Reduction In Pulse Pressure Research Articles

Effects of blood pressure-lowering treatment. 6. Prevention of heart failure and new-onset heart failure--meta-analyses of randomized trials.

Relative effectiveness of blood pressure (BP)-lowering treatment on various outcomes was evaluated by meta-analyses restricted to randomized controlled trials (RCTs) measuring all major outcomes, and the question whether BP lowering and each class of antihypertensive agents prevent new-onset heart failure by meta-analyses limited to RCTs excluding baseline heart failure from randomization. Source of these meta-analyses are our databases of BP-lowering RCTs vs placebo or less-active treatment, and head-to-head comparisons of different antihypertensive classes. Risk ratios (RRs) and 95% confidence intervals of seven outcomes were calculated by a random-effects model. The relationships of outcome reductions to BP differences were investigated by meta-regressions. First, 35 BP-lowering RCTs measured all outcomes, and heart failure [RR 0.63 (0.52-0.75)] and stroke [RR 0.58 (0.49-0.68)] were the outcomes most effectively prevented. Second, heart failure and stroke reductions were significantly related to SBP, DBP and pulse pressure reductions. Third, in 18 BP-lowering RCTs excluding baseline heart failure from recruitment, heart failure reduction ('new-onset' heart failure) [RR 0.58 (0.44-0.75)] was very similar to that in the entire set of RCTs. Fourth, in meta-analyses of head-to-head comparisons of different antihypertensive classes, calcium antagonists were inferior in preventing 'new-onset' heart failure [RR 1.16 (1.01-1.33)]. However, this inferiority disappeared when meta-analysis was limited to RCTs allowing concomitant use of diuretics, β-blockers or renin-angiotensin system blockers also in the calcium antagonist group [RR 0.96 (0.81-1.12)]. BP-lowering treatment effectively prevents 'new onset' heart failure. It is suggested that BP lowering by calcium antagonists is effective as BP lowering by other drugs in preventing 'new-onset' heart failure, unless the trial design creates an unbalance against calcium antagonists.

Preoperative Prediction of Aortic Insufficiency During Ventricular Assist Device Treatment

Survival rate in patients with stage D heart failure has improved significantly owing to the development of continuous flow left ventricular assist devices (LVAD), but aortic insufficiency (AI) still remains one of the major unsolved complications that impairs patient quality of life. There are no established treatments for AI, and preoperative prediction and prevention of AI is needed. The opening of a native aortic valve (AV) is a sufficient condition for prevention of AI, and improvement of LV ejection fraction due to LV reverse remodeling (LVRR) is essential to open a native AV. Preoperative insufficient β-blocker treatment and pulsatile flow LVAD usage are keys for LVRR, opening of an AV, and prevention of AI. The second mechanism that leads to AI is remodeling of the aortic root and degeneration of a native AV, which results from reduced pulse pressure during LVAD support. Centrifugal or pulsatile flow LVAD usage has an advantage in terms of preserving pulsatility, and may prevent AI compared with an axial pump. There is less probability of avoiding AI with sufficient β-blocker treatment, and these patients may be good candidates for concomitant surgical intervention to a native AV at the time of LVAD implantation.

Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes

AimsTo determine the effects of empagliflozin on blood pressure (BP) and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes mellitus (T2DM).MethodsWe conducted a post hoc analysis of data from a phase III trial in patients with T2DM and hypertension receiving 12 weeks' empagliflozin and four phase III trials in patients with T2DM receiving 24 weeks' empagliflozin (cohort 1, n = 823; cohort 2, n = 2477). BP was measured using 24‐h BP monitoring (cohort 1) or seated office measurements (cohort 2).ResultsEmpagliflozin reduced systolic BP (SBP) and diastolic BP in both cohorts (p < 0.001 vs placebo), without increasing heart rate. Empagliflozin reduced pulse pressure (PP; adjusted mean difference vs placebo cohort 1: −2.3 mmHg; cohort 2: −2.3 mmHg), mean arterial pressure (MAP; cohort 1, −2.3 mmHg; cohort 2, −2.1 mmHg) and double product (cohort 1, −385 mmHg × bpm; cohort 2, −369 mmHg × bpm) all p < 0.001 vs placebo. There was a trend towards a reduction in the ambulatory arterial stiffness index (AASI) with empagliflozin in cohort 1 (p = 0.059 vs placebo). AASI was not measured in cohort 2. Subgroup analyses showed that there were greater reductions in PP with increasing baseline SBP in cohort 1 (p = 0.092). In cohort 2, greater reductions in MAP were achieved in patients with higher baseline SBP (p = 0.027) and greater reductions in PP were observed in older patients (p = 0.011).ConclusionsEmpagliflozin reduced BP and had favourable effects on markers of arterial stiffness and vascular resistance.

