to the observed responses, but it seems unlikely from these data that a clinically important drug interaction has occurred.
Journal of Human Hypertension 11/1996; 10(11):763-7. · 2.80 Impact Factor
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J A Staessen,
L Thijs,
L Bieniaszewski,
E T O'Brien,
P Palatini,
C Davidson,
J Dobovisek,
M Jääskivi,
T Laks,
A Lehtonen,
H Vanhanen, J Webster,
R Fagard
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ABSTRACT: This study compares blood pressure (BP) changes during active antihypertensive treatment and placebo as assessed by conventional and ambulatory BP measurement. Older patients (> or = 60 years, n=337) with isolated systolic hypertension by conventional sphygmomanometry at the clinic were randomized to placebo or active treatment consisting of nitrendipine (10 to 40 mg/d), with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d). At baseline, clinic systolic/diastolic BP averaged 175/86 mm Hg and 24-hour and daytime ambulatory BPs averaged 148/80 and 154/85 mm Hg, respectively. After 13 months (median) of active treatment, clinic BP had dropped by 22.7/7.0 mm Hg and 24-hour and daytime BPs by 10.5/4.5 and 9.7/4.3 mm Hg, respectively (P<.001 for all). However, clinic (9.8/1.6 mm Hg), 24-hour (2.1/1.1 mm Hg), and daytime (2.9/1.0 mm Hg) BPs decreased also during placebo (P<.05, except for daytime diastolic BP); these decreases represented 43%/23%, 20%/24%, and 30%/23% of the corresponding BP fall during active treatment. After subtraction of placebo effects, the net BP reductions during active treatment averaged only 12.9/5.4, 8.3/3.4, and 6.8/3.2 mm Hg for clinic, 24-hour, and daytime BPs, respectively. The effect of active treatment was also subject to diurnal variation (P<.05). Changes during placebo in hourly systolic and diastolic BP means amounted to (median) 21% (range, -1% to 42%) and 25% (-3% to 72%), respectively, of the corresponding changes during active treatment. In conclusion, expressed in millimeters of mercury, the effect of antihypertensive treatment on BP is larger with conventional than with ambulatory measurement. Regardless of whether BP is measured by conventional sphygmomanometry or ambulatory monitoring, a substantial proportion of the long-term BP changes observed during active treatment may be attributed to placebo effects. Thus, ambulatory monitoring uncorrected for placebo or control observations, like conventional sphygmomanometry, overestimates BP responses in clinical trials of long duration.
Hypertension 04/1996; 27(3 Pt 1):414-20. · 6.21 Impact Factor
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ABSTRACT: To determine the benefits and risks of drinking alcohol in treated hypertensives.
A prospective study of 6,369 hypertensives (3,161 men) attending primarily hospital clinics in the UK.
Relative risks both for drinkers compared with non-drinkers and for level of alcohol consumption were calculated for mortality from ischaemic heart disease, stroke, non-circulatory and all causes.
At presentation 76% of the men and 48% of the women reported recent alcohol consumption. Compared with drinkers, non-drinkers were older, less likely to smoke and had a higher untreated blood pressure. After adjustment for confounding factors, male drinkers had a reduced risk of stroke mortality and possibly of ischaemic heart disease mortality. Similar results were observed in women for stroke mortality but not for ischaemic heart disease mortality. The trend remained after adjustment for previous cardiovascular disease. In men the lowest risk of ischaemic heart disease mortality occurred at intakes of > 21 units per week and stroke mortality was lowest at 1-10 units per week. Men consuming > 21 units per week had a twofold higher non-circulatory mortality. Total mortality was lowest in men who drank 1-10 units per week. Similar effects of alcohol on cardiovascular mortality were observed in women.
Alcohol intake may reduce stroke mortality in treated hypertensives. Ischaemic heart disease mortality in men may also be reduced, especially at higher intakes ( > 21 units per week). The beneficial effects were offset by increasing incidence of non-circulatory causes of death. Alcohol consumption of 1-10 units per week was associated with the lowest mortality in men.
Journal of Hypertension 09/1995; 13(9):957-64. · 4.02 Impact Factor
