Self-medication of regular headache: a community pharmacy-based survey.

BACKGROUND: This observational community pharmacy-based study aimed to investigate headache characteristics and medication use of persons with regular headache presenting for self-medication. METHODS: Participants (n = 1205) completed (i) a questionnaire to assess current headache medication and previous physician diagnosis, (ii) the ID Migraine Screener (ID-M), and (iii) the Migraine Disability Assessment questionnaire. RESULTS: Forty-four percentage of the study population (n = 528) did not have a physician diagnosis of their headache, and 225 of them (225/528, 42.6%) were found to be ID-M positive. The most commonly used acute headache drugs were paracetamol (used by 62% of the study population), NSAIDs (39%), and combination analgesics (36%). Only 12% of patients physician-diagnosed with migraine used prophylactic migraine medication, and 25% used triptans. About 24% of our sample (n = 292) chronically overused acute medication, which was combination analgesic overuse (n = 166), simple analgesic overuse (n = 130), triptan overuse (n = 19), ergot overuse (n = 6), and opioid overuse (n = 5). Only 14.5% was ever advised to limit intake frequency of acute headache treatments. CONCLUSIONS: This study identified underdiagnosis of migraine, low use of migraine prophylaxis and triptans, and high prevalence of medication overuse amongst subjects seeking self-medication for regular headache. Community pharmacists have a strategic position in education and referral of these self-medicating headache patients.

Efficacy, tolerability and safety of nebivolol in patients with hypertension and diabetes: a post-marketing surveillance study.

BACKGROUND AND OBJECTIVES: Hypertension is a widely prevalent condition of elevated blood pressure (BP) and is the leading risk factor for the development of cardiovascular disease (CVD). Many patients have additional risk factors such as diabetes mellitus (DM) or previous history of CVD. Nebivolol is a third-generation beta (beta)-blockers which has been shown not to influence metabolic parameters in patients with DM. This postmarketing surveillance study aimed to collect information on the efficacy, safety and tolerability of nebivolol in hypertensive patients with concomitant DM. PATIENTS AND METHODS: Hypertensive patients with DM followed by 52 cardiologists, internal medicine specialists and general practitioners, between 24 August 2003 and 9 January 2007 in The Netherlands were included in this study. Physicians were asked to survey nebivolol treatment for 6 months. RESULTS: A total of 510 patients were enrolled. Overall, 93.3% of patients were diagnosed with essential hypertension and 6.7% with secondary hypertension. All patients were co-diagnosed with DM. Nebivolol therapy was associated with a significant reduction in both systolic blood pressure (BP) and diastolic BP versus baseline (p < 0.001 for both). These reductions were seen regardless of reason for initiation of nebivolol (i.e. first diagnosis of hypertension, resistance or intolerance to previous antihypertensive medication, or other reasons). A significant improvement in blood glucose was seen at 4 months (-0.6 mmol/L; p = 0.021). Significant reductions in total cholesterol (-1.45 mmol/L; p = 0.006), low density lipoprotein (LDL) cholesterol (-1.32 mmol/L; p = 0.003) and LDL/high density lipoprotein (HDL) cholesterol ratio (-0.77; p = 0.011) were observed at 2 months. No significant changes were seen in HDL cholesterol and triglycerides. CONCLUSION: Nebivolol treatment was associated with a significantly reduced BP, improved blood glucose and LDL cholesterol levels and was well tolerated in hypertensive patients with concomitant DM.

Arterial structure and function and environmental exposure to cadmium.

