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Background: Despite treatment, there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals. Inadequate reduction of their blood pressure is a likely cause, but the optimum target blood pressure is not known. The impact of acetylsalicylic acid (aspirin) has never been investigated in patients with hypertension. We aimed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension.Methods: 18790 patients, from 26 countries, aged 50-80 years (mean 61.5 years) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg (mean 105 mm Hg) were randomly assigned a target diastolic blood pressure. 6264 patients were allocated to the target pressure < or =90 mm Hg, 6264 to < or =85 mm Hg, and 6262 to < or =80 mm Hg. Felodipine was given as baseline therapy with the addition of other agents, according to a five-step regimen. In addition, 9399 patients were randomly assigned 75 mg/day acetylsalicylic acid (Bamycor, Astra) and 9391 patients were assigned placebo.Findings: Diastolic blood pressure was reduced by 20.3 mm Hg, 22.3 mm Hg, and 24.3 mm Hg, in the < or =90 mm Hg, < or =85 mm Hg, and < or =80 mm Hg target groups, respectively. The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg. Further reduction below these blood pressures was safe. In patients with diabetes mellitus there was a 51% reduction in major cardiovascular events in target group < or =80 mm Hg compared with target group < or =90 mm Hg (p for trend=0.005). Acetylsalicylic acid reduced major cardiovascular events by 15% (p=0.03) and all myocardial infarction by 36% (p=0.002), with no effect on stroke. There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group, and 129 versus 70 non-fatal major bleeds in the two groups, respectively (p<0.001).Interpretation: Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events. The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg. Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infarction. There was no effect on the incidence of stroke or fatal bleeds, but non-fatal major bleeds were twice as common. [ABSTRACT FROM AUTHOR]

The goal of antihypertensive therapy is to lower blood pressure and, by doing so, to decrease cardiovascular risk. Life style changes and drugs are available for the treatment of hypertensive patients. In order to reach the target blood pressure, most patients with hypertension need drug treatment in addition to life style changes. In all hypertensive patients, the target blood pressure is <140/90 mmHg. In patients with diabetes mellitus, with chronic renal failure as well as in patients with complications of hypertension and, thereby a very high cardiovascular risk, the target blood pressure is <130/80 mmHg. Diuretics, beta-blockers, calcium antagonists, ACE-inhibitors and angiotensin receptor blockers are the drugs of first choice in the treatment of hypertension. The selection among these drug classes has to consider probable side effects as well as accompanying diseases and complications of hypertension. One should also take into account that most of the beneficial effects of antihypertensive therapy is due to the decrease of blood pressure per se and that the majority of hypertensive patients require the combination of two or more antihypertensive drugs in order to reach the target blood pressure.

Background: Antihypertensive drugs may have differential, pressure-independent effects on hypertension-associated alterations of arterial function. We compared the effects of a 12-week therapy with the AT(1)-receptor antagonist valsartan (Val) versus the beta-blocker metoprolol (Met) on arterial stiffness and endothelial function in mildly hypertensive patients at rest and during generalized sympathetic stimulation., Methods: Sixty-eight patients (37 male, 31 female, 46 +/- 6 years) were randomized to Val (80-160 mg/d) or Met (50-100 mg/d). Effects of therapy on endothelial function, brachial and carotid artery distensibility coefficients, pulse wave velocity, carotid intima-media thickness and elastic modulus were assessed at rest and during the cold pressor test., Results: Fifty-two patients were available for per protocol analysis. Blood pressure was comparably reduced in both treatment groups. Effects on endothelial function and large artery elastic wall properties did not differ significantly between the two antihypertensive treatment regimens. Trends did not differ significantly between groups for any parameter including carotid intima-media thickness and elastic modulus., Conclusion: Short-term treatment with Val and Met had similar effects on large artery functional vessel wall properties in a population of mildly hypertensive patients.

Intervention studies indicate that beta blockers as well as diuretics have unfavourable effects on lipid metabolism and lead to new onsets of diabetes mellitus more frequently than ACE inhibitors, AT1 antagonists and calcium antagonists. Moreover, a meta-analysis showed an elevated risk for strokes in hypertensive patients treated with beta blockers. Until the conclusion of other controlled studies, beta blockers will nevertheless retain their important role in the treatment of hypertensive patients with coronary heart disease or heart failure. They should continue to be one of the preferred antihypertensives.

