Study rationale and design of the CIMT trial: the Copenhagen Insulin and Metformin Therapy trial.

BACKGROUND: Patients with type 2 diabetes (T2DM) have an increased mortality rate primarily because of macrovascular disease. Where T2DM patients cannot be managed sufficiently through diet, exercise and peroral antidiabetic drugs, that is when haemoglobin A1c (HbA1c) is above 7.0%, it is yet unknown whether a combination of metformin and insulin analogues is superior to insulin analogues alone. Nor is it known which insulin analogue regimen is the optimal. OBJECTIVE: The primary objective of this trial is to evaluate the effect of an 18-month treatment with metformin vs. placebo in combination with one of three insulin analogue regimens, the primary outcome measure being carotid intima-media thickness (CIMT) in T2DM patients. DESIGN: A randomized, stratified, multicentre trial having a 2 x 3 factorial design. The metformin part is double masked and placebo controlled. The insulin treatment is open. The intervention period is 18 months. PATIENT POPULATION: Nine hundred and fifty patients with T2DM and HbA1c > or = 7.5% on treatment with oral hypoglycaemic agents or on insulin treatment and deemed able, by the investigator, to manage once-daily insulin therapy with a long-acting insulin analogue. RANDOMIZATION: Central randomization stratified for age (above 65 years), previous insulin treatment and treatment centre. INTERVENTIONS: Metformin 1 g x two times daily vs. placebo (approximately 475 patients vs. 475 patients) in combination with insulin detemir before bedtime (approximately 315 patients) or biphasic insulin aspart 30 before dinner with the possibility to increase to two or three injections daily (approximately 315 patients) or insulin aspart before the main meals (three times daily) and insulin detemir before bedtime (approximately 315 patients). Intervention follows a treat-to-target principle in all six arms aiming for an HbA1c < or = 7.0%. OUTCOME MEASURES: Primary outcome measure is the change in CIMT from baseline to 18 months. Secondary outcome measures comprises the composite outcome of death, acute myocardial infarction, stroke or amputation assessed by an adjudication committee blinded to intervention, other cardiovascular clinical outcomes, average postprandial glucose increment from 0 to 18 months, hypoglycaemia and any inadvertent medical episodes. In addition, change in plaque formation in the carotids, HbA1c, cardiovascular biomarkers, body composition, progression of microvascular complications and quality of life will be assessed as tertiary outcome measures. TIME SCHEDULE: Patient enrolment started May 2008. Follow-up is expected to finish in March 2011. CONCLUSION: CIMT is designed to provide evidence as to whether metformin is advantageous even during insulin treatment and to provide evidence regarding which insulin analogue regimen is most advantageous with regard to cardiovascular disease.

Soya isoflavone-enriched cereal bars affect markers of endothelial function in postmenopausal women.

Soya isoflavones are thought to be cardioprotective due to their structural similarity to oestrogen. In order to investigate the effect of soya isoflavones on markers of endothelial function we conducted a randomised, double-blind, placebo-controlled, cross-over study with thirty healthy postmenopausal women. The women consumed cereal bars, with or without soya isoflavones (50 mg/d), for 8 weeks, separated by an 8-week washout period. Systemic arterial compliance (SAC), isobaric arterial compliance (IAC), flow-mediated endothelium-dependent vasodilation (FMD) and nitroglycerine-mediated endothelium-independent vasodilation (NMD) were measured at the beginning of the study and after each intervention period. Blood pressure (BP) and plasma concentrations of nitrite and nitrate (NOx) and endothelin-1 (ET-1) were measured at the beginning and end of each intervention period. NMD was 13.4 (SEM 2.0)% at baseline and 15.5 (SEM 1.1) % after isoflavone treatment compared with 12.4 (SEM 1.0)% after placebo treatment (P=0.03). NOx increased from 27.7 (SEM 2.7) to 31.1 (SEM 3.2) microM after isoflavones treatment compared with 25.4 (SEM 1.5) to 20.4 (SEM 1.1) microM after placebo treatment (P=0.003) and a significant increase in the NOx:ET-1 ratio (P=0.005) was observed after the isoflavone treatment compared with placebo. A significant difference in SAC after the isoflavone and placebo treatment was observed (P=0.04). No significant difference was found in FMD, IAC, BP and ET-1. In conclusion, 8 weeks' consumption of cereals bars enriched with 50 mg soya isoflavones/d increased plasma NOx concentrations and improved endothelium-independent vasodilation in healthy postmenopausal women.