OBJECTIVES: Few studies have addressed the effect of cadmium toxicity on arterial properties. METHODS: We investigated the possible association of 24 h urinary cadmium excretion (an index of lifetime exposure) with measures of arterial function in a randomly selected population sample (n = 557) from two rural areas with low and high environmental exposure to cadmium. RESULTS: 24 h urinary cadmium excretion was significantly higher in the high compared with the low exposure group (p<0.001). Even though systolic (p = 0.42), diastolic (p = 0.14) and mean arterial pressure (p = 0.68) did not differ between the high and low exposure groups, aortic pulse wave velocity (p = 0.008), brachial pulse pressure (p = 0.026) and femoral pulse pressure (p = 0.008) were significantly lower in the high exposure group. Additionally, femoral distensibility (p<0.001) and compliance (p = 0.001) were significantly higher with high exposure. Across quartiles of 24 h urinary cadmium excretion (adjusted for sex and age), brachial (p for trend = 0.015) and femoral (p for trend = 0.018) pulse pressure significantly decreased and femoral distensibility (p for trend = 0.008) and compliance (p for trend = 0.007) significantly increased with higher cadmium excretion. After full adjustment, the partial regression coefficients confirmed these associations. Pulse wave velocity (beta = -0.79+/-0.27; p = 0.004) and carotid (beta = -4.20+/-1.51; p = 0.006), brachial (beta = -5.43+/-1.41; p = 0.001) and femoral (beta = -4.72+/-1.74; p = 0.007) pulse pressures correlated negatively, whereas femoral compliance (beta = 0.11+/-0.05; p = 0.016) and distensibility (beta = 1.70+/-0.70; p = 0.014) correlated positively with cadmium excretion. CONCLUSION: Increased cadmium body burden is associated with lower aortic pulse wave velocity, lower pulse pressure throughout the arterial system, and higher femoral distensibility.

Determining carotid artery pressure from scaled diameter waveforms: comparison and validation of calibration techniques in 2026 subjects.

Calibrated diameter distension waveforms could provide an alternative for local arterial pressure assessment more widely applicable than applanation tonometry. We compared linearly and exponentially calibrated carotid diameter waveforms to tonometry readings. Local carotid pressures measured by tonometry and diameter waveforms measured by ultrasound were obtained in 2026 subjects participating in the Asklepios study protocol. Diameter waveforms were calibrated using a linear and an exponential calibration scheme and compared to measured tonometry waveforms by examining the mean root-mean-squared error (RMSE), carotid systolic blood pressure (SBPcar) and augmentation index (AIx) of calibrated and measured pressures. Mean RMSE was 5.2(3.3) mmHg (mean(stdev)) for linear and 4.6(3.6) mmHg for exponential calibration. Linear calibration yielded an underestimation of SBPcar by 6.4(4.1) mmHg which was strongly correlated to values of brachial pulse pressure (PPbra) (R = 0.4, P < 0.05). Exponential calibration underestimated true SBPcar by 1.9(3.9) mmHg, independent of PPbra. AIx was overestimated by linear calibration by 1.9(10.1)%, the difference significantly increasing with increasing AIx (R = 0.25, P < 0.001) and by exponential calibration by 5.4(10.6)%, independently of the value of AIx. Properly calibrated diameter waveforms offer a viable alternative for local pressure estimation at the carotid artery. Compared to linear calibration, exponential calibration significantly improves the pressure estimation.

Three- and four-element Windkessel models: assessment of their fitting performance in a large cohort of healthy middle-aged individuals.

Lumped-parameter models are used to estimate the global arterial properties by fitting the model to measured (aortic) pressure and flow. Different model configurations coexist, and it is still an open question as to which model optimally reflects the arterial tree and leads to correct estimates of arterial properties. An assessment was made of the performance of (a) the three-element Windkessel model (WK3) consisting of vascular resistance R, total arterial compliance C, and characteristic impedance Zc; (b) a four-element model with an inertance element L placed in parallel with Zc (WK4-p); and (c) a four-element model with L placed in series with Zc (WK4-s). Models were fitted to data measured non-invasively in 2404 healthy subjects, aged between 35 and 55 years. It was found that model performance segregated into two groups. In a group containing 20 per cent of the dataset (characterized by low blood pressure and wave reflection) the WK4-p model outperformed the other models, with model behaviour as envisioned by its promoters. In these cases, the WK3 and WK4-s models led to increased overestimation of total arterial compliance and underestimation of characteristic impedance. However, in about 80 per cent of the cases, the WK4-p model showed a behaviour that was very similar to that of the WK3 and WK4-s models. Here, the WK4-s model yielded the best quality of fit, although model parameters reached physically impossible values for L in about 12 per cent of all cases. The debate about which lumped-parameter model is the better approximation of the arterial tree is therefore still not fully resolved.

Remodeling of the vascular tree in hypertension: drug effects.

