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Aims: Peripheral arterial disease (PAD) can be diagnosed in asymptomatic stage, measuring ankle-brachial index (ABI). Low ABI is an indicator of increased cardiovascular risk and its inclusion to traditional risk factors can improve risk prediction. The objective of the present cross-sectional part of our large-scale, multicenter, observational study was to evaluate the prevalence of PAD in a large cohort of hypertensive patients., Methods and Results: A total of 21 892 hypertensive men and women (9162 men; mean age 61.45 years) were included in our prospective study in hypertension clinics. Clinical history, physical examination, and blood analysis were taken, and the ABI was measured with the Doppler method in all patients. The prevalence of PAD (ABI ≤ 0.9) was 14.4%. In 15.6% of the patients an ABI of 0.91-0.99, and in 9.4% of the patients high ABI (>1.3) was measured. In the low, moderate, high, and very high Systematic Coronary Risk Evaluation risk groups, the prevalence of low ABI was 8.1, 11.1, 16.3, and 26%, respectively. The prevalence of PAD was lower in hypertensive patients achieving their blood pressure target (9.6 vs. 16.8%; P < 0.001)., Conclusions: Asymptomatic PAD was highly prevalent in the studied hypertensive population. The use of ABI screening may improve cardiovascular risk prediction. Optimal blood pressure goal values in PAD patients and cardiovascular morbidity/mortality data will be evaluated after the 5-year long prospective phase of the Evaluation of Ankle-Brachial Index in Hungarian Hypertensives program.

Our objective was to assess the prognostic significance of the night-time dipping pattern and the night-day blood pressure (BP) ratio for mortality and cardiovascular events in hypertensive patients without major cardiovascular disease at baseline. We performed a meta-analysis on individual data of 3468 patients from four prospective studies performed in Europe. Age of the subjects averaged 61+/-13 years; 45% were men and 61% were under antihypertensive treatment at the time of ambulatory BP monitoring. The night-day BP ratio and 24-h BP averaged, respectively, 0.907+/-0.085/0.866+/-0.095 and 138.1+/-16.4/82.3+/-11.0 mm Hg. Total follow-up time amounted to 23 164 patient-years. We used multivariable Cox regression analysis to assess the outcome of reverse dippers, non-dippers and extreme dippers vs dippers, and to assess the hazard ratios associated with 1 standard deviation higher night-day BP ratio. In comparison with dippers, and with adjustment for confounders and 24-h BP, the incidence of cardiovascular events was worse in reverse dippers (P

Hypertension is a known risk factor for cardiovascular events, and recent data have pointed to peripheral arterial disease (PAD) as another strong risk factor; together, they cause a surprisingly high total risk. This review deals with the clinical management of this dangerous association. The ankle-brachial index helps in the diagnosis of PAD and the estimation of risk. To control risk, lifestyle adaptation is essential. There is no consensus on a first choice of antihypertensive drug. Arguments favor angiotensin-converting enzyme inhibitors, but most patients require several antihypertensive drugs to reach goal pressure (140/90 mm Hg or lower). Moreover, to control the risk of PAD, antiplatelet drugs, antihypertensive drugs, and statins are recommended.

Objective: To assess the prognostic significance of nighttime and daytime blood pressure (BP), their ratio and the nighttime dipping pattern for mortality and recurrent cardiovascular (CV) events in patients with CV disease at baseline., Background: The prognostic value of ambulatory BP has not been reported in hypertensive patients with a history of CV disease., Methods: We performed a meta-analysis on individual data of 302 patients with hypertension and CV disease from three prospective studies performed in Europe., Results: Age of the patients averaged 69+/-9 years; 50% were men and 62% were under antihypertensive treatment at the time of ambulatory BP monitoring. Office, daytime and nighttime BP averaged 161+/-20/86+/-12, 144+/-16/83+/-11 and 132+/-18/72+/-12 mmHg. Total follow-up time amounted to 2049 patient--years. Multivariable Cox regression analysis revealed that nighttime BP, but not daytime BP significantly predicted CV mortality (P< or =0.05) and major CV events (P< or =0.01) after adjustment for office BP and other confounders. When both nighttime and daytime BP were entered into the models, the predictive power of nighttime BP remained significant (P< or =0.05); daytime BP did not add prognostic precision to nighttime BP. The systolic nightday BP ratio predicted all outcomes, and outcome was significantly worse in reverse dippers and nondippers than in dippers, both before and after adjustment for 24-h BP (P< or =0.05)., Conclusion: Nighttime BP is the better predictor of death and recurrent CV events in hypertensive patients with a history of CV disease. The night-day BP ratio and the dipping pattern significantly predict outcome, even after adjustment for 24-h BP.