The following is a brief statement of the 2003 European Society of Hypertension (ESH)-European Society of Cardiology (ESC) guidelines for the management of arterial hypertension. The continuous relationship between the level of blood pressure and cardiovascular risk makes the definition of hypertension arbitrary. Since risk factors cluster in hypertensive individuals, risk stratification should be made and decision about the management should not be based on blood pressure alone, but also according to the presence or absence of other risk factors, target organ damage, diabetes, and cardiovascular or renal damage, as well as on other aspects of the patient's personal, medical and social situation. Blood pressure values measured in the doctor's office or the clinic should commonly be used as reference. Ambulatory blood pressure monitoring may have clinical value, when considerable variability of office blood pressure is found over the same or different visits, high office blood pressure is measured in subjects otherwise at low global cardiovascular risk, there is marked discrepancy between blood pressure values measured in the office and at home, resistance to drug treatment is suspected, or research is involved. Secondary hypertension should always be investigated. The primary goal of treatment of patient with high blood pressure is to achieve the maximum reduction in long-term total risk of cardiovascular morbidity and mortality. This requires treatment of all the reversible factors identified, including smoking, dislipidemia, or diabetes, and the appropriate management of associated clinical conditions, as well as treatment of the raised blood pressure per se. On the basis of current evidence from trials, it can be recommended that blood pressure, both systolic and diastolic, be intensively lowered at least below 140/90 mmHg and to definitely lower values, if tolerated, in all hypertensive patients, and below 130/80 mmHg in diabetics. Lifestyle measures should be instituted whenever appropriate in all patients, including subjects with high normal blood pressure and patients who require drug treatment. The purpose is to lower blood pressure and to control other risk factors and clinical conditions present. In most, if not all, hypertensive patients, therapy should be started gradually, and target blood pressure achieved progressively through several weeks. To reach target blood pressure, it is likely that a large proportion of patients will require combination therapy with more than one agent. The main benefits of antihypertensive therapy are due to lowering of blood pressure per se. There is also evidence that specific drug classes may differ in some effect or in special groups of patients. The choice of drugs will be influenced by many factors, including previous experience of the patient with antihypertensive agents, cost of drugs, risk profile, presence or absence of target organ damage, clinical cardiovascular or renal disease or diabetes, patient's preference.

The objective of antihypertensive treatment in patients with chronic renal failure, many of whom have elevated blood pressure levels, is to reduce cardiovascular events and to slow down the progression of kidney function impairment. Calcium antagonists have been shown to be effective and safe antihypertensive drugs in patients from different age groups, including children. On the basis of numerous studies, one may conclude that the main benefit of antihypertensive therapy is because of the blood pressure lowering effect per se and that calcium antagonists do not differ from other antihypertensive drugs in the ability to prevent cardiovascular complications of hypertension. In particular, calcium antagonists are not inferior to other groups of antihypertensive agents in the prevention of coronary artery disease. There is, however, now evidence from controlled clinical trials that drugs interfering with the renin-angiotensin system are more beneficial than other antihypertensive agents in patients with chronic renal failure. Thus, several studies have demonstrated that ACE-inhibitors and, in patients with type-2 diabetic nephropathy, AT 1-antagonists are superior to other classes of antihypertensive drugs, including calcium antagonists, in delaying the progression of renal insufficiency. Therefore, in hypertensive patients with chronic renal failure antihypertensive treatment should be initiated with a drug that inhibits the renin-angiotensin system.