The primary aim of current antihypertensive therapy is to lower blood pressure through the reduction of peripheral vascular resistance. Resistance reduction is achieved primarily by interference with acutely acting pressor stimuli. However, recent research has stressed the importance of slow pressor stimuli, which act by gradually remodeling the vascular tree. Long-term remodeling is achieved by a chronic change in vessel number, vascular diameter or wall thickness, involving both physical and chemical factors. The chemical mediators belong to a group of endogenous growth-affecting factors. As Harry Struyker Boudier and colleagues explain in this review, although there are thus far no specific drugs to antagonize the effects of these factors, several therapeutically used antihypertensives influence their action. Moreover, the concept that vascular remodeling is important in hypertension offers exciting new therapeutic targets.

Short- and long-term effects of smoking on arterial wall properties in habitual smokers.

OBJECTIVES: This study investigated the short-term effects of smoking on hemodynamic function and distensibility and compliance of large arteries in habitual smokers. In addition, the effect of smoking was not measured in nonsmokers, but vessel wall properties were compared between smokers and nonsmokers (basal state). BACKGROUND: Smoking is a well known risk factor for atherosclerosis. Loss of distensibility and compliance of large arteries may play a role in the onset of atherosclerosis. METHODS: The distensibility and compliance coefficients of the common carotid and brachial arteries were determined from the arterial wall displacement during systole and the end-diastolic diameter by using a vessel wall movement detector and from the pulse pressure as assessed in the upper arm. Cardiac function (cardiac output, stroke volume) was measured with Doppler echocardiography. Systemic vascular resistance was calculated as mean arterial pressure divided by cardiac output. RESULTS: In habitual smokers, smoking one cigarette caused a sharp increase in blood pressure (6%) and heart rate (14%). Cardiac index increased (16%), mainly because of the marked increase in heart rate. Stroke and systemic vascular resistance indexes did not change significantly. Smoking enhanced forearm blood flow after wrist occlusion (17%), but total forearm blood flow was unchanged, suggesting an increase in muscle blood flow and a decrease in skin flow. Because of higher blood pressure, the diameter of the elastic common carotid artery increased by 3% (passive phenomenon). Distensibility of the carotid artery decreased (7%), and as a result, carotid compliance was preserved. In contrast, despite higher blood pressure, the diameter of the muscular brachial artery did not change, suggesting an increased vascular tone. Brachial distensibility and compliance decreased (18% and 19%, respectively). Habitual smokers were comparable to nonsmokers with regard to blood pressure, cardiac function, vascular resistance and vessel wall properties of large arteries. Heart rate was higher in habitual smokers (14%). CONCLUSIONS: These data indicate that in habitual smokers, smoking one cigarette causes short-term increases in arterial wall stiffness that might be harmful to the artery and increase the risk for plaque rupture. Except for a higher heart rate, no obvious long-term effect of smoking was observed on hemodynamic variables and arterial stiffness. Because acute cardiovascular events are mainly due to plaque rupture, the short-term effects of smoking might be a more important risk than long-term effects for these acute ischemic events.

Vessel wall properties of large arteries in uncomplicated IDDM.

OBJECTIVE: Patients with insulin-dependent diabetes mellitus (IDDM) are at high risk for cardiovascular disease. Arterial distensibility and compliance are vessel wall properties of large arteries. Altered large artery wall properties can be an early feature of vascular dysfunction. This study investigates vessel wall properties in 30 patients with uncomplicated IDDM and 30 matched healthy control subjects. RESEARCH DESIGN AND METHODS: Vessel wall properties of the elastic common carotid (CCA) and the muscular femoral (FA) and brachial arteries (BA) were measured with a vessel wall movement detector system. Blood pressure and heart rate were recorded simultaneously with a semiautomated device. Aortic pulse wave velocity was estimated from the carotido-femoral transit time. RESULTS: Blood pressure (IDDM patients: 118 +/- 10/69 +/- 5 mmHg), pulse pressure (IDDM patients: 49 +/- 8 mmHg), and heart rate (IDDM patients: 65 +/- 9 beats/min) were similar in IDDM patients and control subjects. No statistically significant changes between IDDM patients and control subjects were found for diameter, distensibility, and compliance of the elastic CCA and the muscular BA. Distensibility (IDDM patients: 16.9 +/- 6.4 10(-3)/kPa; control subjects: 22.4 +/- 11.8 10(-3)/kPa) of the muscular FA was decreased in IDDM (P < 0.05). However, FA compliance (IDDM patients: 0.80 +/- 0.23 mm2/kPa; control subjects: 0.94 +/- 0.41 mm2/kPa) and FA diameter (IDDM patients: 7.87 +/- 1.10 mm; control subjects: 7.57 +/- 1.11 mm) did not differ statistically between IDDM patients and control subjects. Aortic pulse wave velocity was the same in IDDM patients and control subjects (IDDM patients: 5.1 +/- 0.6 m/s). No relation was found between vessel wall properties and duration of disease, actual glucose level, and HbA1c for all three arteries (CCA, BA, and FA). But the groups might have been too small to draw conclusions. CONCLUSIONS: The results of the present study show that in this group of patients with uncomplicated IDDM, vessel wall properties of elastic and muscular large arteries were not obviously reduced when compared with healthy control subjects. However, distensibility of the FA was lower in IDDM patients. Early atherosclerotic changes in IDDM frequently occur at this site. A difference related to the duration of diabetes could not be excluded.

