Showing papers by "Luis M. Ruilope published in 2001"

Renal Function and Intensive Lowering of Blood Pressure in Hypertensive Participants of the Hypertension Optimal Treatment (HOT) Study

Abstract: This article reports further analyses of the Hypertension Optimal Treatment (HOT) Study data with the aim to describe (1) the value of baseline serum creatinine and its clearance (estimated by Cockroft and Gault formula) as predictors of cardiovascular events, (2) the effects of intensive lowering of BP on cardiovascular events and renal function in patients with reduced renal function, and (3) the effects on cardiovascular events of adding acetylsalicylic acid to antihypertensive therapy in patients with reduced renal function. The results show that (1) baseline elevation in serum creatinine and a reduction in estimated creatinine clearance are powerful predictors of cardiovascular events and death. (2) Reduced renal function at baseline did not preclude the desired control of BP. In contrast to patients with normal renal function, the incidence of major cardiovascular events did not differ in the three groups of patients with mild renal insufficiency randomized to different diastolic BP targets. No significant changes in serum creatinine were seen at the end of the 3.8-yr treatment period in the great majority of patients. However, there was a small group of patients (0.58% of the total study population) whose renal function deteriorated (increase > or =30% over baseline and final serum creatinine concentration > or =2 mg/dl) despite satisfactory reduction of diastolic BP. (3) The results of this reanalysis of the HOT Study suggest though do not prove that the association of acetylsalicylic acid with intensive antihypertensive therapy offers additional benefit in hypertensive patients with reduced renal function.

The relevance of tissue angiotensin-converting enzyme: Manifestations in mechanistic and endpoint data

Abstract: Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal diseases. Endothelial dysfunction, in response to a number of risk factors or injury such as hypertension, diabetes mellitus, hypercholesteremia, and cigarette smoking, disrupts the balance of vasodilation and vasoconstriction, vascular smooth muscle cell growth, the inflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have deleterious effects on the heart, vasculature, and the kidneys. The imbalance resulting from increased local formation of angiotensin II and increased bradykinin degradation favors cardiovascular disease. Indeed, ACE inhibitors effectively reduce high blood pressure and exert cardio- and renoprotective actions. Recent evidence suggests that a principal target of ACE inhibitor action is at the tissue sites. Pharmacokinetic properties of various ACE inhibitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensives (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the significance of these drug differences and their impact on clinical events.

Effects of individual risk factors on the incidence of cardiovascular events in the treated hypertensive patients of the Hypertension Optimal Treatment Study

Abstract: BackgroundThe Hypertension Optimal Treatment (HOT) Study has provided information about cardiovascular events in 18 790 hypertensives, subjected to pronounced blood pressure (BP) lowering for a mean of 3.8 years. The HOT study data have subsequently been analysed after stratification of the patients

A random comparison of fosinopril and nifedipine GITS in patients with primary renal disease

Abstract: Objective To investigate in a random comparison the capacity of an angiotensin converting enzyme inhibitor (fosinopril), and that of a long-acting dihydropiridine (nifedipine GITS) to modify the decay in renal function in patients with primary renal disease, exhibiting a progressive increase in seru

Hyperuricemia and renal function

Abstract: Increased serum urate concentration is commonly seen in clinical practice. It does not represent a specific disease, nor is it an indication for therapy. Hyperuricemia can be the consequence of increased uric acid production and/or decreased renal capacity to excrete uric acid. In essential hypertension, it has been described in up to one third of patients and is directly related to an increase in renal vascular resistance and inversely correlated with renal plasma flow. In other words, abnormal renal hemodynamics, commonly seen in the initial stages of the disease, account for the increased serum urate concentration. This can be maintained if a decrease in glomerular filtration rate takes place. The increase in uric acid has been shown to be a potent predictor of the development of cardiovascular events and death. In addition, uric acid, particularly when elevated, could represent an independent risk factor. On the other hand, an altered renal function predicts in an independent manner a higher cardiovascular risk. For this reason, the predictive capacity of uric acid could be partly dependent on the fact that hyperuricemia runs in parallel with a deranged renal function.

