Giulia Cartoni

Effect of aliskiren treatment on endothelium-dependent vasodilation and aortic stiffness in essential hypertensive patients

AIMS Aliskiren is a new oral non-peptide renin inhibitor. Its effects on vascular function in human hypertension are unknown. We assessed whether aliskiren may improve peripheral endothelial function and arterial stiffness in essential hypertensive patients (EH), when compared with the angiotensin-converting enzyme-inhibitor ramipril. METHODS AND RESULTS Fifty EH received treatment with aliskiren (150-300 mg/daily) or ramipril (5-10 mg/daily) for 12 weeks, according to a randomized, open with blind endpoints, parallel group design. We studied the forearm blood flow (straingauge plethysmography) response to intrabrachial acetylcholine, repeated under the nitric oxide synthase inhibitor N(G)-monomethyl-l-arginine (l-NMMA) (4 μmol/min), or the antioxidant ascorbic acid (8 mg/100 mL/min). Carotid-to-femoral pulse wave velocity (PWV), central blood pressure and augmentation index (AIx) were obtained by applanation tonometry. Brachial blood pressure was similarly normalized by aliskiren (from 149/94 to 136/86 mmHg) and ramipril (from 148/92 to 135/85 mmHg), as well as central blood pressure. Aliskiren increased (P < 0.001) the vasodilation to acetylcholine and restored the inhibitory effect of l-NMMA on acetylcholine. Ascorbic acid, which at baseline potentiated the response to acetylcholine, no longer improved endothelium-dependent relaxation after aliskiren treatment. In contrast, ramipril failed to affect the response to acetylcholine, the lacking inhibitory effect of l-NMMA, or the potentiating effect of ascorbic acid. Pulse wave velocity was significantly (P < 0.05) and similarly reduced by both drugs. Aliskiren induced a significantly (P < 0.05) greater AIx reduction than ramipril. CONCLUSION Aliskiren increased nitric oxide availability in the forearm resistance arterioles of EH, an effect probably determined by an antioxidant activity, which can also contribute to improved peripheral wave reflection.

Relationship between wave reflection and renal damage in hypertensive patients: a retrospective analysis

Objective: Arterial stiffening has harmful effects; peripheral pulse wave reflections deleteriously increase central pressure, but on the contrary they could also possibly be protective, as the pulse is transmitted to the microcirculation to a lesser extent. The aim of this study was, therefore, to explore the relationship between wave reflection and small vessel damage in the kidney. Methods: In 216 hypertensive patients, data on renal resistive index, obtained by Doppler ultrasound sampling of the interlobar arteries, as well as augmentation index (AIx) and carotid-to-femoral pulse wave velocity (PWV), were retrospectively analyzed. Reflection magnitude was computed through a triangular flow estimate. Results: AIx and reflection magnitude were positively correlated with resistive index; age, BMI, central pulse pressure, and cholesterol, but not AIx or reflection magnitude, were predictors of resistive index in multivariate analyses. Crossing tertiles of PWV and AIx, resistive index did not differ between patients with high AIx and low PWV (n = 25; 0.632 (0.064)) and those with low AIx and high PWV (n = 17; 0.645 (0.053)), despite a difference in reflection magnitude (74.9 (6.7) vs. 51.2 (7.3)%; P < 0.001). Conclusion: Pressure wave reflection is positively correlated with resistive index in a hypertensive population. No negative relationship was found even adjusting for confounders or when it was examined separately from the influence of arterial stiffness. These findings do not support the hypothesis of peripheral wave reflections having a significant protective role for the microcirculation of a low resistance vascular bed such as the kidney.

Carotid and aortic stiffness in essential hypertension and their relation with target organ damage: the CATOD study

Objective: The objective of the study is to investigate in the hypertensive population the possible differential association between increased aortic and/or carotid stiffness and organ damage in multiple districts, such as the kidney, the vessels, and the heart. Methods: In 314 essential hypertensive patients, carotid–femoral pulse wave velocity (cfPWV, by applanation tonometry) and carotid stiffness (from ultrasound images analysis), together with left ventricular hypertrophy, carotid intima–media thickness, urinary albumin–creatinin ratio, and glomerular filtration rate were measured. Increased cfPWV and carotid stiffness were defined according to either international reference values or the 90th percentile of a local control group (110 age and sex-matched healthy individuals). Results: When considering the 90th percentile of a local control group, increased cfPWV was associated with reduced glomerular filtration rate, either when carotid stiffness was increased [odds ratio (OR) 13.27 (confidence limits (CL) 95% 3.86–45.58)] or not [OR 7.39 (CL95% 2.25–24.28)], whereas increased carotid stiffness was associated with left ventricular hypertrophy, either when cfPWV was increased [OR 2.86 (CL95% 1.15–7.09)] or not [OR 2.81 (CL95% 1.13–6.97)]. No association between increased cfPWV or carotid stiffness and target organ damage was found when cutoffs obtained by international reference values were used. The concomitance of both increased cfPWV and carotid stiffness did not have an additive effect on organ damage. Conclusion: Aortic and carotid stiffness are differentially associated with target organ damage in hypertensive patients. Regional arterial stiffness as assessed by cfPWV is associated with renal organ damage and local carotid stiffness with cardiac organ damage.