Evaluation of reproducibility of a vessel wall movement detector system for assessment of large artery properties.

OBJECTIVE: Arterial distensibility (DC) and compliance (CC) are vessel wall properties of large arteries that can be measured non-invasively with a custom made vessel wall movement detector system (VWMDS). This study investigated the reproducibility of this device in 10 volunteers. METHODS: To investigate intraobserver intrasession and intraobserver intersession variability, arterial diameter (D) and relative change in diameter during the heart cycle (delta D/D) were measured in the elastic common carotid artery, and in the muscular femoral and brachial arteries. Interobserver intrasession variability was examined in common carotid artery by two observers, while interobserver variability on the same image was assessed for common carotid and femoral arteries. Variability was expressed as the coefficient of variation. RESULTS: For common carotid artery, intraobserver intrasession variability was 7.9(SEM 1.6)% (delta D/D), 4.5(1.1)% (D), 8.3(1.3)% (DC), and 9.1(2.6)% (CC), respectively. In femoral artery it was 12.4(2.2)% (delta D/D), 2.7(0.6)% (DC), 13.4(2.2)% (DC), and 12.5(2.1)% (CC). For brachial artery it was 13.4(2.8)% (delta D/D), 2.5(0.5)% (D), 16.1(2.5)% (DC), and 15.6(2.6)% (CC). Intraobserver intersession variability was comparable to intraobserver intrasession variability for all vessels. Interobserver intrasession variability for common carotid artery was 11.3(2.6)% (delta D/D) and 8.6(1.9)% (D), but was larger for DC and CC. Interobserver variability on the same image was < 5% for common carotid and femoral arteries. CONCLUSIONS: In conclusion, the vessel wall movement detector system has a good technical reproducibility. Intraobserver intrasession and intersession variability are comparable, and are larger in muscular arteries. This might be due to a larger variation in tone of these arteries, which are under permanent neurohumoral control. Interobserver intrasession variability was larger than intraobserver variability and might be influenced by differences in observers' skill and spontaneous variation in vessel wall properties.

Effects of antihypertensive agents on local arterial distensibility and compliance.

Distensibility and compliance are important vessel wall properties. Distensibility is related to elastic properties of the arterial wall, and compliance reflects the buffering function of the artery. Distensibility is a determinant of stress on the vessel wall. A decreased distensibility might increase the risk of arterial wall damage. Therefore, a preserved local distensibility might be important in protecting the arterial wall of each particular artery and especially of those arteries that are more susceptible to vascular disease. Local distensibility and compliance of various large arteries can be measured noninvasively with echo tracking techniques. Studies on local distensibility and compliance revealed that with the calcium antagonist verapamil and the angiotensin-converting enzyme inhibitor perindopril arterial compliance increased mainly because of an increase in distensibility, with only a minor effect on arterial diameter. In contrast, the nitrate compound isosorbide dinitrate increased compliance mainly by increasing arterial diameter, without an increase in distensibility. This indicates that an increase in arterial compliance does not automatically imply an increase in arterial distensibility. The effect of antihypertensive drugs may also depend on the vascular territory. The diuretic amiloride/hydrochlorothiazide increased brachial artery compliance but not common carotid artery compliance. During angiotensin-converting enzyme inhibition the effect on arterial compliance was smaller at the carotid than the femoral artery. However, the opposite held for the nitrate compound. These distinctive effects of antihypertensive drugs on arterial distensibility and compliance and on vascular territories may be relevant to pharmacological prevention and management of arterial disease.

Vascular effects of 5-HT1B/1D-receptor agonists in patients with migraine headaches.

