Effect of inter-individual blood pressure variability on the progression of atherosclerosis in carotid and coronary arteries: a post hoc analysis of the NORMALISE and PREVENT studies.

Aims: To investigate the relationship between visit-to-visit blood pressure variability (BPV) and the progression of both carotid and coronary artery disease (CAD). Methods and results: Data from two cardiovascular endpoint studies [Norvasc for Regression of Manifest Atherosclerotic Lesions by Intravascular Sonographic Evaluation (NORMALISE) and Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT)] were analysed separately. Systolic BPV was assessed as within-subject standard deviation of systolic BP across visits from 12-weeks onwards. Follow-up was 24 months (NORMALISE) or 36 months (PREVENT). Any association between BPV and progression of atherosclerosis was assessed using quantitative coronary angiography (QCA), intravascular ultrasound (IVUS), or B-mode ultrasound (depending on study). Patients from NORMALISE (n = 261) and PREVENT (n = 688 for QCA; n = 364 for ultrasound) were stratified within study according to median systolic BPV. No significant difference in change of minimal luminal diameter (by QCA in PREVENT) or change in percent atheroma volume or normalized total atheroma volume (by IVUS in NORMALISE) was detected for subjects with low BPV (BPV < median) compared with high BPV (BPV ≥ median), regardless of treatment. In PREVENT, a significantly greater reduction in maximum carotid intima-media thickness (IMT) (left and right common carotid artery far wall) was observed for patients with BPV < median compared with those with BPV ≥ median [least squares mean difference 0.06 (95% confidence interval 0.01, 0.11); P = 0.0271], after adjusting for treatment, carotid artery segment (left or right), baseline maximum carotid IMT, and other baseline and cardiovascular risk factors/covariates. Conclusions: In patients with existing CAD and well-controlled BP, visit-to-visit BPV was not associated with progression of coronary atherosclerosis; however, a significantly greater reduction in maximum carotid IMT was observed for patients with low BPV.

Effect of visit-to-visit blood pressure variability on cardiovascular events in patients with coronary artery disease and well-controlled blood pressure.

This post hoc analysis of CAMELOT and PREVENT analyzed the impact of blood pressure variability (BPV, assessed as within-subject standard deviation of SBP from 12 weeks onward) on the incidence of major adverse cardiovascular events (MACE, defined according to original studies). Patients (n = 1677 CAMELOT; n = 776 PREVENT) were stratified by BPV quartile. Regardless of study, BPV was significantly lower for amlodipine versus other treatments. In CAMELOT, a significant association between BPV quartile and MACE was observed with amlodipine treatment. Significant associations between BPV quartile and MACE were observed for both studies, when analyzed overall (adjusting for treatment). In CAMELOT, with amlodipine treatment, an increased risk for MACE was observed with high (BPV ≥ Q3) versus low BPV (< Q1; adjusting for characteristics and risk factors). In both studies, increased risk for MACE was observed for BPV ≥ Q3 versus BPV < Q1 (analyzed overall, adjusting for treatment and covariates). For both studies, BPV, but not mean SBP, was associated with cardiovascular events. BPV was associated with cardiovascular outcomes in patients with CAD and well-controlled BP.

Development of albuminuria and enhancement of oxidative stress during chronic renin-angiotensin system suppression.

OBJECTIVE: Albuminuria has been recently described in hypertensive patients under chronic renin-angiotensin system (RAS) suppression. We investigated whether this fact could be related to an increase in oxidative stress. METHODS: We examined normoalbuminuric and albuminuric patients in stage 2 chronic kidney disease, both with more than 2 years of RAS blockade. The relationship between albuminuria and circulating biomarkers for both oxidative damage, that is carbonyl and malondialdehyde, as well as antioxidant defense, that is reduced glutathione, thiol groups, uric acid, bilirubin, or catalase, and superoxide scavenging activity, was assessed. RESULTS: We found that only patients with albuminuria showed an important increase in carbonyls (P < 0.001) and malondialdehyde (P < 0.05) compared to normoalbuminuric patients. This increase in oxidative damage was also accompanied by a rise in catalase activity (P < 0.05) and low-molecular-weight antioxidants only when they were measured as total antioxidant capacity (P < 0.01). In order to establish the specific oxidative status of each group, new indexes of oxidative damage and antioxidant defense were calculated with all these markers following a mathematical and statistical approach. Although both pro-oxidant and antioxidant indexes were significantly increased in patients with albuminuria, only the oxidative damage index positively correlated with the increase of albumin/creatinine ratio (P = 0.0024). CONCLUSIONS: We conclude that albuminuria is accompanied by an amplified oxidative damage in patients in early stages of chronic kidney disease. These results indicate that chronic RAS protection must be directed to avoid development of albuminuria and oxidative damage.

Influence of high cardiovascular risk in asymptomatic people on the duration and cost of sick leave: results of the ICARIA study.