Aim: Structural and mechanical properties of the arterial wall are altered in patients with renal failure. The ageing process of the arterial wall appears to be accelerated in patients with end-stage renal failure. The mechanisms responsible for reduced arterial compliance and distensibility in dialysis patients and renal transplant recipients without hypertension remain to be evaluated., Methods: Thirty-five normotensive dialysis patients (D), 35 normotensive renal transplant recipients (T) and 35 healthy volunteers (N) matched for age, sex and blood pressure as controls were enrolled into the study. The arterial blood pressure of all patients was < 140/90 mmHg. The dialysis patients and renal transplant recipients were eligible for the study if the serum creatinine level was < 2 mg/dL. In all subjects, fasting concentrations of serum creatinine, total cholesterol, HDL-cholesterol, LDL-cholesterol and hemoglobin and glucose were determined at enrollment to the study. Blood pressure was measured using an automatic sphygmomanometer. Pulse wave velocity (PWV) was evaluated using non invasive automatic Complior device. The vessel wall properties of the left common carotid artery were studied using multigate pulsed Doppler system. With this method, the end-diastolic diameter (d) and the systolic increase of vessel diameter (distension DELTAd) were measured. From these data the relative systolic increase of vessel diameter (DELTAd/d) and the arterial wall distensibility coefficient (DC) were calculated., Results: Systolic blood pressure (SBP) and central pulse pressure (CPP) were significantly higher in T than in D and N group, respectively 138 +/- 18 mmHg and 59 +/- 16 mmHg vs 128 +/- 13 mmHg and 49 +/- 12 mmHg and 132.12 mmHg and 51 +/- 10 mmHg. The d did not change significantly between all groups. The distension DELTAd was significantly lower in patients group D and T, respectively 466 +/- 38 microm and 511 +/- 37 microm than in controls. Similarly DELTAd/d was in these groups significantly lower than in healthy volunteers, respectively D 6.33 +/- 0.5%, T 6.9 +/- 0.4% vs N 9.15 +/- 0.5%. DC was also significantly lower in D and T than in N groups, respectively D 17.91 +/- 1.5 10-3/kPa and T 18.92 +/- 1.3 10-3/kPa and N 24.28 +/- 0.51-3/kPa. Significant differences were found in the increase of the intima-media thickness (IMT) of carotid artery for dialyzed patients and renal transplant recipients in contrast to the control group, but there were no differences between the patients. PWV in both patient groups was statistically significant higher than in control group correspondingly D 11.1 +/- 1.03 m/s and T 13.3 +/- 1.13 m/s, N 9.4 +/- 0.89 m/s. There was a significant correlation between the change of DC, PWV and CPP in T group (n = 35; r = -0.43; P < 0.01 and n = 35; r = 0.48; P < 0.05). In the T group also an important correlation between PWV and IMT complex (n = 35; r = 0.49, P < 0.001) was found., Conclusions: The elastic and structural properties of arterial wall in dialysis patients and renal recipients are decreased. End-stage renal disease accelerates arterial stiffening despite of arteriosclerosis and hypertension. Renal transplantation does not reverse loss of elastic and morphologic properties of arteries found in patients with end-stage renal insufficiency.

Background: We determined the reliability and repeatability of measurements of arterial compliance (AC) and gender- and age-specific normal ranges for a healthy European population., Methods: Three hundred eight healthy volunteers from seven sites were evaluated. Two measurements were taken during the first visit, repeated on a second visit 1 to 4 weeks later. We used the HDI/PulseWave CR-2000 for measurements of AC., Results: Intravisit measurements, taken 5 min apart, differed by less than 3% (range, 0.36% to 2.97%). All intervisit measures differed by less than 4% (range, 0.24% to 3.67%); none of these differences was statistically significant. All correlation coefficients for pairs of AC parameters measured 5 min apart at the same visit were significant at P < .0001. Paired AC parameters at visit 1 and 2 were highly correlated (P < .0001). Repeated measures GLM (general linear model) failed to detect a significant association between either of the AC parameters and visit (first or second), time (first or second measure at the same visit), and visit-by-time (the interaction of the two preceding factors), suggesting that order of measure had no effect on the final value. Analysis of reliability was used to develop a strictly parallel model estimate of unbiased reliability. Both intravisit and intervisit estimates of reliability indicate good repeatability of measure and were significant (P < .0001). The AC values were found to differ significantly by age group, with an inverse association between each of the AC parameters and age group., Conclusions: Measurement of the arterial waveform with the CR-2000 system is highly reproducible in healthy subjects.