Markers of collagen synthesis is related to blood pressure and vascular hypertrophy: a LIFE substudy.

Cardiac fibrosis and high levels of circulating collagen markers has been associated with left ventricular (LV) hypertrophy. However, the relationship to vascular hypertrophy and blood pressure (BP) load is unclear. In 204 patients with essential hypertension and electrocardiographic LV hypertrophy, we measured sitting BP, serum collagen type I carboxy-terminal telopeptide (ICTP) reflecting degradation, procollagen type I carboxy-terminal propeptide (PICP) reflecting synthesis and LV mass by echocardiography after 2 weeks of placebo treatment and after 1 year of antihypertensive treatment with a losartan- or an atenolol-based regimen. Furthermore, we measured intima-media thickness of the common carotid arteries (IMT), minimal forearm vascular resistance (MFVR) by plethysmography and ambulatory 24-h BP in around half of the patients. At baseline, PICP/ICTP was positively related to IMT (r=0.24, P<0.05), MFVR(men) (r=0.35, P<0.01), 24-h systolic BP (r=0.24, P<0.05) and 24-h diastolic BP (r=0.22, P<0.05), but not to LV mass. After 1 year of treatment with reduction in systolic BP (175+/-15 vs 151+/-17 mmHg, P<0.001) and diastolic BP (99+/-8 vs 88+/-9 mmHg, P<0.001), ICTP was unchanged (3.7+/-1.4 vs 3.8+/-1.4 microg/l, NS) while PICP (121+/-39 vs 102+/-29 microg/l, P<0.001) decreased. The reduction in PICP/ICTP was related to the reduction in sitting diastolic BP (r=0.31, P<0.01) and regression of IMT (r=0.37, P<0.05) in patients receiving atenolol and to reduction in heart rate in patients receiving losartan (r=0.30, P<0.01). In conclusion, collagen markers reflecting net synthesis of type I collagen were positively related to vascular hypertrophy and BP load, suggesting that collagen synthesis in the vascular wall is increased in relation to high haemodynamic load in a reversible manner.

24-h Ambulatory blood pressure in patients with ECG-determined left ventricular hypertrophy: left ventricular geometry and urinary albumin excretion-a LIFE substudy.

This study was undertaken to evaluate the relationships among left ventricular (LV) geometric patterns and urinary albumin excretion in patients with hypertension and electrocardiographic (ECG) LV hypertrophy. In 143 patients with stage II-III hypertension, 24-h ambulatory blood pressure (BP) monitoring, single urine albumin determination, and echocardiography were performed after 14 days of placebo treatment. Mean age was 68+/-7 years, 35% were women, body mass index was 28+/-5 kg/m(2), LV mass index (LVMI) was 125+/-26 g/m(2), and 24% had microalbuminuria. The mean office BP was 176+/-15/99+/-8 mmHg and the mean daytime ambulatory BP was 161+/-18/92+/-12 mmHg. Ambulatory BP, but not office BP, was higher among albuminuric compared to normoalbuminuric patients. In patients with established hypertension, daytime pulse pressure and office BP were different in the four patterns of LV geometry, with the highest pressure in those with abnormal geometry. Furthermore, microalbuminuria was more frequent in hypertensive patients with LV hypertrophy than in those with either normal geometry or concentric remodelling. White coat hypertensives (10%) showed lower LVMI and no microalbuminuria compared to patients with established hypertension. There were no differences in the prevalence of nondippers (26%) among the four LV geometric patterns or in microalbuminuria. In conclusion, increased daytime pulse pressure and office BP were associated with increased prevalence of abnormal LV geometry. Microalbuminuria was more frequent in groups with concentric and eccentric LV hypertrophy. Ambulatory BP, but not office BP, was higher in albuminuric than normoalbuminuric patients. With regard to the relationship among BP, LV geometric patterns, and urine albumin excretion in this population, 24-h ambulatory BP did not provide additional information beyond the office BP.

Sympathetic dysfunction of central origin in patients with ALS.

