Alexandra Yannoutsos

Pathophysiology of hypertension: interactions between macro and microvascular alterations through endothelial dysfunction.

Hypertension is a multifactorial systemic chronic disorder through functional and structural macrovascular and microvascular alterations. Macrovascular alterations are featured by arterial stiffening, disturbed wave reflection and altered central to peripheral pulse pressure amplification. Microvascular alterations, including altered wall-to-lumen ratio of larger arterioles, vasomotor tone abnormalities and network rarefaction, lead to disturbed tissue perfusion and susceptibility to ischemia. Central arterial stiffness and microvascular alterations are common denominators of organ damages. Vascular alterations are intercorrelated, amplifying the haemodynamic load and causing further damage in the arterial network. A plausible precursor role of vascular alterations in incident hypertension provides new insights for preventive and therapeutic strategies targeting macro and microvasculature. Cumulative metabolic burden and oxidative stress lead to chronic endothelial injury, promoting structural and functional vascular alterations, especially in the microvascular network. Pathophysiology of hypertension may then be revisited, based on both macrovascular and microvascular alterations, with a precursor role of endothelial dysfunction for the latter.

Aortic stiffness and cardiovascular risk in type 2 diabetes.

Objective: Damage to large arteries is a major contributor to high cardiovascular morbi-mortality in type 2 diabetic patients. Pulse wave velocity (PWV), depending on both structural and functional characteristics of the arterial wall, has poorly been ascertained in its ability to be a marker of cardiovascular risk in diabetic patients. In order to determine the factors influencing aortic stiffness, and the potential predictor role of this measurement, a cross-sectional study on a cohort of 618 type 2 diabetic patients with or without cardiovascular events was conducted. Methods: Aortic PWV (estimated by carotid-femoral PWV measurement) was determined using an automatic device and cardiovascular risk was determined, using Framingham equation (10-year absolute cardiovascular disease risk), in individuals without previous cardiovascular events. Multilinear regression analysis was performed to assess relationships between aortic PWV, population characteristics and the presence of cardiovascular disease. Multivariate models (with and without PWV) were compared to determine whether aortic PWV improves explicative model of presence of cardiovascular disease. Results: Increased aortic PWV was strongly associated with presence of coronary, cerebral and peripheral vascular diseases. Increased aortic PWV was independently associated with previous cardiovascular events and improved the explicative model of presence of cardiovascular disease above the known cardiovascular risk factors. Conclusion: This study provides evidence that aortic PWV is a forceful independent marker of cardiovascular disease in diabetic patients, as it has already been demonstrated in hypertensive individuals. Prospective trials are needed to assess the improvement in cardiovascular risk prediction for widespread use of aortic PWV in diabetic patients.

Effect of a fixed combination of Perindopril and Amlodipine on blood pressure control in 6256 patients with not-at-goal hypertension: the AVANT'AGE study.

In clinical practice, general practitioners are likely to face hypertensives with uncontrolled blood pressure (BP), whose antihypertensive treatment need to be modified. In the present study, 710 general practitioners have each included the first 10 patients with not-at-goal hypertension, for whom they decided to modify their antihypertensive treatment with addition of a fixed combination of Perindopril and Amlodipine at either of its four dosages: 5/5, 5/10, 10/5, or 10/10 mg. In total, 6256 patients were included, with BP measured both at baseline and after 3 months. At the end of follow-up, a mean reduction of 20.3 ± 12.4 mm Hg in systolic BP and 11.3 ± 9.6 mm Hg in diastolic BP were observed, and 62.3% achieved successful BP control. Body mass index and waist circumference were significant determinants of both systolic and diastolic BP reductions (P ≤ .04). Moreover, in addition to baseline BP level, body mass index was the only significant determinant of BP control of systolic, diastolic BP, and of both (P ≤ .04). Addition of a fixed combination of Perindopril and Amlodipine to BP regimen was efficient, in terms of BP control, for 62.3% of those patients with not-at-goal hypertension. Furthermore, baseline BP level and obesity were important influential factors of BP control.

Hemodynamic parameters in hypertensive diabetic patients.

Objective: Despite adequate glycemic and blood pressure control, diabetic hypertensives remain at increased cardiovascular risk. Aortic stiffness and pulse pressure (PP) amplification may provide complementary information to correct cardiovascular risk. We aim to determine whether these hemodynamic parameters are interrelated or not and to explore the factors related to pressure pulsatility. Methods: A cross-sectional study was conducted in 351 patients, involving controls, hypertensives without diabetes and diabetic patients with or without hypertension. Hemodynamic parameters were determined by applanation tonometry. Multivariate regression analyses evaluated the interest of therapeutic strategies. Results: Aortic stiffness and PP amplification were not interrelated (P = 0.32) in multivariate-adjusted analysis and were both independently associated with previous cardiovascular events. Although disproportionately increased aortic stiffness in diabetic hypertensives (P < 0.001), no difference was found for PP amplification. The present dissociation between these two hemodynamic parameters may be related to the effect of increased heart rate (P < 0.001) in the presence of diabetes, in men and women. In diabetic hypertensives, aortic stiffness was correlated with glycated hemoglobin level (P = 0.04), but not with blood pressure or heart rate. Antihypertensive and statin treatments were correlated with PP amplification but not with aortic stiffness. Conclusion: Aortic stiffness and PP amplification were not interrelated, suggesting that these markers may provide complementary information for cardiovascular risk. New therapeutic strategies targeting pressure pulsatility should take into account the impact of hyperglycemia and increased heart rate in diabetic hypertensives. Gender influence on the role of autonomic nervous system in attenuating pressure wave reflections remains to be further established.

