Susana Vázquez

Spironolactone versus sympathetic renal denervation to treat true resistant hypertension: results from the Denervhta study – a randomized controlled trial

Objective: Both renal denervation (RDN) and spironolactone have been proposed for the treatment of resistant hypertension. However, they have not been compared in a randomized clinical trial. We aimed to compare the efficacy of spironolactone versus RDN in patients with resistant hypertension. Methods: A total of 24 patients with office SBP at least 150 mmHg and 24-h SBP at least 140 mmHg despite receiving at least three full-dose antihypertensive drugs, one a diuretic, but without aldosterone antagonists, were randomized to receive RDN or spironolactone (50 mg) as add-on therapy. Primary endpoint was change in 24-h SBP at 6 months. Comparisons between treatment groups were performed using generalized linear models adjusted by age, sex, and baseline values. Results: Spironolactone was more effective than RDN in reducing 24-h SBP and 24-h DBP: mean baseline-adjusted differences between the two groups were −17.9 mmHg (95%CI −30.9 to −4.9); P = 0.010 and −6.6 mmHg (95%CI −12.9 to −0.3); P = 0.041, for 24-h SBP and 24-h DBP, respectively. As regards changes in office blood pressure, mean baseline-adjusted differences between the two groups were −12.1 mmHg (95%CI −29.1 to 5.1); P = 0.158 and of −5.3 mmHg (95%CI −16.3 to 5.8); P = 0.332, for office SBP and office DBP, respectively. Otherwise, the decrease of estimated glomerular filtration rate was greater in the spironolactone group; mean baseline-adjusted difference between the two groups was −10.7 ml/min per 1.73 m2 (95%CI −20.1 to −1.4); P = 0.027. Conclusion: We conclude that spironolactone is more effective than RDN to reduce 24-h SBP and 24-h DBP in patients with resistant hypertension. Therefore, spironolactone should be the fourth antihypertensive drug to prescribe if deemed well tolerated’ in all patients with resistant hypertension before considering RDN.

Putative endothelial progenitor cells are associated with flow‐mediated dilation in refractory hypertensives

Background. Hypertension has been related to endothelial dysfunction. Patients with refractory hypertension (RH) have a reduced number of endothelial progenitor cells (EPCs). Aim. To evaluate if blood EPC levels relate to endothelium‐dependent vasodilation (ED‐VD) in RH. Methods. We analyzed 29 RH confirmed by 24‐h ambulatory blood pressure monitoring and assessed complete clinical and laboratory evaluation. EPCs were isolated from peripheral mononuclear cells (MNC) by flow cytometry. ED‐VD was determined measuring flow‐mediated dilation (FMD) by venous occlusion plethysmography. Results. Circulating EPCs/105 MNC (median [Q1–Q3]): 23.0 [4.5–53.8]. FMD (median [Q1–Q3]): 211.7 [79.5–365.8]%. Significant correlations with log‐FMD: EPCs (r = 0.469; p = 0.018) and homocysteine (r = −0.414; p = 0.045). There was no collinearity between EPCs and homocysteine. FMD did not correlate with age, gender, office BP, 24‐h systolic blood pressure or 24‐h diastolic blood pressure, laboratory parameters, C‐reactive‐protein, left ventricular‐mass index, dyslipidaemia, smoking habit and statin or angiotensin system blockers treatment. Multiple linear regression analysis showed that after age‐adjustment, EPC (p = 0.027) and homocysteine (p = 0.004) were the only variables that predicted FMD (R = 0.740). After dividing patients according to EPC number, patients in the lower tertile showed a significantly reduced FMD compared with those in the group of the two upper tertiles of EPC: log‐FMD (mean±SD): 4.7±0.9 vs 5.6±0.8, respectively (p = 0.031). Conclusions. ED‐VD independently correlates with circulating EPCs in RH. Homocysteine is also an independent predictor of lower FMD in such patients.