Our aim was to assess the prognostic significance of nighttime and daytime ambulatory blood pressure and their ratio for mortality and cause-specific cardiovascular events in hypertensive patients without major cardiovascular disease at baseline. We performed a meta-analysis on individual data of 3468 patients from 4 prospective studies performed in Europe. Age of the subjects averaged 61+/-13 years, 45% were men, 13.7% smoked, 8.4% had diabetes, and 61% were under antihypertensive treatment at the time of ambulatory blood pressure monitoring. Office, daytime, and nighttime blood pressure averaged 159+/-20/91+/-12, 143+/-17/87+/-12, and 130+/-18/75+/-12 mm Hg. Total follow-up amounted to 23 164 patient-years. We used multivariable Cox regression analysis to assess the hazard ratios associated with 1 standard deviation higher blood pressure. Daytime and nighttime systolic blood pressure predicted all-cause and cardiovascular mortality, coronary heart disease, and stroke, independently from office blood pressure and confounding variables. When these blood pressures were entered simultaneously into the models, nighttime blood pressure predicted all outcomes, whereas daytime blood pressure did not add prognostic precision to nighttime pressure. Appropriate interaction terms indicated that the results were similar in men and women, in younger and older patients, and in treated and untreated patients The systolic night-day blood pressure ratio predicted all outcomes, which only persisted for all-cause mortality after adjustment for 24-hour blood pressure. In conclusion, nighttime blood pressure is in general a better predictor of outcome than daytime pressure in hypertensive patients, and the night-day blood pressure ratio predicts mortality, even after adjustment for 24-hour blood pressure.

The risk of peripheral artery disease is underestimated by many physicians; such risk is further augmented by the presence of hypertension. Detection of these conditions is essential to prevent cardiovascular accidents. This review deals with the management of peripheral artery disease as a risk factor, highlighting the need for triple therapy (antiplatelet drugs, angiotensin-converting enzyme inhibitors, and statins). Treatment of hypertension is approached by reviewing the essentials of the different antihypertensive drugs available, focusing on their peripheral circulatory effect. However, because individual antihypertensive drugs seem not to differ largely in this respect, attention is drawn to the message that the most important task in these patients is to control total cardiovascular risk rather than focusing on the choice of the individual antihypertensive drug.

Peripheral arterial disease (PAD) of the lower limbs is associated with a high cardiovascular morbidity and mortality. Intermittent claudication is the most common symptomatic manifestation of PAD, but is in its own value an important predictor of cardiovascular death, increasing it by three-fold, and increasing all-cause mortality by two-to-five fold. Hypertension is a risk factor for vascular disorders, including PAD. Of hypertensives at presentation, about 2-5% have intermittent claudication, with increasing prevalence with age. Otherwise, 35-55% of patients with PAD at presentation also show hypertension. Patients who suffer from hypertension with PAD have a greatly increased risk of myocardial infarction and stroke. There is no consensus on the specific treatment of hypertension in PAD because of the limited controlled studies on antihypertensive therapy in such specific PAD population. There is an obvious need of such outcome studies, especially since the two conditions are frequently encountered together. However, as risk is high in all PAD patients, the most important goal remains to decrease the global cardiovascular risk in such patients rather than to focus on the control of blood pressure only and on the reduction of symptoms of PAD. Therefore, treatment with antiplatelet drugs, ACE-inhibitors and statins should be considered.

Background: It is uncertain whether ambulatory blood-pressure measurements recorded for 24 hours in patients with treated hypertension predict cardiovascular events independently of blood-pressure measurements obtained in the physician's office and other cardiovascular risk factors., Methods: We assessed the association between base-line ambulatory blood pressures in treated patients and subsequent cardiovascular events among 1963 patients with a median follow-up of 5 years (range, 1 to 66 months)., Results: We documented new cardiovascular events in 157 patients. In a Cox proportional-hazards model with adjustment for age, sex, smoking status, presence or absence of diabetes mellitus, serum cholesterol concentration, body-mass index, use or nonuse of lipid-lowering drugs, and presence or absence of a history of cardiovascular events, as well as blood pressure measured at the physician's office, higher mean values for 24-hour ambulatory systolic and diastolic blood pressure were independent risk factors for new cardiovascular events. The adjusted relative risk of cardiovascular events associated with a 1-SD increment in blood pressure was 1.34 (95 percent confidence interval, 1.11 to 1.62) for 24-hour ambulatory systolic blood pressure, 1.30 (95 percent confidence interval, 1.08 to 1.58) for ambulatory systolic blood pressure during the daytime, and 1.27 (95 percent confidence interval, 1.07 to 1.57) for ambulatory systolic blood pressure during the nighttime. For ambulatory diastolic blood pressure, the corresponding relative risks of cardiovascular events associated with a 1-SD increment were 1.21 (95 percent confidence interval, 1.01 to 1.46), 1.24 (95 percent confidence interval, 1.03 to 1.49), and 1.18 (95 percent confidence interval, 0.98 to 1.40)., Conclusions: In patients with treated hypertension, a higher ambulatory systolic or diastolic blood pressure predicts cardiovascular events even after adjustment for classic risk factors including office measurements of blood pressure., (Copyright 2003 Massachusetts Medical Society)

Objective: To examine the association of clinic and ambulatory heart rate with total, cardiovascular, and noncardiovascular death in a cohort of elderly subjects with isolated systolic hypertension from the Systolic Hypertension in Europe Trial., Methods: A total of 4682 patients participated, whose untreated blood pressure on conventional measurement at baseline was 160 to 219 mm Hg systolic and lower than 95 mm Hg diastolic. Clinic heart rate was the mean of 6 readings during 3 visits. Ambulatory heart rate was recorded with a portable intermittent technique in 807 subjects., Results: Raised baseline clinic heart rate was positively associated with a worse prognosis for total, cardiovascular, and noncardiovascular mortality among the 2293 men and women taking placebo. Subjects with heart rates higher than 79 beats/min (bpm) (top quintile) had a 1.89 times greater risk of mortality than subjects with heart rate lower than or equal to 79 bpm (95% confidence interval, 1.33-2.68 bpm). In a Cox regression analysis, predictors of time to death were heart rate (P<.001), age (P<.001), serum creatinine level (P =.001), presence of diabetes (P =.002), previous cardiovascular disease (P =.01), triglyceride readings (P =.02), smoking (P =.04), and elevated systolic blood pressure (P =.05), while total cholesterol level was found to be nonsignificant in the model. In the ambulatory monitoring subgroup, clinic and ambulatory heart rates predicted noncardiovascular but not cardiovascular mortality. However, in a Cox regression analysis in which clinic and ambulatory heart rates were included, a significant association with noncardiovascular mortality was found only for clinic heart rate (P =.004). In the active treatment group, the weak predictive power of clinic heart rate for mortality disappeared after adjustment for confounders., Conclusions: In untreated older patients with isolated systolic hypertension, a clinic heart rate greater than 79 bpm was a significant predictor of all-cause, cardiovascular, and noncardiovascular mortality. Ambulatory heart rate did not add prognostic information to that provided by clinic heart rate.