Influence of aerobic exercise training on post-exercise responses of aortic pulse pressure and augmentation pressure in postmenopausal women.

Central arterial blood pressure (BP) is more predictive of future cardiovascular events than is brachial BP because it reflects the BP load imposed on the left ventricle with greater accuracy. However, little is known about the effects of exercise training on central hemodynamic response to acute exercise. The purpose of the present study was to determine the influence of an aerobic exercise regimen on the response of aortic BP after a single aerobic exercise in postmenopausal women. Nine healthy postmenopausal women (age: 61 ± 2 years) participated in a 12-week aerobic exercise training regimen. Before and after the training, each subjects performed a single bout of cycling at ventilatory thresholds for 30 min. We evaluated the post-exercise aortic BP response, which was estimated via the general transfer function from applanation tonometry. After the initial pre-training aerobic exercise session, aortic BP did not change significantly: however, aortic pulse pressure and augmentation pressure were significantly attenuated after the single aerobic exercise session following the 12-week training regimen. The present study demonstrated that a regular aerobic exercise training regimen induced the post-exercise reduction of aortic pulse pressure and augmentation pressure. Regular aerobic exercise training may enhance post-exercise reduction in aortic BP.

Association of aortic stiffness and wave reflections with coronary flow reserve in women without obstructive coronary artery disease: An ancillary study from the National Heart, Lung, and Blood Institute–sponsored Women’s Ischemia Syndrome Evaluation (WISE)

Increased aortic stiffness and reduced coronary flow reserve (CFR) independently predict adverse outcomes. But information about relationships between arterial properties and CFR in subjects without obstructive coronary artery disease (CAD) is limited. CFR was measured (Doppler flow wire and intracoronary adenosine) in 50 women (age 53 ± 11 years) with symptoms and signs of myocardial ischemia without obstructive CAD. Aortic pulse wave velocity (aPWV), a measure of aortic stiffness, was obtained via catheter pullback; radial artery pressure waves were measured by applanation tonometry and central aortic pressure synthesized. Overall, CFR (mean 2.61 ± 0.47) was significantly correlated with aPWV (r = -0.51), pulse wave amplification (r = 0.45), augmented pressure (r = -0.48), augmentation index (AIx, r = -0.44), aortic systolic pressure (r = -0.49), left ventricular wasted energy (LVEw, r = -0.47) (all P < .001), systolic pressure time index (r = -0.37, P < .008), and rate pressure product (r = -0.29, P < .04). In the multiple regression model including aPWV, CFR was still significantly correlated with aPWV (P < .008) and aortic systolic pressure (P < .01). No other measures contributed significant additional information. Women with CFR ≤2.5 versus those with CFR >2.5 had greater aPWV (894 ± 117 vs 747 ± 93 cm/s, P < .001), augmented pressure (14 ± 4.9 vs 11 ± 4.1 mmHg, P < .008), AIx (32 ± 6.6 vs 27 ± 6.6%, P < .003), LVEw (30 ± 12 vs 21 ± 10 dyne-s/cm(2) × 10(2), P < .02) and reduced pulse pressure amplification (1.20 ± .07 vs 1.26 ± .10, P < .008) and pressure wave travel time (133 ± 7.3 vs 138 ± 6.9 milliseconds, P < .04). Among symptomatic women without obstructive CAD, CFR was inversely related to aortic systolic pressure and indices of aortic stiffness. These changes in arterial properties increase left ventricular afterload requiring the ventricle to generate additional, but wasted, energy that increases indices of myocardial oxygen demand, reduces CFR and increases vulnerability to ischemia.

Blood pressure lowering efficacy of dual alpha and beta blockers for primary hypertension.

