Julian Segura

Clinical Features of 8295 Patients With Resistant Hypertension Classified on the Basis of Ambulatory Blood Pressure Monitoring

We aimed to estimate the prevalence of resistant hypertension through both office and ambulatory blood pressure monitoring in a large cohort of treated hypertensive patients from the Spanish Ambulatory Blood Pressure Monitoring Registry. In addition, we also compared clinical features of patients with true or white-coat–resistant hypertension. In December 2009, we identified 68 045 treated patients with complete information for this analysis. Among them, 8295 (12.2% of the database) had resistant hypertension (office blood pressure ≥140 and/or 90 mm Hg while being treated with ≥3 antihypertensive drugs, 1 of them being a diuretic). After ambulatory blood pressure monitoring, 62.5% of patients were classified as true resistant hypertensives, the remaining 37.5% having white-coat resistance. The former group was younger, more frequently men, with a longer duration of hypertension and a worse cardiovascular risk profile. The group included larger proportions of smokers, diabetics, target organ damage (including left ventricular hypertrophy, impaired renal function, and microalbuminuria), and documented cardiovascular disease. Moreover, true resistant hypertensives exhibited in a greater proportion a riser pattern (22% versus 18%; P<0.001). In conclusion, this study first reports the prevalence of resistant hypertension in a large cohort of patients in usual daily practice. Resistant hypertension is present in 12% of the treated hypertensive population, but among them more than one third have normal ambulatory blood pressure. A worse risk profile is associated with true resistant hypertension, but this association is weak, thus making it necessary to assess ambulatory blood pressure monitoring for a correct diagnosis and management.

Prevalence and Factors Associated With Circadian Blood Pressure Patterns in Hypertensive Patients

Ambulatory blood pressure (BP) monitoring has become useful in the diagnosis and management of hypertensive individuals. In addition to 24-hour values, the circadian variation of BP adds prognostic significance in predicting cardiovascular outcome. However, the magnitude of circadian BP patterns in large studies has hardly been noticed. Our aims were to determine the prevalence of circadian BP patterns and to assess clinical conditions associated with the nondipping status in groups of both treated and untreated hypertensive subjects, studied separately. Clinical data and 24-hour ambulatory BP monitoring were obtained from 42 947 hypertensive patients included in the Spanish Society of Hypertension Ambulatory Blood Pressure Monitoring Registry. They were 8384 previously untreated and 34 563 treated hypertensives. Twenty-four-hour ambulatory BP monitoring was performed with an oscillometric device (SpaceLabs 90207). A nondipping pattern was defined when nocturnal systolic BP dip was <10% of daytime systolic BP. The prevalence of nondipping was 41% in the untreated group and 53% in treated patients. In both groups, advanced age, obesity, diabetes mellitus, and overt cardiovascular or renal disease were associated with a blunted nocturnal BP decline (P<0.001). In treated patients, nondipping was associated with the use of a higher number of antihypertensive drugs but not with the time of the day at which antihypertensive drugs were administered. In conclusion, a blunted nocturnal BP dip (the nondipping pattern) is common in hypertensive patients. A clinical pattern of high cardiovascular risk is associated with nondipping, suggesting that the blunted nocturnal BP dip may be merely a marker of high cardiovascular risk.

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.

Effectiveness of Blood Pressure Control Outside the Medical Setting

We studied the effectiveness of blood pressure (BP) control outside the clinic by using ambulatory BP monitoring (ABPM) among a large number of hypertensive subjects treated in primary care centers across Spain. The sample consisted of 12 897 treated hypertensive subjects who had indications for ABPM. Office-based BP was calculated as the average of 2 readings. Twenty-four–hour ABPM was then performed using a SpaceLabs 90207 monitor under standardized conditions. A total of 3047 patients (23.6%) had their office BP controlled, and 6657 (51.6%) were controlled according to daytime ABPM. The proportion of office resistance or underestimation of patients’ BP control by physicians in the office (office BP ≥140/90 mm Hg and average daytime ambulatory BP <135/85 mm Hg) was 33.4%, and the proportion of isolated office control or overestimation of control (office BP <140/90 mm Hg and average daytime ambulatory BP ≥135/85 mm Hg) was 5.4%. BP control was more frequently underestimated in patients who were older, female, obese, or with morning BP determination than in their counterparts. BP control was more frequently overestimated in those who were younger, male, nonobese, smokers, or with evening BP determination. Ambulatory-based hypertension control was far better than office-based hypertension control. This conveys an encouraging message to clinicians, namely that they are actually doing better than is evidenced by office-based data. However, the burden of underestimation and overestimation of BP control at the office is still remarkable. Physicians should be aware that the likelihood of misestimating BP control is higher in some hypertensive subjects.