This study evaluated prospectively whether there is still a relationship between left ventricular mass and blood pressure once hypertension is treated and determined the relative importance of daytime vs night-time blood pressure, systolic vs diastolic blood pressure and office vs ambulatory blood pressure. A total of 649 patients (305 or 47% female) with essential hypertension, treated with antihypertensive drugs for at least 3 months, underwent office blood pressure measurement and both daytime and night-time ambulatory blood pressure measurement, electrocardiography and echocardiography. Correlations were made between blood pressure values and parameters of left ventricular mass. Electrocardiographic voltage criteria and even more so echocardiographic parameters correlate significantly albeit weakly (r < or = 0.28) with blood pressure in treated hypertension. Correlations are consistently higher when systolic blood pressure is considered. Overall, the best correlations are found between 24-h ambulatory systolic or night-time blood pressure and the Sokolow-Lyon voltage as well as the echocardiographic age and body mass index adjusted left ventricular mass. In conclusion, once hypertension is treated, the relationship between blood pressure and left ventricular mass is low. Nevertheless, in this the largest single centre study of its kind, echocardiographic parameters of left ventricular mass in treated hypertensive subjects correlate better with blood pressure than electrocardiographic parameters. Parameters of hypertrophy are more closely related to systolic blood pressure than to diastolic blood pressure. In accordance with the finding that dippers have a better prognosis than non-dippers, night-time blood pressure consistently correlates better with left ventricular mass than daytime blood pressure.

Background and Aims: The Hypertension Optimal Treatment (HOT) study showed that when antihypertensive treatment reduces diastolic blood pressure well below 90 mmHg, there can be a further reduction of cardiovascular events, particularly myocardial infarction, with no evidence of a J-shaped curve at lower pressures. Office measurement, however, gives no information about blood pressure outside the office. This paper describes a HOT substudy in which patients underwent both office measurement and 24 h ambulatory blood pressure monitoring., Methods: The mean age of the substudy population was 62 +/- 7 years. Substudy patients were treated for a median period of 2 years. All received the dihydropyridine calcium antagonist felodipine, while some also received an ACE-inhibitor, a beta-blocker or a diuretic. Average 24 h, day and night ambulatory blood pressure values were computed at baseline (n = 277) and during treatment (n = 347): 112 patients had been randomized to a target office diastolic blood pressure

Although the aldosterone escape mechanism is well known, aldosterone has often been neglected in the pathophysiologic consequences of the activated renin-angiotensin-aldosterone system in arterial hypertension and chronic heart failure. There is now evidence for vascular synthesis of aldosterone aside from its secretion by the adrenal cortex. Moreover, aldosterone is involved in vascular smooth muscle cell hypertrophy and hyperplasia, as well as in vascular matrix impairment and endothelial dysfunction. The mechanisms of action of aldosterone may be either delayed (genomic) or rapid (nongenomic). Deleterious effects of aldosterone leading to vascular target-organ damage include (besides salt and water retention) decreased arterial and venous compliance, increased peripheral vascular resistance, and impaired autonomic vascular control due to baroreflex dysfunction.

Objective: Our aim is to quantify steady and pulsatile components of arterial load in a concise and sensitive way by means of a new non-invasive cardiovascular index (NICI)., Methods and Results: NICI is based on non-invasively measured pressure (sphygmomanometer), stroke volume index and cardiac index (Doppler echocardiography and ECG) and yields a numerical value (in mm Hg). It expresses the difference between the actual arterial load and reference loading conditions as determined in a control group (29 M/35 F, age 34 +/- 13 yr.) of healthy subjects, with blood pressure 116/61 mm Hg (systolic/diastolic), stroke volume index (SVI) 34 +/- 18 ml.m-2 and cardiac index (CI) 2.1 +/- 0.5 l.min-1.m-2. NICI was calculated in the control group and in 23 borderline hypertensive subjects (10 M/13 F, age 65 +/- 12 yr.) with blood pressure 156/79 mm Hg, SVI 36 +/- 10 ml.m-2 and CI 2.4 +/- 0.6 l.min-1.m-2. NICI was higher in borderline hypertensives (33 +/- 51 vs. 0 +/- 34 mm Hg; P < 0.001) and was strongly correlated with total peripheral resistance index (r = 0.89; P < 0.001) and with the ratio of SVI and pulse pressure (r = -0.89; P < 0.001), expressing the combined effect of both known determinants of cardiac load. NICI was also correlated with effective arterial elastance index (r = 0.89; P < 0.001)., Conclusions: NICI quantifies, within a logical biomechanical framework, the arterial load as seen by the ejecting ventricle. It combines steady and pulsatile components of arterial load and has a single control value of zero mm Hg.

