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Biomedical subjects

F V Costa

Publications and source records attributed to F V Costa.

At least 19 recordsLinked to original sources

The role of losartan in cost-effective hypertension control.

Despite recent guidelines emphasising the need for aggressive treatment in patients with elevated blood pressure, the control of hypertension in Europe and the USA is poor, imposing a considerable burden in terms of patient morbidity and mortality, and associated healthcare costs. A major factor contributing to the suboptimal control of hypertension is the failure of patients to adhere to their prescribed therapy. Drug side-effects are an important cause of non-compliance and prescribing a well-tolerated agent that promotes good compliance is therefore the key to the cost-effective management of hypertension. Several studies have demonstrated that patients are more likely to remain on therapy with the angiotensin II antagonist losartan than other antihypertensives. Although the acquisition costs of new antihypertensives such as losartan are greater than for older drugs, such costs represent only a small proportion of the total cost of prescribing antihypertensive therapy. When accessory costs are also considered, the total cost of care with newer antihypertensives is comparable with those for diuretics. The costs involved if therapy has to be switched due to unacceptable side-effects also need to be taken into account when assessing relative cost effectiveness. Furthermore, savings may accrue from the non-haemodynamic benefits of losartan, such as improved cognitive function and renal protection. Further studies will increase awareness of the true cost effectiveness of antihypertensive drugs.

Antihypertensive Agents↗

Use of statins and blood pressure control in treated hypertensive patients with hypercholesterolemia.

High serum cholesterol has been frequently reported in patients with arterial hypertension in whom it might influence the blood pressure control. The aim of this study was to compare the extent of blood pressure changes in 41 patients with hypertension and hypercholesterolemia, taking antihypertensive drugs and treated for 3 months with statins (HC-S; pravastatin or simvastatin) and compared with matched controls with high (HC-D; 44) or normal serum cholesterol (NC-D; 45) undergoing antihypertensive treatment combined with dietary treatment alone. After 3 months of follow-up, a greater reduction of systolic (SBP) and diastolic (DBP) blood pressure values was observed in HC-S patients (ASBP/DBP, -11.3 +/-3/-10.6 +/- 2%) when compared with both HC-D (deltaSBP/DBP, -6.6 +/- 2/-6.1 +/- 2%; p < 0.05) and NC-D (deltaSBP/DBP, -6.9 +/- 2/-6.8 +/- 1.5%; p < 0.05). In statin-treated patients, a slight linear relation has been found between the percentage changes in DBP and those in plasma total cholesterol (R = 0.37, p = 0.043), whereas no relation was found with SBP changes (R =0.11; p = 0.35). In conclusion, the results of this study demonstrate that the use of statins in combination with antihypertensive drugs can improve blood pressure control in patients with uncontrolled hypertension and high serum cholesterol levels. The additional blood pressure reduction observed in patients treated with statins is clinically relevant and only partially related to the lipid-lowering effect.

Adult↗

Cost-effectiveness calculations from trials.

EFFECTIVENESS OF ANTIHYPERTENSIVE THERAPY: Data on the effectiveness of antihypertensive therapy derived from the results of large clinical trials are of great importance, but also have a number of significant flaws and probably underestimate the real effectiveness of treatment. In the next few years much more information is likely to become available on the effects of the newer classes of drugs and thus evaluations of cost-effectiveness will have fewer limitations than at present. ECONOMIC VALUE OF SAVING A LIFE: Today, in every country worldwide, priority should be given to determining the economic cost of avoiding the morbidity and mortality caused by hypertension. Each society must decide the price per life-year gained that it is willing to pay. This is the most difficult task of all, since the economic value of saving a life is not easily evaluable.

Antihypertensive Agents↗

Low dose of ACE-inhibitor enhances sodium excretion in volume expanded patients with borderline hypertension.

The purpose of the present study was to separately investigate the effects of two different dosages of captopril on pressor, vascular and humoral response to acute extracellular volume expansion in patients with borderline hypertension (BHT). Thirty-five patients were randomly allocated in two groups undergoing acute saline infusion (0.40 ml/min/kg for 45 min and 0.15 ml/min/kg for 75 min)before and after a 7-day period of treatment with either placebo or captopril at the dose of 12.5 (LD-CAP) or 50 mg (HD-CAP) twice a day. At baseline the effects of LD-CAP were limited to an increase in PRA and to a decrease in plasma aldosterone whereas HD-CAP decreased systolic and diastolic blood pressure (SBP, DBP), forearm vascular resistance (FVR) and increased venous distensibility (VV(30)) as well. After saline loading patients treated with HD-CAP showed an increase in SBP, DBP not observed in patients allocated to LD-CAP. Urinary sodium excretion in response to NaCl loading was selectively enhanced by LD-CAP (+25%) whereas HD-CAP did not (+6.3%). The present data suggest that low-doses of ACE-inhibitors acting through a selective blockade of RAA not associated with hemodynamic changes can enhance the natriuretic response to acute volume expansion in borderline hypertensives.