Clinical differences between resistant hypertensives and patients treated and controlled with three or less drugs.

Background and aim: Clinical characteristics of resistant hypertensive patients in comparison to controlled patients have not been fully investigated in large cohorts. The aim of the study was to evaluate clinical differences, target organ damage and ambulatory blood pressure monitoring in resistant hypertensive patients and patients controlled on three or less drugs. Methods: In December 2010, from the Spanish Ambulatory Blood Pressure Monitoring Registry, we identified 14 461 patients fulfilling criteria of resistant hypertension and 13 436 hypertensive patients controlled on three or less drugs. Clinical characteristics were compared between these two groups. Results: Compared to controlled patients, those having resistant hypertension were older, more obese and had longer hypertension duration. They also had more frequently diabetes, dyslipidemia, reduced renal function, microalbuminuria, left-ventricular hypertrophy and previous history of cardiovascular events. In multivariate analyses, hypertension duration, obesity, abdominal obesity, left-ventricular hypertrophy, reduced estimated glomerular filtration rate, and microalbuminuria were independently associated with resistant hypertension. Resistant hypertensive patients had higher ambulatory blood pressures, but differences between office and ambulatory blood pressure (white-coat effect) were also more pronounced in this group, revealing a proportion of 40% of patients with normal 24-h blood pressure. On the contrary, values of 24-h blood pressure above 130 and/or 80 mmHg (masked hypertension) were present in 31% of apparently controlled patients. Conclusion: Resistant hypertension is associated with obesity, longer hypertension duration and kidney and cardiac damage. Ambulatory blood pressure monitoring reveals that white-coat hypertension is common among resistant hypertensive patients, as well as is masked hypertension among apparently controlled patients.

Ambulatory blood pressure monitoring in hypertensive patients with high cardiovascular risk: a cross-sectional analysis of a 20,000-patient database in Spain.

Objective To evaluate ambulatory blood pressure monitoring (ABPM) parameters in a broad sample of high-risk hypertensive patients. Methods The Spanish Society of Hypertension is developing a nationwide project in which more than 900 physicians send ABPM registries and corresponding clinical records to a central database via www.cardiorisc.com. Between June 2004 and July 2005 a 20 000-patient database was obtained; 17 219 were valid for analysis. Results We identified 6534 patients with high cardiovascular risk according to the 2003 European Society of Hypertension/European Society of Cardiology guidelines stratification score. Office blood pressure (BP) was 158.8/89.9 mmHg and 24-h BP was 135.8/77.0 mmHg. Patients with grade 3 BP in the office showed ambulatory systolic BP values less than 160 mmHg in more than 80%. A non-dipping pattern was observed in 3836 cases (58.7%), whereas this abnormality was present in 47.9% of patients with low-to-moderate risk [odds ratio (OR) 1.54; 95% confidence interval (CI) 1.45–1.64]. The prevalence of non-dippers was higher as ambulatory BP increased (≈ 70% when 24-h systolic BP > 155 mmHg) and was similar in both groups. At the lowest levels of BP (24-h systolic BP < 135 mmHg) a non-dipping pattern was more prevalent in high-risk cases (56.6 versus 45.7%; OR 1.51; 95% CI 1.40–1.64). Conclusion There was a remarkable discrepancy between office and ambulatory BP in high-risk hypertensive patients. The prevalence of a non-dipper BP pattern was almost 60%. In the lowest levels of ambulatory BP, high-risk patients showed a higher prevalence of non-dipping BP than lower-risk cases. These observations support the recommendation of a wider use of ABPM in high-risk hypertensive patients.

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.

Ambulatory blood pressure monitoring and development of cardiovascular events in high-risk patients included in the Spanish ABPM registry: the CARDIORISC Event study.

