Increased Pulse Pressure Research Articles

A specific feature of the diagnosis of primary arterial hypertension in elderly patients

Objective the analysis of a group of factors, leading to the increase of pulse pressure in the direction from aorta to microcirculation vessels, in order to define the diagnostic criterion for exception of primary arterial hypertension.
 Material and methods.In the study, the modelling of the functions of arteries in cardiovascular system was used.
 Results.The role of the increase of pulse pressure to the periphery of blood circulation was regarded as the diagnostic attribute of exception of the primary arterial hypertension. It was noted, that physical factors of the increase of pulse pressure to the periphery of blood circulation were insignificant. The cardiovascular reflex has the major influence on the increase of pulse pressure, its deterioration results in the decrease of this pressure.
 Conclusion.The analysis revealed the fact, that the normal ankle-brachial index allows for exclusion of primary arterial hypertension in a patient, even if the absolute values of arterial pressure are in the limits corresponding to this disease.

The Effects of Hypocapnia on Brain Tissue Pulsations.

Hypocapnia is known to affect patients with acute stroke and plays a key role in governing cerebral autoregulation. However, the impact of hypocapnia on brain tissue pulsations (BTPs) is relatively unexplored. As BTPs are hypothesised to result from cerebrovascular resistance to the inflow of pulsatile arterial blood, it has also been hypothesised that cerebral autoregulation changes mediated by hypocapnia will alter BTP amplitude. This healthy volunteer study reports measurements of BTPs obtained using transcranial tissue Doppler (TCTD). Thirty participants underwent hyperventilation to induce mild hypocapnia. BTP amplitude, EtCO2, blood pressure, and heart rate were then analysed to explore the impact of hypocapnia on BTP amplitude. Significant changes in BTP amplitude were noted during recovery from hypocapnia, but not during the hyperventilation manoeuvre itself. However, a significant increase in heart rate and pulse pressure and decrease in mean arterial pressure were also observed to accompany hypocapnia, which may have confounded our findings. Whilst further investigation is required, the results of this study provide a starting point for better understanding of the effects of carbon dioxide levels on BTPs. Further research in this area is needed to identify the major physiological drivers of BTPs and quantify their interactions with other aspects of cerebral haemodynamics.

Poor Increase in Pulse Pressure During Cardiopulmonary Exercise Testing Predicts Cardiovascular Death of Patients With Heart Failure With Reduced Ejection Fraction.

The increase in stroke volume during inotropic stimulation in patients with heart failure with reduced ejection fraction (HFrEF) is called the "pump function reserve." Few studies have reported on the relationship between pump function reserve and HF prognosis. In HFrEF patients who have pump function reserve, stroke volume increases during exercise. Simply put, the pulse pressure change (∆PP) during cardiopulmonary exercise testing (CPX) is closely related to the prognosis of patients with HFrEF. We hypothesized that ∆PP could predict disease severity and cardiovascular death in patients with HFrEF. A total of 224 patients with HFrEF who underwent symptom-limited maximal CPX between 2012 and 2016 were enrolled. During a median follow-up of 1.5 years, cardiovascular death occurred in 54 participants (24%). Patients who died demonstrated a lower ∆PP between rest and peak exercise (∆PP [peak-rest]) than those who survived (P<0.001). Cox regression analyses revealed that ∆PP, slope of the relationship between minute ventilation and carbon dioxide production, and B-type natriuretic peptide level were independent predictors of cardiovascular death in patients with HFrEF (P=0.001, 0.021, and <0.001, respectively). ∆PP (peak-rest) can accurately predict cardiovascular death in patients with HFrEF and may be a useful new prognostic indicator in these patients.

Changes in 24-h ambulatory blood pressure following restoration of sinus rhythm in patients with atrial fibrillation

The interplay between atrial fibrillation and blood pressure (BP) is insufficiently studied. In symptomatic patients with persistent atrial fibrillation, electrical cardioversion (ECV) is often used to restore sinus rhythm. In this prospective study, we investigated how restoration of sinus rhythm affected 24-h ambulatory BP. Ninety-eight patients with persistent atrial fibrillation were examined with 24-h ambulatory BP monitoring before and approximately a week after ECV. Sixty-two patients remained in sinus rhythm at the time of the second ambulatory BP monitoring (AF-SR group), whereas 36 patients had relapsed into atrial fibrillation (AF-AF group). In the AF-SR group, there was a significant increase in mean systolic 24-h BP (5.6 mmHg), a significant decrease in mean diastolic 24-h BP (-4.7 mmHg) and accordingly, a significant 25% (10.4 mmHg) increase in mean 24-h pulse pressure. These findings may reflect the haemodynamic conditions that are prevalent in atrial fibrillation, ambulatory BP measurement bias in atrial fibrillation or a combination of both factors. From a clinical standpoint, our results suggest that an increased attention to BP is needed when sinus rhythm is restored, as underlying hypertension may be masked by BP changes during atrial fibrillation. From a general standpoint, it may be speculated that BP, as indicated by the relatively large difference in pulse pressure, may be inherently different in atrial fibrillation and may therefore not be interpretable in the equivalent manner as BP in sinus rhythm.