Adult↗

Factors associated with the development of stable hypertension in young borderline hypertensives.

OBJECTIVES: To identify factors predisposing subjects to the development of stable hypertension and to estimate their relative importance in 70 young patients with borderline hypertension monitored for 10 years. DESIGN: Longitudinal evaluation of the incidence of stable hypertension [diastolic blood pressure (DBP) > 95 mmHg]. METHODS: Patients were examined at baseline by determination of resting blood pressure, intracellular sodium level and individual pressor response to mental arithmetic and to intravenous saline loading. They were re-examined after 10 years to assess the prevalence of established hypertension and the importance of some prognostic variables identified prospectively (age, sex, intracellular sodium level, baseline blood pressure, pressor response to stress and acute salt-sensitivity). RESULTS: The prevalence of sustained hypertension (DBP > 95 mmHg) was 35.8% after 10 years of follow-up study. Subjects developing hypertension were older (26.9 +/- 1.3 versus 21.0 +/- 1.8 years) and showed a higher percentage of family history of hypertension (92 versus 64%) and of acute salt-sensitivity (72 versus 53%). The pressor response to mental arithmetic was greater in patients who developed hypertension (systolic blood pressure 26.9 +/- 1 versus 22.7 +/- 0.9 mmHg, P = 0.005 DBP = 16.6 +/- 0.8 versus 13.1 +/- 0.7 mmHg, P = 0.005), who also showed higher levels of intracellular sodium (30.7 +/- 0.6 versus 27.3 +/- 0.5 mmol/kg, P = 0.001). The same variables were found to be related to the development of hypertension in a multivariate analysis and the concomitant presence of 4-5 risk factors was associated with a reasonable predictive power for the identification of patients at high risk (sensitivity 72%, specificity 67%, predictive accuracy 76%). CONCLUSIONS: The present study demonstrates that borderline hypertensives at high risk of stable hypertension can be identified by the concomitant evaluation of some clinical and cellular characteristics directly related to long-term development of high blood pressure.

Adult↗

[Problems in the treatment of arterial hypertension].

During the last 20 years antihypertensive treatment has given excellent results in terms of prevention of cardiovascular complications. However these results, for some reasons, are less satisfactory than those theoretically possible. The problems we need to solve are many and all contribute to reduce the efficacy of therapy. First of all it is necessary to make a correct diagnosis of hypertension to avoid treating normotensive subjects. The use of continuous ambulatory blood pressure monitoring in some cases can be useful to clarify these situations and also to better evaluate the efficacy of therapeutic regimens. In the vast majority of cases, however, the traditional blood pressure recordings, if correctly performed, can give satisfactory and sufficient information. After a correct diagnosis is made the physician must start with the patient an open-minded cooperation based on confidence. He must clearly explain the goals and the methods of therapy and encourage, instead of frighten, the patient. The next step is the choice of the kind of treatment in which many factors must be kept in mind and in which the physician must have a deep knowledge of the patient and of the drugs. Treatment has a high probability rate of a good patient's compliance only if it does not cause adverse reactions and if the therapeutic scheme is simple. Studies on compliance have shown that it is possible to identify those patients at risk of low compliance even before the beginning of therapy and it has been shown that adverse reactions especially if the patient has not been informed by the doctor, can cause a dramatic fall in compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗

Relationship between acute suppression of plasma renin activity and lymphocyte Na+:H+ exchange rate in young patients with borderline hypertension.