Amyotrophic lateral sclerosis (ALS) is a severe, progressive disease affecting both the central and peripheral parts of the motor nervous system. Some studies have shown unequivocal indications of a more disseminated disease also affecting the autonomic nervous system. We therefore evaluated the centrally and peripherally mediated autonomic vascular reflexes by (i) the local 133-Xenon washout technique, and (ii) the head-up tilt table test. The results correlated to clinical scores. We examined nine ALS patients and 15 age-matched controls. The 133-Xenon washout test showed a significant reduction in the centrally mediated sympathetic vasoconstrictor response, but a preserved locally mediated response in the patients. In the head-up tilt table test, the patients had a significantly higher mean arterial blood pressure (MAP) compared with controls, probably due to a general increase in vascular resistance. There were no correlations between the ALS Severity Scores and blood flow changes, diastolic blood pressure or MAP. Our study supports previous results, but indicates abnormalities consistent with a solely centrally located sympathetic dysfunction in ALS, independent of the stage of the disease.

Effects of a Ginkgo biloba extract on forearm haemodynamics in healthy volunteers.

The aim was to validate possible vasodilating effects of a Ginkgo biloba extract with a secondary aim of finding a pharmacodynamic signal relating to the active component of these extracts. We studied the effect of G. biloba extract on forearm haemodynamics in 16 healthy subjects (nine females, seven males) with a median age of 32 years (range: 21-47). The study was conducted as a randomized, double-blinded cross-over design using oral treatment with G. biloba extract (Gibidyl Forte(R) t.i.d. or placebo for 6 weeks. Forearm blood flow and venous capacity were measured by strain-gauge plethysmography. Blood pressure was measured by standard sphygmomanometry, and forearm vascular resistance (FVR) was derived. Measurements were made at baseline and after 3, 6, 9 and 12 weeks of treatment. Forearm blood flow was significantly higher during active treatment after 3 and 6 weeks as compared with placebo treatment for 3 and 6 weeks (P<0.05). Mean arterial blood pressure was unchanged, making the calculated FVR significantly lower during active treatment (P<0.02). It is concluded that oral treatment with a G. biloba extract (Gibidyl Forte(R)) is able to dilate forearm blood vessels causing increments in regional blood flow without changing blood pressure levels in healthy subjects. The increments in blood flow may be used as a biological signal for pharmacokinetic studies.

Hemodynamic changes after levothyroxine treatment in subclinical hypothyroidism.

In hypothyroidism, lack of thyroid hormones results in reduced cardiac function (cardiac output [CO]), and an increase of systemic vascular resistance (SVR). We speculated whether hemodynamic regulation in subjects with subclinical hypothyroidism (SH) (defined as mildly elevated thyrotropin [TSH] despite free thyroxine [T(4)] and triiodothyronine [T(3)] estimates within reference range) would benefit from levothyroxine (LT(4)) substitution. CO was measured by impedance cardiography, which is an observer independent method with high precision, and mean arterial pressure (MAP) by oscillometry. SVR was then calculated as MAP/CO. Measurements were performed before and after 60 degrees head-up tilting, and before and after LT(4) substitution. Plasma levels of catecholamines were also measured. In 16 otherwise healthy women with SH (ages 44-74 years; serum TSH in mean 17.1 mU/L (range, 6.8-27), and normal free T(4) and T(3) estimates) LT(4) treatment resulted in 6% reduction in supine MAP (p < 0.01), 14% increase in upright CO (p < 0.05), and 13%-20% decrease in SVR (supine and upright position, respectively) (p < 0.05). Plasma norepinephrine as well as epinephrine decreased during LT(4) treatment (p < 0.05). These changes were qualitatively similar but quantitatively less pronounced than in 15 women with overt hypothyroidism, also studied. Taking the two groups together (n = 31), pretreatment thyroid function (expressed as either TSH or free T(4) estimate) correlated to CO and SVR as well as the changes induced by LT(4) (p < 0.05), i.e., the lower the thyroid function the lower the CO and the higher the SVR, and the greater the response to LT(4). We conclude, that LT(4) treatment in SH results in changes in hemodynamic parameters of potentially beneficial character. SH and overt hypothyroidism should be regarded as a continuum, and our data favor earlier and more aggressive treatment of SH.

Haemodynamic changes following treatment of subclinical and overt hyperthyroidism.