OBJECTIVES: Second-generation triptans are believed to have fewer cardiovascular effects than sumatriptan. This was investigated in vivo by comparing the vascular effects of equipotent therapeutic dosages of selective 5-HT1B/1D-receptor agonists. METHODS: Sixteen patients with migraine headaches completed a double-blind, placebo-controlled, four-way crossover study. With ultrasonography and applanation tonometry used 1.5 hours after the oral intake of sumatriptan (50 mg), rizatriptan (10 mg), zolmitriptan (2.5 mg), or placebo arterial vessel wall properties, blood flow and pressure waveforms were measured in common carotid, brachial, and temporal arteries. At the brachial artery, flow-induced vasodilation (an endothelium-dependent process) was evaluated, and blood pressures were recorded. RESULTS: Mean arterial pressure, 91 +/- 2 mm Hg after placebo, increased (P < .05) by 4% to 6% after administration of each triptan. Each active treatment decreased (P < .001) both brachial and carotid artery diameter. Isobaric compliance of the brachial artery, 0.077 +/- 0.010 mm2/kPa after placebo, decreased (P < .01) by 11% +/- 8%, 11% +/- 11%, and 23% +/- 7% after administration of sumatriptan, rizatriptan, and zolmitriptan, respectively. Isobaric compliance of the carotid artery was 1.31 +/- 0.10 mm2/kPa after placebo (no change). Zolmitriptan was the only triptan that decreased temporal artery diameter significantly (by 12% +/- 3%, P < .001). The resistance of the temporal artery vascular bed increased after administration of sumatriptan (by 26% +/- 11%, P < .05) and zolmitriptan (by 40% +/- 9%, P = .001). Flow-induced vasodilation was unaffected. CONCLUSIONS: Selective 5-HT1B/1D-receptor agonists induce vasoconstriction and decrease compliance of conduit arteries. These effects are more pronounced at muscular (temporal, brachial) compared with elastic (carotid) arteries. Resistance is only increased at the temporal artery vascular bed, suggesting cranioselectivity for resistance vessels. Endothelial function is not differently affected by any of the triptans tested.

Is it possible to develop drugs that act more selectively on large arteries?

BACKGROUND: Patients with high pulse pressures have an increased risk for cardiovascular events. Drugs that selectively decrease high pulse pressure may be of interest for these patients. Such drugs have a more pronounced effect on large arteries than on resistance vessels. OBJECTIVE: To compare the selectivity to large arteries of the new nitric oxide donor sinitrodil with the classic nitrate isosorbide dinitrate in healthy young men in order to investigate whether it is possible to develop drugs that act more selectively on large arteries. DESIGN: The study had a double-blind, 5-way cross-over design. In randomized order, subjects received a single oral dose of 10 mg sinitrodil, 20 mg sinitrodil, 40 mg sinitrodil, isosorbide dinitrate and placebo. Measurements were performed before and 45 min after administration of the drugs. Between each drug administration, at least 3 days of wash-out was allowed. METHODS: The effects of the drugs on large arteries and resistance vessels were assessed by their effects on brachial artery compliance and total peripheral resistance, respectively. RESULTS: Brachial artery compliance increased gradually with increasing doses of sinitrodil (by 10, 20 and 27% with 10, 20 and 40 mg sinitrodil, respectively). Total peripheral resistance index decreased with isosorbide dinitrate (by 11%) and 40 mg sinitrodil (by 7%), while it remained unchanged with 10 mg and 20 mg sinitrodil. CONCLUSIONS: The results of this study show that it may be possible to develop drugs with a higher selectivity for large arteries. Such drugs may be good candidates to decrease high pulse pressure without substantially decreasing mean and diastolic blood pressures.

Vascular distensibility and compliance in salt-sensitive and salt-resistant borderline hypertension.