AIMS: We investigated the potential influence of a moderate-to-high cardiovascular (CV) risk (CVR) (defined as a Systematic COronary Risk Evaluation model, or SCORE ≥ 4%), in the absence of an established CV disease, on the duration and cost of CV and non-CV sick leave (SL) resulting from common and occupational accidents or diseases. METHODS AND RESULTS: We conducted a prospective cohort study on 690 135 workers with a 1-year follow-up and examined CV- and non-CV-related SL episodes. To obtain baseline values, CVR factors were initially assessed at the beginning of the year during routine medical examination. The CVR was calculated with the SCORE charts for all subjects. Moderate-to-high CVR was defined as SCORE ≥ 4%. A baseline SCORE ≥ 4% was associated with a higher risk for long-term CV and non-CV SL, as revealed by follow-up assessment. This translated into an increased cost, estimated at €5 801 464.18 per year. Furthermore, pharmacological treatment for hypertension or hyperlipidaemia was significantly associated with longer SL duration. CONCLUSION: Moderate-to-high CVR in asymptomatic subjects was significantly associated with the duration and cost of CV and non-CV SL. These results constitute the first body of evidence that the SCORE charts can be used to identify people with a non-established CV disease, which might ultimately translate into more lost workdays and therefore increased cost for society.

Manejo de la hipertensión resistente en una unidad multidisciplinaria de denervación renal: protocolo y resultados / Management of resistant hypertension in a multidisciplinary unit of renal denervation: protocol and results

Introducción y objetivos. La hipertensión resistente es un problema clínico por la dificultad de su tratamiento y el aumento de morbimortalidad que conlleva. Se ha demostrado que la denervación renal por catéter mejora el control de estos pacientes. Se describen los resultados de la creación de una unidad multidisciplinaria para la implementación de la denervación renal en el tratamiento de la hipertensión resistente. Métodos. Un equipo compuesto por nefrólogos y cardiólogos diseñó un protocolo para la selección, la intervención y el seguimiento de los pacientes. Se incluyó a 197 pacientes con hipertensión esencial mal controlada pese a la toma de tres o más fármacos. A la técnica de ablación descrita, se añadió el soporte de un navegador basado en angiografía rotacional. Se comparó la presión arterial basal y tras el seguimiento utilizando el test de Wilcoxon para muestras apareadas. Resultados. Se excluyó a 108 (55%) pacientes con hipertensión seudorresistente. A los otros 89, se les administraron antialdosterónicos, a los que respondieron 60 pacientes (30%). Fueron candidatos a denervación los 29 (15%) pacientes restantes. Se realizó ablación a 11 pacientes, con una presión arterial de 164/99mmHg, en tratamiento con 4,4 fármacos. Tras un seguimiento de 72 días, las presiones arteriales sistólica y diastólica se redujeron en 25mmHg (p=0,02) y 10mmHg (p=0,06) respectivamente. En 10 pacientes (91%) se suspendió al menos un fármaco. Conclusiones. La denervación renal implementada mediante un programa multidisciplinario ofrece una mejora en la presión arterial similar a la de estudios previos, con mayor reducción de fármacos antihipertensivos (AU)

Introduction and objectives. Resistant hypertension is a clinical problem because of its difficult management and increased morbidity and mortality. Catheter-based renal denervation has been demonstrated to improve control in these patients. The results of establishing a multidisciplinary unit for the implementation of renal denervation in the management of resistant hypertension are described. Methods. A team of nephrologists and cardiologists created a protocol for patient selection, intervention, and follow-up. One hundred and ninety-seven patients with poorly controlled essential hypertension, despite taking 3 or more drugs, were included. The ablation technique previously described was supported by a navigator based on rotational angiography. Blood pressure at baseline and after follow-up was compared using the Wilcoxon test for paired samples. Results. One hundred and eight patients (55%) with pseudo-resistant hypertension were excluded. The other 89 were given antialdosteronic drugs, to which 60 patients (30%) responded. The remaining 29 patients (15%) were candidates for denervation. Eleven patients, with blood pressure 164/99mmHg and taking 4.4 antihypertensive drugs, were ablated. After 72 days of follow-up, systolic and diastolic blood pressure fell by 25 mmHg (P=.02) and 10 mmHg (P=.06), respectively. In 10 patients (91%) at least 1 drug was discontinued. Results. One hundred and eight patients (55%) with pseudo-resistant hypertension were excluded. The other 89 were given antialdosteronic drugs, to which 60 patients (30%) responded. The remaining 29 patients (15%) were candidates for denervation. Eleven patients, with blood pressure 164/99mmHg and taking 4.4 antihypertensive drugs, were ablated. After 72 days of follow-up, systolic and diastolic blood pressure fell by 25 mmHg (P=.02) and 10 mmHg (P=.06), respectively. In 10 patients (91%) at least 1 drug was discontinued. Conclusions. Renal denervation performed by a multidisciplinary team led to an improvement in blood pressure similar to previous studies, with a greater reduction of antihypertensive drugs. Conclusions. Renal denervation performed by a multidisciplinary team led to an improvement in blood pressure similar to previous studies, with a greater reduction of antihypertensive drugs (AU)

Guidelines updates in the treatment of obesity or metabolic syndrome and hypertension.