The participation of the cellular sodium content and renin-angiotensin-aldosterone system in the development of high blood pressure has been frequently suggested. To elucidate the role of a mechanism responsible for renal sodium reabsorption on the time-course of renin suppression, 16 young borderline hypertensive patients were studied by analyzing the relationship between the level of baseline activation of lymphocyte Na+:H+ exchange and the degree of plasma renin activity (PRA) suppression in response to saline loading. In the whole hypertensive population, a significant correlation (R = 0.64; p < 0.01) was found between the lymphocyte Na+:H+ exchange activity and the percentage degree of PRA suppression induced by saline loading. Urinary sodium excretion was enhanced in patients with lesser activation of lymphocyte Na+:H+ exchange and greater PRA suppression (3.5 +/- 5 vs. 2.4 +/- .1 umol/min/kg; p < 0.05). These findings suggest that a mechanism influencing renal sodium reabsorption as Na+:H+ exchange could also affect the control of plasma renin activity, and concur with the development of salt-sensitive high blood pressure.

Adult↗

Atrial natriuretic factor response to acute volume expansion in borderline hypertension. Role of ACE-inhibition and changes in peripheral venous tone.

Abnormalities in the response of atrial natriuretic factor (ANF) to volume expansion have been reported in hypertensive-prone animals and men as well as in hypertensive patients undergoing ACE-inhibition. To investigate some of the mechanisms affecting ANF release in borderline hypertensive patients (BHT) we have studied 16 subjects by assessing their neuro-humoral and hemodynamic response to a two-hour isotonic i.v. NaCl infusion carried out during short-term administration of either placebo or captopril. ACE-inhibition increased baseline venous distensibility (VV30:1.4 vs 1.6 ml/100 ml; p < .05) and reduced the prompt (45') ANF response to saline loading (10.3 +/- 13 vs 42.7 +/- 15%; p < .05)) without affecting the overall ANF release (120':92 +/- 25 vs 65.8 +/- 20%; NS)). A significant pressor increase in response to NaCl loading was observed exclusively after ACE-inhibition (SBP: 5.2 +/- 2 vs 2.4 +/- 1%; p < .05--DBP: 7.1 +/- 3 vs 2 +/- 3%; p < .025) and occurred along with a peripheral arterial and venous constriction and with an increase in plasma levels of an endogeneous Na+/K+ATPase inhibitor (8.8 +/- 4 vs -2 +/- 4%; p < .05). We conclude that the ANF response to saline infusion is delayed by ACE-inhibition in borderline hypertensives. The abnormalities observed in ANF response could follow the changes in peripheral venous distensibility and contribute to the pressor and neuro-humoral derangements described in borderline hypertensives during volume expansion.

Adolescent↗

Factors associated with acute salt-sensitivity in borderline hypertensive patients.

The acute sensitivity to sodium loading has been investigated in 26 borderline hypertensive patients (BHT) undergoing acute i.v. NaCl infusion. Measurements included blood pressure (BP), forearm vascular resistance (FVR) and venous distensibility (VV30), plasma renin activity (PRA), plasma aldosterone, plasma atrial natriuretic factor (ANF), and plasma levels of endogenous Na+/K+ATPase inhibitor. Sodium loading was associated with a greater than 8% increase in mean BP in 12 patients defined as salt-sensitive (NaCl-SENS) in comparison to salt-insensitive (NaCl-INSENS) subset. NaCl-SENS patients in comparison to NaCl-INSENS exhibited 1) a greater baseline VV30 (2.1 vs 1.4 ml/100 ml; p less than .005), and a response to saline characterized by 2) increased FVR (21.4 vs -6.5%; p less than .005), 3) blunted PRA suppression (-42 vs -67%; p less than .05), 4) delayed ANF response and 5) release of a Na+/K+ATPase inhibitor. Post-loading cumulative urinary sodium excretion was reduced in NaCl-SENS borderline hypertensives compared to NaCl-INSENS (2.6 vs 3.8 mumol/min/Kg; p less than .05). We conclude that acute salt-sensitivity in BHT is characterized by a blunted hormonal response to sodium loading which could be responsible of the activation of hemodynamic as well as humoral mechanisms leading to progressive blood pressure increase.

Adult↗

Atrial natriuretic factor modulates the plasma levels of a Na+/K+ATPase inhibitor in volume expanded borderline hypertensives.