Neither Preoperative Pulse Pressure nor Systolic Blood Pressure Is Associated With Cardiac Complications After Coronary Artery Bypass Grafting.

Increased pulse pressure has been associated with adverse cardiovascular events, cardiac and all-cause mortality in surgical and nonsurgical patients. Whether increased pulse pressure worsens myocardial injury and dysfunction after cardiac surgery, however, has not been fully characterized. We examined whether cardiac surgical patients with elevated pulse pressure are more susceptible to myocardial injury, dysfunction, cardiac-related complications, and mortality. Secondarily, we examined whether pulse pressure was a stronger predictor of the outcomes than systolic blood pressure. This retrospective observational study included adult cardiac surgical patients having elective isolated on-pump coronary artery bypass grafting (CABG) between 2010 and 2017 at the Cleveland Clinic. The association between elevated pulse pressure and (1) perioperative myocardial injury, measured by postoperative troponin-T concentrations, (2) perioperative myocardial dysfunction, assessed by the requirement for perioperative inotropic support using the modified inotropic score (MIS), and (3) cardiovascular complications assessed by the composite outcome of postoperative mechanical circulatory assistance or in-hospital mortality were assessed using multivariable linear regression models. Secondarily, the association between pulse pressure versus systolic blood pressure and the outcomes were compared. Of 2704 patients who met the inclusion/exclusion criteria, complete data were available for 2003 patients. Increased pulse pressure over 40 mm Hg was associated with elevated postoperative troponin-T level, estimated to be 1.05 (97.5% confidence interval [CI], 1.02-1.09; P < .001) times higher per 10 mm Hg increase in pulse pressure. The association between pulse pressure and myocardial dysfunction and the composite outcome of cardiovascular complications and death were not significant. There was no difference in the association with pulse pressure versus systolic blood pressure and troponin-T concentrations. Elevated preoperative pulse pressure was associated with a modest increase in postoperative troponin-T concentrations, but not postoperative cardiovascular complications or in-hospital mortality in patients having CABG. Pulse pressure was not a better predictor than systolic blood pressure.

Heart rate and blood pressure dependence of aortic distensibility in rats: comparison of measured and calculated pulse wave velocity.

Objectives:When assessing arterial stiffness, heart rate (HR) and blood pressure (BP) are potential confounders. It appears that the HR/BP dependences of pulse wave velocity (PWV) and distensibility are different, even though both assess arterial stiffness. This study aims to compare aortic PWV as measured using pulse transit time (PWVTT) and as calculated from distensibility (PWVdist) at the same measurement site and propose a solution to the disparity in dependences of PWVTT and PWVdist.Methods:Adult anaesthetized rats (n = 24) were randomly paced at HRs 300–500 bpm, at 50 bpm steps. At each step, aortic PWVTT (two pressure-tip catheters) and PWVdist (pressure-tip catheter and ultrasound wall-tracking; abdominal aorta) were measured simultaneously while BP was varied pharmacologically.Results:HR dependence of PWVdist paradoxically decreased at higher levels of BP. In addition, BP dependence of PWVdist was much larger than that of PWVTT. These discrepancies are explained in that standard PWVdist uses an approximate derivative of pressure to diameter, which overestimates PWV with increasing pulse pressure (PP). In vivo, PP decreases as HR increases, potentially causing a PWVdist decrease with HR. Estimating the full pressure-diameter curve for each HR corrected for this effect by enabling calculation of the true derivative at diastolic BP. This correction yielded a PWVdist that shows HR and BP dependences similar to those of PWVTT. As expected, BP dependence of all PWV metrics was much larger than HR dependence.Conclusion:Measured and calculated PWV have different dependences on HR and BP. These differences are, at least in part, because of approximations made in using systolic and diastolic values to calculate distensibility.