Atorvastatin prevents glomerulosclerosis and renal endothelial dysfunction in hypercholesterolaemic rabbits.

Abstract: Background. Numerous studies have shown that elevated plasma cholesterol can exacerbate renal disease. However, the effect of lipids on renal structure and vascular function in normal kidneys is less well established. Therefore, the aim of this study was to evaluate the impact of hypercholesterolaemia on glomerular structure and vascular reactivity of segmental arteries in rabbits. In addition, we also studied whether or not atorvastatin can prevent these structural and vascular alterations in hypercholesterolaemic rabbits. Methods. Male New Zealand rabbits were fed either a normal rabbit chow or a diet containing 1% cholesterol and treated or not with atorvastatin (1 mg/kg/ day) for 12 weeks. Dose--response curves to acetylcholine (10 -9 -10 -4 mol/l) and sodium nitroprusside (10 -9 -10 -4 mol/l) were studied in segmental arteries in the presence or absence of the thromboxane A 2 /PGH 2 receptor antagonist ifetroban (10 -5 mol/l). Glomerular size and structure were also evaluated. Results. Compared with control animals, hypercholesterolaemic rabbits presented glomerular hypertrophy and several types of injuries (capillary collapse, hyalinosis and alterations of Bowman's capsule), suggesting diffuse glomerulosclerosis. Segmental arteries also showed relaxing responses to acetylcholine and sodium nitroprusside which were lower than and similar to, respectively, those of control animals. The presence of ifetroban improved the acetylcholine response only in hypercholesterolaemic rabbits. Atorvastatin treatment prevented vascular and most glomerular changes associated with hypercholesterolaemia even in the presence of very high cholesterol levels. Conclusions. Atorvastatin exerts a protective effect on renal damage associated with hypercholesterolaemia even in the presence of deleterious levels of plasma cholesterol.

Effect of losartan on TGF‐β1 and urinary albumin excretion in patients with type 2 diabetes mellitus and microalbuminuria

Abstract: Background. The aim of the present study was to determine the effect of losartan on transforming growth factor-β1 (TGF-β1) plasma levels and urinary albumin excretion (UAE) in patients with type 2 diabetes mellitus, mild hypertension and microalbuminuria. Methods. Fourteen patients (eight males, aged 55 ± 6 years) with type 2 diabetes mellitus, mild arterial hypertension and microalbuminuria, participating in an open, uncontrolled, pilot study were included. Patients were treated for 8 weeks with losartan. TGF-β1 plasma levels, UAE and 24-h blood pressure monitoring were determined at baseline and at 4 and 8 weeks. Results. At 4 and 8 weeks of treatment, a reduction was observed in TGF-β1 plasma levels (5.5 ± 4.5 vs 2.0 ± 0.6 and 2.6 ± 1.0 ng/ml, P<0.005), UAE (96 ± 65 vs 59 ± 59 and 64 ± 47 μg/min, P<0.01), 24-h systolic blood pressure (136 ± 9 vs 129 ± 9 and 130 ± 10 mmHg, P<0.01) and 24-h diastolic blood pressure (77 ± 9 vs 74 ± 8 and 74 ± 7 mmHg, P<0.03). Stratifying the patients by baseline TGF-β1, seven had TGF-β1 plasma values higher than normal controls. At 4 and 8 weeks, they showed a marked reduction in TGF-β1 values (9.0 ± 3.9 to 2.1 ± 0.7 and 2.5 ± 0.7 ng/ml, P<0.01) and UAE (106 ± 83 to 49 ± 42 and 38 ± 26 μg/min, P<0.05), with good correlation between the percentage reduction of both parameters (r=0.83, P<0.01). The remaining seven patients, with normal baseline TGF-β1 plasma levels, showed no change in TGF-β1 plasma levels and UAE after treatment. Conclusion. Treatment with losartan decreases TGF-β 1 plasma values and UAE in type 2 diabetes mellitus patients with high baseline TGF-β1 levels, suggesting that TGF-β1 may be a marker to detect patients who may particularly benefit from renin-angiotensin system blockade.