Objective: Besides arterial blood pressure, nonhemodynamic factors are known to induce cardiac hypertrophy. In Cushing's syndrome, severe ventricular hypertrophy has been linked not only to increased aortic pressure, but also to elevated plasma cortisol. The aim of this study was to examine the relationship between the cortisol/cortisone levels and left ventricular mass index (LVMI) in essential arterial hypertension with and without echocardiographic left ventricular hypertrophy (LVH)., Design: Eighteen untreated Caucasian patients (nine men, nine women, mean age 48+/-6 years) with essential hypertension (163+/-26/100+/-14 mm Hg) were enrolled. An age-matched control group of 13 subjects (seven men, six women) with normotension (121+/-9/79+/-7 mm Hg) were enrolled also. Left ventricular dimensions were echocardiographically assessed and cortisol production evaluated by 24-h urinary free cortisol and cortisone concentrations., Results: LVMI averaged 115+/-31 g/m2 and 24-h urinary free cortisol and cortisone were 23+/-14 microg per 24 h and 31+/-18 microg per 24 h. Prevalence of echocardiographic LVH was 56%. LVMI correlated significantly with 24-h urinary free cortisol (r = 0.61, P = 0.007) and cortisone (r = 0.60, P = 0.009). Patients with echocardiographic LVH were characterized by higher daytime ambulatory blood pressure, LVMI (particularly the posterior wall), and 24-h urinary cortisol, while office blood pressure, septal: posterior wall ratio and 24-h urinary cortisone were comparable in all patients. In control individuals, LVMI averaged 91+/-18 g/m2 and 24-h urinary free cortisol and cortisone, respectively, were 34.7+/-6.6 microg per 24 h and 64.3+/-10.8 microg per 24 h (P<0.05 versus patients). Neither LVMI nor the contributing ventricular dimensions showed significant correlation with 24-h urinary free cortisol or cortisone in the control group., Conclusions: Our data provide evidence for a significant relationship between LVMI and cortisol production independently of arterial blood pressure in untreated mild to moderate hypertension.

Calcium antagonists are widely used in the treatment of arterial hypertension and, or in ischemic heart disease. During the last 3 years, controversial articles and editorials have been published concerning the potential risk of calcium antagonists in regard to mortality, cancer and haemorrhage. The information has been mainly derived from case-control studies. The major concern about such observational studies of treatment outcome is the large potential for systematic error to affect the results. However, overviews of controlled trials with calcium antagonists do not provide clear evidence of an effect of calcium antagonists on mortality, risk of cancer and risk of bleeding.

Blood pressure homeostasis and variability are the resultant of many complicated neurohumoral interactions. The autonomic nervous system plays a key role in the process. Since arterial hypertension is characterized by an increased sympathetic tone, the determination of the sympatho-vagal balance can give more insight in the autonomic nervous function in this pathology. The assessment of sympatho-vagal balance has been derived from reflex manoeuvres as the study of the baroreceptor function by phenylephrine or nitroglycerin test, by the application of negative or positive pressure around the neck or at the lower limbs or by tilting. Other reflex manoeuvres are hand-grip, cold pressure test, Valsalva manoeuvre, mental arithmetics and microneurography, providing information about the sympathetic reflex activity, and deep breathing about vagal reflex activity. These reflex tests have several limitations, because they request cooperation of the patient. Power spectral analysis of beat-to-beat blood pressure and RR-interval recordings permit to evaluate autonomic activity at baseline conditions and to separate the different components of variability which seem to reflect specific regulatory mechanisms. For the RR-interval, the high frequency component (HF) is a marker of vagal activity, while the low frequency component (LF) is a marker of sympathetic and vagal activity. The LF/HF ratio can be considered as a marker of sympatho-vagal balance. The significance of the LF and HF components of arterial blood pressure variability is less clear. Spectral analysis can be used to study the effect of antihypertensive drugs on sympatho-vagal balance.

Erythrocyte sodium-lithium countertransport (SLC) activity is elevated in essential arterial hypertension. With the growing attention to the genetic substrate of disturbed biochemical tests associated with essential arterial hypertension, we were particularly interested in the involvement of key genes for the regulation of SLC, possibly related to the pathophysiology of essential arterial hypertension. Consequently, the aim of the present study was to investigate SLC and its determining factors in essential hypertension. The influence of haptoglobin (Hp)-polymorphism, insertion/deletion polymorphism of angiotensin converting enzyme (ACE-I/D) and MNS blood group system on the regulation of SLC was studied. SLC activity was studied in a cross-sectional case-control study including 90 Caucasians: 60 patients with essential arterial hypertension who had been treated for at least 1 year and 30 normotensive controls. In essential hypertension, the SLC activity is significantly higher (P = 0.00005) than in controls. In normotensive patients, no differences in SLC are observed for the different polymorphisms studied. However, in the hypertensive group, SLC activity is higher (P = 0.003) in Hp 2-1 phenotype and independent of ACE-I/D genotyping and MNS blood group polymorphism. Multifactor analysis of variance in essential hypertension reveals significant (P = 0.001) differences in SLC activity for the presence or absence of Hp 2-1 phenotype and for body weight (P = 0.0003). Multivariate regression analysis shows the same parameters to be independent determining factors of SLC in essential arterial hypertension. No relation is found between SLC activity and target organ damage which includes coronary artery disease, peripheral arterial occlusive disease, left ventricular hypertrophy and cerebrovascular accident. We conclude that erythrocyte SLC activity is elevated despite pressure-lowering therapy. In essential arterial hypertension, individuals of Hp 2-1 phenotype show higher SLC activity than patients of other Hp-types, suggesting genetic heterogeneity of essential arterial hypertension. The presence or absence of Hp 2-1 phenotype is an independent determining factor of SLC activity whereas body weight codetermines SLC activity in essential hypertension.

