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Biomedical subjects

A Zanchetti

Publications and source records attributed to A Zanchetti.

At least 109 records · Page 6Linked to original sources
PubMed1997

Electrophysiological evidence of ipsilateral reno-renal reflexes in the cat.

To verify the existence of ipsilateral reno-renal reflexes we studied the effect of surgical denervation of one kidney on the ipsilateral efferent renal nerve activity (ERNA), in the absence of contralateral afferent renal nerve activity. Thus the ipsilateral renal denervation was performed 1 h later than the contralateral renal denervation. The experiments were done on 9 anesthetized cats. Arterial pressure, urine flow rate (UFR) of both kidneys and ERNA to the ipsilateral kidney were measured. All variables were monitored during a 3 min control period and for 13 min after either contralateral and ipsilateral renal denervations. ERNA significantly increased (+20 +/- 9%) and UFR concomitantly decreased (-11 +/- 10%) after the surgical denervation of the contralateral kidney which showed an increase (+91 +/- 19%) in UFR. The subsequent ipsilateral denervation caused a significant increase in UFR (+117 +/- 25%) and ERNA (79 +/- 23%) of the same kidney, while on the opposite side UFR did not change. During the two procedures, arterial pressure did not change. Our data demonstrate the existence of ipsilateral reno-renal reflexes that exert a tonic inhibitory effect on ipsilateral ERNA.

Animals↗
PubMed1997

Antihypertensive therapy: how to evaluate the benefits.

For more than 30 years, the benefits of antihypertensive therapy have been assessed in randomized trials that monitor cardiovascular events. Even greater benefits can result if prevention of (1) congestive heart failure, (2) left ventricular hypertrophy, and (3) progression to more severe hypertension is taken into consideration. However, quantifying the benefits in order to calculate the cost-effectiveness of treatment is not easy. Taking absolute risk and benefit as the only guide to treatment decisions may result in limiting therapy only to elderly hypertensive patients and hypertensive patients with complications. Furthermore, randomized trials, of which the duration is necessarily short, are likely to underestimate treatment benefits. An alternative to such an approach is the actuarial approach: treatment benefits are calculated from the actuarial data showing the reduction in life expectancy associated with any given blood pressure increase. The cost of antihypertensive therapy per year of life gained calculated in this way is much lower than the cost calculated from randomized trials. In an uncertain area such as that of cost-effectiveness evaluation, it is important that both approaches are taken into consideration by physicians, patients, politicians, and officers of national health systems.

Actuarial Analysis↗
PubMed1997

Ambulatory blood pressure is superior to clinic blood pressure in predicting treatment-induced regression of left ventricular hypertrophy. SAMPLE Study Group. Study on Ambulatory Monitoring of Blood Pressure and Lisinopril Evaluation.

BACKGROUND: In cross-sectional studies, ambulatory blood pressure (ABP) correlates more closely than clinic BP with the organ damage of hypertension. Whether ABP predicts development or regression of organ damage over time better than clinic BP, however, is unknown. METHODS AND RESULTS: In 206 essential hypertensive subjects with left ventricular hypertrophy (LVH), we measured clinic supine BP, 24-hour ABP, and left ventricular mass index (LVMI, echocardiography) before and after 12 months of treatment with lisinopril (20 mg UID) without or with hydrochlorothiazide (12.5 or 25 mg UID). Measurements included random-zero, clinic orthostatic, and home BP. In all, 184 subjects completed the 12-month treatment period. Before treatment, clinic supine BP was 165 +/- 15/105 +/- 5 mm Hg (systolic/diastolic), 24-hour average BP was 149 +/- 16/95 +/- 11 mm Hg, and LVMI was 158 +/- 32 g/m2. At the end of treatment, they were 139 +/- 12/87 +/- 7 mm Hg, 131 +/- 12/83 +/- 10 mm Hg, and 133 +/- 26 g/m2, respectively (P < .01 for all). Before treatment, LVMI did not correlate with clinic BP, but it showed a correlation with systolic and diastolic 24-hour average BP (r = .34/.27, P < .01). The LVMI reduction was not related to the reduction in clinic BP, but it was related to the reduction in 24-hour average BP (r = .42/.38, P < .01). Treatment-induced changes in average daytime and nighttime BPs correlated with LVMI changes as strongly as 24-hour BP changes. No substantial advantage over clinic supine BP was shown by clinic orthostatic, random-zero, and home BP. CONCLUSIONS: In hypertensive subjects with LVH, regression of LVH was predicted much more closely by treatment-induced changes in ABP than in the clinic BP. This provides the first longitudinally controlled evidence that ABP may be clinically superior to traditional BP measurements.