Obesity and overweight are nowadays very prevalent worldwide. They are known to be linked with an increased risk of developing cardiovascular comorbidities and mortality. Abdominal obesity is frequently associated with a collection of metabolic disorders that include elevated blood pressure, characteristic lipid abnormalities (low high-density lipoprotein cholesterol and high triglycerides) and increased fasting glucose, with an underlying situation of insulin resistance, which has been defined as metabolic syndrome, conferring a high cardiovascular risk profile to these subjects. A multidisciplinary approach is required, including lifestyle changes and pharmacological and surgical approaches. Intensive management of all the risk factors of the metabolic syndrome is also needed to reduce body weight and waist circumference, lessen insulin resistance and avoid the development of new-onset diabetes and cardiovascular disease associated with this entity. This article will review the recently published literature and guideline updates on this topic, although it is not yet included in the highlights.

Management of resistant hypertension in a multidisciplinary unit of renal denervation: protocol and results.

INTRODUCTION AND OBJECTIVES: Resistant hypertension is a clinical problem because of its difficult management and increased morbidity and mortality. Catheter-based renal denervation has been demonstrated to improve control in these patients. The results of establishing a multidisciplinary unit for the implementation of renal denervation in the management of resistant hypertension are described. METHODS: A team of nephrologists and cardiologists created a protocol for patient selection, intervention, and follow-up. One hundred and ninety-seven patients with poorly controlled essential hypertension, despite taking 3 or more drugs, were included. The ablation technique previously described was supported by a navigator based on rotational angiography. Blood pressure at baseline and after follow-up was compared using the Wilcoxon test for paired samples. RESULTS: One hundred and eight patients (55%) with pseudo-resistant hypertension were excluded. The other 89 were given antialdosteronic drugs, to which 60 patients (30%) responded. The remaining 29 patients (15%) were candidates for denervation. Eleven patients, with blood pressure 164/99 mmHg and taking 4.4 antihypertensive drugs, were ablated. After 72 days of follow-up, systolic and diastolic blood pressure fell by 25 mmHg (P=.02) and 10 mmHg (P=.06), respectively. In 10 patients (91%) at least 1 drug was discontinued. CONCLUSIONS: Renal denervation performed by a multidisciplinary team led to an improvement in blood pressure similar to previous studies, with a greater reduction of antihypertensive drugs.

Microalbuminuria breakthrough under chronic renin-angiotensin-aldosterone system suppression.

OBJECTIVES: Microalbuminuria has been shown to be a potent predictor for future development of cardiovascular and renal events that can be prevented by the use of angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs). Both classes of drugs are now-a-days widely used in the treatment of arterial hypertension since the very early stages of the cardiorenal continuum when only cardiovascular risk factors are detected. We describe here the development of de-novo microalbuminuria in patients chronically treated with either an ACEi or an ARB at adequate doses. METHODS: We reviewed the evolution of 1433 patients (mean age 60.5 ±â€Š12.4 years, 50.3% men, 6.6% having type 2 diabetes), arriving in our hospital-based Hypertension Unit previously treated for a least 2 years either with an ACEi or an ARB, at adequate doses, alone or in combination with other antihypertensive drugs. RESULTS: A total of 184 (16.1%) patients developed new-onset microalbuminuria, whereas macroalbuminuria was detected in 11 (1.0%) patients at the end of follow-up. Albuminuria appeared at any level of blood pressure (BP) from below 130/80 mmHg, albeit the highest percentage was seen when SBP was above 160 mmHg. De-novo microalbuminuria was more frequent in those patients presenting with established cardiovascular disease and predicts the future development of cardiovascular events but was not accompanied by a significant worsening of renal function. CONCLUSION: These data indicate that a reappraisal of renin-angiotensin-aldosterone system (RAAS) suppression is required when microalbuminuria appears in patients under chronic RAAS suppression.

Validation of a therapeutic scheme for the treatment of resistant hypertension.

We tested the hypothesis that a therapeutic strategy of substituting the diuretic (most commonly hydrochlorothiazide) with chlorthalidone (50 mg/day), and, if needed, the calcium channel blocker with the highest dose of the most commonly used calcium antagonist (amlodipine 10 mg), and adding on top a direct renin inhibitor (aliskiren 300 mg) is effective to treat resistant hypertensive patients not responding to spironolactone. The scheme was tested in a group of 76 patients who had true treatment resistant hypertension (24-hour mean blood pressure ≥130/80 mm Hg while receiving three or more drugs). An effective response to spironolactone was defined as 24-hour ambulatory systolic blood pressure (SBP) drop by more than 20 mm Hg, and was obtained with 25-50 mg in 60 patients (78.9%). In patients with inadequate response to spironolactone (n = 16), we administered the triple combination plus the remaining therapy, a mean decrease of 29 mm Hg (95% CI 11-48; P = .004) for SBP and 12 mm Hg (95% CI: 4-20 mm Hg) for diastolic BP were observed. In only 1 of 16 patients (6%), the response was considered as insufficient. These data indicate the need for further testing this scheme that looks really promising to treat resistant hypertensive patients not responding to spironolactone.