Office and Out-of-Office Blood Pressure Changes Over a Quarter of Century: Findings From the PAMELA Study.

Findings regarding long-terms variations in blood pressure (BP) taken in different setting (ie, office, home, and ambulatory BP) in the community are scanty. We sought to assess this issue in members of the general population enrolled in the PAMELA (Pressioni Monitorate E Loro Associazioni) study. The study included 562 participants who attended the second and third survey of the PAMELA study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, anthropometric parameters, office, home, ambulatory BP, and standard blood examinations. Office, home, and 24-hour systolic BP over the 25-year interval between the first and third survey increased in a parallel way (ie, 12%, 10%, and 15.5%). The increments in office, home, and 24-hour diastolic BP were lower than the systolic BP ones (ie, 3.3%, 5.6%, and 6.1%). Thus, the combined changes in systolic BP and diastolic BP from the first to the third data collection resulted in a marked increase in pulse pressure (ie, 29%, 19%, and 30%). The prevalence of hypertension assessed at office visits and out-of-office either by self-BP measurements at home and ambulatory blood pressure monitoring increased ≈3 to 4× (3.1 office, 3.3 home, 3.9 ABPM, respectively). This trend was associated with adiposity indexes and worsening of the glucose profile. This community-based longitudinal study suggests that the progressive and marked increase in hypertension with age, consistently documented with different BP measurement methods, represents an epochal challenge for the prevention of cardiovascular diseases, due to the rapid growth the elderly population worldwide.

Distinct Contribution of Systemic Blood Flow to Hypertension in an African Population Across the Adult Lifespan

Although hypertension in groups of African ancestry is volume-dependent, the relative impact of systemic flow (stroke volume, peak aortic flow [Q]) versus vascular mechanisms (systemic vascular resistance, aortic characteristic impedance [Zc], total arterial compliance) components of arterial load has not been evaluated across the adult age range. In participants of African ancestry (n=824, age=16-99 years, 68.3% female), using central arterial pressure and aortic velocity and diameter measurements in the outflow tract, we determined the hemodynamic correlates of age-related increases in blood pressure. Strong independent positive relations between age and stroke volume or peak aortic Q were noted (P<0.0001), effects associated with ventricular end diastolic volume and aldosterone-to-renin ratios. Age-related increases in mean arterial pressure were associated with stroke volume and not systemic vascular resistance. Although age-Q relations began from early adulthood, initially an inverse association between age and aortic Zc (P<0.0001) driven by increments in aortic root diameter (P<0.0001) prevented an enhanced systolic blood pressure and pulse pressure. When Zc began to positively relate to age (P<0.0001), age-Q relations translated into increases in forward wave pressures and hence systolic blood pressure and pulse pressure. Age relations with pulse pressure were as strongly determined by Q as by Zc or total arterial compliance (0.027±0.001 versus 0.028±0.001 and 0.032±0.003 mm Hg per yearly increase in pulse pressure produced by Q, Zc, and total arterial compliance; P<0.0001). Uncontrolled hypertension (confirmed with 24-hour blood pressure) was determined more by Q, Zc, and total arterial compliance than by increases in systemic vascular resistance (P<0.0005 for comparison). In conclusion, relationships between age and systemic blood flow contribute markedly to hypertension in groups of African origins.

Cerebrovascular reactivity: a new frontier for measuring cognitive health in models of accelerated ageing?

Cerebrovascular reactivity: a new frontier for measuring cognitive health in models of accelerated ageing?