Eprosartan versus enalapril in elderly patients with hypertension: a double-blind, randomized trial.

Abstract: Aim : To compare the efficacy and safety of eprosartan and enalapril to lower systolic blood pressure in elderly patients with essential hypertension. Methods : 334 patients >65 years with sitting systolic blood pressure (sitSBP) S 160 mmHg and diastolic blood pressure (sitDBP) 90–114 mmHg were randomized to 12 weeks of double-blind treatment with eprosartan, 600–800 mg once daily (o.d.) or enalapril (5–20 mg o.d.), with flexible dose titration to lower systolic blood pressure below 140 mmHg. The primary outcome measure was change in sitSBP at endpoint. Results : Least-squares mean changes from baseline in sitSBP were–18.0 and–17.4 mmHg in the eprosartan and enalapril groups, respectively (difference eprosartan– enalapril–0.6, 95% confidence interval, CI,–4.1 to 3.0, p = 0.76). The corresponding figures for sitDBP were–9.4 and–9.6 mmHg (difference eprosartan–enalapril 0.2, 95% CI–1.7 to 2.0, p = 0.84). Normalization and response rates were also similar in the two groups. Adverse events were recorded in...

Diabetes and hypertension.

Abstract: The incidence of hypertension is increased in individuals with diabetes mellitus. This is especially true in patients with type 2 diabetes. In these patients high blood pressure is common at the time of diagnosis of diabetes, but the development of diabetes is often preceded by a period during which hyperinsulinemia and insulin resistance is already present. Diabetes represents by itself a major risk of cardiovascular morbidity and mortality. This risk is considerably enhanced by the co-existence of hypertension. One of the main complications of type 2 diabetes is nephropathy, which manifests initially by microalbuminuria, then by clinical proteinuria, leading to a progressive chronic renal failure and end-stage renal disease. Microalbuminuria is considered today as an indicator of renal endothelial dysfunction as well as an independent predictor of the cardiovascular risk. During recent years a number of studies have shown that tight blood pressure control is essential in diabetic patients in order to provide maximal protection against cardiovascular events and the deterioration of renal function. Of note, there is recent evidence indicating that blockade of the renin-angiotensin system with angiotensin II antagonists has marked nephroprotective effects in patients with hypertension and type 2 diabetes, both at early and late stages of renal disease.

Blood pressure control and benefits of antihypertensive therapy: does it make a difference which agents we use?

Abstract: — — This article debates the important question of whether blood pressure lowering alone is responsible for the benefits accrued from antihypertensive therapy as demonstrated in many multicenter randomized clinical trials with different antihypertensive agents or whether there is evidence that some agents have special properties that result in benefits that go beyond those resulting from lowering blood pressure. Over the past ≥30 years, it has been demonstrated beyond any doubt that lowering blood pressure in severe forms of hypertension, and more recently in systolic and even mild hypertension, will result in reduced incidence of stroke and slower progression of heart and renal failure. These effects have been easier to demonstrate in sicker patients, because enough end points may be counted in the 3 to 5 years that these clinical trials last. However, risk attributable to high blood pressure comes, to a greater degree, from the much larger group of hypertensive individuals who have less severe forms of hypertension. Blood pressure lowering offers less protection from coronary heart disease, which is highly prevalent in hypertensive patients, than from stroke. With the introduction of agents such as renin-angiotensin system inhibitors or calcium channel blockers, it has been demonstrated that hypertensive vascular remodeling and endothelial dysfunction may be corrected. It has therefore been suggested that benefits beyond blood pressure lowering may be achieved with the use of specific drugs to lower blood pressure. Although some evidence suggests that this may be the case, it is difficult to extrapolate from mechanistic studies to prevention of hard end points in outcome trials and vice versa. The question remains for the time being largely unanswered.

