Carlos Campo

Blood Pressure Control and Physician Management of Hypertension in Hospital Hypertension Units in Spain

Goal blood pressure (BP) was defined by the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) and the World Health Organization–International Society of Hypertension (WHO/ISH) as <140 mm Hg systolic and <90 mm Hg diastolic for the general and <130 mm Hg systolic and <85 mm Hg diastolic for special high-risk populations. However, there are few reports that address BP control among special subgroups of hypertensives by reference to targeted BP. We therefore conducted a study to evaluate BP control of 4049 hypertensives in 47 hospital-based hypertension units in Spain. Overall, 42% of patients achieved goal BP (<140 mm Hg systolic and <90 mm Hg diastolic). Only 13% of diabetic patients and 17% of those with renal disease achieved the BP goal (<130 mm Hg systolic and <85 mm Hg diastolic), and only 10% and 12%, respectively, achieved the even more rigorous goal (<130 mm Hg systolic and <80 mm Hg diastolic). Likewise, only 18% of patients in JNC-VI risk group C and 17% of WHO/ISH high-risk patients attained a goal BP <130 mm Hg systolic and <85 mm Hg diastolic. BP control (<125 mm Hg systolic and <75 mm Hg diastolic) was extremely low (2%) in patients with proteinuria >1 g/d. Poorer BP control was observed among patients at high risk, with diabetes, renal disease, or obesity, than in lower-risk groups. BP control was lower for systolic than for diastolic BP. In >50% of uncontrolled patients, no measures were taken by doctors to optimize pharmacologic treatment, and approximately one-third of patients were still using drug monotherapy. Control of BP, particularly of systolic BP, is still far from optimal in hospital-based hypertension units. Patients at high risk, with diabetes or proteinuria, warrant focused attention. Moreover, a more aggressive behavior of doctors treating uncontrolled hypertension is needed.

Development Of Chronic Kidney Disease and Cardiovascular Prognosis in Essential Hypertensive Patients

The existence of a significant percentage of treated hypertensive patients presenting a diminished renal function has been recently described. Mild renal function abnormalities are recognized as powerful predictors of cardiovascular morbidity and mortality. However, longitudinal data demonstrating this association are lacking. The objectives of this study have been analysis of the evolution of GFR, assessed as creatinine clearance (CrCl), during long-term follow-up of hypertensive patients and evaluation of the impact of the development of chronic kidney disease (CKD) on cardiovascular prognosis. A historical cohort of 281 patients attending our Hypertension Unit was selected according to the following criteria: essential hypertension, more than 5 yr of follow-up, and normal GFR at baseline (CrCl > 90 ml/min per 1.73 m(2)). Patients had an average follow-up of 13.2 +/- 4.8 yr. Forty-one patients (14.6%) developed CKD (CrCl < 60 ml/min per 1.73 m(2)) attributed to hypertensive nephrosclerosis. Initial serum creatinine, age, systolic BP at baseline, and average total cholesterol during follow-up were independent predictors of CKD development. Forty-nine (17.4%) of 281 patients presented a cardiovascular event during follow-up: 17 patients (40.6%) who developed CKD and 32 patients (13.3%) with preserved renal function (log rank test P < 0.001). After adjustment in a Cox multivariate analysis, age, development of CKD during follow-up, and male gender were independent predictors of the appearance of cardiovascular events. In essential hypertensive patients with normal renal function at baseline, the development of CKD during the follow-up is strongly and independently related with poor cardiovascular prognosis.

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 decreasesand 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.