Drugs with combined alpha and beta blocking activity are commonly prescribed to treat hypertension. However, the blood pressure (BP) lowering efficacy of this class of beta blockers has not been systematically reviewed and quantified. To quantify the dose-related effects of various types of dual alpha and beta adrenergic receptor blockers (dual receptor blockers) on systolic and diastolic blood pressure versus placebo in patients with primary hypertension. We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ClinicalTrials.gov for randomized controlled trials up to October 2014. The WHO International Clinical Trials Registry Platform (ICTRP) is searched for inclusion in the Group's Specialised Register. Randomized double blind placebo controlled parallel or cross-over trials. Studies contained a beta blocker monotherapy arm with a fixed dose. Patients enrolled in the studies had primary hypertension at baseline. Duration of the studies was from three to 12 weeks. Drugs in this class of beta blockers are carvedilol, dilevalol and labetalol. Two review authors (GW and AL) confirmed the inclusion of studies and extracted the data independently. RevMan 5.3 was used to synthesize data. We included eight studies examining the blood pressure lowering efficacy of carvedilol and labetalol in 1493 hypertensive patients. Five of the included studies were parallel design; three were cross-over design. The two largest included studies were unpublished carvedilol studies. The estimates of BP lowering effect (systolic BP/diastolic BP millimeters of mercury; SPB/DBP mm Hg) were -4 mm Hg (95% confidence intervals (CI) -6 to -2)/-3 mm Hg (95% CI -4 to -2) for carvedilol (>1000 subjects) and -10 mm Hg (95% CI -14 to -7)/-7 mm Hg (95% CI -9 to -5) for labetalol (110 subjects). The effect of labetalol is likely to be exaggerated due to high risk of bias. Carvedilol, within the recommended dose range, did not show a significant dose response effect for SBP or DBP. Carvedilol had little or no effect on pulse pressure (-1 mm Hg) and did not change BP variability. Overall, once and twice the starting dose of carvedilol and labetalol lowered BP by -6 mm Hg (95% CI -7 to -4) /-4 mm Hg (95% CI -4 to -3) (low quality evidence) and lowered heart rate by five beats per minute (95% CI -6 to -4) (low quality evidence). Five studies (N = 1412) reported withdrawal due to adverse effects; the risk ratio was 0.88 (95% CI 0.54 to 1.42) (moderate quality evidence). This review provides low quality evidence that in patients with mild to moderate hypertension, dual receptor blockers lowered trough BP by an average of -6/-4 mm Hg and reduced heart rate by five beats per minute. Due to the larger sample size from the two unpublished studies, carvedilol provided a better estimate of BP lowering effect than labetalol. The BP lowering estimate from combining carvedilol once and twice the starting doses is -4/-3 mm Hg. Doses higher than the recommended starting dose did not provide additional BP reduction. Higher doses of dual receptor blockers caused more bradycardia than lower doses. Based on indirect comparison with other classes of drugs, the blood pressure lowering effect of dual alpha- and beta-receptor blockers is less than non-selective, beta1 selective and partial agonist beta blockers, as well as thiazides and drugs inhibiting the renin angiotensin system. Dual blockers also had little or no effect on reducing pulse pressure, which is similar to the other beta-blocker classes, but less than the average reduction of pulse pressure seen with thiazides and drugs inhibiting the renin angiotensin system. Patients taking dual receptor blockers were not more likely to withdraw from the study compared to patients taking placebo.

Hemodynamics changes with acute carotid baroreceptor field stimulation are age-dependent in normotensive rats.