Structural and functional abnormalities may occur at the left ventricle and in different large arteries in essential hypertension. Noninvasive high resolution pulsed doppler echo-tracking technique allows calculation of regional arterial wall properties, which might be determined by either hemodynamic or non-hemodynamic factors. Therefore we aimed to study regional arterial wall properties in three different vascular territories and examined whether hemodynamic and non-hemodynamic parameters were significantly associated to a specific vascular territory. In 30 patients (mean age 47 +/- 2 years) with newly diagnosed and untreated essential arterial hypertension, arterial wall properties were determined at the carotid (common, external and internal), femoral, and brachial artery using a noninvasive ultrasound wall movement detector system. The study parameters were arterial diameter, relative diameter change, arterial distensibility (DC) and cross-sectional compliance (CC) coefficient. On the day of the experiments office blood pressure (BP) was measured as well as an ambulatory 24 h BP profile performed on an outpatient basis. Blood samples were taken on the day of the vascular examination for the determination of plasma renin activity (PRA), aldosterone, intact (1-84) parathyroid hormone (PTH), insulin and plasma noradrenaline and adrenaline. Among the studied vascular territories, only DC and CC of the common carotid artery were significantly (P < 0.01) correlated with office and ambulatory systolic BP. Intact PTH was significantly correlated with the diameter (r = 0.61, P = 0.005) and DC (r = -0.53, P = 0.01) of the internal carotid artery. Noradrenaline was inversely correlated with DC of the femoral artery (r = - 0.55, P < 0.01). All correlations remained significant after adjustment for age and body mass index as confounding variables. In conclusion, in mild to moderate arterial essential hypertension there is a heterogeneity of vascular wall properties and their relationship to BP and humoral factors between brachial, femoral and carotid (common, external and internal) arteries. Our findings might renew interest in the old concept of the 'circulatory paradox'.

This study aimed to examine the changes in RR interval and blood pressure (BP) variability and humoral factors during postural changes in borderline arterial hypertension. Twenty-nine patients (44 +/- 3 year; BP, 145 +/- 3/84 +/- 3 mm Hg) with borderline hypertension and a control group of 38 subjects (35 +/- 2 year; BP, 123 +/- 3/70 +/- 2 mm Hg) underwent power spectrum analysis of RR interval and BP (low frequency (LF), 0.05 to 0.15 Hz; high frequency (HF), 0.15 to 0.40 Hz) in the supine and standing positions. Concentrations of plasma renin activity, angiotensin II, and aldosterone in supine and standing positions had been determined in the hypertensive group. Borderline hypertensives are characterized by higher oscillations of systolic and diastolic BP, but not of RR interval in the supine position versus the control group. Low frequency and HF components of systolic and diastolic BP expressed as absolute data are also significantly higher in borderline hypertensives. Moreover, standing tended to increase the LF/HF ratio of both RR interval and BP variability compared to controls. The standing position was able to further activate the LF but not the HF component of BP variability. In borderline hypertension renin release during postural changes correlated well with the decrease in the power of the HF vagal component of RR interval variability (r = -0.70, P < .001) and with the increase of the LF component of diastolic blood pressure variability (r = 0.43, P = .03). In conclusion, our results indicate that in borderline arterial hypertension, LF and HF oscillations of BP are already significantly increased at rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Many cases of refractory hypertension cannot be attributed to specific identifiable factors. Haptoglobin polymorphism has been suggested as a candidate genetic marker in essential hypertension. The aim of this study was to investigate the distribution of haptoglobin types in patients with refractory hypertension., Methods: Haptoglobin polymorphism was studied in 383 patients with non-refractory and 62 patients with refractory hypertension. Haptoglobin was typed using starch gel electrophoresis of haemoglobin-supplemented serum., Results: In the group of patients with refractory hypertension, the relative allele frequency of haptoglobin 1 (0.266) was lower than in the group with non-refractory hypertension (0.385: P < or = 0.05). The relative frequency of haptoglobin 2-2 was 39% in the non-refractory compared with 56% in the refractory group (P < or = 0.05). In the latter group, the relative frequency of haptoglobin 2-2 was highest (75%) in patients requiring medication with four classes of drug., Conclusion: Hypertension patients with the haptoglobin 2-2 phenotype are at higher risk of developing refractory hypertension than those with other haptoglobin phenotypes.