P0755CALCIUM/MAGNESIUM RATIO: NEW PREDICTOR OF INCREASED PULSE PRESSURE IN CHRONIC KIDNEY DISEASE PATIENTS

Abstract Background and Aims Cardiovascular disease (CVD) is the main cause of death in chronic kidney patient. Increase pulse pressure (PP) is associated with adverse cardiovascular outcomes and is an independent risk factor of progression of chronic kidney disease. In this study we aim to identify the risk factors associated with increased PP in a population with severely decreased glomerular filtration rate. Method This was a prospective analysis conducted in an outpatient nephropathy clinic between 2005-2018, enrolling 692 patients with stage 4 CKD. Patients were divided into two groups according to their pulse pressure. Group 1 mean PP&amp;lt; 50 mmHg, Group2 mean PP &amp;gt;50 mmHg. Based on the calcium/magnesium ratio (rCaMg), the subjects were also divided into 4 risk groups according to the following criteria: &amp;lt;25th percentile (rCaMg &amp;lt; 3.8mg/dl; n=168) – G1; 25-50th percentile (rCaMg: 3.8-4.7; n=171) – G2; 50-75th percentile (rCaMg: 4.7-8.6; n=188) – G3; and &amp;gt;75th percentile (rCaMg: &amp;gt; 8.6; n=165) - G4. We used descriptive analysis, Student's t test, Univariate logistics regression analysis and CHAID analysis to determine the relationship between variables and PP. Results Total of 682 patients, with mean age 70 (SD 12.5), female 54%. An independent t-test was conducted to compare groups. There was a significant difference in mean hemoglobin level (p=0.005), calcium (p=0.029), phosphorus (p=0.017), magnesium (p&amp;lt;0.001), Ca/Mg ratio (p&amp;lt;0.001) and eGFR (p=0.034). Phosphorus OR 1.906 (CI 1.338-2.715) p&amp;lt;0.001, eGFR OR 1.440 (CI 1.023-2.027) p=0.037 were all associated with increased PP. We also compared PP with the subjects of the 4 groups based on calcium/magnesium ratio. Results: G2= OR 7.003 (CI 4.162-11.783) p&amp;lt;0.001; G3= OR 5.136 (CI 3.205-8.230) p&amp;lt;0.001; G4= OR 6.695 (CI 3.999-11.208) p&amp;lt;0.001. After adjusting for confounding variables only sex OR 0.613 (CI 0.420-0.896) p=0.012 and rCa/Mg groups: G1 OR 7.392 (CI 4.362-12.527) p&amp;lt;0.001, G2 OR 6.436 (CI 3.361-12.323) p&amp;lt;0.001 and G3 OR 8.485 (CI 4.009-17.957) p&amp;lt;0.001, showed significant differences. CHAID analysis identified rCa/Mg G2, G3, G4 (82.4%) as the more likely significant predictor to PP&amp;gt; 50 mmHg (p&amp;lt;0.001) in association with male gener (86.2%) (p=0.037). The model correctly classified 76.2% of patients and the estimate of the risk misclassification of events was 0.238±0.016. Conclusion These results suggest increased calcium/magnesium rate and male gender were associated with increased pulse pressure in a population with stage 4 CKD. Further studies are needed to understand this relationship.

MO056MODIFICATION OF P16, P21 AND NRF2 EXPRESSION IN A MODEL OF UREMIC VASCULAR CALCIFICATION

Abstract Background and Aims Vascular calcification (VC) is a consequence of ageing that confers development of future cardiovascular events. Accumulation of senescent cells can lead to structural and functional abnormalities in vessel wall towards increased stiffness, reduced compliance and impaired contractile and dilatory capacity. Thus, accumulation of senescent cells in the arterial wall could also contribute to the pathophysiology of VC. To test this hypothesis, the presence of cellular markers of senescence, p16, p21 and NRF2, was assessed in aorta from rat model of VC associated with chronic kidney disease (CKD). Method Six-week-old Sprague-Dawley rats underwent 5/6th subtotal nephrectomy (SNx, n=6) or no surgery (Control, n=1). After 8 weeks of renal failure, the regular chow was supplemented with high phosphate (1.2%) and vitamin D (1 µg/day, 5 days per week) for 1 or 4 weeks to initiate vascular calcification (SNx-VC group). At the end of the protocol (Figure 1), blood pressure was measured, and thoracic aorta was taken for determination of calcification by Von Kossa staining, and protein and gene expressions of p16, p21, and NRF2 by immunostaining and qPCR, respectively. Results After 4 weeks of dietary intervention, SNx rats showed an increase in pulse pressure (88±15mmHg vs 35 mmHg for the control). Marked VC was also observed in these animals, 17% of calcified area vs &amp;lt;1 % in the control rat. Calcification was focal giving strong and no calcified areas on the same aorta. Expressions of p16, p21and NRF2 proteins were enhanced at the site of calcification in the SNx-VC 4-week (4W) group whereas it was unchanged in aortic media without calcification compared to the control rat (Figure 2). In SNx-VC 1-week (1W) rats, no change in pulse pressure or vascular calcification was observed without obvious changes for staining patterns of selected markers. Using qPCR we found p16 gene expression to be higher in the most calcified aortas (4W) (fold-change = 4.32 vs 1W) and p21 gene expression to be slightly increased (fold-change = 0.53 vs 1W). NRF2 gene expression was enhanced in 1W group compared to control, but decreased in the most calcified samples (4W). Conclusion This pilot study suggests that uraemia-induced cellular senescence accompanies VCs, as suggested by the modified expression of p16 or NRF2 genes. Our observations deserve exploration in larger studies using additional senescence markers for validation. If so, cellular senescence kinetics will be evaluated in order to test whether senolytics compounds could be a therapeutic option to arrest VC in CKD.