Carotid baroreceptor stimulation can treat resistant hypertension with possible effects on the vasculature beyond the decrease in arterial pressure. This study aims to characterize age-dependency of vascular hemodynamics changes with unilateral field stimulation of carotid baroreceptors in normotensive rats to infer underlying hemodynamic mechanisms. Anesthetized Wistar-Kyoto rats divided into two groups (young: n=10, 13-33 weeks; old: n=6, 52-58 weeks) were instrumented to measure heart rate (HR) and mean arterial pressure (MAP), and flow in the abdominal aorta and renal artery. Measures of aortic and renal artery stiffness and resistance were calculated. Baroreceptor stimulation caused a consistent reduction in MAP, HR, pulse pressure and aortic pulse wave velocity. In young rats reduced MAP (77 ± 10 to 64 ± 13 mmHg, p<;0.001) was concomitant with reduced mean aortic (40 ± 15 to 32 ± 11 ml/min, p<;0.05) and renal flow (3.0 ± 1.6 2.2 ± 1.1 ml/min, p<;0.001). However, in old rats reduced MAP (76 ± 14 to 64 ± 10 mmHg, p<;0.05) occurred with a reduced aortic resistance (1.8 ± 0.9 to 1.6 ± 0.9 mmHg.min/ml, p<;0.05), renal artery resistance (17.4 ± 2.4 to 16.5 ± 2.3 mmHg.min/ml, p<;0.05) and mean renal flow (4.5 ± 1.2 to 4.0 ± 1.1 ml/min, p<;0.05). This was consistent with reduced characteristic impedance in older rats in both the aorta (0.17 ± 0.08 to 0.13 ± 0.08 mmHg.min/ml, p<;0.05) and renal artery (4.97 ± 1.16 to 3.97 ± 1.08 mmHg.min/ml, p<;0.05). Stimulation caused a leftward shift in renal impedance phase frequency spectrum in both age groups indicating changes in wave reflection from the renal bed. Findings show that the reduction in MAP due to carotid barostimulation is associated with different hemodynamic mechanisms that depend on age.

Chronic antihypertensive treatment improves pulse pressure but not large artery mechanics in a mouse model of congenital vascular stiffness.

Increased arterial stiffness is a common characteristic of humans with Williams-Beuren syndrome and mouse models of elastin insufficiency. Arterial stiffness is associated with multiple negative cardiovascular outcomes, including myocardial infarction, stroke, and sudden death. Therefore, identifying therapeutic interventions that improve arterial stiffness in response to changes in elastin levels is of vital importance. The goal of this study was to determine the effect of chronic pharmacologic therapy with different classes of antihypertensive medications on arterial stiffness in elastin insufficiency. Elastin-insufficient mice 4-6 wk of age and wild-type littermates were subcutaneously implanted with osmotic micropumps delivering a continuous dose of one of the following: vehicle, losartan, nicardipine, or propranolol for 8 wk. At the end of treatment period, arterial blood pressure and large artery compliance and remodeling were assessed. Our results show that losartan and nicardipine treatment lowered blood pressure and pulse pressure in elastin-insufficient mice. Elastin and collagen content of abdominal aortas as well as ascending aorta and carotid artery biomechanics were not affected by any of the drug treatments in either genotype. By reducing pulse pressure and shifting the working pressure range of an artery to a more compliant region of the pressure-diameter curve, antihypertensive medications may mitigate the consequences of arterial stiffness, an effect that is drug class independent. These data emphasize the importance of early recognition and long-term management of hypertension in Williams-Beuren syndrome and elastin insufficiency.

Changes in pulse pressure during hemodialysis treatment and survival in maintenance dialysis patients.

Pulse pressure has been shown as a risk factor for mortality in patients on maintenance hemodialysis (MHD). However, the effect of change in pulse pressure during hemodialysis on survival in a large cohort of patients on MHD has not been sufficiently investigated. This study examined the association between time-varying Δ pulse pressure (postdialysis minus predialysis pulse pressure) and mortality in a cohort of 98,577 patients on MHD (July 2001-June 2006) using Cox proportional hazard models with restricted cubic splines. The average patient age was 62 years old; among the patients, 33% were black and 59% had diabetes. During 134,814 patient-years of at-risk time, 16,054 (16%) patients died, with 6827 (43%) of the deaths caused by cardiovascular causes. In the models including adjustment for either predialysis systolic BP or mean arterial BP, there was a U-shaped association between change in pulse pressure during hemodialysis and all-cause mortality. In the systolic BP plus case mix plus malnutrition-inflammation complex syndrome-adjusted model, large declines in pulse pressure (>-25 mmHg) and increases in pulse pressure >5 mmHg were associated with higher all-cause mortality (reference: ≥-5 to <5 mmHg): hazard ratios (95% confidence intervals [95% CIs]) for change pulse pressures of <-25, ≥-25 to <-15, ≥-15 to <-5, 5 to <15, 15 to <25, and ≥25 mmHg were 1.21 (95% CI, 1.14 to 1.29), 1.03 (95% CI, 0.97 to 1.10), 1.01 (95% CI, 0.96 to 1.06), 1.06 (95% CI, 1.01 to 1.11), 1.17 (95% CI, 1.11 to 1.24), and 1.15 (95% CI, 1.08 to 1.23), respectively. The U-shaped association was observed with cardiovascular death. Modest reductions in pulse pressure after hemodialysis are associated with the greatest survival, whereas large declines or rises in pulse pressure are related to higher mortality. Trials determining how to modify pulse pressure response to improve survival in the hemodialysis population are indicated.