To evaluate the existence of a relationship between atrial natriuretic factor (ANF) and plasma Na+/K+ATPase inhibitory activity in humans, we examined the hemodynamic and humoral response to volume expansion in 41 borderline hypertensive patients (BHT) with either normal (n = 33) or low plasma renin activity (n = 8). The study was carried out by measuring blood pressure, forearm circulation, plasma renin activity (PRA), ANF, and plasma levels of an endogenous Na+/K+ATPase inhibitor before and after 2 h of acute intravenous NaCl infusion (0.22 mL/min/kg bodyweight). The early (45 min) changes of ANF and those of Na+/K+ATPase inhibitory activity attained at the end of saline infusion were inversely related in BHT with normal PRA and directly related in the low-PRA population (r = 0.64). The time-course of ANF response to sodium loading was significantly delayed in BHT characterized by normal venous distensibility. They also showed a greater increase in plasma Na+/K+ATPase inhibitory activity occurring with an hypertensive, vasoconstrictive, and sodium retaining response as well. We conclude that in normal PRA borderline hypertensives, ANF may modulate the release of a plasma Na+/K+ATPase inhibitor in a setting where extracellular volume is acutely expanded. Our findings also suggest that dissimilarities in peripheral venous distensibility are able to influence the time-course of ANF response. The blunted ANF increase observed in response to NaCl loading in a subset of BHT could represent an early marker of the attitude of such patients to develop high blood pressure leading to the release of a Na(+)-pump inhibitor and influencing individual salt-sensitivity.

Adult↗

Pattern of peripheral venous response to volume expansion in borderline systemic hypertension.

An increased venous tone responsible for changes in systemic hemodynamics has been described in borderline hypertensive patients along with the release, in response to intravenous sodium chloride, of an endogenous sodium ion/potassium ion adenosine triphosphatase (Na+/K+ ATPase) inhibitor with vasoconstrictive properties. The hemodynamic and humoral effects of a 2-hour intravenous saline infusion were studied in 25 borderline hypertensives characterized on the basis of their forearm venous distensibility (VV30) in normal (n = 15) and low (n = 10) VV30. VV30 was slightly reduced by saline in the entire hypertensive group (1.47 vs 1.36 ml/100 ml; p less than 0.05), whereas blood pressure and plasma Na+/K+ ATPase inhibitor were unchanged. Normal VV30 showed a sudden increase in plasma Na+/K+ ATPase inhibitor in response to saline associated with an increase in blood pressure, a forearm arterial and venous constriction, and a sluggish suppression in plasma renin activity, whereas low VV30 exhibited a completely opposite pattern. The changes in plasma Na+/K+ ATPase inhibitor inversely correlated to VV30 decreases in borderline hypertensives with normal VV30 (r = -0.49; p less than 0.05), whereas they did not in all hypertensive patients. Atrial natriuretic peptide response to saline infusion was delayed in normal VV30 and inversely related to the changes in Na/K+ ATPase inhibitory activity (r = -42; p less than 0.05) attained after 2 hours of infusion in the entire hypertensive population. Results of this study suggest the ability of acute volume expansion to reduce peripheral venous distensibility in borderline hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Purification of a Na+/K+ ATPase inhibitor from borderline hypertensives' plasma.

Increasing experimental evidences suggest an involvement of an endogenous Na+/K+ ATPase inhibitor in regulating water and electrolytes balance as well as in the pathogenesis of hypertension. However, conflicting results on the nature and the chemical structure of this substance still make it difficult to understand exactly its physiological mechanism of action. In the present study an attempt was made to purify a Na+/K+ ATPase inhibitor from hypertensives' plasma by solid phase extraction followed by 2 HPLC steps using reverse and normal phase columns. The fractions, from both columns, were able to inhibit Na+/K+ ATPase, 3H-ouabain binding to enzyme, ouabain sensitive 86Rb uptake and pNPPase activity in a manner not affected by boiling. Ultrafiltration experiments demonstrate that inhibitory activity is largely due to a low-molecular weight substance. These findings seem to confirm the presence in hypertensives plasma of a Na+/K+ ATPase inhibitor with some similarities with ouabain.

Chromatography, High Pressure Liquid↗

Captopril improves hemodynamic response to static exercise in patients with congestive heart failure: a double-blind, placebo-controlled, randomized trial.