ACE Inhibitors and Appearance of Renal Events in Hypertensive Nephrosclerosis

Abstract: Nephrosclerosis constitutes a major cause of end-stage renal disease. Independently of blood pressure control, ACE inhibitors (ACEIs) are considered to be more nephroprotective than other antihypertensive agents. We have reviewed the long-term evolution of renal function in our series of essential hypertensive patients diagnosed as having nephrosclerosis when first seen in our unit. The analysis was performed depending on whether or not their antihypertensive therapy contained an ACEI alone or in combination for the whole follow-up. The end point was defined as the confirmation of a 50% reduction in creatinine clearance or entry in a dialysis program. A historical cohort of 295 patients was included in the analysis. Mean follow-up was 7.4+/-3.9 years. Diabetes prevalence was higher in ACEI-treated patients (25.7% versus 7.1%, P=0.000), but the diagnosis of diabetic nephropathy could not be confirmed on clinical grounds, including renal biopsy. Twenty-three out of 183 (12.6%) patients in the ACEI group and 23 out of 112 (20.5%) patients in the non-ACEI group experienced a renal event (P=0.0104 by log rank test). Similar results were observed when only nondiabetic patients were considered for the analysis. Cox regression analysis showed that baseline serum creatinine, absence of ACEI administration, mean proteinuria during follow-up, and age were independent predictors for the development of a renal event. In hypertensive nephrosclerosis, therapy containing an ACEI alone or in combination significantly reduces the incidence of renal events. This effect is independent of blood pressure control.

Relevance of endothelium-derived hyperpolarizing factor in the effects of hypertension on rat coronary relaxations.

Abstract: Objectives To evaluate the relative participation of nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and prostanoids in the relaxing responses induced by acetylcholine and isoproterenol in isolated coronary arteries from adult Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Design and methods Male adult WKY rats and SHR were used in the study. Segments from left coronary arteries (approximately 350-380 pm internal diameter and 2 mm long) were mounted in an isometric myograph and pre-contracted with serotonin. Dose-response curves to acetylcholine and isoproterenol were carried out in absence and presence of the NO synthesis inhibitor N G -nitro-L-arginine methyl ester (LNAME), the inhibitor of the cyclo-oxygenase, indomethacin and KCI. Areas under the respective dose-response curves were used to calculate the approximate relative participation of NO, EDHF and prostanoids. Results Relaxations to either acetylcholine or isoproterenol were lower in SHR than in WKY rats. In WKY rats, presence of LNAME diminished (P< 0.05) relaxation to acetylcholine from 10 -9 to 10 -6 mol/l, and induced a contracting response at 10 -5 and 10 -4 mol/I of acetylcholine. Addition of indomethacin did not significantly affect dose-related relaxation to acetylcholine 10 -9 to 10 -6 mol/I in WKY rats, and reduced (P< 0.05) the contracting response observed at 10 -5 mol/I of acetylcholine. In SHR, addition of LNAME markedly reduced (P< 0.05) acetylcholine relaxations, but did not produce any contracting effect. Addition of indomethacin on top of LNAME slightly (P< 0.05) enhanced relaxing response to acetylcholine in SHR. Presence of LNAME in the media diminished (P< 0.05) relaxation to isoproterenol in both WKY rats and SHR. Addition of indomethacin on top of LNAME increased (P< 0.05) isoproterenol-relaxing response to levels similar to and higher than control conditions in WKY rats and SHR, respectively. Addition of KCI blunted both acetylcholine- and isoproterenol-relaxations in both groups. Conclusions NO and EDHF are the main endothelium-derived relaxing factors underlying acetylcholine and isoproterenol relaxations in rat coronary arteries, respectively. EDHF reduction, and not only NO reduction play a key role in the diminished coronary relaxations induced by acetylcholine and isoproterenol in SHR. An arachidonic acid derivative with contracting activity released by acetylcholine and isoproterenol in a differential manner, could oppose the relaxing actions of NO and EDHF.