Effects of hydrochlorothiazide on oxidative stress and pulse pressure in hypertensive patients with chronic stroke: the EMINENT study.

Thiazide diuretics are reported to have antioxidant effects and reduce pulse pressure (PP). The aim of this study was to elucidate whether hydrochlorothiazide additionally exerts such effects in stroke patients under treatment with losartan. This study was an open-label, randomized, multicenter study. Patients with a history of chronic stroke and treatment with angiotensin receptor blockers or angiotensin-converting enzyme inhibitors for essential hypertension were enrolled. Fifty-five hypertensive patients were randomly assigned to two groups: those further treated with hydrochlorothiazide and those further treated with non-diuretic antihypertensive drugs. Both groups showed a significant decrease in PP over six months (hydrochlorothiazide group: 67±12 mmHg to 58±12, p<0.001; non-diuretic group: 72±12 to 61±12, p<0.001), although no significant differences were observed between the two groups. The malondialdehyde-modified low-density lipoprotein levels did not change significantly after treatment in either group. In this study, hydrochlorothiazide treatment did not provide any additional benefits over non-diuretic antihypertensive drugs in terms of antioxidant effects or reducing PP.

Effects of blood pressure lowering on outcome incidence in hypertension. 1. Overview, meta-analyses, and meta-regression analyses of randomized trials.

Antihypertensive treatment is based on randomized controlled trials (RCTs) started since 1966. Meta-analyses comprehensive of all RCTs but limited to RCTs investigating blood pressure (BP) lowering in hypertensive patients are lacking. Two clinical questions were investigated: the extent of different outcome reductions by BP lowering in hypertensive patients, and the proportionality of outcome reductions to SBP, DBP, and pulse pressure (PP) reductions. PubMed between 1966 and December 2013 (any language), Cochrane Collaboration Library and previous overviews were used as data sources for identifying and selecting all RCTs comparing the antihypertensive drugs with placebo or less intense BP lowering (intentional BP-lowering RCTs); comparing BP-lowering drugs with placebo without BP-lowering intention, but with BP difference (nonintentional BP-lowering RCTs); and enrolling at least 40% hypertensive patients. RCTs on acute myocardial infarction, heart failure, acute stroke, and dialysis were excluded. RCT quality was assessed by scoring. Risk ratios and 95% confidence interval (CI), standardized to 10/5 mmHg SBP/DBP reduction, of seven fatal and nonfatal outcomes were calculated (random-effects model). The relationships of different outcome reductions to SBP, DBP, and PP reductions were investigated by meta-regressions. A total of 68 RCTs (245,885 individuals) were eligible, of which 47 (153,825 individuals) were 'intentional' RCTs. All outcomes were reduced (P < 0.001) by BP lowering, stroke [-36% (-29, -42)], and heart failure [-43% (-28, -54)] to a greater extent, with smaller reductions for coronary events [coronary heart disease (CHD): -16% (-10, -21)], cardiovascular [-18% (-11, -24)], and all-cause mortality [-11% (-5, -16)]. Absolute risk reductions were 17 (14, 20) strokes, 28 (19, 35) cardiovascular events, and 8 (4, 12) deaths prevented every 1000 patients treated for 5 years. Logarithmic risk ratios were related to SBP, DBP, and PP reductions (P = 0.001-0.003) for stroke and composite cardiovascular events, but not for CHD. Meta-analyses of all BP-lowering RCTs involving hypertensive patients provide precise estimates of benefits (larger for stroke and heart failure, but also significant for CHD and mortality). Absolute risk reductions are substantial. Relationships of logarithmic risk ratios with BP reductions imply risk reduction increases progressively to a smaller extent the larger the BP reduction.

Blood pressure lowering efficacy of partial agonist beta blocker monotherapy for primary hypertension.