Adult↗
PubMed1997

Blood-pressure control in the hypertensive population.

BACKGROUND: In large-scale surveys of individuals with hypertension those whose clinic blood pressure is reduced to 140/90 mm Hg or less have been found to represent only a small fraction of the hypertensive population. We assessed whether these results arise because of a white-coat effect elevating clinic blood pressure. METHODS: We randomly selected 2400 individuals from the town of Monza, Italy, and invited them to take part in our study. We measured clinic blood pressure as well as home (morning and evening measurements), and 24 h ambulatory blood pressure-ie, blood pressures largely devoid of a white-coat effect. Based on clinic blood pressure participants were then classified as normotensive, untreated hypertensive (clinic blood pressure > 140 mm Hg systolic and/or > 90 mm Hg diastolic), or treated hypertensive (having antihypertensive treatment). The mean blood pressures for each group were calculated. FINDINGS: 1651 people took part in the study. The clinic blood pressure of treated hypertensives (n = 207; 146.9 [SD 18] mm Hg/90.2 [8.6] mm Hg) was only slightly less than in untreated hypertensives (n = 402; 148 [15.2] mm Hg/93.3 [8] mm Hg) and in both groups the blood pressure values were much greater than those of normotensive individuals (n = 1042; 119.5 [10.3] mm Hg/78.1 [6.6] mm Hg) p < 0.001. Averaged home and 24 h blood pressures were lower than clinic blood pressures but similarly higher in untreated and treated hypertensive individuals when compared with normotensive individuals. This was also the case for day and night average blood pressures. The number of treated hypertensive patients found to have blood pressures within the normal limits was small not only when based on clinic blood pressure values but also when based on ambulatory blood-pressure values. INTERPRETATION: In the hypertensive population the number of patients with inadequate blood-pressure control is high not only when assessed in the clinic but also when assessed by ambulatory-blood-pressure monitoring or at home. The high blood-pressure values commonly found in treated hypertensive individuals cannot be accounted for by a white-coat effect but by a true lack of daily-life blood-pressure control.

Adult↗
PubMed1997

Effects of erythropoietin administration on blood pressure and urinary albumin excretion in rats.

The effects of recombinant human erythropoietin (rHuEPO) administration on blood pressure and urinary albumin excretion were studied in normotensive Wistar-Kyoto rats (WKY), in spontaneously hypertensive rats (SHR), and in SHR rats treated with an angiotensin converting enzyme inhibitor (SHR-ACEi). Rats were housed in metabolic cages and treated with rHuEPO (150 U/kg body weight [bw] three times a week) for 6 weeks. Control animals received the vehicle only (0.25 mL of physiological saline). An angiotensin converting enzyme inhibitor was administered in the drinking water for 6 weeks (spirapril 5 mg/kg bw). Systolic blood pressure (SBP), and 24 h urinary albumin excretion (UAE) were measured once a week. No significant differences in SBP were observed between rHuEPO and vehicle-treated normotensive animals at the end of the treatment (171.9 +/- 4.9 v 172.1 +/- 5.6 mm Hg, respectively). After 6 weeks, SBP was significantly higher in SHR and SHR-ACEi groups treated with rHuEPO than in control groups (239.8 +/- 7.3 and 243.0 +/- 7.3 mm Hg v 218.1 +/- 6.0 and 187.9 +/- 4.6 mm Hg, respectively); UAE was significantly higher in groups treated with rHuEPO than in control groups (WKY: 265.9 +/- 19.5 v 127.0 +/- 12.3 microg/100 g bw, SHR: 1668.4 +/- 564.6 v 234.8 +/- 22.9 microg/100 g bw, and SHR-ACEi: 1522.7 +/- 448.3 v 143.0 +/- 18.9 microg/100 g bw, respectively). We concluded that erythropoietin treatment causes an increase in arterial pressure in SHR only, and an increase in UAE in both normotensive and hypertensive rats. The albuminuric effect was not entirely dependent on increased blood pressure. The treatment with an angiotensin converting enzyme inhibitor did not modify either the proteinuric or the pressor effects.