OBJECTIVE: To gain insight into the relationship between vascular compliance and sodium sensitivity. DESIGN: Arterial and venous compliance was determined in 17 sodium-sensitive and 28 sodium-resistant, young, borderline hypertensive males and in 10 age-matched normotensive controls, during regular sodium intake. METHODS: The carotid, femoral and brachial arteries were studied using a non-invasive ultrasound vessel wall movement detector system, and venous compliance was determined using forearm strain-gauge plethysmography. Cardiac output, plasma volume and hormonal factors, such as plasma renin activity, were also measured to assess their possible influence on vascular compliance. RESULTS: Large artery compliance was significantly less in the sodium-sensitive than in the sodium-resistant subjects in all arteries studied. Compared with controls, arterial compliance was reduced significantly in the sodium-sensitive group, whereas the sodium-resistant group did not differ significantly from the controls. Venous compliance was reduced equally in the two hypertensive groups compared with the controls, although the differences did not reach statistical significance. Cardiac output, blood pressure, plasma volume and hormonal factors did not differ between sodium-sensitive and sodium-resistant subjects and could not have been responsible for the observed differences in arterial compliance. CONCLUSIONS: The results of this study suggest that sodium-sensitive borderline hypertensives have reduced large artery compliance compared with age-matched sodium-resistant subjects. Since this finding could not be explained by differences in haemodynamic or hormonal factors between the groups, this suggests alterations to the viscoelastic properties of the arterial walls in sodium-sensitive subjects.

The influence of perindopril and the diuretic combination amiloride+hydrochlorothiazide on the vessel wall properties of large arteries in hypertensive patients.

OBJECTIVE: To compare the cardiovascular effects of 6 months of treatment with the angiotensin converting enzyme inhibitor perindopril and with the diuretic combination amiloride+hydrochlorothiazide, and to study possible persistence of observed treatment effects after discontinuation of antihypertensive therapy. DESIGN: A placebo run-in period preceded a 6-month active-treatment phase in 41 patients with essential hypertension, according to a double-blind, randomized, parallel-group design. Patients received either 4 mg perindopril or 2.5/25 mg amiloride+hydrochlorothiazide once a day. Patients were then studied for a 3-month single-blind placebo run-out period. RESULTS: After 6 months of treatment, systolic blood pressure was reduced significantly by perindopril (supine by 11%, sitting by 10%) and by amiloride+hydrochlorothiazide (supine by 8%, sitting by 12%). Diastolic blood pressure was also decreased significantly by perindopril (supine by 8%, sitting by 11%) and by amiloride+hydrochlorothiazide (supine by 4%, sitting by 9%). Mean arterial pressure decreased significantly during treatment with perindopril (by 9%) and with amiloride+hydrochlorothiazide (by 6%). Cardiac index increased with perindopril (by 6%), because of an increased stroke index (by 5%), but amiloride+hydrochlorothiazide did not change cardiac function. Systemic vascular resistance index decreased significantly more with perindopril (by 14%) than with amiloride+hydrochlorothiazide (by 8%). The distensibility of the common carotid artery was significantly enhanced by perindopril (by 16%), but not changed by amiloride+hydrochlorothiazide (1% difference). The difference between perindopril and amiloride+hydrochlorothiazide for carotid distensibility was statistically significant. The compliance of the common carotid artery tended to be increased more by perindopril (by 7%) than by amiloride+hydrochlorothiazide, which induced a 5% decrease in carotid compliance. After withdrawal of therapy, for both drugs, all treatment-induced changes were reversed to pretreatment values within 7 weeks. CONCLUSION: The distensibility of the elastic common carotid artery was increased by perindopril, but not by amiloride+hydrochlorothiazide. Large-artery properties of the muscular arteries and systemic vascular resistance improved with both drugs, but in general the changes were more pronounced with perindopril than with amiloride+hydrochlorothiazide. The present results indicate a more pronounced effect of perindopril at both macro- and microcirculatory levels, which will consequently lead to a larger decrease in cardiac afterload. After discontinuation of therapy all parameters returned to baseline values within 7 weeks.

The effect of weight loss with or without exercise training on large artery compliance in healthy obese men.

