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Biomedical subjects

Luis M Ruilope

Publications and source records attributed to Luis M Ruilope.

At least 73 records · Page 4Linked to original sources

Doxazosin GITS versus hydrochlorothiazide as add-on therapy in patients with uncontrolled hypertension.

The objective of this prospective, randomized, open-label, parallel-arm comparative study, with a 4-month follow-up, was to assess the antihypertensive efficacy, tolerability and metabolic safety of doxazosin GITS (gastrointestinal therapeutic system) 4-8 mg/day vs hydrochlorothiazide (HCTZ) 12.5-25 mg/day as add-on therapy in patients not controlled with monotherapy with other drugs. Ninety-eight patients completed the study (mean age 57.4 +/- 15 years, 53% female). Mean systolic/diastolic blood pressure reduction was 8.2/4.5 mmHg in the HCTZ group and 8.9/5.0 mmHg in the doxazosin GITS group, and a strict blood pressure control was achieved in 79% and 83% of the patients, respectively. The incidence rates of adverse events were low and similar in both groups. However, metabolic differences were seen between the groups, doxazosin GITS vs HCTZ, respectively: total cholesterol (mg/dl) 210 +/- 53 vs 231 +/- 62 (p < 0.05), low-density lipoprotein (LDL) cholesterol (mg/dl) 139 +/- 40 vs 161 +/- 57 (p < 0.01), high-density lipoprotein (HDL) cholesterol (mg/dl) 58 +/- 16 vs 48 +/- 13 (p < 0.01), HDL/total cholesterol ratio 27.6 +/- 8 vs 21.2 +/- 7 (p < 0.001), plasma uric acid (mg/dl) 5.3 +/- 2.6 vs 6.8 +/- 3.1 (p < 0.05) and serum potassium (mEq/l) 4.1 +/- 1.3 vs. 3.7 +/- 1.2 (p < 0.01). In conclusion, doxazosin GITS has a tolerability and efficacy profile similar to low doses of thiazide diuretics, with a better evolution of metabolic and electrolyte parameters. Therefore, in patients not controlled with monotherapy, doxazosin GITS can be considered an alternative to the addition of thiazide diuretics.

Adolescent↗

Is it time to measure microalbuminuria in hypertension?

Former guidelines on hypertension never made a commitment to the detection of microalbuminuria for screening or follow-up of hypertensive patients. On the other hand, growing evidence support the contributory role of microalbuminuria in the prediction of absolute cardiovascular risk in hypertension and document the potential relevance of this parameter to the initial choice of antihypertensive treatment. Upcoming new guidelines and diagnostic algorithms in hypertension need to underscore the clinical positioning of microalbuminuria for stratification of risk and follow-up purposes.

Albuminuria↗

Renal participation in cardiovascular risk in essential hypertension.

The kidney plays a relevant role in the origin of essential hypertension in humans, and it suffers the consequences of sustained elevated blood pressure in the absence of therapy. Recently, a relevant prevalence of mild renal insufficiency both in general population than in hypertensive patients has been described. A direct relationship seems to exist between the level of cardiovascular risk and the prevalence of the renal disorder, whether this is detected as an elevation in serum creatinine or as a diminution of estimated creatinine clearance. This renal function impairment is a strong predictor of cardiovascular risk in patients with chronic heart failure and following myocardial infarction. Prevention of renal and cardiovascular damage in these patients will be one of the most relevant tasks in the future. The aim of this short review is to discuss the evidence in favor of a relevant prevalence of mild renal insufficiency in hypertensive patients, as well as the association of this disorder with a very significant increment in global cardiovascular risk.

Blood Pressure↗

Combination is better than monotherapy with ACE inhibitor or angiotensin receptor antagonist at recommended doses.