Albuminuria↗
PubMed1997

The role of ambulatory blood pressure monitoring in clinical practice.

The introduction of noninvasive techniques for the repetitive measurement of blood pressure in ambulant subjects has permitted improved precision in the assessment of hypertension during normal daily life. The traditional clinic (or "office") method of blood pressure measurement has the advantages of simplicity and low cost, and forms the basis of the current operational definitions of hypertension, but it is limited by the normal variability of blood pressure and the "white coat effect." By contrast, ambulatory blood pressure provides information on circadian variations in blood pressure and alterations due to changes in behavior, and may, therefore, be more appropriate for diagnosing hypertension. However, it is important to note that the values used to define normotension and hypertension for clinic blood pressure are not appropriate for ambulatory blood pressure. Recent population studies have proposed that the upper limit for 24-h ambulatory pressure should be 119 to 126/75 to 80 mm Hg, and failure to recognize this may account for at least some cases of "white-coat hypertension." There is increasing evidence that ambulatory blood pressure is more effective than clinic blood pressure in predicting the organ damage associated with hypertension, whereas data from intervention studies indicate that a reduction in ambulatory pressure is correlated with a reduction in left ventricular (LV) mass. Finally, ambulatory blood pressure measurements may provide a number of advantages in the development of antihypertensive therapies: by permitting better identification of trough and peak effects, by confirming that the efficacy of formulations for once-daily dosing is maintained throughout the 24-h period, and by minimizing the placebo effect.

Antihypertensive Agents↗
PubMed1997

The hypertensive patient with multiple risk factors: is treatment really so difficult?

Multiple risk factors for cardiovascular disease, particularly hypercholesterolemia, are often present in the hypertensive patient. Recent guidelines, ranging from those prepared by the World Health Organization/International Society of Hypertension to those of the three European Societies of Cardiology, Atherosclerosis, and Hypertension, stress the importance of evaluating global risk, based on the presence of all cardiovascular risk factors in an individual or in a group of subjects. It has also been suggested that treatment should aim to correct all modifiable risk factors. This is a reasonable recommendation, but although observational epidemiologic studies have shown that the effects of concomitant risk factors are additive, if not multiplicative, it is surprising that no intervention trial has been undertaken to determine whether the benefits of treating more than one risk factor are also additive. The Plaque Hypertension Lipid-Lowering Italian Study (PHYLLIS) is the first such study. Its aim is to investigate the potential benefit of lowering blood pressure and plasma cholesterol on the progression of carotid plaque in hypertensive patients with elevated plasma cholesterol. Using a factorial design, the antiatherosclerotic effect of two different antihypertensive drugs, the angiotensin-converting enzyme (ACE) inhibitor fosinopril and the diuretic hydrochlorothiazide will be compared. The study aims to confirm animal experiments demonstrating the benefit of ACE inhibitors on experimental atherosclerosis. PHYLLIS will also compare the effects of two lipid-lowering regimens, diet plus placebo and diet plus pravastatin, in the study population. This 3-year, multicenter, double-blind, randomized Italian study, using B-mode ultrasound evaluation of the carotid walls with central reading of the ultrasound scans (Bowman Gray University, Winston-Salem, NC) is now underway and should provide useful evidence about the benefits of multiple risk factor treatment in the hypertensive patient.

Aged↗
PubMed1997

Renal afferents responsive to chemical and mechanical pelvic stimuli in the rabbit.

1. Afferent nerve fibres sensitive to changes in the renal chemical environment have been found in the rat. To verify the existence of these fibres in the rabbit and their response pattern, afferent renal nerve activity was recorded during pelvic perfusions with NaCl solutions at different concentrations. 2. The experiments were carried out in 13 anaesthetized rabbits. Arterial pressure from a femoral catheter and afferent renal nerve activity from the distal stump of a cut renal nerve bundle were recorded. Three catheters were inserted into the renal pelvis to measure pelvic pressure, to allow pelvic perfusions at constant rates and to drain pelvic fluids. 3. After a control period, the pelvis was perfused with physiological saline (0.14 mol/l for 2 min), followed by one of a series of solutions containing increasing concentrations of NaCl (0.5, 0.75, 1.0 and 1.5 mol/l for 2 min). Pelvic perfusion was performed both at a low (0.2 ml/min) and a high (0.8 ml/min) flow rate for each solution tested. 4. In all animals arterial pressure was not modified during pelvic perfusions. Physiological saline did not change afferent renal nerve activity at the low perfusion rate, but it significantly increased afferent renal nerve activity and pelvic pressure at the high rate. Hypertonic NaCl solutions caused progressive increases in afferent renal nerve activity at both perfusion rates, and these effects were larger at the high perfusion rate. 5. These data demonstrate, in the rabbit, the existence of renal afferent nerves sensitive to discrete changes in pelvic ionic or osmotic concentration. The neural response is enhanced when renal mechano- and chemo-receptors are simultaneously activated.