Hypertension confirmation and blood pressure control rates in epidemiological surveys

Background Scarce knowledge about hypertension confirmation and control after a single blood pressure (BP) measurement is available. The objective of this study was to evaluate hypertension confirmation and control rates after 6-year follow-up in a population-based cohort. Methods A cohort of 1748 participants representative of a Spanish population received standardized BP measurements. Systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg was found in 617 participants. Three hundred and thirty-four of them had no history of hypertension and the remaining 283 had been previously diagnosed or received antihypertensive treatment. All were advised to consult their physicians. We discarded for follow-up 109 participants with already well-controlled hypertension (27.8% of all hypertensive participants). We followed 583 participants (94.5% of the cohort) for 6 years (14 died and 20 were lost to follow-up). Results The diagnosis of hypertension was confirmed during follow-up in 139 (44.4%) of those with no previously known hypertension, making the overall prevalence for the cohort equal to 30.4% (n = 531). The hypertension control rate at the end of follow-up was 50.1 %, whereas it was 27.9% at baseline. Diabetes was the only factor to be independently associated with good control of hypertension. Conclusion Six years after a single-occasion blood pressure measurement, hypertension was confirmed in almost half of the participants with systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg and no history of hypertension. Hypertension control achieved with this screening procedure is almost double that observed in the baseline examination, and is highest among diabetic participants.

Urinary Albumin Excretion at Follow-Up Predicts Cardiovascular Outcomes in Subjects With Resistant Hypertension

BACKGROUND Renal function and albuminuria predict cardiovascular disease (CVD) in general population. However, their prognostic value in patients with resistant hypertension (RH) is somewhat unknown. OBJECTIVE To determine the ability of renal function and albuminuria to predict CVD in RH patients. METHODS One hundred and thirty-three RH (blood pressure [BP] ≥140/90mmHg despite treatment with ≥3 drugs) patients were evaluated. Median follow-up was 73 months. Primary endpoint was a composite of non-fatal cardiovascular events or cardiovascular death. Serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) were determined. Microalbuminuria was defined as a urinary albumin-to-creatinine ratio (UACR) ≥30mg/g. RESULTS Twenty-two patients (16.5%) reached the primary endpoint. Long-term elevated UACR (66 vs. 17mg/g, P=0.045), but not at baseline, was associated with the primary endpoint, after adjusting for age, prior CVD, and both eGFR and office systolic-BP at baseline and during follow-up. Although baseline SCr and eGFR were associated with CVD, significance was lost after baseline risk adjustment. Baseline microalbuminuria prevalence was 45% and 41% in patients with and without CVD (P=0.813), while percentages of patients with microalbuminuria at follow-up were 67% and 28%, respectively (P=0.002). More patients with de novo CVD, compared with those without CVD, developed microalbuminuria at follow-up (28% vs. 6%) or had persistent microalbuminuria (39% vs. 21%), while fewer patients with CVD had microalbuminuria regression (11% vs. 19%) or remained normoalbuminurics (22% vs. 53%; overall P=0.005). CONCLUSION In RH patients, the inability to microalbuminuria regression, either due to persistence or new appearance, independently predicts CVD.

Renal Denervation vs. Spironolactone in Resistant Hypertension: Effects on Circadian Patterns and Blood Pressure Variability

BACKGROUND Sympathetic renal denervation (SRD) has been proposed as a therapeutic alternative for patients with resistant hypertension not controlled on pharmacological therapy. Two studies have suggested an effect of SRD in reducing short-term blood pressure variability (BPV). However, this has not been addressed in a randomized comparative trial. We aimed to compare the effects of spironolactone and SRD on circadian BP and BPV. METHODS This is a post-hoc analysis of a randomized trial in 24 true resistant hypertensive patients (15 men, 9 women; mean age 64 years) comparing 50mg of spironolactone (n = 13) vs. SRD (n = 11) on 24-hour BP. We report here the comparative effects on daytime (8 AM–10 PM) and nighttime (0 AM–6 AM) BP, night-to-day ratios and BP and heart rate variabilities (SD and coefficient of variation of 24-hour, day and night, as well as weighted SD and average real variability (ARV)). RESULTS Spironolactone was more effective than SRD in reducing daytime systolic (P = 0.006), daytime diastolic (P = 0.006), and nighttime systolic (P = 0.050) BP. No differences were observed in the night-to-day ratios. In contrast, SRD-reduced diastolic BPV (24 hours, daytime, nighttime, weighted, and ARV; all P < 0.05) with respect to spironolactone, without significant differences in systolic BPV. CONCLUSION Spironolactone is more effective than SRD in reducing ambulatory BP. However, BPV is significantly more reduced with SRD. This effect could be important in terms of potential prevention beyond BP reduction and deserves further investigation.