Background and aim: Ambulatory blood pressure monitoring (ABPM) is superior to conventional BP measurement in predicting outcome, with baseline 24-h, daytime and night-time absolute values, as well as relative nocturnal decline, as powerful determinants of prognosis. We aimed to evaluate ABPM estimates on the appearance of cardiovascular events and mortality in a cohort of high-risk treated hypertensive patients. Methods and results: A total of 2115 treated hypertensive patients with high or very high added risk were evaluated by means of office and 24-h ABPM. Cardiovascular events and mortality were assessed after a median follow-up of 4 years. Two hundred and sixty-eight patients (12.7%) experienced a primary event (nonfatal coronary or cerebrovascular event, heart failure hospitalization or cardiovascular death) and 114 died (45 from cardiovascular causes). In a multiple Cox regression model, and after adjusting for baseline cardiovascular risk and office BP, night-time SBP predicted cardiovascular events [hazard ratio for each SD increase: 1.45; 95% confidence interval (CI) 1.29–1.59]. Values above 130 mmHg increased the risk by 52% in comparison to values less than 115 mmHg. Conclusion: In addition to clinical determinants of cardiovascular risk and conventional BP, ABPM performed during treatment adds prognostic significance on the development of cardiovascular events in high-risk hypertensive patients. Among different ABPM-derived values, night-time SBP is the most potent predictor of outcome.

Obesity, essential hypertension and renin–angiotensin system

Abdominal obesity is a risk factor for cardiovascular disease worldwide, and it is becoming a dramatic issue for national health systems. Overweight and obesity are highly associated with multiple comorbidities, elevated blood pressure values, dyslipidaemia, reduced insulin sensitivity and alterations of large and minor vessels. Activation of the renin-angiotensin system (RAS) in adipose tissue may represent an important link between obesity and hypertension. Angiotensin II has been shown to play a role in adipocyte growth and differentiation. Adipocytes also secrete adiponectin, enhancing insulin sensitivity and preventing atherosclerosis. Blockade of the RAS with either an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker results in a substantial increase in adiponectin levels and improved insulin sensitivity. Obesity-related hypertension needs a comprehensive approach to treatment including both weight loss and pharmacological therapies. Antihypertensive drugs prescription should be based on guidelines recommendations for management of hypertension, taking into account the growing evidences about the relationship between some antihypertensive drugs and the development of new-onset diabetes. This review discusses the role of RAS in the relationship between obesity, essential hypertension and insulin resistance.

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

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 serum creatinine during the previous 2 years. Methods A randomized, open-label, multicenter study with a minimum follow-up of 3 years. A total of 241 patients were included in the study. All of them were hypertensive and had a 25% or at least 0.5 mg/dl increase in the value of serum creatinine during the 24 months prior to entering the study. Initial doses of fosinopril and nifedipine GITS were 10 and 30 mg respectively, and titration to 30 and 60 mg was performed if needed to obtain the expected blood pressure goal (< 140/90 mmHg). Furosemide, atenolol, and doxazosin were added as second, third, and fourth drugs if necessary, for blood pressure control. The primary end-point of the study was the appearance of double the serum creatinine values and/or the need to enter a dialysis programme. Secondary end-points were cardiovascular events, death, changes in 24 h proteinuria, and the evolution of serum creatinine. Data reflect the analysis performed by intention to treat. Results Mean age of the group was 54 ± 14, and 59% were males. Primary glomerulonephritis (31%), nephrosclerosis (26%) and polycystic kidney disease (19%) were the three most frequent diagnostic findings. After 3 years of follow-up, 21% (27/127) of patients treated with fosinopril, and 36% (40/112) of those receiving nifedipine GITS presented a primary end-point, (OR 0.47, 95% confidence intervals 0.26–0.84, P = 0.01). Renal survival was significantly better when fosinopril constituted the first step therapy (P = 0.002). These results did not seem to be influenced by the type of primary renal disease. Proteinuria decreased at the end of the study by a mean of 57% in the fosinopril group and increased by 7% in the group receiving dihydropiridine. Blood pressure control did not differ among groups for diastolic values. During follow-up, however, the patients receiving ACEi showed systolic blood pressure values 4–6 mmHg lower. Conclusion In patients with chronic renal failure and hypertension due to primary renal disease, fosinopril significantly differed from nifedipine GITS by its capacity to slow the progressive decay in renal function . The drugs also differed by their capacity to lower blood pressure. The better control, in particular of systolic blood pressure, in the fosinopril arm could have contributed in a relevant manner to the attainment of a better outcome when the ACEi was employed.