Animals↗
PubMed1997

Effects of antihypertensive treatment on vasopressin secretion and on its osmoregulation in moderate hypertension.

BACKGROUND: Changes in plasma osmolality and arterial pressure can affect the secretion of vasopressin (AVP). OBJECTIVE: To investigate the effect of a drug-induced lowering of the arterial pressure on the plasma concentration of AVP and on its osmoregulation in moderately severe uncomplicated hypertensives. DESIGN AND METHODS: A group of 33 moderate uncomplicated and untreated essential hypertensives of both sexes (mean age 48 +/- 1 years, average arterial pressure 171 +/- 3/108 +/- 2 mmHg) was studied. We measured AVP and other plasma and urine variables in 21 of them before and after administration of a hypertonic NaCl solution (100 mmol NaCl in 50 ml). Antihypertensive treatment with a single drug or, if necessary, with a combination of drugs was initiated for eight of these subjects and hypertonic saline administration was repeated after 1 month of treatment. The hypertonic stimulus was administered to the other 12 subjects after acute lowering of the arterial pressure by continuous intravenous infusion either of 0.3 mg clonidine in 100 ml (n = 6) or of 50 mg sodium nitroprusside in 250 ml (n = 6). RESULTS: Administration of hypertonic saline to untreated hypertensives increased their AVP level from 1.6 +/- 0.28 to 5.4 +/- 0.7 pg/ml (n = 21, P < 0.01). Their mean arterial pressure was lowered after pharmacological treatment for 1 month (n = 8) from 125 +/- 2 to 101 +/- 2 mmHg; their baseline AVP level remained unchanged (1.2 +/- 0.21 versus 0.9 +/- 0.25 pg/ml); after hypertonic saline had been administered to hypertensives with lowered arterial pressures, their AVP level increased to 6.0 +/- 1.03 pg/ml (P < 0.01). The AVP level in subjects whose MAP had been lowered acutely by administration of clonidine (n = 6) or of sodium nitroprusside (n = 6; on the average, from 132 +/- 3 to 110 +/- 4 mmHg) increased concurrently from 1.6 +/- 0.63 to 3.4 +/- 0.7 pg/ml (P < 0.05); after administration of the hypertonic saline the AVP level increased to 10.8 +/- 2.22 pg/ml (P < 0.01). This stimulated value was significantly (P < 0.01) higher than that observed after hypertonic saline had been administered to untreated hypertensives (5.4 +/- 0.7 pg/ml). CONCLUSIONS: Acute lowering of the arterial pressure in moderate essential hypertension appears to facilitate the secretion and osmoregulation of AVP. On the other hand, during prolonged antihypertensive treatment, baroreflex regulation of the secretion of AVP appears to be set at a lower operating point, thus exerting the same influence on the release of AVP as it did before antihypertensive treatment.

Adult↗
PubMed1997

Clinical results of the Verapamil inHypertension and Atherosclerosis Study. VHAS Investigators.