Background: Increase in left ventricular mass (LVM) may be linked to morbidity and mortality in hypertensive patients. Arterial stiffness, systolic blood pressure (BP), and pulse pressure (PP) seem to be the main determinants of LVM. The perindopril/indapamide combination normalizes systolic BP, PP, and arterial function to a greater extent than atenolol. The aim of this study was to compare the effects of perindopril (2 mg)/indapamide (0.625 mg) first-line combination with atenolol (50 mg) on LVM reduction in hypertensive patients., Methods: Two hundred fourteen patients with essential hypertension participating in the PREterax in Regression of Arterial Stiffness in a ContrOlled Double-BliNd (REASON), randomized, double-blind, parallel-group study, underwent M-mode two-dimensional-guided echocardiography., Results: Perindopril/indapamide and atenolol were both effective at brachial BP reduction during the 12-month period. The systolic BP reduction was significantly greater with perindopril/indapamide than with atenolol (-21.2 v -15.3 mm Hg), whereas the reduction in diastolic BP was similar between treatment groups (-12.1 v -11.3 mm Hg). Reduction in LVM was higher with perindopril/indapamide than with atenolol. The between-group difference was significant for LVM (-13.6 v -4.3 g, P = .027), LVM/body surface area (LVMI1, P = .032), and LVM/body height2.7 (LVMI2, P = .013). The 124 patients with LV hypertrophy at baseline showed greatest LVM regression (LVM: -22.5 v -8.9 g, P = .009; LVMI1, P = .031; LVMI2, P = .028). The reduction in LVM adjusted for brachial systolic BP and heart rate was still significantly greater with perindopril/indapamide than with atenolol., Conclusions: Treatment, based on a first-line perindopril/indapamide combination in hypertensive patients, was more effective than atenolol on regression of echocardiographic indices of LVM and LV hypertrophy., (Copyright 2004 American Journal of Hypertension, Ltd.)

Background: Circadian blood pressure (BP) measurements provide more information on hypertensive complications than office BP measurements. The purpose of this study was to analyze the efficacy of the first-line combination of perindopril 2 mg plus indapamide 0.625 mg versus atenolol 50 mg on BP parameters and variability over 24 h in patients with hypertension., Methods: A double-blind, randomized, controlled, 12-month study comparing perindopril/indapamide and atenolol was performed in 201 patients (age 55.0 years) with uncomplicated sustained essential hypertension. Ambulatory BP measurements (ABPM) were done every 15 min over 24 h., Results: After 1 year of treatment, the decrease in systolic BP was significantly greater for perindopril/indapamide than for atenolol during the entire 24-h period (-13.8 v -9.2 mm Hg), the daytime and the nighttime periods (P <.01). Diastolic blood pressure (DBP) variations were comparable for the two groups (-7.2 v -8.3 mm Hg, NS). Pulse pressure (PP) reduction was also significantly greater for perindopril/indapamide than for atenolol (for the whole 24 h, -6.6 v -0.9 mm Hg, P <.001). The through to peak (T/P) BP ratio and the smoothness index were comparable in the two groups for DBP. For systolic blood pressure (SBP), higher values of the T/P ratio (0.80 v 0.59) and the smoothness index (1.45 v 0.98; P <.02) were achieved for the perindopril/indapamide combination than for atenolol., Conclusions: The perindopril/indapamide first-line combination decreased SBP and PP more effectively than atenolol. Moreover, the BP control effect was smooth and consistent throughout the 24-h dosing interval and BP reduction variability was lower than the one induced by atenolol.