Central Hemodynamics for Risk Reduction Strategies: Additive Value Over and Above Brachial Blood Pressure

Reduction strategies of blood pressure, as a modifiable cardiovascular risk, are currently based on office assessment of brachial artery blood pressure. However, antihypertensive treatment based on brachial BP values reduces cardiovascular risk but cannot completely reverse the hypertension-induced risk of morbidity events. As is well known, BP varies in different arterial systems and invasive and non-invasive studies have demonstrated that brachial BP does not necessarily reflect central aortic BP. Emerging evidences now suggest that central pressure may predict cardiovascular diseases better than brachial BP; moreover, it may differently respond to certain antihypertensive drugs. The potential effects beyond peripheral BP control may be due to specific protective properties of different antihypertensive drugs in affecting central aortic pressure and arterial stiffness. Although data on direct cardiovascular benefit impact of central blood pressure treatment in randomized clinical trials are still lacking, it is likely that the improvement of quality of care and the individualized assessment of the hypertension-associated cardiovascular risk are achievable with the use of central hemodynamics. Therefore, basing antihypertensive treatment guidance on central pressures rather than on peripheral blood pressure may be the key for future antihypertensive strategies.

Central hemodynamics in risk assessment strategies: additive value over and above brachial blood pressure.

Although the clinical relevance of brachial blood pressure (BP) measurement for cardiovascular (CV) risk stratification is nowadays widely accepted, this approach can nevertheless present several limitations. Pulse pressure (PP) amplification accounts for the notable increase in PP from central to peripheral arterial sites. Target organs are more greatly exposed to central hemodynamic changes than peripheral organs. The pathophysiological significance of local BP pulsatility, which has a role in the pathogenesis of target organ damage in both the macro- and the microcirculation, may therefore not be accurately captured by brachial BP as traditionally evaluated with cuff measurements. The predictive value of central systolic BP and PP over brachial BP for major clinical outcomes has been demonstrated in the general population, in elderly adults and in patients at high CV risk, irrespective of the invasive or non-invasive methods used to assess central BP. Aortic stiffness, timing and intensity of wave reflections, and cardiac performance appear as major factors influencing central PP. Great emphasis has been placed on the role of aortic stiffness, disturbed arterial wave reflections and their intercorrelation in the pathophysiological mechanisms of CV diseases as well as on their capacity to predict target organ damage and clinical events. Comorbidities and age-related changes, together with gender-related specificities of arterial and cardiac parameters, are known to affect the predictive ability of central hemodynamics on individual CV risk.

Aortic stiffness improves the prediction of both diagnosis and severity of coronary artery disease

Elective coronography has low diagnostic yield for obstructive coronary artery disease (CAD). We aim to determine whether non-invasive aortic stiffness assessment improves diagnostic accuracy of CAD screening by reducing the number of false-positive results from the cardiac stress test. A cross-sectional study was conducted from January 2013 to September 2014 in our medical center. Electrocardiogram (ECG) stress test coupled with nuclear imaging was performed in 367 consecutive patients routinely followed for myocardial ischemia screening. Aortic pulse wave velocity (PWV) was assessed by applanation tonometry in the overall population. Forty-two patients underwent elective coronography because of ischemia. Theoretical PWV was calculated according to age, blood pressure and gender. The results were expressed as an index ((measured PWV–theoretical PWV)/theoretical PWV) for each patient. Ten patients presented with obstructive CAD, 16 patients had non-obstructive CAD and 16 patients had normal coronary angiography. PWV index and severity of CAD were positively correlated (P=0.001). All patients with obstructive CAD had a positive PWV index. When considering the PWV index retrospectively, the false positive results of cardiac stress test were significantly reduced (P<0.001). Twenty-three procedures may have been avoided in the present study cohort. The salient finding of this study was that in patients with known or suspected CAD, routinely followed aortic PWV index may be considered clinically useful for reducing the rate of unnecessary invasive angiographies. The clinical relevance of this individualized decision approach should be confirmed in a large-scale study. Prospective studies have the potential to evaluate the PWV index as a marker of CAD.