Hypertensive Renal Damage in Metabolic Syndrome Is Associated with Glucose Metabolism Disturbances

Recent evidence highlights the relationship between metabolic syndrome (MS) and increased risk of cardiovascular (CV) diseases. Mild renal function abnormalities are associated with an enhanced CV risk, considered to be due to the presence of associated risk factors. Hence, MS and renal abnormalities could be linked and contribute to augment CV risk. For estimating the prevalence of diminished creatinine clearance (CC; <60 ml/min per 1.73 m(2)) in hypertensive patients with or without MS and for investigating the factors accompanying this abnormality, 1625 hypertensive patients, aged 18 yr or older, were included. The presence of MS was defined according to the Adult Treatment Panel III criteria. The overall prevalence of MS was 49.4% (n = 802). No significant difference was found for CC between those with and without MS, albeit the presence of MS was accompanied by greater urinary albumin excretion (P = 0.01). The prevalence of a diminished CC was also similar in the two groups. MS-positive patients presented a progressive decay in CC when classified as normoglycemic (n = 319), impaired fasting glucose (n = 237), and diabetic patients (n = 246; 85.9 +/- 30.2, 81.8 +/- 26.8, and 75.2 +/- 25.7 ml/min per 1.73 m(2), respectively; P = 0.0007 linearity test) and the opposite for microalbuminuria (29.5 +/- 45.5, 45.0 +/- 96.6, and 74.1 +/- 146.3 mg/24 h, respectively; P = 0.001 linearity test). In multiple regression analysis, factors related to the finding of a diminished CC in MS and non-MS patients were similar. Hypertensive patients at a relatively young age present with an elevated prevalence of minor abnormalities of renal function that is mostly related to the presence of metabolic alteration of glucose together with age and BP.

How relevant and frequent is the presence of mild renal insufficiency in essential hypertension

Recent analyses of the influence of renal function on the cardiovascular outcome in essential hypertensive patients have confirmed the relevance of the kidney in cardiovascular prognosis even in the initial stages of renal failure. The evaluation of renal function in clinical practice is based mainly on the finding of changes in serum creatinine, but the estimation of creatinine clearance or its determination after 24‐hour urine collection is not usually performed. The objective of this study was to analyze the prevalence of mild chronic renal insufficiency (MCRI) through the determination of creatinine clearance in patients with essential hypertension to reinforce the need to consider using this parameter in daily clinical practice. We analyzed clinical and biochemical data from 2686 essential hypertension patients referred to our unit from 1979–1999. MCRI was defined as a serum creatinine ≥1.5 mg/dL in men and ≥1.4 mg/dL in women, or a creatinine clearance estimated by the Cockroft‐Gault formula or by a 24‐hour urine collection of <60 mL/min. A prevalence of MCRI was found in 7.6% according to serum creatinine levels. This prevalence increased to 22.3% and 21.5% respectively when the diagnostic criteria for MCRI was the estimation of 24‐hour creatinine clearance in urine, or its estimation using the Cockroft‐Gault formula. When classified by creatinine clearance values, patients with MCRI were characterized by older age, elevated systolic blood pressure, higher serum total cholesterol, low‐density lipoprotein cholesterol, and triglycerides, lower levels of high‐density lipoprotein cholesterol, higher serum uric acid, fasting serum glucose, serum potassium, and higher levels of urinary albumin excretion. In summary, MCRI is more prevalent in essential hypertension than previously thought, particularly if the estimated creatinine clearance is used to define MCRI. The finding of an altered renal function is associated with a significant increase in cardiovascular risk. This fact reinforces the need to pay attention to any of the manifestations of renal damage observed in the usual clinical assessment of any hypertensive patient.

Range of simple scaling and critical amplitudes near a LCST. The 2-butoxyethanol + water system

Abstract The closed-loop coexistence curve of 2-butoxyethanol + water has been determined with special attention to the region near the LCST. The results have been analyzed in terms of extended scaling equations. The range of validity of simple scaling has been determined, and found to be similar to that of other binary systems with UCST. The first correction-to-scaling amplitude has been found to be negative, in agreement with numerical solutions of three-dimensional Ising models, and in contradiction with the results of the field theoretical models proposed so far. Using a decorated lattice model, the order parameter can be described very accurately at temperatures where the simple scaling is no longer valid. The diameter of the coexistence curve has been found to show a (1 - α) anomaly when the weight fraction is used as composition variable.

Blood pressure control, proteinuria and renal outcome in chronic renal failure.