Combination therapy with lercanidipine and enalapril reduced central blood pressure augmentation in hypertensive patients with metabolic syndrome

Arterial stiffness and blood pressure (BP) augmentation are independent predictors of cardiovascular events. In a randomized, open, parallel group study we compared the effect on these parameters of combination therapy with an ACE-inhibitor plus calcium channel blocker or thiazide diuretic in 76 hypertensive patients with metabolic syndrome uncontrolled by ACE-inhibitor monotherapy. After 4weeks run-in with enalapril (ENA, 20mg), patients were randomized to a combination therapy with lercanidipine (LER, 10-20mg) or hydrochlorothiazide (HCT, 12.5-25mg) for 24weeks. Aortic stiffness (carotid to femoral pulse wave velocity, PWV), central BP values and augmentation (augmentation index, AIx) were measured by applanation tonometry. The two groups showed similar office and central BP after run-in. Office (ENA/LER: from 149.1±4.9/94.5±1.5 to 131.7±8.1/82.2±5.3; ENA/HCT: from 150.3±4.7/94.7±2.1 to 133.1±7.1/82.8±5.3mmHg) and central BP (ENA/LER 127.4±17.1/85.2±12.1 to 120.5±13.5/80.0±9.5mmHg; ENA/HCT 121.6±13.4/79.3±9.5mmHg) were similarly reduced after 24weeks. PWV was comparable after run-in and not differently reduced by the two treatments (ENA/LER from 8.6±1.5 to 8.1±1.3m/s, p<0.05; ENA/HCT from 8.5±1.2 to 8.2±1.0m/s, p<0.05). Finally, both combinations reduced AIx, but its reduction was significantly greater (p<0.05) in ENA/LER (from 26.8±10.9 to 20.6±9.1%) than in ENA/HCT arm (from 28.2±9.0 to 24.7±8.7%). In conclusion, the combination with LER caused a similar PWV reduction as compared to HCT, but a greater reduction in AIx in hypertensive patients with metabolic syndrome not controlled by ENA alone. These results indicate a positive effect of the combination of ENA/LER on central BP augmentation, suggesting a potential additive role for cardiovascular protection.

Hypertension in special populations: athletes

Physical exercise is known to lower blood pressure and reduce cardiovascular risk through a wide range of mechanisms. Nevertheless, hypertension is the most prevalent cardiovascular disease among athletes and physically active subjects. This article reviews the state of the art in practical approaches to this issue, focusing on special aspects a physician should take into account when diagnosing hypertension, such as screening of secondary causes, assessment of global cardiovascular risk and target organ damage and, in addition, the treatment choice in athletes.

4D.06: PROGRESSION OF CAROTID ARTERY REMODELING AND STIFFNESS IN HYPERTENSIVE PATIENTS: A PROSPECTIVE COHORT STUDY.