Objectives: To investigate the relationship between arterial blood pressure, left ventricular mass, diastolic filling and maximal exercise capacity in patients with newly diagnosed essential hypertension., Design: Asymptomatic untreated patients with office blood pressure > 140/90 mmHg were studied prospectively after exclusion of associated disease., Methods: Twenty consecutive white patients (14 male, 6 female; age 43 +/- 12 years) with office blood pressure 164 +/- 23/103 +/- 10 mmHg, mean 24-h ambulatory blood pressure 142 +/- 25/89 +/- 15 mmHg and normal systolic cardiac function underwent an echocardiographic examination to determine left ventricular mass and diastolic filling parameters and performed a bicycle ergometer test to determine maximal voluntary exercise capacity., Results: In single regression analysis exercise time and maximal oxygen uptake were related to sex and age. A multiple regression showed that only age was related to exercise capacity, however. On subgroup analysis of male patients between 30 and 50 years (n = 10), exercise time (659 +/- 134 s) was significantly inversely related to mean 24-h ambulatory diastolic blood pressure (92 +/- 11 mmHg) (r = -0.67; p = 0.03) and positively to diastolic filling expressed as ratio of peak early to peak atrial filling velocity (Emax/Amax ratio; 1.34 +/- 0.40) (r = 0.65; p = 0.04) or as ratio of velocity time integral (VTI) of early filling phase to VTI of atrial filling phase (VTIE/VTIA ratio; 1.94 +/- 0.72) (r = 0.02). Maximal oxygen consumption (22.3 +/- 4.1 ml/kg/min) was significantly inversely correlated with mean 24-h ambulatory diastolic blood pressure (r = -0.67; p = 0.03), mean 24-h ambulatory systolic blood pressure (147 +/- 25 mmHg) (r = -0.82; p < 0.01), left ventricular mass (312 +/- 143 g) (r = -0.86; p < 0.01), left ventricular mass index (135 +/- 41 g/m2) (r = -0.76, p = 0.01) and positively with diastolic filling expressed as Emax/Amax ratio (r = 0.71; p = 0.02) or as VTIE/VTIA ratio (r = 0.70; p = 0.02)., Conclusion: This study shows the important interrelation between blood pressure, cardiac mass, diastolic filling and exercise capacity. High blood pressure entrains a larger cardiac mass but slows cardiac filling and decreases exercise capacity.

This study aimed to correlate blood pressure (BP) level assessed either by casual or by 24-h ambulatory BP monitoring and regional (calf and finger) blood flow and associated vascular resistance in subjects with low, intermediate, and high BP. In 75 subjects covering the range from low BP to normo- and hypertension, blood flow at calf and finger vessels were simultaneously measured using an ECG-triggered venous occlusion plethysmograph. Correlations were calculated between regional blood flow or vascular resistance and BP defined from casual and from 24-h ambulatory BP registrations, at rest, and after 3 min of arterial occlusion (reactive hyperemia). Correlations over the whole BP range, between calf and finger vascular resistances and BP, were highly significant both for casual (0.650 < r < 0.776) and for ambulatory (0.531 < r < 0.781) BP. The relations remained significant after adjustment for the age dependency of the blood pressure. At any BP level skin (finger) blood flow at rest and after arterial occlusion was higher than muscle (calf) blood flow. These data indicate that there is a progressive decrease in vasodilating capacity from low to high BP in both muscle and skin vessels. However, in the zone of borderline to moderate essential hypertensives, blood flow after 3 min arterial occlusion was already significantly decreased in the muscle circulation when compared to normotensives, while still maintained in the skin circulation.

Objective: Salt sensitivity and the magnitude of systolic blood pressure have been linked to haptoglobin (Hp) polymorphism in normotensives. The aim of the present study was to investigate the indices of hypertension, the severity of complications and the occurrence of coronary and peripheral artery disease for the various haptoglobin phenotypes and their relation to the therapeutic needs (number and class of drugs) of established arterial hypertensives., Design: Haptoglobin polymorphism was studied in 302 Caucasians with established essential arterial hypertension who had been treated for at least 1 year., Methods: Haptoglobin polymorphism was studied using starch-gel electrophoresis of haemoglobin-supplemented serum., Results: The relative allele frequencies of Hp 1 and Hp 2 (0.036 and 0.640, respectively) in established hypertensives were comparable with those of the control population. Logistic regression analysis confirmed that Hp 2-2 contributes to the therapeutic needs in hypertension. The most important factors determining therapeutic needs were coronary artery disease, Hp 2-2 phenotype, body mass index (BMI) and left ventricular hypertrophy. Although no contributive effect of serum haptoglobin concentration could be derived from the logistic regression approach, analysis of serum haptoglobin concentration demonstrated a concentration-related effect on therapeutic needs for the Hp 2-2 phenotype only., Conclusions: The present study suggests that hypertensives with an Hp 2-2 phenotype need more complex combinations of antihypertensive drugs to reduce blood pressure to the same level. The hypertensive patient carrying Hp 2-2 is more likely to accumulate atherosclerotic lesions of the coronary or peripheral arteries, despite comparable lipid levels, smoking habits and BMI. Hp 1-1 patients are characterized by a younger age at diagnosis and a lower complication rate. In view of the greater therapeutic needs and the higher complication rate, Hp 2-2 hypertensives need more careful follow-up.

Although left ventricular hypertrophy (LVH) is an adaptive response to the increased load imposed on the heart in patients with hypertension, it ultimately is itself a major risk factor for cardiovascular disease. The influence of LVH on left ventricular function and on the coronary circulation, and the occurrence of serious ventricular arrhythmias are the major mechanisms of this increased risk. There is no doubt that regression of LVH occurs, but there are clear differences in this respect among antihypertensive drugs: angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists produce the best response. Whether regression of LVH also causes an improvement in left ventricular function is unclear; various studies using the same drugs have yielded contradictory results. Furthermore, it has yet to be determined whether regression of LVH has a positive influence on the long-term prognosis in such patients; the results of the European Multicenter Study OvA will help in shedding more light on this important question.