OBJECTIVE: Hyperthyroidism has profound effects on the cardiovascular system, including reduced systemic vascular resistance (SVR) due to relaxation of vascular smooth muscle cells, enhanced heart rate (HR) and cardiac output (CO) due to an increase in cardiac diastolic relaxation, contractility and heart rate. Subclinical hyperthyroidism is characterised by reduced serum TSH levels despite free thyroxine (T4) and tri-iodothyronine (T3) estimates within the reference range, in subjects with no obvious symptoms of hyperthyroidism. We measured haemodynamic changes (using impedance cardiography) in subjects with endogenous subclinical hyperthyroidism in order to elucidate whether these patients had signs of excess thyroid hormone at the tissue level. DESIGN: The patients were otherwise healthy women with a multinodular goitre (n=6; age 47-81 years; serum TSH 0.006-0.090 mU/l and normal free T4 and T3 estimates), studied before and after normalisation of TSH (0.280-1.120 mU/l) by means of radioiodine treatment, and they were compared with 9 overt hyperthyroid patients (2 with multinodular goitre and 7 with Graves' disease) in the untreated state and after euthyroidism had been obtained. RESULTS: Treatment of the subclinical hyperthyroid women resulted in 11% reduction in HR (P<0.02), 19% reduction in CO from (means+/-s.d.) 6.93+/-2.15 l/min to 5.58+/-1.94 l/min (P<0.05), and 30% increase in SVR (P<0.02). Similar but more pronounced changes were seen in the hyperthyroid group: 17% reduction in HR, 25% reduction in CO and 46% increase in SVR (all at least P<0.05). Taking all 15 patients together, thyroid function (as measured by free T3 index (FT3I) or TSH) correlated significantly to the haemodynamic parameters as follows: the higher the thyroid function the lower the mean arterial pressure and SVR, and the higher the CO and central aortic compliance (stroke volume/pulse pressure) (P<0.05). Plasma norepinephrine increased significantly after treatment of the overt hyperthyroid patients, whereas epinephrine did not change, and no changes were seen among subclinical hyperthyroid patients. CONCLUSION: Treatment of endogenous subclinical hyperthyroidism resulted in significant changes in several haemodynamic parameters regarding the heart and the vascular system, compatible with some degree of excess tissue exposure to thyroid hormones in the untreated state. Our data favour more aggressive treatment of these patients, and endogenous subclinical hyperthyroidism might be regarded as a mild form of hyperthyroidism.

Diagnostic value of the Nycocard, Nycomed D-dimer assay for the diagnosis of deep venous thrombosis and pulmonary embolism: a retrospective study.

The relatively new D-dimer assay from Nycomed Pharma (Nycocard), which has shown both high sensitivity and specificity in diagnosing deep venous thrombosis (DVT) and pulmonary embolism (PE) in earlier studies, was re-evaluated retrospectively. The diagnostic value of the D-dimer assay for DVT was evaluated with contrast venography as reference. The diagnostic value of the D-dimer assay for PE was evaluated with pulmonary scintigraphy as reference. D-dimer tests were examined from 54 consecutive patients. The D-dimer assay was found to have a sensitivity and specificity of 50% and 58%, respectively, for the diagnosis of DVT, with a positive predictive value (PPV) and negative predictive value (NPV) of 55% and 54%, respectively. Using reference diagnostic results of high probability and low probability for the diagnosis of PE, the D-dimer test sensitivity and specificity was found to be 40% and 94%, respectively (PPV: 86%, NPV: 64%). The diagnostic value of the Nycocard(R) assay appears to be very limited for the diagnosis of DVT and PE. This retrospective study suggests that it is unsuitable as a screening method. Further re-evaluation of D-dimer assays is recommended prior to routine clinical use.

Measurement of arterial compliance in vivo.