Partial agonists are a subclass of beta blockers used to treat hypertension in many countries. Partial agonist act by stimulating beta receptors when they are quiescent and blocking beta receptors when they are active. The blood pressure (BP) lowering effect of partial agonist beta blockers has not been quantified. To quantify the dose-related effects of various partial agonists beta blockers on systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate versus placebo in patients with primary hypertension. We searched the Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, EMBASE and ClinicalTrials.gov for randomized controlled trials up to October 2014. The WHO International Clinical Trials Registry Platform (ICTRP) is searched for inclusion in the Group's Specialised Register. Randomized double-blinded placebo-controlled parallel or cross-over trials. Studies must contain a partial agonist monotherapy arm with fixed dose. Patients enrolled into the studies must have primary hypertension at baseline (defined as SBP/DBP > 140/90 mmHg). Duration of studies must be between three to 12 weeks. Two authors (GW and HB) confirmed the inclusion of studies and extracted the data independently. Thirteen randomized double-blinded placebo-controlled trials that examined the blood pressure lowering efficacy of six partial agonists in 605 hypertensive patients were included in this review. Five of the included studies were parallel studies and the other eight were cross-over studies. The overall risk of bias is high in this review due to the small sample size and high risk of detection bias. Pindolol, celiprolol and alprenolol lowered SBP and DBP compared to placebo. Acebutolol lowered SBP but there was no clear evidence that it lowered DBP. There was no clear evidence that pindolol and oxprenolol lowered SBP or DBP. Other than for celiprolol, sample sizes were generally small increasing the uncertainty in findings for individual agents versus placebo. In patients with moderate to severe hypertension, partial agonists (considered as a subclass) lowered peak BP by an average of 8 mmHg systolic (95% CI, -10 to -6, very low quality evidence), 4 mmHg diastolic (95%CI, -5 to -3, very low quality evidence) and reduced heart rate by five beats per minute (95%CI, -6 to -4, very low quality evidence). Higher dose partial agonists did not appear to provide additional BP lowering effects compared to lower dose. The maximum BP lowering effect of the overall subclass occurred at the starting dose. Partial agonists reduced pulse pressure by 4 mmHg (95% CI, -5 to -2, very low evidence). Only one study reported withdrawal due to adverse effects, the risk ratio (95% confidence interval) was 0.72 (0.07, 7.67). There was very low quality evidence that in patients with moderate to severe hypertension, partial agonists lowered peak BP by an average of 8/4 mmHg and reduced heart rate by five beats per minute. There was no evidence of a greater effect at doses higher than the initial doses. This estimate was probably exaggerated as it was subject to a high risk of bias. Based on the indirect comparison of the results in this review and two Cochrane reviews on angiotensin-converting-enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), which also used similar inclusion criteria as this review, the BP lowering effect appeared to be less than the effect in patients with mild to moderate elevated BP who were taking ACE inhibitors and ARBs based on an indirect comparison. Withdrawals due to adverse effects were only reported in one trial so it is impossible to assess the harm of these drugs.

Subject-specific estimation of central aortic blood pressure via system identification: preliminary in-human experimental study.

This paper demonstrates preliminary in-human validity of a novel subject-specific approach to estimation of central aortic blood pressure (CABP) from peripheral circulatory waveforms. In this "Individualized Transfer Function" (ITF) approach, CABP is estimated in two steps. First, the circulatory dynamics of the cardiovascular system are determined via model-based system identification, in which an arterial tree model is characterized based on the circulatory waveform signals measured at the body's extremity locations. Second, CABP waveform is estimated by de-convolving peripheral circulatory waveforms from the arterial tree model. The validity of the ITF approach was demonstrated using experimental data collected from 13 cardiac surgery patients. Compared with the invasive peripheral blood pressure (BP) measurements, the ITF approach yielded significant reduction in errors associated with the estimation of CABP, including 1.9-2.6 mmHg (34-42 %) reduction in BP waveform errors (p < 0.05) as well as 5.8-9.1 mmHg (67-76 %) and 6.0-9.7 mmHg (78-85 %) reductions in systolic and pulse pressure (SP and PP) errors (p < 0.05). It also showed modest but significant improvement over the generalized transfer function approach, including 0.1 mmHg (2.6 %) reduction in BP waveform errors as well as 0.7 (20 %) and 5.0 mmHg (75 %) reductions in SP and PP errors (p < 0.05).