In a group of 36 untreated patients with mild-to-moderate essential hypertension (office systolic blood pressure [SBP] 160 +/- 3.4 mm Hg, office diastolic blood pressure [DBP], 102 +/- 1.5 mm Hg), 24-hour ambulatory blood pressure monitoring, and determination of left ventricular (LV) mass index according to the formula of Devereux were performed. After an overnight fast, blood samples were taken for the determination of serum aldosterone levels and plasma renin activity. Urinary catecholamine concentrations were assayed from 24-hour urine collections. Left ventricular mass index (143.7 +/- 8 g/m2) did not correlate significantly with either office SBP or office DBP. The correlation of LV mass index with mean 24-hour SBP (145 +/- 3 mm Hg) was statistically significant: r = 0.395, p = 0.026. However, the best correlation was obtained with mean 24-hour DBP (90 +/- 3 mm Hg) with r = 0.499 (p = 0.004). Urinary catecholamine levels did not correlate with LV mass index. In addition, LV mass index correlated significantly with plasma renin activity (r = 0.346, p = 0.050) and serum aldosterone levels (r = 0.559, p = 0.0009). There was a strongly significant correlation between LV mass index and serum aldosterone levels even after adjustment for mean 24-hour SBP (r = 0.496, p = 0.005) and DBP (r = 0.514, p = 0.004). These results demonstrate that ambulatory blood pressure determinations but not office blood pressure parameters correlate well with left ventricular hypertrophy in essential hypertension. Nonhemodynamic factors are important determinants of left ventricular mass as well.(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind, randomized crossover study was performed in 21 patients with essential arterial hypertension. Nitrendipine 20 mg o.d. and lisinopril 20 mg o.d. were given in a randomized order during a period of each 8 weeks. Nitrendipine and lisinopril decreased systolic and mean arterial blood pressure to a similar level without a significant increase in heart rate. The mean diastolic blood pressure was smaller with the lisinopril treatment than with the nitrendipine treatment. The blood pressure decrease was maintained in the sitting and standing position. Furthermore, only nitrendipine decreased the pulsatility index at the tibial posterior arteries, while lisinopril did not influence it significantly. This finding means that mechanisms other than the blood-pressure lowering effect are involved in the decrease of the pulsatility index.

In a series of 35 newly diagnosed, previously untreated patients (mean age 46 years) with mild to moderate essential hypertension, office blood pressure measurements, 24-hour ambulatory blood pressure monitoring, and determination of left ventricular mass index by echocardiography according to the formula of Devereux were performed. We aimed at correlating left ventricular mass index with systolic and diastolic office blood pressure, mean 24-hour systolic and mean 24-hour diastolic blood pressure, systolic and diastolic load. Left ventricular mass index did not correlate with office systolic and office diastolic blood pressure. On the contrary, all correlations with ambulatory blood pressure parameters and left ventricular mass index turned out to be significant (mean 24-hour systolic blood pressure: r = 0.344, P = 0.026; systolic load: r = 0.408, P = 0.020; mean 24-hour diastolic blood pressure: r = 0.490, P = 0.004; diastolic load: r = 0.504, P = 0.003). These results clearly demonstrate that ambulatory blood pressure determinants but not the office blood pressure parameters are well correlated with left ventricular mass index in mild to moderate essential hypertension. Blood pressure load is as important as mean 24-hour blood pressure in this regard.

Objective: The aim of this study was to correlate capillary morphology and erythrocyte velocity to blood pressure in mild-to-moderate essential arterial hypertension., Design: Ambulatory blood pressure measurement may provide more precise information about a patient's mean blood pressure than office measurements., Methods: Fifteen patients with recently diagnosed, previously untreated mild-to-moderate essential hypertension underwent 24-h ambulatory blood pressure recording and a capillaroscopic examination of finger microcirculation. Erythrocyte velocity was determined by the flying spot technique., Results: Both mean 24-h ambulatory systolic blood pressure (SBP) and mean 24-h ambulatory diastolic blood pressure (DBP) were significantly inversely correlated with capillary erythrocyte velocity. However, the correlation between erythrocyte velocity and office SBP and office DBP was less significant. Capillary length was related to 24-h ambulatory DBP but not to office DBP. Capillary number was not related to any blood pressure parameter., Conclusions: These results indicate that, in patients with mild-to-moderate essential hypertension, erythrocyte velocity is significantly lower than for matched controls. It is also inversely related to mean 24-h ambulatory SBP and 24-h ambulatory DBP.

At the end of a short-term (3-month) study of antihypertensive treatment of mild-to-moderate hypertension, 141 of the 200 study patients continued into a 2-year follow-up of isradipine as monotherapy or in combination with other antihypertensive agents. Although all 141 patients completed the first year, only 102 completed the study. Twenty-four patients dropped out: 2 with flushing; 1 each with arrhythmia, edema, angina, and headache; 12 who were noncompliant; 2 with disease unrelated to the study drug; and 4 for reasons unknown. Before the follow-up, 70% of the 141 patients were taking isradipine; after 2 years, 63% were still taking isradipine as monotherapy. During the follow-up study, the blood pressure remained stable (142.9/86.8 mm Hg after 3 months, and 142.9/86.2 mm Hg after 2 years), whereas the normalization rate was only slightly changed (73 vs. 75.2%). The incidence of reported adverse events decreased with time. At the end of the short-term study, 44.7% of patients had reported one or more adverse events; after 2 years of treatment, only 14.4% reported adverse events. Two patients had ECG signs of left ventricular hypertrophy: one showed no relevant changes while the other presented clear signs of regression. No clinically relevant laboratory abnormalities were noted during the study. In conclusion, isradipine is effective, well tolerated and safe in the long-term treatment of mild-to-moderate hypertension.