Measurement of arterial compliance is of interest in evaluating patients with atherosclerosis and other diseases which affect the vessels. Arterial compliance is the relation between changes in transmural pressure and volume of an arterial segment, where a high compliance signifies large changes in volume per change in transmural pressure. The relation between changes in transmural pressure and volume is far from linear as compliance increases progressively with decreases in blood pressure. A change in compliance could indicate static changes in arterial wall composition, i.e. the relation between elastic and collagen fibres and accumulation of disease related deposits or dynamic changes caused by alterations in muscular tone. The most used method reflecting arterial compliance is the measurement of pulse wave velocity. However, the pulse wave velocity method measures compliance at ambient transmural pressures and is affected both by the actual blood pressure and the rate of pressure change. Another commonly used method employs the echo-tracking technique to measure the arterial diameter simultaneously with continuous blood pressure monitoring. By this method it is possible to calculate arterial compliance for continuous pressure values between the diastole and the systole. The volume-oscillometry method is based on the fact that the artery can be made to collapse at the end of the diastole by an occlusive cuff while it remains open in a pressure dependent manner during the rest of the cardiac cycle. Changes in the arterial volume is transmitted to the cuff, where it induces a measurable change in pressure, and hence the volume of the artery can be calculated at different values of transmural pressures. Using this method on normal subjects has shown that the arterial compliance decreases with increasing age and that females have lower compliance than males primarily due to a smaller diameter of their arteries. It has also been shown that patients with essential (diastolic) hypertension have compliances which are higher or equal to those of normal subjects, and that patients with systolic hypertension have lower arterial compliances than normal subjects. The former finding is in contrast with pulse wave velocity measurements, where diastolic hypertension was associated with low arterial compliance.

Benazepril versus felodipine as supplement to bendroflumethiazide: evaluation by office and ambulatory blood pressure.

OBJECTIVE: To compare a combination of a thiazide diuretic and an angiotensin converting enzyme inhibitor with a thiazide diuretic and a calcium antagonist. DESIGN: A double-blind randomized trial with subjects in two parallel groups administered either 10-20 mg benazepril once daily or 5-10 mg extended-release felodipine once daily, both titrated according to diastolic office blood pressure. During run-in and all 12 weeks of the study members of both groups were administered 2.5 mg bendroflumethiazide once daily. We measured 24 h ambulatory blood pressure with thiazide alone and after 12 weeks of combination therapy. SETTING: General practices. PATIENTS: We studied 96 hypertensive patients (50 women and 46 men), aged 25-75 years, whose blood pressures were insufficiently regulated (i.e. office diastolic blood pressure >/= 95 mmHg) despite treatment with a thiazide diuretic for at least 3 months. RESULTS: The responses of office blood pressure after 12 weeks of treatment did not differ between the groups and neither did the proportions of responders. The ambulatory recordings revealed, after 12 weeks of treatment, a fall in daytime blood pressure of 16.3/10.3 mmHg in members of the benazepril group compared with a fall of 8.5/5.2 mmHg in members of the felodipine group (P < 0.001/<0.001). Analysis of variance showed that the systolic but not the diastolic office blood pressure in members of the benazepril group was significantly lower during the 12-week study period. When evaluating rising single quote, left (low)white-coat-positive' patients separately, there was a tendency for there to be a more pronounced reduction of their (normal) blood pressure with benazepril therapy. There was a significant reduction in weight of patients in the benazepril group (by 0.9 kg), but not of patients in the felodipine group. We observed no difference in side effects between the two treatment groups.CONCLUSION: Add-on therapies both with benazepril and with felodipine are effective and both drug regimens are well tolerated, but ambulatory blood pressure monitoring yielded differing results.

[Ambulatory 24-hour blood pressure monitoring. A comparative study of oscillometric and auscultatory blood pressure measurement]. / Ambulant 24-timers-blodtryksmonitorering. En sammenlignende undersøgelse af oscillometrisk og auskultatorisk blodtryksmåling.

The purpose of this study was to investigate the compatibility between oscillometric and auscultatory methods, and to determine whether one is preferable to the other for ambulatory 24 h blood pressure monitoring. We used an A & D TM 2421 blood pressure monitoring device. Our investigation included 281 patients with suspected hypertension or undergoing treatment for hypertension. We were able to compare 18,790 paired measurements. The difference (auscultatoric--oscillometric) in paired single readings between the two methods was 1.4 +/- 19 mmHg (mean +/- SD) for systolic and -2.4 +/- 18 mmHg for diastolic readings. The difference for 24 h monitoring amounted to 0.7 +/- 4 mmHg for systolic and -2.2 +/- 6 mmHg for diastolic measurements. The auscultatory method showed a uniformed distribution of errors throughout the 24 h, whereas the oscillometric method had fewer errors in the evenings, but more during working hours. A weak correlation between the difference and systolic blood pressure levels, age and pulse pressure was found. Difference in diastolic blood pressure correlated only weakly with the level of pulse pressure. Although we found a considerable SD on single readings, there was a good agreement between the mean values for the 24 h monitoring for the two methods. The findings suggest that, for this equipment, the oscillometric method is preferable for 24 h ambulatory blood pressure monitoring because it provides a much higher rate of successful readings.