Should blood pressure goal be individualized in hypertensive patients

Graphical abstract Figure. No caption available. &NA; The aim of the present review is to consider the clinical relevance of individualized blood pressure (BP) goal under treatment in hypertensive patients according to their age, comorbidities or established cardiovascular (CV) disease. Evidence from large‐scale randomized trials to support a lower BP goal, as initially recommended by guidelines in high‐risk hypertensive patients, were lacking. Recently, the randomized intervention SPRINT trial studied two treatment targets for systolic BP (120 mm Hg versus 140 mm Hg in the intensive and standard treatment group, respectively) among high‐risk hypertensive patients, without diabetes and without a history of prior stroke. The trial was stopped prematurely owing to a significantly lower rate of the primary composite outcome and all‐cause mortality in the intensive treatment group. Several practical questions have to be considered. First, using an automated measurement system at an office visit during the SPRINT protocol, while the patient was seated alone after 5 min of quiet rest, may likely have resulted in lower BP values than would normally be obtained with the routine BP measurement. A target systolic of 120 mm Hg in SRPINT trial may be thus equated to a target systolic BP of 130 mm Hg in the real‐world office setting. Second, careful and repeated examinations of SPRINT participants may have led to fewer adverse events (more frequent in the intensive treatment group) than that expected in the real‐world setting. The safety profile of this intensive treatment approach should therefore remain a matter of concern in clinical practice, especially in elderly patients, in diabetic patients or with established CV or renal disease. Orthostatic hypotension should alert the clinician to withhold up titration. Third, beyond the question of BP goal, choice of antihypertensive medication and effective 24‐h BP control are important to consider in the context of BP‐lowering strategy. In particular, ambulatory BP measurements and during nighttime should be considered for an individualized hypertension care.

Longitudinal Study of Hypertensive Subjects With Type 2 Diabetes MellitusNovelty and Significance: Overall and Cardiovascular Risk

Despite adequate glycemic and blood pressure control, treated type 2 diabetic hypertensive subjects have a significantly elevated overall/cardiovascular risk. We studied 244 816 normotensive and 99 720 hypertensive subjects (including 7480 type 2 diabetics) attending medical checkups between 1992 and 2011. We sought to identify significant differences in overall/cardiovascular risk between hypertension with and without diabetes mellitus. Mean follow-up was 12.7 years; 14 050 all-cause deaths were reported. From normotensive to hypertensive populations, a significant progression in overall/cardiovascular mortality was observed. Mortality was significantly greater among diabetic than nondiabetic hypertensive subjects (all-cause mortality, 14.05% versus 7.43%; and cardiovascular mortality, 1.28% versus 0.7%). No interaction was observed between hemodynamic measurements and overall/cardiovascular risk, suggesting that blood pressure factors, even during drug therapy, could not explain the differences in mortality rates between diabetic and nondiabetic hypertensive patients. Using cross-sectional regression models, a significant association was observed between higher education levels, lower levels of anxiety and depression, and reduced overall mortality in diabetic hypertensive subjects, while impaired renal function, a history of stroke and myocardial infarction, and increased alcohol and tobacco consumption were significantly associated with increased mortality. Blood pressure and glycemic control alone cannot reverse overall/cardiovascular risk in diabetics with hypertension. Together with cardiovascular measures, overall prevention should include recommendations to reduce alcohol and tobacco consumption and improve stress, education levels, and physical activity.

[PP.25.19] TREATMENTS OF HYPERTENSION DUE TO PRIMARY HYPERALDOSTERNISM: EFFICACY, EFFICIENCE AND ADVERSE EFFECTS

Objective: Primary Hyperaldosteronism (PA) (10% of all hypertensive patients) is characterized by the Conns Syndrome or by bilateral hyperplasia. The aim of this observational, retrospective study was to investigate the different strategy to diagnose and to treat the PA and we evaluate the efficiency and adverse effects of both. Figure. No caption available. Design and method: We conducted a retrospective study, considering patientsdiagosed with PA in our department from 1992 to 2014. 64 patients were included: 26 with conn adenoma and 38 with bilateral adrenal hyperplasia. Results: Patient suffering from Conn Adenoma (CA) (n=26) and from Bilateral Hyperplasia of adrenal gland (BH) (n = 38) were similar in age, systolic blood pressure or diastolic blood pressure and for the sex. The delay in years between the diagnostic of Hypertension and PA was different (9,3 ± 6,7 for CA vs 13,9 ± 9,3 BH p = 0,034). Kaliemia was lower in CA (2,9 ± 0,5) vs BH(3,4 ± 0,5) p < 0,001. Spironolactone was the main treatment in the two groups. 50% of the patient in the CA group underwent a surgery and all other patients were medically treated. Hypertension control was higher in CA 76,9% vs HB 52,6% p = 0,03. There was no difference between the two groups on hypokalemia control and 15,4% of patients took potassium supplementation at the end of the follow up. Main side effects were gynecomastia 20,3% and sexual dysfunction 12,5% in all the population with PA. Mean number of treatment during the last visit was lower in CA group than in the BH group, p < 0,001. We used more beta-blockers, thiazide diuretics and angiotensin-converting enzyme inhibitors in the BH group than in the CA group. Conclusions: Diagnosis of PA is performed with long delay, especially for BH. Moreover, adverse events and hypertension control are worse in BH. Our study shows that the management of those patients still needs to be improved.