BACKGROUND: Obesity is an independent risk factor for cardiovascular morbidity and mortality. Large artery compliance is thought to be associated with cardiovascular risk. The effect of weight loss on large artery compliance is not yet clarified. OBJECTIVE: To investigate the effect of weight loss, with or without exercise, on vessel wall properties in healthy obese men. DESIGN: This was a pair-matched randomized intervention study. All subjects were on an energy-restricted diet. One subject from each pair was also on an exercise programme. Measurements were performed before and at the end of the study period. The study lasted for 3 months. METHODS: The vessel wall properties of the brachial and common carotid artery were assessed using a vessel wall movement detector system in combination with applanation tonometry. RESULTS: The mean body mass index was 32.3+/-0.4 kg/m2 and decreased (P < 0.001) to 27.6+/-0.4 kg/mm2 during the study. The mean blood pressure decreased (P < 0.001) by 6%. At operating pressures, carotid artery distensibility was 27.5+/-1.7 x 10(-3)/kPa at the start of the study and 31.1+/-1.8 x 10(-3)/kPa (P < 0.04) at the end of the study. Brachial and carotid artery compliances were 0.11+/-0.01 and 1.35+/-0.08 mm2/kPa at the start of the study and tended to increase to 0.12+/-0.001 (P = 0.06) and 1.48+/-0.08 mm2/kPa (P = 0.057), respectively, at the end of the study. Isobaric compliance did not change. The diet-and-exercise group did not differ statistically from the only-diet group in the effects on weight loss, blood pressure and arterial compliance. CONCLUSION: This study shows that weight loss increased carotid artery distensibility at operating pressures, but not under isobaric conditions. This increase is probably due to the decrease in blood pressure. The addition of exercise did not result in an additional effect within 3 months.

Non-invasive assessment of local arterial pulse pressure: comparison of applanation tonometry and echo-tracking.

OBJECTIVES: Pulse pressure is not constant throughout the arterial tree. Use of pulse pressure at one arterial site as surrogate for pulse pressure at another arterial site may be erroneous. The present study compares three non-invasive techniques to measure local pulse pressure: (i) internally calibrated readings from applanation tonometry, (ii) alternative calibration of pressure waves obtained with applanation tonometry and (iii) alternative calibration of arterial distension waves obtained with echo-tracking. Alternative calibration assumes mean and diastolic blood pressure constant throughout the large artery tree. DESIGN AND METHODS: Study 1 used invasive measurements in the ascending aorta as a reference method and internally calibrated tonometer readings and alternatively calibrated pressure waves at the common carotid artery as test methods. Study 2 used alternatively calibrated pressure waves as a reference method and alternatively calibrated distension waves and internally calibrated applanation tonometer readings as test methods. RESULTS: In study 1, pulse pressure from internally calibrated tonometer readings was 10.2+/-14.3 mmHg lower and pulse pressure from alternatively calibrated pressure waves was 1.8+/-5.2 mmHg higher than invasive pulse pressure. Pulse pressure from calibrated distension waves was 3.4+/-6.9 mmHg lower than pulse pressure from alternatively calibrated pressure waves. According to British Hypertension Society criteria, pulse pressure from the internally calibrated tonometer achieved grade D and pulse pressure from alternatively calibrated pressure waves achieved grade A. Pulse pressure from calibrated distension waves achieved grade B when alternatively calibrated pressure waves were used as a reference method. CONCLUSIONS: Pulse pressure obtained from alternatively calibrated tonometer-derived pressure waves and echo-tracking-derived distension waves demonstrates good accuracy. Accuracy of pulse pressure from internally calibrated applanation tonometer readings at the carotid artery is poor.

Disparate effects of antihypertensive drugs on large artery distensibility and compliance in hypertension.

Distensibility and compliance are large artery properties, that may be important in cardiovascular disease. Distensibility is a determinant of the pulsatile stress on the vessel wall and is thought important in ageing and atherosclerotic disease. Compliance reflects the buffering capacity of the arteries and is a major determinant of the afterload on the heart. In hypertension large arteries are getting stiffer, resulting in a decreased distensibility and compliance. Decrease in blood pressure by itself can improve large artery properties. Despite a decrease in blood pressure, not all antihypertensive drugs improve large artery properties. Compliance is improved by firstline antihypertensive drugs such as angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, beta-blockers with vasodilating properties, selective beta 1-blockers and some diuretics. Recent data suggest that ACE inhibitors such as perindopril improve distensibility and compliance of large arteries more than diuretics such as amiloride/hydrochlorothiazide. Apart from the indirect effect (decrease in blood pressure), this makes a direct effect of perindopril on large artery properties very likely. ACE inhibitors such as perindopril decrease the afterload on the heart more than diuretics such as amiloride/hydrochlorothiazide by both a more pronounced decrease in systemic vascular resistance and an increase in large artery compliance.

Diurnal variation in prorenin in relation to other humoral factors and hemodynamics.