Structural and mechanical properties of the arterial wall are altered in patients with renal failure. Age and hypertension are known to affect the vessel wall structure. Aging process of arterial wall appears to be accelerated in patients with end-stage renal failure. The mechanisms responsible for reduced arterial compliance and distensibility in dialyse patients and renal transplant recipients without hypertension remain to be evaluated. 20 normotensive dialyse patients (D), 20 normotensive renal transplant recipients (T) and 20 healthy volunteers (N) matched for age, sex and blood pressure as controls were enrolled in to the study. Patients with cardiovascular risk factors and diabetes were excluded. The arterial blood pressure of all patients placed below 140/90 mmHg. The dialyse patients and renal transplant recipients were eligible for the study if the serum creatinine level was below 2 mg/dl. In all subjects, fasting concentrations of serum creatinine, total cholesterol, HDL-cholesterol, LDL-cholesterol, hemoglobin and glucose were determined at enrollment to the study. Long-term immunosuppression consisted of cyclosporine and prednisolone. Blood pressure was measured using an automatic sphygmomanometer (Criticon Dinamap model 1846 SX). Pulse wave velocity (PWV) was evaluated using non-invasive automatic Complior device. The vessel wall properties of the left common carotid artery were studied using multigate pulsed Doppler's system (Pie Medical Equipment BV Maastricht, The Netherlands). The frequency of transducer used was 7.5 MHz. With this non-invasive method, the end-diastolic diameter (d) and the systolic increase of vessel diameter (distension delta d) were measured using ECG trigger. From these data relative systolic increase of vessel diameter (delta d/d) and arterial wall distensibility coefficient (DC) were calculated. Simultaneously with the ultrasound measurements at the left common carotid artery carotid pulse waveforms are recorded using applanation tonometry (Micro Tip Pulse Transducer, SPT 301 and Transducer Control Unit TCB-500, Millar Instruments, Houston, TX, USA). Systolic blood pressure (SBP) and central pulse pressure (CPP) were significantly higher in (T) than in (D) and (N) group respectively 139 +/- 18 mmHg and 58 +/- 16 mmHg vs 127 +/- 13 mmHg and 49 +/- 11 mmHg and 132 mmHg and 50 +/- 11 mmHg. The end-diastolic diameter (d) did not change significantly between all groups. The systolic increase of vessel diameter (distension delta d) was significantly lower in patients group (D) and (T) respectively 461 +/- 33 microm and 501 +/- 34 microm than in controls. Similar relative systolic increase of vessel diameter (delta d/d) was in these groups significantly lower than in healthy volunteers, respectively (D) 6.26 +/- 0.5%, (T) 6.91 +/- 0.4% vs (N) 9.14 +/- 0.4%. The distensibility coefficient were also significantly lower in (D) and (T) than in (N) groups respectively (D) 18.31 +/- 1.4 10(-3)/kPa and (T) 17.97 +/- 1.4 10(-3)/kPa and (N) 24.3 +/- 0.5 10(-3)/kPa. PWV in both groups of patients was statistically significant higher than in control group correspondingly (D) 11.2 +/- 1.02 m/s and (T) 12.8 +/- 1.12 m/s, (N) 9.5 +/- 0.88 m/s. There was significant correlation between the change of arterial DC, PWV and CPP in (T) group (n = 20; r = -0.42; p < 0.01 and n = 20; r = 0.47; p < 0.05). The arterial wall elastic properties in dialyse and renal recipients patients are decreased. End-stage renal disease accelerates arterial stiffening despite arteriosclerosis and hypertension. Renal transplantation do not reverse lost of elastic properties of arteries in end-stage renal insufficiency.

Antihypertensive therapy improves the prognosis of essential hypertension. Therapy reduces mortality and decreases the incidence of myocardial infarction, sudden cardiac death and stroke. Target blood pressure in patients with essential hypertension are levels < or = 140/90 mmHg. In patients with essential hypertension and concomitant diabetes mellitus type 2, blood pressure should be lowered to < or = 130/80 mmHg. Diuretics, beta-blockers, calcium antagonists, angiotensin-converting enyzme (ACE) inhibitors, and angiotensin I (AT(1)) antagonists may nowadays be regarded as drugs of first choice in the treatment of essential hypertension. The Joint National Committee in the USA recommends to start treatment with a thiazide diuretic. A Guidelines Committee of European Society of Hypertension-European Society of Cardiology considers the Endgroups of drugs mentioned above to be equally suitable for the initiation and maintenance of antihypertensive therapy. Both groups of experts agree that in the majority of patients with essential hypertension, a combination of two or more drugs is required to reach target blood pressure. Both groups of experts emphasize that the main benefits of antihypertensive therapy are due to decreasing blood pressure per se.