Differential Effect of Chronic Antihypertensive Treatment on Vascular Smooth Muscle Cell Phenotype in Spontaneously Hypertensive Rats

Abstract: —The aim of this study was to investigate the effect of chronic losartan or captopril on vascular smooth muscle cell (VSMC) phenotype and vascular function in spontaneously hypertensive rats. Male 12-week-old rats were treated for 16 weeks with losartan (15 mg/kg per day) or captopril (60 mg/kg per day) in their drinking water. Systolic blood pressure, measured by the tail-cuff method, was reduced ≈40 mm Hg in both treatment groups compared with a nontreated control group. Cell structure and proliferation studies were performed in VSMCs obtained from rat carotid arteries. Cells from the losartan-treated group showed a significant reduction in size, total protein content, and nucleus number, as well as proliferation after stimulation with 10% fetal calf serum and an increased percentage of cells in the G 1 phase compared with the control and captopril-treated groups. Functional studies were performed in isolated carotid arteries from these groups. Contractions elicited by 75 mmol/L KCl or 10 − 7 mol/L norepinephrine and relaxations elicited by acetylcholine were similar in all groups. Concentration-response curves to angiotensin I or angiotensin II (10 − 10 to 3×10 − 7 mol/L) were almost abolished in the losartan-treated group and were not modified by preincubation with the angiotensin type 2 receptor antagonist PD 123,319. These results suggest that long-term losartan treatment significantly changes VSMC phenotype and proliferative status, apparently unrelated to blood pressure lowering or to endothelial function improvements.

The kidney in arterial hypertension

Abstract: The kidney facilitates the development of arterial hypertension and suffers its consequences. Once renal damage is clinically manifested, a clear increase in cardiovascular risk appears. The coincidence of renal and cardiovascular damage strengthens the need for therapies attempting the simultaneous protection of both the kidney and the cardiovascular system.

Renal participation in cardiovascular risk in essential hypertension.

Abstract: The possibility that the kidney plays a relevant role in the origin of essential hypertension in humans has been amply debated [1–3]. However, it has also been shown that the kidney suffers the consequences of sustained elevated blood pressure in the absence of therapy [4]. Nephrosclerosis together with diabetic nephropathy are the most common causes of end-stage renal disease [5]. A review of the literature published in the last decade transmits the picture that, with an "adequate" blood pressure control with standard antihypertensive therapy, the kidney is well protected and very few patients will suffer the consequences of blood pressure increments [6, 7]. The aim of this short review is to present the evidence supporting the existence of mild renal insufficiency in hypertensive patients, but also to show the association of this disorder with a very significant increment in global cardiovascular risk.

Relationship between severity of essential arterial hypertension and the prevalence hyperuricemia

Abstract: BACKGROUND: Hyperuricemia has been associated with an increased risk of cardiovascular disease in hypertensive patients. However, the relation between serum urate and severity of hypertension has not been conclusively defined as yet. We aimed at finding out whether there exists an independent relationship between changes in the prevalence of hyperuricemia and severity of hypertension. PATIENTS AND METHOD: We studied 3 cohorts of patients aged 35 to 60 years with essential hypertension diagnosed at a university hospital in Madrid, Spain. The first cohort (before 1981) included 325 patients, the second (from 1981 to 1989) comprised 271 patients and the third cohort (from 1990 to 1999) included 545 patients. Disease severity ranged from 1 to 6 according to blood pressure levels at diagnosis (WHO/ISH grades 1, 2 or 3 were assigned 1, 2 or 3 points, respectively) and target organ damage (left ventricular hypertrophy, hypertensive retinal vascular changes, and proteinuria above 300 mg/day; one point each). RESULTS: Mean serum urate concentrations in the 3 cohorts were 6.6, 5.8 and 5.5 mg/dL, respectively (p 7.0 mg/dL whereas only 18.1% patients in the third group showed hyperuricemia (difference: 20.9%; 95% CI, 10.1 to 32.3; p < 0.05). Severity of hypertension was higher in the first cohort (mean SD, 2.50 1.31 points) than in the third group (1.96 1.06 points; p < 0.05), with the second cohort showing an intermediate severity (2.23 1.01 points). Serum urate levels were directly related to the severity of hypertension in the 3 groups (r = 0.08, p < 0.05). In a multivariate analysis, after adjustment for confounding variables, serum urate had no significant association with severity of hypertension. However, target organ damage, systolic blood pressure and serum creatinine were all independent predictors of severity. CONCLUSIONS: Favourable changes in the severity of hypertension for a time period significantly correlate with decreases in hyperuricemia prevalence in the same period. On the other hand, hyperuricemia appears to be an indirect marker of hypertensive renal damage.