Diurnal variation has been demonstrated for blood pressure and heart function. Several hormones influence these hemodynamic parameters. This study investigates the diurnal variation in plasma prorenin in relation to renin, atrial natriuretic peptide (ANP), norepinephrine, and hemodynamic changes. Circulating plasma prorenin may be able to serve as a marker for the activity of the local renin-angiotensin system. In 12 healthy male volunteers who were allowed to carry out quiet activity, hemodynamic factors and the plasma levels of hormones were monitored at 2-h intervals for 26 h. Blood pressure was measured every hour. In accordance with the literature, during the night blood pressure (4%), cardiac index (19%), stroke index (10%), and heart rate (10%) decreased in a classic day-night pattern. Systemic vascular resistance increased during the night (23%). No classic day-night pattern was found for ANP, although it increased (15%) at night and showed a peak early in the night. This peak seemed to be influenced by posture. A classic day-night pattern was demonstrated for norepinephrine and prorenin. Norepinephrine was lower (18%) at night and increased as soon as the subjects awoke, while they were still in bed. Therefore, plasma norepinephrine levels seemed to be related to awakening. Plasma prorenin decreased at night (6%). Renin fluctuated throughout the day, but showed no clear day-night pattern. In conclusion, renin fluctuated throughout the day and did not show a classic day-night pattern. In contrast, prorenin fluctuated less and showed 6% higher levels during the day compared to the night. The origin and clinical significance of this small diurnal variation in prorenin is not clear yet.

Influence of aging on arterial compliance.

With aging, pulse pressure increases. A high pulse pressure has been recognised as an important cardiovascular risk factor. The increase in pulse pressure with aging is mainly due to a decrease in large artery compliance. Compliance and distensibility are large artery wall properties. Compliance is the buffering capacity of the vessel. Distensibility reflects much more the elasticity of the artery. Compliance is related to distensibility and arterial diameter. These large artery wall properties can be measured non-invasively using new echo-tracking techniques. With these techniques it has been shown that the elasticity (distensibility) and the buffering capacity (compliance) of the common carotid artery is decreasing with aging, while diameter of the artery increases. This increase in diameter might be a compensating mechanism to limit the decrease in compliance. There are indications that the effect of aging on large artery wall properties may not be similar at all vascular territories. A decrease in compliance leads to a high pulse pressure and isolated systolic hypertension. The drug of choice for the treatment of isolated systolic hypertension should increase large artery compliance with no, or only minor effect on resistance vessels. This would lead to a decrease in pulse pressure without decreasing mean blood pressure. As a result, systolic but not diastolic blood pressure decreases. It appears that nitrates better than other anti-hypertensive drugs can decrease pulse pressure. They therefore have been advocated for the treatment of isolated systolic hypertension.

Impact of antihypertensive treatment on quality of life: comparison between bisoprolol and bendrofluazide.

OBJECTIVES: To compare quality of life with the selective beta1-blocker bisoprolol and the thiazide diuretic bendrofluazide in patients with mild to moderate hypertension. DESIGN AND SETTING: Multi centric, randomised, double-blind, two-way crossover study carried out at six general practice centres. SUBJECTS: Eighty-one patients with newly diagnosed or previously treated hypertension, who had a mean diastolic blood pressure (BP) of 95-120 mm Hg after receiving placebo for 4-6 weeks. INTERVENTIONS: In random order, patients received bisoprolol (5 mg once daily) or bendrofluazide (2. 5 mg once daily) for 8 weeks. MAIN OUTCOME MEASURES: Quality of life and antihypertensive effect. RESULTS: Decrease in systolic/diastolic BP did not differ between bisoprolol (10 +/- 2/13 +/- 1 mm Hg) and bendrofluazide (9 +/- 2/11 +/- 1 mm Hg). Between bisoprolol and bendrofluazide neither in the intention-to-treat nor in the efficacy analysis any difference was found in quality of life variables, such as Health Status Index, somatic symptoms, anxiety, depression, total psychiatric morbidity, cognitive symptoms and hostility score. Compared to baseline the Health Status Index improved (P < 0.05) during bisoprolol. None of the other investigated quality of life variables changed compared to baseline. No patients dropped out during bisoprolol or bendrofluazide treatment. Although, the total number of reported adverse events appeared lower during bendrofluazide than during bisoprolol treatment, it is unclear whether drug related adverse events also differ between the two drugs. CONCLUSIONS: At equipotent antihypertensive dosages, the effect of an 8-week treatment on quality of life does not differ between the selective beta1-blocker bisoprolol and the thiazide diuretic bendrofluazide.