Smoking related to 24-h ambulatory blood pressure and heart rate: a study in 352 normotensive Danish subjects.

This study shows the association between smoking and both office and ambulatory blood pressure. By means of stratification, a uniform number of subjects of both sexes and spanning 6 decades (aged 20 to 79 years) were recruited randomly from the local community register. A total of 352 subjects participated, including 161 smokers. Smokers (both sexes and all age groups summed), as compared with nonsmokers had statistically significant lower office blood pressure as follows (mean systolic +/- SED/mean diastolic +/- SED): (systolic and diastolic, -6.8 +/- 2.1/-3.9 +/- 1.3); day ambulatory blood pressure (diastolic, /-2.8 +/- 1.0); and night ambulatory blood pressure (systolic and diastolic, -4.2 +/- 1.8/-3.9 +/- 1.1). The intraperson variability of the day ambulatory blood pressure (as measured every 15 min) was identical for the smokers and the nonsmokers. Smokers were found to have a diminished "white coat" effect; this diminished white coat effect has not previously been described. The major white coat effect was seen in the older nonsmokers, whereas the diminished white coat effect was most pronounced in the older male smokers and in the younger female smokers. Smokers seem to have a diminished white coat effect, as well as a lower ambulatory blood pressure throughout the day (diastolic) and at night (systolic and diastolic). The similar intraperson variability found in the smokers' and nonsmokers' blood pressure further speaks for a consistently lower blood pressure in smokers as compared with nonsmokers.

[Round-the-clock blood pressure measurements in 352 persons--a reference material]. / 24 timers ambulant blodtryk hos 352 personer--et referencemateriale.

The aim of this study was to establish reference values for 24-hour ambulatory blood pressure in a Danish population stratified for gender and age in the decades from 20 to 79 years of age. A sample of 352 persons, 179 men and 173 women randomly selected from the local community register, age 20-79 years underwent 24-h ambulatory blood pressure monitoring. For men age < 50 daytime ambulatory blood pressure (median) was 125/79 mmHg and night time was 106/65 mmHg, for women the respective pressures were 113/77 mmHg and 97/64 mmHg. For men age > or = 50 daytime ambulatory blood pressure was 133/83 mmHg and night time was 124/86 mmHg, for women the respective pressures were 122/83 mmHg and 105/65 mmHg. Presently, we can only relate cardiovascular risk to clinic blood pressure. Therefore we have calculated corresponding ambulatory blood pressure values to WHO's upper limit 160/90 mmHg for normal blood pressure in the clinic and found 154/87 mmHg for daytime and 134/74 mmHg at night. For a clinic pressure of 95 mmHg the corresponding daytime value was 91 mmHg, for 100 mmHg it was 95 mmHg.

The effect of antihypertensive treatment with dihydropyridine calcium antagonists on white-coat hypertension.

OBJECTIVE: To investigate the interrelations between blood pressure variables and treatment effects in white-coat and established hypertensive patients. DESIGN: A substudy on data from a randomized clinical trial on two dihydropyridine calcium antagonists, in which treatment intensity relied on office blood pressure, but with ambulatory blood pressure recordings performed before and after treatment. PATIENTS: Ninety-two hypertensive patients from general practices. RESULTS: Office and ambulatory blood pressures were only poorly correlated (r = 0.27-0.49). There was no significant correlation between treatment effects evaluated in terms of office and ambulatory blood pressures. Seventeen patients were classified as white-coat hypertensives; these differed in that their office blood pressure declined more with placebo, but similarly when administered active treatment, whereas their ambulatory blood pressure was not affected. An initial ambulatory blood pressure amounting to 127.4/84.8 mmHg was associated with no ambulatory treatment effect on average. CONCLUSION: These findings expose the shortcomings of office blood pressure measurements and strengthen the conception that white-coat hypertensives should not be treated pharmacologically.