Two multicenter European trials studying the correlation between ambulatory blood pressure and long-term prognosis of hypertension are at present underway. The Office versus Ambulatory trial (OvA) has accepted primary hypertensives of all ages, with systolic and diastolic hypertension; in the Systolic Hypertension in the Elderly study (Syst-Eur) only elderly patients with systolic hypertension are being studied. In both trials, blood pressure is being recorded at intervals of 30 min over 24 h, using fully validated non-invasive recorders. Treatment in both studies is based on office blood pressure. As both studies are expected to answer many current questions on the value of ambulatory blood pressure recordings, participation is strongly encouraged.

In a group of 36 untreated patients with mild to moderate essential hypertension (office systolic and diastolic blood pressures (BPs) 160 +/- 3.4 and 102 +/- 1.5 mm Hg, respectively), a 24-hour ambulatory BP monitoring and determination of left ventricular (LV) mass index according to the formula of Devereux were performed. After an overnight fast, blood samples were taken for the determination of serum aldosterone, plasma renin activity and serum parathyroid hormone. Urinary catecholamines were sampled for 24 hours. LV mass index (143.7 +/- 8 g/m2) did not correlate significantly either with office systolic or diastolic BP. The correlation of LV mass index with mean 24-hour systolic BP (145 +/- 3 mm Hg) was statistically significant: r = 0.395, p = 0.026. However, the best correlation was obtained with mean 24-hour diastolic BP (90 +/- 3 mm Hg) with r = 0.500 (p = 0.004). Urinary catecholamines were not correlated with LV mass index. LV mass index correlated significantly with plasma renin activity (r = 0.346, p = 0.050), and aldosterone (r = 0.559, p = 0.001). There was a very significant correlation between LV mass index and parathyroid hormone (r = 0.719, p = 0.00001) even after adjustment for mean 24-hour systolic and diastolic BPs. These results clearly demonstrate that ambulatory BP determinants but not office BP parameters are well correlated with LV hypertrophy in essential hypertension. Nonhemodynamic factors are important determinants of LV mass as well. Besides the renin-angiotensin-aldosterone system, parathyroid hormone appears to play an important role in cardiac hypertrophy.

In a randomized double-blind, placebo-controlled, crossover study of isradipine (5 mg twice daily), effects on peripheral hemodynamic reflex responses were studied in nine patients (mean age 48 years) at baseline and after six weeks of active treatment. Assessments included vital signs, resting blood flow in the calf and finger (using an electrocardiograph-triggered venous occlusion plethysmograph), reflex responses during isometric exercise and cold pressor resistance, and venous capacitance in the forearm and calf. Isradipine lowered systolic and diastolic blood pressure as well as mean arterial pressure in patients with mild-to-moderate essential hypertension without reflex tachycardia or venoconstriction. All of the reflex responses studied were attenuated. It is concluded that vasodilatation of the peripheral circulation induced by isradipine contributes partially to the blood pressure-lowering effect.

The long-term prognostic value of ambulatory blood pressure recordings in essential hypertension is poorly documented. A European Multicenter study has been set up to evaluate office versus ambulatory (OvA) recordings during a follow-up period of 5 years in a minimum of 2000 patients. The end-point of the study is the question of whether ambulatory blood pressure measurements are better correlated with patient morbidity and mortality than office recordings. In a specific substudy, short-term evolution (6 months) of left ventricular hypertrophy will be followed in untreated hypertensives with randomly allocated treatment. A number of readaptations of the primary protocol are discussed.

The relation between vasodilation and the blood pressure-reducing action of spironolactone was studied in a randomized, placebo-controlled, double-blind, crossover study using 9 patients with essential hypertension. Vasodilation was studied by measuring blood flow in finger and calf (representative of skin and muscle circulation) by an electrocardiographic-triggered venous-occlusion plethysmograph. Treatment with spironolactone (100 mg twice daily for 4 weeks) produced significant decreases in systolic and diastolic blood pressure without significantly affecting heart rate. Blood flow through finger and calf increased, sometimes markedly, in 6 of the 9 patients, while vascular resistance decreased. This study confirms that the antihypertensive action of spironolactone is associated with vasodilation in many patients.

The effect of beta-adrenergic blockade on blood pressure variation was studied in ten patients with moderate hypertension. Supine systolic and diastolic blood pressures were measured every 5 min during six hours sessions, using an ultrasonic method. Systolic and diastolic variation in each six hour session was defined as the standard deviation of the mean of systolic and diastolic readings made in that period. After 3 weeks of single-blind placebo, a 12 week double-blind randomized crossover study was initiated with placebo (6 weeks) and atenolol (100 mg b.i.d. for 3 weeks and 200 mg b.i.d. for 3 weeks). Systolic and diastolic blood pressure and heart rate decreased significantly (p less than 0.01) during atenolol treatment. Diastolic variation did not change significantly, whereas systolic variation decreased slightly but significantly (p less than 0.05) when expressed in absolute values, but not when expressed as a percentage of systolic blood pressure. It is concluded that beta-adrenergic blockade decreases blood pressure and heart rate without causing significant changes in spontaneous systolic or diastolic variation.