Impairment of Renal Vasodilation With l-Arginine Is Related to More Severe Disease in Untreated Hypertensive Patients

Abstract: Data remain insufficient to place the decreased response to l-arginine in hypertensive patients within a consistent pathophysiological sequence. The aim of the present study in patients with essential hypertension was to assess the relationships between the response to l-arginine and a set of relevant clinical and laboratory parameters. In this prospective, interventional study, we administered l-arginine to untreated hypertensive individuals and healthy control subjects and measured the clearance of inulin and of para -aminohippurate and a set of biochemical and clinical variables. l-Arginine infusion revealed major differences between control subjects and 1 subgroup (group B) of hypertensive individuals. Group B hypertensives (n=18) had no increase in inulin clearance and no decrease in renal vascular resistance with l-arginine; however, in another subset of hypertensive patients (group A, n=27), the insulin clearance increased and renal vascular resistance decreased similar to the control group (group C, n=11). The ambulatory blood pressure monitoring in group B showed both an increased mean diastolic pressure and a “nondipper” pattern in the nocturnal regulation of arterial pressure. These findings in group B were accompanied by significant alterations in optic fundus and left ventricle hypertrophy and increased microalbuminuria (all, P <0.05). Furthermore, group B individuals had significantly lower values of HDL cholesterol and a higher baseline atherogenic index, plasma insulin level, and glucose/insulin index. We disclose a previously undescribed relationship between end organ repercussion and decreased renal hemodynamic response to l-arginine. Our results may help to understand the mechanisms that lead to target organ damage in hypertension.

Valsartan and the kidney: review of preclinical and clinical data.

Abstract: In both diabetic and nondiabetic renal disease, reducing blood pressure with antihypertensive therapy has beneficial effects on renal function. The key role of the renin-angiotensin system in blood pressure and volume homeostasis has long been established, but its importance for the overall normal functioning of the kidney itself is also increasingly being recognized. Angiotensin-converting enzyme (ACE) inhibitors, widely and successfully used in the treatment of hypertension, may also provide renal protection independent of blood pressure reduction; however, their relatively nonspecific mode of action in blocking an early metabolic step entails major clinical disadvantages, such as accumulation of bradykinin and substance P, that may cause the characteristic ACE-inhibitor side effects of persistent dry cough and, more rarely, angioneurotic edema. Angiotensin II antagonists or receptor blockers, a new class of antihypertensive agent, selectively antagonize the AT1 receptor subtype and, because of greater specificity, do not give rise to the side effects associated with ACE inhibitors. More important, these new drugs may have mechanistic advantages over other antihypertensives, including ACE inhibitors.

Relación entre la gravedad de la hipertensión arterial esencial y la prevalencia de hiperuricemia