OBJECTIVE: The Verapamil in Hypertension and Atherosclerosis Study (VHAS) is a prospective randomized study the objective of which was to compare the long-term effects of verapamil and chlorthalidone on the blood pressure, clinical safety, and the progression/regression of carotid wall lesions in members of a large population of hypertensive patients. DESIGN: After a 3-week placebo run-in period, 1414 hypertensive patients [692 men and 722 women, aged 53.2 +/- 7 years, blood pressure 168.9 +/- 10.5/ 102.2 +/- 5.0 mmHg (means +/- SD)] were assigned randomly to be administered either 240 mg sustained-release verapamil (n = 707) or 25 mg chlorthalidone (n = 707) once a day for 2 years. The study design was double blind for the first 6 months and open thereafter. 25-50 mg/day captopril were added to the treatment of non-responding patients; subsequently, patients not responding to combined therapy were switched to any therapy chosen by the treating doctors (free therapy). The blood pressure of the sitting subject, heart rate, and a standard clinical safety profile (electrocardiogram, laboratory tests, adverse events, cardiovascular events, and deaths) were assessed regularly throughout the study. RESULTS: After 2 years the systolic and diastolic blood pressures were reduced significantly in members of both treatment groups (by 16.3/16.6% with verapamil and by 16.9/16.2% with chlorthalidone, both by analysis of variance, P < 0.0001). The patients for whom we added captopril treatment constituted 22.6% of the verapamil and 26.2% of the chlorthalidone group; while 11.6 and 12.2% of patients in these groups, respectively, were administered free therapy. Normalization of the diastolic blood pressure (to < or = 90 mmHg or to < or = 95 mmHg with a > or = 10% decrease) was achieved for 69.3% of the verapamil and 66.9% of the chlorthalidone group. A decrease in heart rate (by 5.8%) occurred in members of the verapamil group only. A decrease in total serum cholesterol (from 223.6 to 216.9 mg/dl, P < 0.01) and in the total cholesterol: high-density lipoprotein cholesterol ratio (from 4.9 to 4.5, P < 0.01) was noted for the verapamil group only, whereas significantly greater rates of hyperuricemia (plasma urate > 7.0 mg/dl; 10.8 versus 3.9%) and hypokalemia (serum K < 3.5 mmol/l; 24.6 versus 4.4%) were observed for the chlorthalidone group (P < 0.01, versus verapamil for both). Adverse events were reported by 32.5% of patients treated with verapamil and by 33.4% of those treated with chlorthalidone. The most frequent adverse events were constipation in members of the verapamil group (13.7%) and asthenia in members of the chlorthalidone group (8.5%). In total 315 dropped out (153 from the verapamil and 162 from the chlorthalidone group). The occurrence of cardiovascular events was similar for both treatments (42 events for verapamil and 43 for chlorthalidone, NS). CONCLUSION: Similar antihypertensive efficacies, tolerabilities and cardiovascular event rates were observed with verapamil and with chlorthalidone. However, treatment with chlorthalidone was associated with significantly higher incidences of hyperuricemia and hypokalemia than was treatment with verapamil.

Adult↗
PubMed1997

24-hour blood pressure control by once-daily administration of irbesartan assessed by ambulatory blood pressure monitoring. Irbesartan Multicenter Investigators' Group.

OBJECTIVES: To compare 24 h ambulatory blood pressure and trough office blood pressure lowerings after 8 weeks of therapy with 75 mg irbesartan once a day, 150 mg irbesartan once a day , and 75 mg irbesartan twice a day versus placebo; and to assess safety and tolerability of irbesartan therapy. DESIGN: Multicenter, double-blind, randomized, placebo-controlled trial. SETTING: Sixteen centers in Italy. PATIENTS: Caucasian patients (n = 215) aged > or = 18 years with seated diastolic blood pressure 95-110 mmHg and ambulatory diastolic blood pressure (ADBP) > or = 85 mmHg. PRIMARY OUTCOME: Mean 24 h ADBP after 8 weeks of irbesartan therapy. RESULTS: Mean changes (value before treatment minus value after treatment) in ADBP for placebo, 75 mg irbesartan once a day, 150 mg irbesartan once a day, and 75 mg irbesartan twice a day were -0.2, -5.4, -7.2, and -7.2 mmHg, respectively; respective changes in ambulatory systolic blood pressure were +1.6, -8.3, -10.5, and -9.7 mmHg. All irbesartan regimens reduced trough office seated diastolic blood pressure and seated systolic blood pressure after 2 and 8 weeks of treatment (all P < 0.01, versus placebo except for seated systolic blood pressure in patients in the 75 mg irbesartan once a day group). Trough: peak ratios were > or = 55% with 150 mg irbesartan once a day. Percentages of patients whose blood pressures were normalized with 150 mg irbesartan once a day (45%) and 75 mg irbesartan twice a day (47%) were greater than those with placebo (14%, P < 0.01) and with 75 mg irbesartan once a day (19%, NS, versus placebo). Adverse events with irbesartan were similar to those with placebo. CONCLUSIONS: All irbesartan regimens significantly reduced mean 24 h ADBP and ambulatory systolic blood pressure, and were well tolerated. Administration of 150 mg irbesartan once a day provided significant reduction of blood pressure for 24 h, equivalent to that obtained with the same daily dose divided into two separate administrations.