OBJECTIVE: The combination of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II (Ang II) receptor antagonist (ARB) could provide a higher degree of blockade of the renin-angiotensin system(RAS) than either agent alone. The primary aim of this study was to look at the effect of three therapeutic regimens (titrated ACE inhibitor (ACE-I) versus titrated ARB versus the combination of an ACE-I and an ARB) on the attainment of adequate blood pressure (BP) control and antiproteinuric effect. Both ACE-I and ARB were titrated as monotherapy up to the maximal recommended dose. METHODS: A pilot randomised, parallel group open-label study was conducted in 36 patients with primary renal disease, proteinuria above 1.5 g/day and BP >140/90 mmHg while on therapy with an ACE-I. Patients were randomly assigned to (1) benazepril, n=12; (2) valsartan, n=12; or (3) benazepril plus valsartan, n=12. Other antihypertensive therapies could also be added to attain goal BP (<140/90 mmHg). The primary endpoint was the change in proteinuria during six months of follow-up. RESULTS: In the presence of similar BP decreases and stable creatinine clearance values, mean proteinuria decreases were 0.5+1.7, 1.2+2.0 and 2.5+1.8 g/day in groups 1, 2 and 3, respectively. When compared with baseline values, only the fall induced by the combination of ARB and ACE-I attained statistical significance (p<0.05). CONCLUSION: The antiproteinuric capacity of monotherapy at recommended doses with either an ACE-I or an ARB is lower than that obtained with the combination of the two drugs.

Adult↗

ACE inhibition or angiotensin receptor blockade: which should we use in diabetic patients?

Blockade of the effects of angiotensin II (Ang II) by using an angiotensin-converting enzyme (ACE) inhibitor has been proven to be of value in Type 1 diabetic nephropathy and in non-diabetic renal disease. Evidence in favour of Ang II blockade in Type 2 diabetic patients with renal damage is still lacking for ACE inhibitors (ACE-Is), while recent data indicate that angiotensin receptor blockers (ARBs) could be the drugs of choice in this situation. On the other hand, renal damage from the onset of disease is accompanied by a very significant increment in global cardiovascular risk. This fact, as well as that of simultaneous renal and cardiovascular protection, have to be considered for drug selection. In this sense, ACE-Is have been shown to be the drugs of choice when secondary cardiovascular prevention is required, while the evidence in primary prevention in hypertensive patients has been shown with losartan in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. All these facts led to the conclusion that both ACE-Is and ARBs can be considered when both renal and cardiovascular protection are aimed for in Type 2 diabetic patients.

Angiotensin Receptor Antagonists↗

New-onset diabetes and antihypertensive therapy: comments on ALLHAT trial.

The development of new-onset diabetes is frequent during the follow-up of treated hypertensive patients. The prevalence of such an event seems to differ depending on the type of antihypertensive therapy used to control blood pressure. Diuretics and b-blockers and their association are particularly harmful in this regard. On the contrary, calcium channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, alone or in association with diuretics, are associated with a lower prevalence of this metabolic complication. These statements are confirmed by data from the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study. Long-term studies are required to determine the relevance of development of new-onset diabetes in treated hypertensive patients.

Antihypertensive Agents↗

Evaluation of the extent and duration of the "ABPM effect" in hypertensive patients.

OBJECTIVES: The goal of this study was to test and quantify the extent and duration over time of a possible pressor effect due to ambulatory monitoring. BACKGROUND: The use of ambulatory blood pressure monitoring has provided a method of blood pressure (BP) assessment that compensates for some of the limitations of office values. While a "white-coat" pressor effect on conventional measurements has been defined and frequently used for the improved evaluation of hypertensive patients, there has not been clear indication that the ambulatory technique could also influence BP. METHODS: We studied 538 mild-to-moderate hypertensive patients (233 men), 54.2 +/- 14.2 (mean +/- SD) years of age. Blood pressure and heart rate were measured at 20-min intervals during the day and at 30-min intervals at night for 48 consecutive hours, and physical activity was simultaneously evaluated at 1-min intervals with a wrist actigraph. One-third of the patients were evaluated twice or more times. RESULTS: In both treated and untreated hypertensive patients evaluated for the first time, results indicate a statistically significant (p < 0.001) reduction during the second day of monitoring as compared with the first in the diurnal mean of systolic and diastolic BP, but not in heart rate or physical activity. This pressor effect remains statistically significant for the first 6 h to 8 h of monitoring independently of gender, days of the week of monitoring or number of antihypertensive drugs used by the treated patients. The nocturnal mean of BP was, however, similar between both days of sampling. This "ambulatory monitoring effect" was not observed when the patients were evaluated after the same sampling scheme for the second or successive times three months apart. CONCLUSIONS: Ambulatory monitoring for 48 consecutive hours reveals a statistically significant pressor response that could reflect a novelty effect in the use of the monitoring device for the first time. This effect has marked implications in both research and clinical daily practice for a proper diagnosis of hypertension and evaluation of treatment efficacy by the use of ambulatory monitoring.