Abstract: Fundamento La hiperuricemia se asocia con un riesgo cardiovascular incrementado en pacientes hipertensos. Sin embargo, la relacion entre acido urico serico y la gravedad de la hipertension no ha sido definida con precision. Nuestro objetivo fue evaluar si existe una relacion independiente entre cambios en la prevalencia de hiperuricemia y la gravedad de la hipertension arterial. Pacientes y metodo Estudiamos a tres poblaciones de pacientes de entre 35 y 60 anos con hipertension arterial (HTA) esencial diagnosticada en un hospital universitario en Madrid. La primera poblacion (anterior a 1981) incluia a 325 pacientes, la segunda (entre 1981 y 1989), a 271 y la tercera (entre 1990 y 1999), a 545. Se asigno una escala de puntuacion entre 1 y 6 a la gravedad de la hipertension basada en los valores de presion arterial al diagnostico (a los grados 1, 2 y 3 de la OMS/SIH se les asigno 1, 2 o 3 puntos) y la lesion en organo diana (hipertrofia ventricular izquierda, retinopatia hipertensiva y proteinuria de mas de 300 mg/dia con un punto cada uno). Resultados La concentracion de acido urico serico en las tres poblaciones fue de 6,6, 5,8 y 5,5 mg/dl, respectivamente (p En la primera poblacion el 39% de los pacientes presentaba una concentracion de acido urico serico superior a 7,0 mg/dl mientras que solo en el 18,1% de los pacientes en la tercera poblacion se evidenciaba hiperuricemia (diferencia del 20,9%; intervalo de confianza [IC] del 95%: 10,1-32,3; p Conclusiones Los cambios favorables en la gravedad de la HTA en el tiempo se correlacionan de forma significativa con el descenso de prevalencia de la hiperuricemia en el mismo periodo de tiempo. Inversamente, el hallazgo de hiperuricemia seria un marcador indirecto de repercusion visceral hipertensiva renal.

Principal results from the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT)

Abstract: Background We compared the effects of a long-acting calcium-channel blocker with a thiazide-amiloride combination on cardiovascular mortality and morbidity in patients with additional cardiovascular risk factors. The primary objective was to demonstrate 25% superiority of nifedipine GITS. A secondary objective was to establish non-inferiority compared with co-amilozide. Methods A prospective, randomized, double-masked trial was carried out in Europe and Israel, involving 6321 patients of 55–80 years of age with hypertension (blood pressure \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({\geq}\ {150}/{95}\) \end{document} mmHg or systolic ≥ 160 mmHg). Patients were also required to have at least one out of ten additional cardiovascular risk factors, such as diabetes or hypercholesterolaemia. Patients were assigned randomly to initial treatment with either nifedipine GITS (N), 30 mg, or co-amilozide (C) (hydrochlorothiazide, 25 mg, and amiloride, 2·5 mg), so that similar numbers of patients with each risk factor could be compared between the two drugs. Dose titration was principally by dose doubling, and addition of atenolol, 25–50 mg, or enalapril, 5–10 mg. Patients were followed for a mean period of 3 years. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, heart failure or stroke, Secondary outcome variables included death from any cause. Superiority analysis was of time to first event, by intention-to-treat. Non-inferiority analysis required the difference (Δ) in event-rate, and the 95% CI around Δ, to be <2% in patients remaining on randomized treatment. Findings Mean blood pressure was decreased similarly in both treatment groups, from \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({173}/{99}\ ({14}/{8})\) \end{document} mmHg to \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({138}/{82}\) \end{document} (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({12}/{7}\) \end{document}) mmHg; 72% of patients were controlled on monotherapy. There were more withdrawals from the N group than from the C group, because of peripheral oedema in 8% and because of more serious adverse events (880 vs 776, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(P\ =\ 0{\cdot}02\) \end{document}) in the C group. A primary end-point occurred in 200 (6·3%) of 3157 patients in the N group (18·2 events per 1000 patient-years) and in 182 (5·8%) of 3164 patients in the C group (16·5 events per 1000 patient-years; relative risk 1·1 [95% CI 0·90-1·3], \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(P=0{\cdot}35\) \end{document}). Adding secondary variables, there were end-points in 383 (12·1%) of the N group (35·1 per 1000 patient-years), and 397 (12·7%) of the C group (36·5 per 1000 patient-years; relative risk 0·97 [95% CI 0·84-1·11], \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(P=0{\cdot}32\) \end{document}). Deaths were predominantly non-vascular (N, 176 vs C, 172; \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(P=0{\cdot}81\) \end{document}). Interpretation The INSIGHT treatment regimens achieve optimal blood pressure control in most high-risk patients. This appears to be more important than choice of individual drugs in determining outcome in hypertension. Against a previous ‘gold standard’, nifedipine GITS was found to be effective in preventing cardiovascular or cerebrovascular complications, and may be regarded as appropriate first-line therapy in hypertension.