Aged↗
PubMed1997

The calcium channel blocker controversy in perspective.

Periodically in the history of hypertensive therapy there have been minor storms that have significantly affected the utilization of entire classes of agents. The first storm struck with the case-control studies suggesting that reserpine was associated with an increased risk of carcinoma of the breast, a claim subsequently disproved by a number of other studies. The second storm was initiated by a subanalysis of the Multiple Risk Factor Intervention Trial (MRFIT), from which it was inferred that, in a subset of hypertensive patients, diuretic treatment may have been harmful rather than beneficial. Despite this claim and other speculations, diuretics-especially at low doses-remain a gold standard of antihypertensive therapy. Recently, a third storm has developed in the field of antihypertensive therapy: a case-control study report and a non-randomized cohort study have questioned the use of calcium channel blockers in hypertension. The case-control study suffers from the limitations inherent in this study design, which often gives rise to conflicts and contradiction. In fact, another case-control study published in 1995 reached exactly the opposite conclusions and claimed that calcium channel blockers were associated with significantly less myocardial infarction than traditional antihypertensive therapy. A meta-analysis was also presented as supporting the non-randomized studies questioning the safety of calcium channel blockers. However, it refers to patients with coronary heart disease, not to patients with hypertension, and also combined studies performed with different aims, and data from short-term and long-term studies using short-acting formulations of calcium channel blockers. The controversies generated by these reports have gone well beyond their scientific merit. For final judgement we should wait for well-designed prospective studies, several of which are under way. For the time being, there is no reason to change the current practice of antihypertensive therapy, as summarized in the recommendations of both the United States Joint National Committee and the World Health Organization/International Society of Hypertension Committee, that is, diuretics and beta-blockers are among those antihypertensive agents with clearly proven benefits in mortality-morbidity studies, but calcium channel blockers as well as ACE inhibitors and alpha-blockers can also be used profitably in the treatment of hypertension.

Adrenergic beta-Antagonists↗
PubMed1997

Ambulatory and home blood pressure normality in the elderly: data from the PAMELA population.

To determine ambulatory blood pressure (BP) means and distributions in an elderly population, we studied a random sample of 800 subjects stratified by sex and representative of residents aged 65 to 74 years of the city of Monza. Participation was 50%. Measurements consisted of clinic BP (average of three measurements with mercury sphygmomanometry), home BP (average of morning and evening measurements with a semiautomatic device), and ambulatory BP (SpaceLabs 90207). Clinic BP was obtained before and after home and ambulatory BP measurements. In normotensive and untreated hypertensive subjects (n=248), clinic, home, and ambulatory BPs were significantly related (P<.001). The means of the clinic BPs obtained on consecutive days were very similar and markedly higher than 24-hour average BP (+25 mm Hg systolic and + 10 mm Hg diastolic, P<.001). Nighttime BP was markedly less than daytime BP (-14 and -13 mm Hg, P<.001), whereas home BP values occurred approximately midway between clinic and 24-hour average BP values. Only minor differences existed between data in men and women, and the differences in clinic, home, and ambulatory BP values occurred in both normotensive and untreated hypertensive subjects. All BPs were similar in the untreated and treated hypertensive groups. Thus, as previously reported in subjects younger than 65 years, in the elderly fraction of the population, 24-hour average BP is much lower than clinic BP. The upper limit of normality for 24-hour average BP (calculated as the value corresponding to 140/90 mm Hg clinic BP) is about 120 mm Hg systolic and 76 mm Hg diastolic. At variance with data from younger subjects, home BP in the elderly is higher than 24-hour average BP. However, similar to data from younger subjects, clinic, home, and ambulatory BPs are higher in treated hypertensive than normotensive elderly subjects, indicating that in hypertensive elderly subjects, antihypertensive treatment does not commonly achieve full BP control both inside and outside the clinic environment.

Age Factors↗
PubMed1997

Lack of effect of short-term lisinopril administration on left ventricular filling dynamics in hypertensive patients with diastolic dysfunction.