Adult↗

Proteinuria: an underappreciated risk factor in cardiovascular disease.

Changes in renal function produced by hypertension appear to be associated with higher cardiovascular morbidity and mortality. Indices of altered renal function (eg, microalbuminuria, increased serum creatinine concentrations, decrease in estimated creatinine clearance, or overt proteinuria) are independent predictors of cardiovascular morbidity and mortality. The Framingham Heart Study documented the relevance of proteinuria for cardiovascular prognosis in the community. The International Nifedipine GITS study: Intervention as a goal in Hypertension Treatment (INSIGHT) study assessed the role of proteinuria as a very powerful risk factor. Several studies demonstrated that microalbuminuria is a predictor of cardiovascular disease. It has been shown that the presence of microalbuminuria in primary hypertension carries an elevated cardiovascular risk. Furthermore, recent data indicate that even minor derangements of renal function are associated with an increase in cardiovascular risk factors, and promote progression of atherosclerosis. All these parameters should routinely be evaluated in clinical practice, and in the future must be considered in any stratification of cardiovascular risk in hypertensive patients.

Albuminuria↗

Renal dysfunction as a cardiovascular risk factor.

Indices of altered renal function (eg, microalbuminuria, increased serum creatinine concentration, or decrease in estimated creatinine clearance, particularly overt proteinuria) are independent predictors of cardiovascular morbidity and mortality. These parameters should be routinely evaluated in the elderly and in high cardiovascular risk populations, particularly when hypertension is present. Hypertensive kidney damage should be prevented by early aggressive treatment of hypertensive patients with microalbuminuria. To avoid further aggravation of high cardiovascular risk, antihypertensive agents devoid of unwanted metabolic side effects should be used. Epidemiologic information suggests that renal and cardiovascular outcome run parallel in this segment of the population.

Antihypertensive Agents↗

Renal protection by antihypertensive therapy.

The attainment of adequate renal protection requires strict blood pressure control and a diminution of proteinuria or microalbuminuria to values as near from normalcy as possible. It has been considered that by getting the first, the second could be attained at the same price. Recent data have confirmed that renal protection in hypertensive patients, diabetics or not, requires combination therapy that has to include an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker. A calcium channel blocker can be added to this without renal compromise. A diuretic will also be needed in most cases. Proteinuria will diminish with this combination in particular if up-titration of the drug blocking the effects of angiotensin II is performed. The control of other associated risk factors is also required, in particular smoking and lipids.

Angiotensin Receptor Antagonists↗

ACE inhibition and cardiovascular mortality and morbidity in essential hypertension: the end of the search or a need for further investigations?

Scientific evidence currently available supports the concept that renin-angiotensin blockade with angiotensin converting enzyme inhibitors as a first-line treatment exhibits in arterial hypertension beneficial effects in the prevention of mortality and morbidity comparable to those achieved with diuretics and beta-blockers. In addition, the renin-angiotensin blockade has also proved to be beneficial in the secondary prevention of several complications of hypertensive disease such as after myocardial infarction and congestive heart failure, as well as in the prevention of the incidence of type 2 diabetes, and the progression of diabetic and nondiabetic nephropathy. In this later regard, recent evidence with angiotensin II receptor antagonists in reducing the progression of nephropathy in type 2 diabetes strongly confirms that antagonism of the renin-angiotensin system is an effective approach to cardiovascular and renal disease. Finally, the renin-angiotensin blockade in high-risk patients may reduce cardiovascular mortality independently of the effect on blood pressure (BP). The effect of other antihypertensive drugs on cardiovascular risk in patients with high-normal BP should be investigated to establish whether they exhibit a comparable effect or whether there is a class-related benefit of drugs blocking the renin-angiotensin system. Such a strategy could also be encouraged to design future interventional studies with the newer classes of compounds (angiotensin II AT1-receptor antagonists, vasopeptidase inhibitors, endothelin antagonists), which would have the additional potential advantage of providing information more easily transferable to large-scale clinical practice.

