César Cerezo

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.

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.

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.

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.

TRENDS IN ALBUMINURIA UNDER RENIN-ANGIOTENSIN SYSTEM SUPPRESSION: HT.3.05

Introduction: RAS suppression is considered as the therapy of choice, together with a strict BP control, to prevent the development and to impede the progression of albuminuria. Objective: We have reviewed the evolution of albuminuria in a group of 1433 patients (mean age 60.5 yr; 50.3% male), arriving in our unit as a consequence of arterial hypertension with varying degrees of associated cardiovascular risk factors. All had in common the existence of previous therapy with an ACEi or an ARB for a minimum of two years before arrival in the Unit. Results: When first seen 67.7% were normoalbuminuric (albumin-to-creatinine ratio [ACR] <10 mg/g for male, <15 mg/g for female), 11.9% exhibited high-normal values of albuminuria (ACR 10–20 mg/g for male, 15–30 mg/g for female), 16.4% were microalbuminuric (ACR 20–200 mg/g for male, 30–300 mg/g for female) and 4% had macroalbuminuria (ACR >200 mg/g for male, >300 mg/g for female). At that time measured creatinine clearance was 96.8 ± 49.6 and 54.1% had BP values below 140/90 mmHg. All of them were followed for three years during which RAS suppression was maintained, while BP control improved. At the end of follow-up, only 54.9% were normoalbuminuric, 16.1% presented high-normal albuminuria, 21.6% were microalbuminuric and 7.4% macroalbuminuric (p < 0.004). The changes were seen in non-diabetic (p < 0.005) but were more marked in diabetics with only 37.5% of patients being normoalbuminuric. Conclusions: These results indicate that albuminuria develops in the presence of chronic RAS suppression at adequate doses and progresses continuously. Long-term RAS suppression needs to be revisited in order to control this alteration.

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.

The Long-Term Effects of RAAS Blockade on Renal Function

Chronic kidney disease is frequently observed in patients with arterial hypertension. Microalbuminuria and a decreased estimated glomerular filtration rate (<60 ml/min/1.73 m2) are both accompanied by a significant increase in cardiovascular risk. It is well recognized that the reduction of blood pressure levels contributes to diminish the risk of development and progression of cardiovascular and renal disease. Renin-angiotensin system suppressors, both angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), have demonstrated favourable effects on cardiovascular and renal prognosis, but some limitations have been described, as is the angiotensin and aldosterone breakthrough. The addition of an ACEi to an ARB or viceversa was initially considered as a way to obtain a stronger suppression of renin-angiotensin-aldosterone system, but recent evidences have shown that the combination of these two classes of drugs does not seem to demonstrate the expected increase in benefit. Recent data show that cardiorenal disease could progress even under chronic renin-angiotensin system blockade, so future studies will be necessary to elucidate which is the ideal management for enhancing renin-angiotensin system suppression with the aim of decreasing cardiorenal damage.