Systemic and peripheral hemodynamic response to isometric exercise by handgrip test at 30% maximal voluntary contraction (MVC) for 3 minutes was assessed in 16 patients with congestive heart failure (CHF) after short-term treatment with either captopril or placebo given according to a double-blind, randomized, cross-over sequence. During placebo, isometric exercise increased blood pressure (BP) and total peripheral vascular resistance (TPVR) and decreased cardiac index (CI). Captopril reduced the pressor response to exercise (mean +/- SD) (% systolic: from 14.7 +/- 6 to 11.7 +/- 3; p less than .05/% diastolic: from 12.4 +/- 4 to 8 +/- 3; p less than .005) and increased CI (from 2.3 +/- .6 to 2.6 +/- .9 liters/min/m2; p less than .01) whereas TPVR remained virtually unchanged (from 1479 +/- 597 to 1594 +/- 692 U; NS). The changes in mean BP after exercise were inversely related to the early increase in forearm blood flow (FBF) in exercising forearm during both placebo (r = .67) and captopril (r = .71). The extent of reduction in mean BP response after captopril was inversely related to the extra increase in exercising FBF determined by the drug when compared to placebo (r = .73). We conclude that captopril is able to improve the hemodynamic response to static exercise in patients with CHF, probably by increasing the blood supply to exercising muscles during contraction, thus blunting the extent of reflex pressor response.

Blood Pressure↗

Hemodynamic and humoral effects of chronic antihypertensive treatment with fenquizone: importance of aldosterone response.

The effects of 1-year antihypertensive treatment with the diuretic fenquizone were evaluated in 16 patients with mild essential hypertension. During treatment with placebo, after 2, 4, 24, and 52 weeks of treatment we measured blood pressure, heart rate, forearm blood flow (FBF) and vascular resistance (FVR) at rest and after 10 minutes ischemia, and forearm venous distensibility. Subjects whose diastolic blood pressure after fenquizone was reduced at least 10% were classified as responders. On this basis, 56% of patients after 1 month and 68% after 1 year responded to fenquizone. Responders, in comparison to nonresponders, were characterized by a greater increase in FBF and a greater decrease in FVR. The reduction in diastolic blood pressure was significantly related to the fall in FVR whereas no correlation was found between blood pressure and venous compliance changes. Nonresponders had a PRA increase similar to that observed in responders but they showed a much greater increase in aldosterone, whose changes were inversely related to modifications of both FVR and blood pressure. Our results demonstrate that chronic therapy with fenquizone causes a reduction of FVR, and that nonresponders have an exaggerated rise in aldosterone. This observation further reinforces the hypothesis that factors influencing the secretion of aldosterone are important determinants of the antihypertensive mechanism of diuretics.

Adult↗

Short-term plasma renin activity suppression by saline and release of a plasma endogenous Na/K ATPase inhibitor in essential hypertension.

The present study was conducted in 15 essential hypertensives to evaluate the modifications of plasma levels of an endogenous Na/K ATPase inhibitor, blood pressure, forearm hemodynamics and plasma renin activity (PRA) elicited by an intravenous saline infusion (0.9% NaCl at the mean rate of 0.22 mL/min/kg body weight for 2 h). The response to saline was determined in the whole hypertensive population as well as in two subgroups of patients classified according to their rate of PRA suppression in response to volume expansion by comparison with normotensive controls (Normal- and Low-suppressors: N-S, L-S). Over the whole group of hypertensive patients, NaCl load provoked an increase in Na/K ATPase inhibitory activity, measured by enzyme-coupled assay, which was linearly related to PRA decline (r = 0.73) and to the increase in mean blood pressure (r = 0.57). These effects were clearly enhanced by considering L-S patients alone. Urinary Na/K ratio after saline infusion was significantly higher in L-S as result of a lesser potassium excretion in this subgroup. Our results support the hypothesis that acute volume expansion with saline causes an increase in plasma levels of an endogenous sodium pump inhibitor with hemodynamic effects and whose release is related to the individual handling of infused fluids and to the degree of renin-angiotensin-aldosterone suppression.

Adult↗

Alarm reaction and serum K+ in hypertensive patients.

The effect of serum K+ of the alarm reaction induced by the participation to an experimental noninvasive study was evaluated in 35 subjects with borderline hypertension and in 18 essential hypertensives. A group of 44 inpatients undergoing routine blood sampling served as a control. Serum K+, blood pressure and heart rate were measured before (casual) and after (baseline) 20 min of rest in the recumbent position. Baseline serum K+ values were significantly higher than casual values in patients participating to the experimental protocol while no change was observed in inpatients undergoing routine blood sampling. The increase in serum K+ induced by relaxation was significantly related to heart rate decrease (r = 0.73). After relaxation 75% of patients had an increase in serum K+ with a change greater than 10% in about 35% of patients. In a subgroup of patients who repeated the same test three times, the alarm reaction was still evident and not reproducible within each patient. These data suggest that when potassium levels are measured in outpatients undergoing diagnostic or experimental procedures falsely reduced levels can be found in a large proportion of subjects.

Adult↗