Angiotensin-Converting Enzyme Inhibitors↗

Hypertension guidelines: criteria that might make them more clinically useful.

Cardiovascular disease prevention depends on reduction of risk factors, including hypertension. Guidelines designed to improve management of hypertension are widely available. Their purpose is to assemble the available data from basic biomedical science, epidemiology, and clinical science in an accessible form with which physicians and patients can make reasoned decisions for individual cases. However, guidelines have been neither widely accepted, nor effectively implemented. We recommend a strategy for guideline preparation designed to yield a product more user friendly, accessible, and effective. Guideline recommendations and the evidence used to make them should be based on an explicit grading system. Relevant clinical as well as nonclinical factors must be considered. Moreover, because the goal of antihypertensive therapy is to prevent cardiovascular events, and the likelihood of such events is determined by multifactor or absolute risk assessment, risk, rather than level of blood pressure (BP), should determine the need for therapy. Similarly, the benefit of therapy must be assessed by reduction in cardiovascular disease morbidity and mortality.

Humans↗

Cardiovascular therapy in patients with renal insufficiency.

Chronic renal failure and arterial hypertension run in parallel. New goal blood pressure levels have been established in 130/85 mmHg and 125/75 mmHg depending on the level of proteinuria being below or above 1 g/day. New and lower threshold BP (>130/85 mmHg) to initiate pharmacologic therapy are required in the presence of renal failure in order to facilitate the strict BP control that is required. Renal insufficiency is accompanied since its initial stages by a marked increase in cardiovascular risk and serum creatinine, its estimated clearance and the presence of proteinuria are very powerful predictors of a bad cardiovascular outcome. Hence, the need to consider that both renal and cardiovascular protection are obtained with such a strict BP control which, otherwise seems to require blockade of angiotensin II effects when proteinuria above 1g/day is present. Prevention of renal failure related to elevated blood pressure requires of strict blood pressure control, usually obtained with combination of two or more antihypertensive agents, one of them capable of blocking angiotensin II. Besides this, strict control of associated cardiovascular risk factors is also required.

Angiotensin-Converting Enzyme Inhibitors↗

Long-term protection in at-risk hypertensive patients--a role for nifedipine GITS?

Hypertensive patients who are at high risk of developing cardiovascular (CV) complications have become the focus of modern treatment guidelines. The choice of antihypertensive therapies in these patients should be evidence-based: in particular, there should be evidence of a beneficial impact on CV events in addition to blood pressure-lowering effects. The International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT) is the first, large, randomized, double-blind study undertaken exclusively in high-risk hypertensive patients, with CV events as a prospectively defined primary end-point. The choice of a diuretic (co-amilozide) as a comparator reflects the fact that this group of antihypertensive drugs has been shown to reduce CV events in high-risk hypertensive patients. Nifedipine, administered in a long-acting gastrointestinal-transport-system (GITS) formulation, and co amilozide were equally effective in preventing overall CV or cerebrovascular complications. This finding extended to the subgroup of patients with diabetes at baseline. Substudies to INSIGHT showed that, compared with coamilozide, nifedipine GITS was significantly more effective at preventing an increase in intima-media thickness in the carotid artery and significantly slowed the progression of coronary calcification. The results from INSIGHT support incorporating nifedipine GITS in the management of high-risk hypertensive patients to prevent atherosclerosis-related illness and death.

Amiloride↗

Antihypertensive efficacy and tolerability of lercanidipine in daily clinical practice. The ELYPSE Study. Eficacia de Lercanidipino y su Perfil de Seguridad.