Abstract 474: Efficacy and Safety of LCZ696 Compared with Olmesartan in Japanese Patients with Systolic Hypertension

Objective: To evaluate the efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) vs olmesartan in Japanese patients with systolic hypertension (SH). Methods: Patients aged ≥20 yrs with mean sitting (ms) SBP ≥150-&lt;180 mmHg were randomized to once-daily LCZ696 200 mg or 400 mg (forced-titrated from 1-week LCZ696 200 mg), or olmesartan 20 mg for 8 weeks. The primary objective of this study was to test if LCZ696 200 mg is superior over olmesartan in msSBP reductions from baseline at week 8. Secondary endpoints were reductions in msSBP with LCZ696 400 mg, reductions in msDBP and ms pulse pressure (PP), BP control rate, and safety for all treatment groups at week 8. Efficacy and safety was also assessed by age (&lt;65 and ≥65 years). Results: A total of 1161 patients (LCZ696 200 mg, n=387; LCZ696 400 mg, n=385; olmesartan, n=389) were randomized. Demographic and baseline characteristics were generally comparable across the treatment groups with mean age of 58.7 yrs (&lt;65 yrs, 771 [67.1%]; ≥65 yrs, 382[32.9%]). The msSBP reductions at week 8 with LCZ696 200 mg were statistically significantly superior to olmesartan and significantly greater with LCZ696 400 mg than olmesartan (Table). Reductions in msDBP and msPP were significantly greater and BP control rates were significantly higher with LCZ696 vs olmesartan. Greater BP and PP lowering with LCZ696 vs olmesartan was independent of age. The incidence of AEs was similar across the treatment and age groups. Conclusion: Treatment with LCZ696 is effective and generally well-tolerated in Japanese patients with SH regardless of age and LCZ696 200 mg showed superior BP lowering effect than olmesartan 20 mg.

Thiazide-like/calcium channel blocker agents: a major combination for hypertension management.

In recent years, treatment strategies for hypertension have often focused on combination therapies that include diuretics and renin angiotensin aldosterone system blockers such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. However, in clinical practice, a significant number of patients do not respond completely to these combination treatments, and long-term reduction of cardiovascular risk remains insufficient. The particularly high residual cardiovascular risk of hypertensive patients, even when adequately treated with strategies based on renin angiotensin aldosterone system blockers, speaks in favor of new, innovative strategies. Thus, it has become relevant to consider whether it is always necessary to block plasma renin activation and whether other guideline-approved combinations should be considered routinely. Diuretic/calcium channel blocker combinations, which are supported by significant long-term evidence, are put forth as a preferred combination in the main guidelines, but are still underused by physicians who do not yet have easy access to such treatments. Fixed-dose indapamide sustained release/amlodipine is the first such single-pill combination to become available. Complementary mechanisms of action of these two molecules are expected to lead to greater and longer-term reductions in systolic blood pressure and pulse pressure and potentially to the reduction of cardiovascular risk.

Treatment of hypertension and metabolic syndrome: lowering blood pressure is not enough for organ protection, new approach-arterial destiffening.

Cardiovascular risk factors (CVRFs) have been shown to induce end organ damage. Until now, the main approach to reduce CVRF-induced end organ damage was by normalization of CVRFs; this approach was found effective to reduce damage and cardiovascular (CV) events. However, a residual risk always remained even when CVRFs were optimally balanced. An additional risk factor which has an immense effect on the progression of end organ damage is aging. Aging is accompanied by gradual stiffening of the arteries which finally leads to CV events. Until recently, the process of arterial aging was considered as unmodifiable, but this has changed. Arterial stiffening caused by the aging process is similar to the changes seen as a result of CVRF-induced arterial damage. Actually, the presence of CVRFs causes faster arterial stiffening, and the extent of damage is proportional to the severity of the CVRF, the length of its existence, the patient's genetic factors, etc. Conventional treatments of osteoporosis and of hormonal decline at menopause are potential additional approaches to positively affect progression of arterial stiffening. The new approach to further decrease progression of arteriosclerosis, thus preventing events, is the prevention of age-associated arterial structural changes. This approach should further decrease age-associated arterial stiffening. A totally new promising approach is to study the possibility of affecting collagen, elastin, and other components of connective tissue that participate in the process of arterial stiffening. Reduction of pulse pressure by intervention in arterial stiffening process by novel methods as breaking collagen cross-links or preventing their formation is an example of future directions in treatment. This field is of enormous potential that might be revolutionary in inducing further significant reduction of cardiovascular events.