Objective: To evaluate the rate progression over time of carotid and aortic stiffness and carotid remodeling in hypertensive patients in real-life and explore determinants of stiffness changes over time. Design and method: In this prospective observational study, 153 hypertensive patients were evaluated at Visit 0 (V0) and after a 3.6 ± 1.2-year follow-up (V1). Carotid-femoral pulse wave velocity (PWV), carotid intima-media thickness (cIMT) and carotid stiffness (CS) were assessed. Results: Diastolic BP was reduced during follow-up, (from 142.4 ± 15.6/82.2 ± 8.8 to 141.2 ± 17.2/79.7 ± 10.9 mmHg, p = ns for systolic BP, p = 0.026 for diastolic BP), due to increased number of antihypertensive drugs (1.2 ± 1.0 to 1.8 ± 1.0, p < 0.001). PWV, cIMT, CS were unchanged from V0 to V1. Conversely a significant increase in carotid diameter was observed (from 7,49 ± 0,85 to 7,80 ± 0,81 mm, p = 0,002). The study population was divided in tertiles according to reduction (delta V1-V0 < -0.5 m/s), stability or increase (delta V1-V0 > 0.5 m/s) in PWV or CS. Patients with reduced PWV during follow-up showed at V0 greater values of systolic BP (146.3 ± 14.4, 139.8 ± 13.6, 141.0 ± 17.4mmHg, p = 0.077), PWV (10.1 ± 2.1, 8.7 ± 1.8, 8.9 ± 1.8m/s, p < 0.05) and mean carotid diameter (7.82 ± 0.93, 7.26 ± 0.75, 7.41 ± 0.72 mm, p < 0.05) than those with stable or increased PWV. They also experienced an increased systolic BP reduction over time (-7.9 ± 17.0, -2.0 ± 15.1, +3.5 ± 18.2 mmHg, p < 0.0001) and no further carotid enlargement (+0.16 ± 0.58, +0.40 ± 0.53, +0.39 ± 0.47 mm, p = 0.046). Patients with reduced CS over time showed at V0 higher systolic BP values (146.9 ± 15.3, 144.6 ± 13.0, 135.8 ± 16.3 mmHg, p = 0,0008) than those with stable or increased CS, a greated BP reduction over time (-10.6 ± 18.1, -4.5 ± 16.3, +7.6 ± 12.8 mmHg, p < 0.0001) and no further carotid enlargement over time (+0.13 ± 0.57, +0.35 ± 0.50,+0.45 ± 0.50 mm, p = 0,016). Patients with increased CS over time had a lower rate of BP-lowering grug uptitration (54.7, 51.1, 31.9%, p = 0.05). Conclusions: In a cohort of hypertensive patients, followed-up for about 3 years in a real-life setting, aortic and carotid stiffness, as well as cIMT did not change over time, but there was a progression of carotid artery maladaptive remodeling. Patients with reduced PWV and CS over time showed higher BP values at baseline, greater BP reduction over time and no further carotid enlargement, possibly due to more intensive drug treatment.

DIFFERENT IMPACT OF HYPERTENSION AND TYPE 2 DIABETES ON AORTIC, CAROTID AND PERIPHERAL VASCULAR STIFFNESS: PP.10.408

Objective: Type-2 diabetes and hypertension both induce early vascular aging. Aim of the study is to explore the impact of diabetes, hypertension, and their combination on aortic, carotid and peripheral stiffening. Design and Method: 114 subjects (18 normotensives-NT, 37 hypertensives-HT, 20 diabetic normotensives-DMNT, and 39 diabetic hypertensives-DMHT) were enrolled. Applanation tonometry was used to measure aortic (carotid to femoral) and peripheral (carotid to radial) pulse wave velocity (aPWV and pPWV respectively). Common carotid intima-media thickness (IMT) and diameter were obtained by B-mode ultrasound image sequences, using the real-time computerized contour-tracking system “Carotid Studio”. Common carotid stiffness (CS) was determined from stroke change in lumen area and local pulse pressure obtained by applanation tonometry. Results: pPWV was superimposable in all groups. aPWV significantly increased ranging from NT (7.2 ± 1.0m/s) to HT (8.1 ± 1.4m/s) and DMNT (8.2 ± 0.8m/s), reaching the highest value in the DMHT group (10.6 ± 1.9m/s). CS behaved similarly (NT 6.0 ± 0.7m/s, DMNT 6.5 ± 1.2m/s, HT 6.6 ± 1.2m/s, DMHT 7.3 ± 1.2m/s). The presence of hypertension carried a 6.9-fold (confidence limits 5–95%: 1.9–24.8) increased risk of having an increased (above the median value) aPWV, a 2.8-fold (1.1–7.4) increased risk of having an increased CS, and a 3.9-fold (1.4–10.6) increased risk of having an increased carotid diameter, regardless of age and diabetes, while the analysis was not significant for pPWV and IMT. The presence of diabetes carried a 9.6-fold (3.3–27.2) increased risk of having an increased aPWV and a 2.7-fold (1.1–6.6) increased risk of having an increased IMT, regardless of age and hypertension, while the analysis was not significant for pPWV, carotid diameter and stiffness. Conclusions: Both diabetes and hypertension are associated with normal pPWV and increased aPWV, and their combination induces an even greater aortic stiffness. Hypertension is characterized by vascular stiffness at both the aortic and carotid level. In contrast, diabetes is associated only with increased aPWV. The two conditions are also different for carotid remodeling characteristics, since hypertension determines dilation while diabetes wall thickening.