Arterial hypertension may be associated with altered left ventricular filling dynamics. The specific goal of this study was to evaluate whether short-term administration of the ACE inhibitor lisinopril in hypertensive patients with an altered diastolic pattern induced an improvement of left ventricular dynamics, assessed by the echocardio-Doppler technique, independently of effects on left ventricular mass. In a double-blind cross-over study 39 essential hypertensive patients with a ratio of peak early to peak atrial velocity (E/A) < 1 were randomized, after a run-in period of 2 weeks without any antihypertensive treatment, to receive lisinopril (20 mg once a day) and placebo for 4 weeks, respectively. At the end of both the run-in and the treatment periods, blood pressure and heart rate were measured and an echocardio-Doppler examination was carried out. The echocardio-Doppler evaluation was performed both at rest and at the peak of a hand-grip test (3 min at 30% of maximal strength). Left ventricular dimensions were obtained from two-dimensionally guided M-mode tracings using the criteria of the American Society of Echocardiography. Left ventricular peak filling rates and filling rate integrals were measured by a pulsed Doppler technique. Lisinopril caused a significant reduction in systolic and diastolic blood pressure at rest (-13/-9 mmHg vs baseline values, p < 0.05; -6/-4 mmHg vs placebo values, p < 0.05) and during isometric exercise (-17/-9 mmHg vs baseline period, p < 0.05; -6/-5 mmHg vs placebo, p < 0.05). Lisinopril did not induce any significant change in left ventricular structure and systolic function. All the left ventricular filling parameters considered (E velocity, A velocity, E/A ratio) both at rest and during isometric exercise did not significantly differ after lisinopril treatment when compared to those obtained in basal conditions and after placebo administration. This double-blind cross-over study demonstrates that short-term afterload reduction induced by lisinopril does not modify altered diastolic dynamics in hypertensive patients. Diastolic dysfunction of the left ventricle is a complex process influenced by a number of functional and structural factors and apparently cannot be significantly improved by short-term blood pressure reduction by antihypertensive therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

The Hypertension Optimal Treatment (HOT) Study: 24-month data on blood pressure and tolerability.

The Hypertension Optimal Treatment (HOT) Study is an ongoing prospective randomized, multicentre trial conducted in 26 countries. There are two main aims of the study. The first is to evaluate the relationship between three levels of target diastolic blood pressure (< or = 90, < or = 85 or < or = 80 mmHg) and the incidence of cardiovascular morbidity and mortality in hypertensive patients. The second is to determine the effect on morbidity and mortality of a low dose, 75 mg daily, of acetylsalicylic acid (ASA, aspirin) compared with placebo. Altogether 18,790 patients have been recruited and randomized, and two-year data are now available for all patients. This is a report on the blood pressures achieved, the tolerability, and other available data after 24 months of follow-up of all patients. Special emphasis is given to the subgroup of elderly patients (> or = 65 years, n = 5988) compared with young patients (< 65 years, n = 12 802). On average, patients in the < or = 90 mmHg diastolic blood pressure target group have reached 85 mmHg, in the < or = 85 mmHg target group patients have reached 83 mmHg and in the < or = 80 mmHg target group patients have reached 81 mmHg. The percentage of those achieving target blood pressure in each target group at 24 months of follow-up is 85% in the < or = 90 mmHg target group, 75% in the < or = 85 mmHg target group and 57% in the < or = 80 mmHg target group. In the elderly subgroup (> or = 65 years of age), the percentage of patients achieving target at 24 months is higher for all target groups, namely 89% in the < or = 90 mmHg group, 80% in the 85 mmHg group and 62% in the 80 mmHg group. Antihypertensive treatment was initiated with a calcium antagonist, felodipine, at a dose of 5 mg once daily. If target blood pressure was not reached, additional antihypertensive therapy, with either an angiotensin converting enzyme (ACE) inhibitor or a beta-adrenoceptor blocking agent, was given. Further dose adjustments were made in accordance with a set protocol. As a fifth, and final, step, a diuretic could be added. There have been relatively few side effects in this large, multinational study of hypertensive patients. Only ankle oedema and coughing exceed a frequency of 0.5% (ankle oedema 1.3% in young and 1.7% in elderly; coughing 0.5% in young and elderly). After two years, 84% of all patients are still taking their baseline therapy, felodipine. The 24-month data presented here indicate that it should be possible to fulfil the primary aims of the HOT Study.

Aged↗