A core promoter variant of angiotensinogen gene and interindividual variation in response to angiotensin-converting enzyme inhibitors.

The polymorphic angiotensinogen (AGT) gene is one of the most promising candidates for essential hypertension. The aim of this study was to examine the association between the A-6G variant of the AGT gene and the blood pressure response to angiotensin-converting enzyme (ACE) inhibitors in hypertensive subjects. Five hundred and nine mildly to moderately hypertensive subjects received ACE inhibitors for six weeks after a two-week run-in period. AGT genotyping was performed by direct polymerase chain reaction amplification and deoxyribonucleic acid (DNA) nucleotide sequencing from peripheral blood. The AA genotype, AG genotype, and GG genotype were present in 301 (59.1%), 186 (36.6%), and 22 (4.3%) of patients, respectively. As compared with patients carrying the AA or AG genotype, those carrying the GG genotype had significantly greater reductions in systolic blood pressure, diastolic blood pressure, pulse pressure and mean arterial pressure (p=0.007, 0.014, 0.027 and 0.005, respectively). Moreover, stepwise multiple linear regression analysis showed that the A-6G genotype was a significant predictor of systolic blood pressure and pulse pressure reductions (p=0.040 and 0.019, respectively). Our study indicates that the A-6G variant of the AGT gene may be an important determinant of interindividual variation in the response to ACE inhibitors.

Hypotensive effects of solitary addition of conventional nonfat dairy products to the routine diet: a randomized controlled trial

The high consumption of low-fat and nonfat dairy products is associated with reduced risk of high blood pressure. We aimed to investigate whether the solitary addition of nonfat dairy products to the normal routine diet was capable of lowering blood pressure in middle-aged and older adults with elevated blood pressure. With the use of a randomized, crossover intervention-study design, 49 adults (56% women) with elevated blood pressure (mean ± SEM age: 53 ± 2 y; systolic blood pressure: 135 ± 1; diastolic blood pressure: 80 ± 1 mm Hg) underwent a high-dairy condition (+4 servings conventional nonfat dairy products/d) and isocaloric no-dairy condition (+4 servings fruit products/d) in which all dairy products were removed. Both dietary conditions lasted 4 wk with a 2-wk washout before crossing over into the alternate condition. The high-dairy condition produced reductions in systolic blood pressure (135 ± 1 to 127 ± 1 mm Hg) and pulse pressure (54 ± 1 to 48 ± 1 mm Hg) (both P < 0.05). The hypotensive effects were observed within 3 wk after the initiation of the dietary intervention and in both casual seated and ambulatory (24-h) measurements (P < 0.05). Pulse pressure was increased after the removal of all dairy products in the no-dairy condition (54 ± 1 to 56 ± 1 mm Hg; P < 0.05). There were no changes in diastolic blood pressure after either dietary condition. We concluded that the solitary manipulation of conventional dairy products in the normal routine diet would modulate blood pressure in middle-aged and older adults with prehypertension and hypertension. This trial was registered at clinicaltrials.gov as NCT01577030.

Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension.

Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension.

Evaluation of the Hemodynamic Effectiveness of Aortic Dissection Treatments via Virtual Stenting

Aortic dissection treatment varies for each patient and stenting is one of a number of approaches that are utilized to Stabilize the condition. Information regarding the hemodynamic forces in the aorta in dissected and virtually stented cases could support clinicians in their choices of treatment prior to medical intervention. Computational fluid dynamics coupled with lumped parameter models have shown promise in providing detailed information that could be used in the clinic; for this, it is necessary to develop personalized workflows in order to produce patient-specific simulations. In the present study, a case of pre- and post-stenting (virtual stent-graft) of an aortic dissection is investigated with a particular focus on the role of personalized boundary conditions. For each virtual case, velocity, pressure, energy loss, and wall shear stress values are evaluated and compared. The simulated single stent-graft only marginally reduced the pulse pressure and systemic energy loss. The double stent-graft results showed a larger reduction in pulse pressure and a 40% reduction in energy loss as well as a more physiological wall shear stress distribution.Regions of potential risk were highlighted. The methodology applied in the present study revealed detailed information about two possible surgical outcome cases and shows promise as both a diagnostic and an interventional tool.