A comparison between the oscillometric and the auscultatory method for ambulatory 24 h blood pressure monitoring.

OBJECTIVES: To investigate the compatibility between oscillometric and auscultatory methods, and to determine whether one is preferable over the other for ambulatory 24 h blood pressure monitoring. METHODS: For the blood pressure monitoring system we used an A&D TM 2421 device (Takeda), which enabled us to measure the blood pressure simultaneously with the two methods on the same arm. Our investigation included 281 patients (122 women and 159 men, aged 18-85 years) with suspected hypertension or undergoing treatment for hypertension. RESULTS: We obtained 23 531 measurements by the oscillometric method, which was 98% of the maximal possible number, and 81% of the maximal possible number were obtained by the auscultatory methjod. We were able to compare 98% of the paired measurements. The auscultatory method showed a uniform distribution of errors throughout the 24 h. Compared to the auscultatory method, the oscillometry method had fewer errors in the evenings, but more when the subjects were at work. There was a difference in paired single readings between the two methods amounting to 1.4+/-19 mmHg (mean+/-SD) for systolic and -2.4+/-18 mmHg for diastolic readings (auscultatory - oscillometric). The differences in mean values for the 281 cases of 24 h monitoring amounted to 0.7+/- 4 mmHg for systolic and -2.2+/-6 mmHg for diastolic measurements. For the mean systolic blood pressure, we found a difference of 0.3+/-4 mmHg in the daytime and 0.3+/-8 mmHg during the night. The mean diastolic pressures differed by -2.0+/-6 mmHg in the daytime and -1.6+/-8 mmHg during the night. We found only a weak correlation between the differences in the readings by the two methods and systolic blood pressure levels, age, pulse pressure and body mass index, and no correlations between these differences and the diastolic blood pressure levels. CONCLUSION: Although we found a considerable SD on single readings by the two methods, there was a good agreement between the mean values of the 24 h monitoring for the two methods. We obtained a significantly higher success rate by the oscillometric method. The findings suggest that, for this equipment, the oscillometric method is preferable for 24 h ambulatory blood pressure monitoring because it provides a much higher rate of successful readings.

[Determination of diurnal blood pressure variations in cirrhosis]. / Bestemmelse af døgnblodtryksvariationer ved cirrose.

Cirrhotic patients have disturbed systemic haemodynamics with reduced arterial blood pressure, but this has not been investigated during daily activity and sleep. Systolic (SBP), diastolic (DBP), and man arterial blood pressure (MAP), and heart rate (HR) were measured by an automatic ambulatory device for monitoring blood pressure in 35 patients with cirrhosis and 35 healthy matched controls. During the day-time, SBP, DBP and MAP were significantly lower in the patients than in the controls (median 118 vs 127; 70 vs 78; 86 vs 94 mmHg, p < 0.0001 to p < 0.05). The night-time blood pressures were almost similar in the two groups (108 vs 110; 65 vs 67; 78 vs 82 mmHg, NS). Conversely, HR was significantly higher in the patients both in the day-time (86 vs 72 min-1, p < 0.0001) and night (80 vs 64 min-1, p < 0.0001). Consequently, the reduction in blood pressure and HR from day-time to night-time was significantly lower in the patients than in the controls (p < 0.0001 to p < 0.01). Multiple regression analysis revealed HR, serum albumin, serum sodium, and clotting factors 2, 7 and 10 as significant independent predictors of SBP in cirrhosis. In conclusion, cirrhotic patients have elevated HR, but surprisingly normal arterial blood pressure during the night-time, and the circadian variation in blood pressure and HR is diminished probably due to an almost unaltered cardiac output during the 24 hours. These results may reflect a major defect in the ability of optimal regulation of blood pressure in cirrhotic patients.

24-h ambulatory blood pressure in 352 normal Danish subjects, related to age and gender.