The presence of proteinuria has been shown to be an excellent predictor for a worse outcome of renal function. Both proteinuria and arterial hypertension often coexist in the same patient, and therapy must be directed at decreasing protein excretion in the urine as well as lowering the blood pressure. Any antihypertensive agent has the capacity to lower proteinuria simply by lowering blood pressure. Furthermore, the antiproteinuric capacity of angiotensin-converting enzyme inhibitors can be equalized by other agents or their combination, provided that the fall in blood pressure is great enough. For this reason studies are needed in which the strict control of arterial hypertension combined with a decrease in proteinuria are considered.

Hyperuricemia, low urine urate excretion and target organ damage in arterial hypertension

Background: Hyperuricemia can be the consequence of an increased urate production, a decreased renal excretion, or both. An increased prevalence of hyperuricemia has been described in essential hypertensive patients partly due to a decreased renal urinary urate excretion (UUE). Hyperuricemia has been shown to be associated with an increased risk of cardiovascular disease in hypertensive patients in some but not in all epidemiological studies in which this relationship has been investigated. Objective: To assess the influence of low UUE in the association between serum urate, renal function and hypertension severity. Patients and Methods: This cross‐sectional study was carried out in a sample of 677 male hypertensive patients, aged 35–60 years, with essential arterial hypertension consecutively attended in a hospital hypertension unit. The presence of hypertension‐related organ damage at diagnosis was classified according to classical WHO criteria as grade 1, 2 or 3. Urate underexcretion was defined as 24‐h urinary urate below the product serum urate × 100. Results: Mean serum urate levels were 6.4 ± 1.6 mg/dl in the total sample. Hyperuricemia (serum urate >7 mg/dl) was present in 28.5% of patients and only 17.0% had underexcretory hyperuricemia. This subgroup of patients exhibited the higher rate of hypertension‐related target organ damage (TOD). A multivariate analysis, showed that underexcretory hyperuricemia but not hyperuricemia remained an independent predictor of TOD (odds ratio 2.5. 95% CI 1.6–3.89). Serum urate correlated positively with serum creatinine in hyperuricemic patients (r = 0.50, p < 0.001), but not in patients with underexcretory hyperuricemia (r = 0.21, p = 0.18). Conclusions: Underexcretory hyper‐uricemia is strongly related to hypertensive organ damage and this relationship does not seem to be mediated by a decreased renal function. This aspect could underline the predictive value of hyperuricemia independently of serum creatinine. UUE could improve the clinical predictive value of hyperuricemia as a cardiovascular risk factor.

Factors Influencing the Systolic Blood Pressure Response to Drug Therapy

In the early stage of hypertension, diastolic blood pressure has greater prognostic importance, but in the elderly, systolic blood pressure is the most important marker of cardiovascular complications. Therefore, the need for more strict control of this component of blood pressure must be reconsidered. The benefit obtained in different studies in the elderly suggests that the treatment of isolated systolic hypertension is associated with a reduction in overall cardiovascular mortality of 22%, in coronary heart disease mortality of 26%, and in stroke mortality of 33%. However, a higher percentage of patients (73%) attain the diastolic goal of <90 mm Hg, while only 34% have systolic pressure reduced to <140 mm Hg. In a review of randomized trials comparing at least four different antihypertensive drugs, significant differences in systolic blood pressure reduction have not been demonstrated, except in black populations, in whom calcium channel blockers and diuretics seem to be more effective. In patients with isolated systolic hypertension, data are inconclusive, but calcium channel blockers and diuretics appear to lower blood pressure to a greater degree than do other antihypertensive drugs. Two main predictors of difficulty in controlling systolic blood pressure are the baseline blood pressure and the presence of diabetes. Other predictors are the duration of arterial hypertension, older age, the presence of target organ damage and associated clinical conditions (myocardial infarction, stroke, chronic renal failure), and an elevated serum uric acid level. It appears that the profile of patients with a poorer therapeutic response includes a greater severity of hypertension and/or the presence of cardiovascular disease.

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.