Central blood pressure variability is increased in hypertensive patients with target organ damage

We aimed to evaluate the association of aortic and brachial short‐term blood pressure variability (BPV) with the presence of target organ damage (TOD) in hypertensive patients. One‐hundred seventy‐eight patients, aged 57 ± 12 years, 33% women were studied. TOD was defined by the presence of left ventricular hypertrophy on echocardiogram, microalbuminuria, reduced glomerular filtration rate, or increased aortic pulse wave velocity. Aortic and brachial BPV was assessed by 24‐hour ambulatory BP monitoring (Mobil‐O‐Graph). TOD was present in 92 patients (51.7%). Compared to those without evidence of TOD, they had increased night‐to‐day ratios of systolic and diastolic BP (both aortic and brachial) and heart rate. They also had significant increased systolic BPV, as measured by both aortic and brachial daytime and 24‐hours standard deviations and coefficients of variation, as well as for average real variability. Circadian patterns and short‐term variability measures were very similar for aortic and brachial BP. We conclude that BPV is increased in hypertensive‐related TOD. Aortic BPV does not add relevant information in comparison to brachial BPV.

Organ damage changes in patients with resistant hypertension randomized to renal denervation or spironolactone: The DENERVHTA (Denervación en Hipertensión Arterial) study

Renal denervation and spironolactone have both been proposed for the treatment of resistant hypertension, but their effects on preclinical target organ damage have not been compared. Twenty‐four patients with 24‐hour systolic blood pressure ≥140 mm Hg despite receiving three or more full‐dose antihypertensive drugs, one a diuretic, were randomized to receive spironolactone or renal denervation. Changes in 24‐hour blood pressure, urine albumin excretion, arterial stiffness, carotid intima‐media thickness, and left ventricular mass index were evaluated at 6 months. Mean baseline‐adjusted difference between the two groups (spironolactone vs renal denervation) at 6 months in 24‐hour systolic blood pressure was −17.9 mm Hg (95% confidence interval [CI], −30.9 to −4.9; P = .01). Mean baseline‐adjusted change in urine albumin excretion was −87.2 (95% CI, −164.5 to −9.9) and −23.8 (95% CI, −104.5 to 56.9), respectively (P = .028). Mean baseline‐adjusted variation of 24‐hour pulse pressure was −13.5 (95% CI, −18.8 to −8.2) and −2.1 (95% CI, −7.9 to 3.7), respectively (P = .006). The correlation of change in 24‐hour systolic blood pressure with change in log‐transformed urine albumin excretion was r = .713 (P < .001). At 6 months there was a reduction in albuminuria in patients with resistant hypertension treated with spironolactone as compared with renal denervation.

Cuff-Based Oscillometric Central and Brachial Blood Pressures Obtained Through ABPM are Similarly Associated with Renal Organ Damage in Arterial Hypertension

Background/Aims: Central blood pressure (BP) has been suggested to be a better estimator of hypertension-associated risks. We aimed to evaluate the association of 24-hour central BP, in comparison with 24-hour peripheral BP, with the presence of renal organ damage in hypertensive patients. Methods: Brachial and central (calculated by an oscillometric system through brachial pulse wave analysis) office BP and ambulatory BP monitoring (ABPM) data and aortic pulse wave velocity (PWV) were measured in 208 hypertensive patients. Renal organ damage was evaluated by means of the albumin to creatinine ratio and the estimated glomerular filtration rate. Results: Fifty-four patients (25.9%) were affected by renal organ damage, displaying either microalbuminuria (urinary albumin excretion ≥30 mg/g creatinine) or an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Compared to those without renal abnormalities, hypertensive patients with kidney damage had higher values of office brachial systolic BP (SBP) and pulse pressure (PP), and 24-h, daytime, and nighttime central and brachial SBP and PP. They also had a blunted nocturnal decrease in both central and brachial BP, and higher values of aortic PWV. After adjustment for age, gender, and antihypertensive treatment, only ABPM-derived BP estimates (both central and brachial) showed significant associations with the presence of renal damage. Odds ratios for central BP estimates were not significantly higher than those obtained for brachial BP. Conclusion: Compared with peripheral ABPM, cuff-based oscillometric central ABPM does not show a closer association with presence of renal organ damage in hypertensive patients. More studies, however, need to be done to better identify the role of central BP in clinical practice.