AIM: Lercanidipine, a long-acting dihydropyridine with a good antihypertensive efficacy and tolerability in clinical use. With the aim to determine the efficacy and tolerability of this drug in usual clinical practice we performed the ELYPSE trial. METHODS: Grade 1 or 2 essential hypertensive patients in whom their physicians considered to prescribe a dihydropyridine were conferred to Lercanidipine 10 mg once daily with a 3-month follow-up; 9059 patients were included (age: 63 +/- 11 years; 58% women, 60% over 60 years, 56% grade 2 hypertensives and 69% previously treated with other antihypertensive drugs). A subgroup of 1267 patients (14%) who were included in the study had experienced adverse reactions with other drugs. Electronic case-report forms and a central database (Internet) were used in this trial. RESULTS: At baseline, blood pressure (BP) was 160.1 +/- 10.2/95.6 +/- 6.6 mmHg; and heart rate (HR) 77.3 +/- 9.3 beats/min. Significant reductions in both systolic and diastolic BP were attained at 1 month with slight additional decreases 2 months later. At 3 months, BP was 141.4 +/- 11.3/ 83.1 +/- 6.9 mmHg, and HR 75.2 +/- 8.2 beats/min (p < 0.001 versus baseline). At the study end. 64% of the patients achieved a diastolic BP < 90 mmHg, BP control (< 140/90 mmHg) was attained in 32%. In the subgroup of diabetics (n = 1269) an adequate BP control (< 130/85) was attained in only 16.4%. The overall incidence of adverse events was 6.5%, of which the most frequent were headache (2.9%), ankle oedema (1.2%), flushing (1.1%) and palpitations (0.6%). Withdrawal rate was < 1%. The efficacy and tolerability in the subgroup of patients included in the study due to adverse events with other drugs were similar to the whole study group. CONCLUSION: In this study Lercanidipine has shown a good efficacy and tolerability in daily clinical practice. These findings are concordant with those reported in randomized controlled trials.

Adult↗

N-acetylcysteine potentiates the antihypertensive effect of ACE inhibitors in hypertensive patients.

Sulfhydryl group donors, such as N-acetylcysteine (NAC), may enhance the antihypertensive effect of some drugs through a nitric oxide (NO) mechanism. It has been observed that the hypotensive effect of angiotensin-converting enzyme inhibitors (ACEIs) is, at least partially, mediated by NO. We performed a within patient crossover study with the aim to investigate the potential effect of NAC on the ACEI antihypertensive action, via an NO-dependent mechanism. We studied 18 smoker (> 10 years of habit and > 10 cigarettes daily) hypertensive patients (15 males and three females, aged 69 +/- 5 years) on ACEI therapy (11 captopril and seven enalapril). Patients were randomly allocated to two treatment arms. In one arm, the patients (n = 10) initially received the addition of NAC (600 mg t.i.d.) to the ACEI regimen. In the other group (n = 8), the patients remained only on ACEI. After 21 days, the therapeutic patterns were crossed. The first group received only ACEI, and the second group received ACEI and NAC and completed other 21-day treatment period. We evaluate the effect of NAC on each patient by ambulatory blood pressure monitoring (ABPM), performed at the end of each therapeutic regimen. A significant decrease in systolic and diastolic 24-h blood pressure (24 hBP) and daytime BP (dtBP) was achieved with the combination of ACEI and NAC (ACEI + NAC) when compared to the period with only ACEI: 24 hBP = 146.1 +/- 4.2 vs 137 +/- 3.1 (p < 0.05) and 89.2 +/- 2.8 vs 83.5 +/- 3.7mmHg (p = 0.01). DtBP: 149.7 +/- 5.6 vs 141 +/- 3.7 and 92.1 +/- 4 vs 86 +/- 3.2 (both, p < 0.05). No significant difference was observed in night-time BP (ntBP). The NAC effect was not statistically different for the two ACEIs. In conclusion, the addition of NAC to an ACEI potentiates its antihypertensive effect during 24hBP and dtBP in smoker hypertensives. This effect may be mediated by an NO-dependent mechanism, probably through the protective effect of NAC on NO oxidation.

Acetylcysteine↗