A Prospective Comparison of Four Antihypertensive Agents in Daily Clinical Practice

Abstract: Clinical trials for comparison of antihypertensive agents seem to greatly differ from clinical practice. One limitation of clinical trials is the absence of a random distribution of target organ damage that can determine differences in the response to a given therapy. This study was designed to evaluate, within the conditions of daily clinical practice, the capacity of four different antihypertensive drugs to control blood pressure in essential hypertensive patients randomly distributed according to an assessment of target organ damage. A group of 200 mild essential hypertensives (44.4±12.5 years old; 50.3% male) sent to our unit for routine evaluation and therapy of their hypertension were included in the study. They were randomly allocated to four different therapeutic agents (atenolol, lisinopril, nisoldipine, or losartan). There were 50 patients in each group. After a 4-week washout of previous antihypertensive therapy, or without it if previously untreated (43 %), patients received one of the four medications in an open fashion. A random distribution was performed for sex, age, and the presence of target organ damage, including left ventricular hypertrophy determined by echocardiography, alterations (plaque or thickening) on carotid Doppler ultrasonograms, and/or the presence of microalbuminuria (>30 mg/24 h). Efficacy and tolerability were evaluated after 12 weeks of therapy. Left ventricular hypertrophy was detected in 32% of patients, diastolic dysfunction in 30.1%, and systolic dysfunction in 1.9%. Carotid plaques were detected in 41.5% of subjects, but only 10.4% had more than one plaque. Medial/intimal thickness of >1.00 mm was present in 41.5% of patients. Finally, 27% exhibited microalbuminuria. The expected correlations among the different components of target organ damage were found. After 12 weeks of therapy, blood pressure reductions were similar in all groups, and the expected goal of control (diastolic pressure of <90 mm Hg) was attained in 64.6% of atenolol patients, 68.8% on lisinopril, 62.2% on nisoldipine, and 60.8% on losartan. No severe adverse events were observed, and the withdrawal rates were 20% with atenolol, 10% with lisinopril and nisoldipine, and 8% with losartan. In conclusion, the four antihypertensive agents showed equal antihypertensive efficacy in patients with a similar degree of target organ damage. The β blocker exhibited the lowest tolerability. These results are in agreement with those obtained in prospective clinical trials.

The calcium channel blocker controversy in patients with diabetic nephropathy: Is there an issue?

Abstract: Chronic renal failure, proteinuria, and arterial hypertension run in parallel in the presence of diabetic nephropathy. New goal blood pressure levels have been established in diabetic patients: 130/85 mm Hg and 125/75 mm Hg depending on the level of proteinuria being below or above 1 g/d. New and lower threshold blood pressure (> 130/85 mm Hg) to initiate pharmacologic therapy is required in the presence of diabetes mellitus in order to facilitate the strict blood pressure control that is required. It must be considered that both renal and cardiovascular protection are obtained with strict blood pressure control, which otherwise seems to require blockade of angiotensin II effects when proteinuria above 1 g/d is present. While awaiting the publication of long-term follow-up studies looking at renal and cardiovascular outcome in diabetic and other nephropathies in which calcium channel blockers are compared with other antihypertensive drugs, calcium channel blockers will remain the drugs needed to attain the expected goal blood pressure in diabetics, both alone (in the absence of microalbuminuria or macroalbuminuria) or in combination, particularly with angiotensin converting enzyme inhibitors.

What is the optimal blood pressure target in renal patients

Abstract: Chronic renal failure and arterial hypertension run in parallel. New goal BP levels have been established as 130/85 mm Hg and 125/75 mm Hg, depending on whether the level of proteinuria is less than or greater than 1 g/d. New and lower threshold BP (> 130/85 mm Hg) to initiate pharmacologic therapy is required in the presence of renal failure, to facilitate the strict BP control that is required. Hence, it is necessary to consider that both renal and cardiovascular protection are obtained with strict BP control, which otherwise seems to require blockade of angiotensin II effects when proteinuria above 1 g/d is present.