UNLABELLED: The study was conducted to determine age and sex stratified normal values for 24-h ambulatory blood pressure. A sample of 352 healthy subjects (all white) were randomly selected from the community register and stratified by sex and age groups in decades from 20 to 79 years of age. Persons with a history of hypertension, cerebral apoplexy, diabetes, myocardial or renal disease, and who were taking blood pressure-influencing medication were excluded. Ambulatory blood pressure was recorded over 24 h, with measurements taken every 15 min from 07:00 to 22:59, and every 30 min from 23:00 to 6:59. Systolic blood pressure increased only slightly with age and was significantly higher in men than in women. The diastolic blood pressure increased only slightly with age in both sexes until the 50 to 59 years age group and declined thereafter. The diastolic blood pressure was not different for the two sexes. Both systolic and diastolic blood pressure were approximately 15% lower during the night regardless of age or sex. Ambulatory blood pressure during the daytime was on an average of 5 mm Hg lower than office blood pressure, but the mean difference between the two measurements increased with age. The variability of the difference also increased with age. IN CONCLUSION: Normal values for ambulatory blood pressure are presented in a randomly selected age- and gender-stratified population. Differences between office blood pressure and ambulatory blood pressure increased with age suggesting that the previously observed higher blood pressure seen in the elderly partly might be explained by a greater impact of white coat hypertension in older people.

Office and ambulatory blood pressure: a comparison between amlodipine and felodipine ER. Danish Multicentre Group.

The anti-hypertensive efficacy and safety of extended-release (ER) felodipine (5, 10 or 20 mg) and amlodipine (5 or 10 mg) once daily were compared in patients with mild-to-moderate essential hypertension in a double-blind, double-dummy, randomised, comparative study. A total of 118 patients were allocated to a 12-week, double-blind treatment with either felodipine ER (n = 57) or amlodipine (n = 61). The anti-hypertensive effect was evaluated by measuring office blood pressure (BP) at baseline and after 4, 6, 8 and 12 weeks, together with 24 h ambulatory blood pressure monitoring (ABPM) at baseline, on day 1 of treatment and at the end of the study. The mean office BP changes from baseline to week 12 were -13.4 (+/- 15.7)/-11.8 (+/- 6.9) mmHg for felodipine ER (mean daily dose 11.2 mg) and -15.3 (+/- 17.0)/-12.9 (+/- 7.3) mm Hg for amlodipine (mean daily dose 7.4 mg). All BP reductions were significant (P < 0.01) with respect to time, but differences between treatment groups were not significant. The mean ambulatory BP changes from baseline to end of the study were -11.6 (+/- 5.2)/-10.0 (+/- 2.0) mmHg for felodipine ER and -16.3 (+/- 4.4)/-9.6 (+/- 3.0) mm Hg for amlodipine, both significant (P < 0.01). The fall in ambulatory SBP was significantly greater (P < 0.001) in the patients treated with amlodipine compared with felodipine ER whereas there was no difference between the groups with respect to ambulatory DBP. Both drgs were well tolerated with a withdrawl rate of 12% equally distributed.(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive 24-hour ambulatory arterial blood pressure monitoring in cirrhosis.

Cirrhotic patients have disturbed systemic hemodynamics with reduced arterial blood pressure, but this has not been investigated during daily activity and sleep. Systolic (SBP), diastolic (DBP), and mean arterial blood pressure (MAP), and heart rate (HR) were measured by an automatic ambulant device for monitoring blood pressure in 35 patients with cirrhosis and 35 healthy matched controls. During the daytime, SBP, DBP, and MAP were significantly lower in the patients than in the controls (median 118 vs. 127; 70 vs. 78; 86 vs. 94 mm Hg, P < .0001 to P < .05). The nighttime blood pressures were almost similar in the two groups (108 vs. 110; 65 vs. 67; 78 vs. 82 mm Hg, NS). Conversely, HR was significantly higher in the patients both in the daytime (86 vs. 72/min, P < .0001) and at night (80 vs. 64/min, P < .0001). Consequently, the reduction in blood pressure and HR from daytime to nighttime was significantly lower in the patients than in the controls (P < .0001 to P < .01). Multiple regression analysis showed HR, serum albumin, serum sodium, and clotting factors 2, 7, and 10 as significant independent predictors of SBP in cirrhosis. In conclusion, cirrhotic patients have elevated HR, but surprisingly normal arterial blood pressure during the nighttime, and the circadian variation in blood pressure and HR is diminished, probably because of an almost unaltered cardiac output during the 24 hours. These results may reflect a major defect in the ability of optimal regulation of blood pressure in cirrhotic patients.