P0699EVALUATION OF CALCIUM/MAGNESIUM RATE AND OTHER PREDICTORS OF CARDIOVASCULAR MORTALITY IN CHRONIC KIDNEY DISEASE

Abstract Background and Aims Cardiovascular disease (CVD) is the main cause of death in chronic kidney patient. The interaction between calcium and magnesium and mineral metabolism have been identified as risk markers for CVD. The main objective was to identify the variables associated with cardiovascular and other causes of mortality in a group of patients with stage 4 of chronic kidney disease (CKD). Method This was a prospective analysis conducted in an outpatient nephropathy clinic between 2005-2018, enrolling 692 patients with stage 4 CKD. Based on the calcium/magnesium ratio (rCaMg) the subjects were divided into 4 risk groups according to the following criteria: &amp;lt;25th percentile (rCaMg &amp;lt; 3.8mg/dl; n=168) – G1; 25-50th percentile (rCaMg: 3.8-4.7; n=171) – G2; 50-75th percentile (rCaMg: 4.7-8.6; n=188) – G3; and &amp;gt;75th percentile (rCaMg: &amp;gt; 8.6; n=165) - G4. Descriptive statistics, ANOVA, chi-square and Log Rank test were used for comparison between groups. Bonferroni test was used as a post-hoc test. Kaplan-Meier analysis was used to evaluate mortality. The Kaplan-Meier method for measuring patient survival rate was applied and a comparison between the four percentiles was based on the log rank test The multinomial regression models were used to assess predictive factors for cardiovascular mortality. CHAID analysis was used to assign patients to risk groups. Results The mean age was 70 years, 53.5% women, with an eGFR of 19.9 ml/min (sd 8.1). Differences among groups were evaluated with the use of an analysis of variance (ANOVA) model. Age (p&amp;lt;0.001), hemoglobin (p&amp;lt;0.001), phosphorous (p&amp;lt;0.001), pulse pressure (p&amp;lt;0.001), parathormone (p&amp;lt;0.001), estimated glomerular filtration rate (p&amp;lt;0.001) showed significant differences between groups. A post HOC analysis showed that G4 (rCaMg: &amp;gt; 8.6) were older (p&amp;lt;0.001), had lower hemoglobin levels (p&amp;lt;0.001), increased pulse pressure (p&amp;lt;0.001), higher phosphorus (p&amp;lt;0.001) and parathormone levels (p&amp;lt;0.001) and lower eGFR (p&amp;lt;0.001), than groups 1 and 2. Survival at 84 months was progressively shorter with higher rCaMg (G- 1=81.4%, G-2:70.7, G- 3=60.5%, G- 4=28.4%. log Rank =xxx, p=0.004) Multinomial regression analysis showed that Phosphorus; ORa: 1.946 (CI 1.194-3.169), p=0.007, rCaMg; ORa: 1.106 (CI 1.071-1.261) p=0.031, Age: ORa; 1.032 (CI 1.007-1.058) p=0.013, Pulse pressure: ORa; 1.033 (CI 1.007-1.060) p=0.011 were linked to increased cardiovascular mortality. CHAID analysis identified that in 43.7% of patients with P&amp;gt; 4.1 mg/dl, 15.5% were associated with cardiovascular mortality (p&amp;lt;0.001), the model correctly classified 84.1% of patients and the estimate of the risk misclassification of events was 0.159±0.014. Conclusion The calcium/magnesium ratio was shown to be a strong predictor of cardiovascular mortality in patients with stage 4 chronic kidney disease. After CHAID analysis the phosphorus level was assumed to be strongest predictor of cardiovascular mortality in this group of patients.

Pericardial adipose tissue is an independent risk factor of coronary artery disease and is associated with risk factors of coronary artery disease

ObjectivePericardial adipose tissue volume (PATV) is related to the mechanism of coronary artery disease (CAD), but its association with CAD risk factors is not clear. This study aimed to investigate the relationships between PATV and its associated factors.MethodsA total of 682 inpatients were consecutively enrolled in this study. Patients were divided into the high PATV group (PATV ≥174.5 cm3; n = 506) and low PATV group (PATV < 174.5 cm3; n = 176). Multiple linear regression analysis was conducted to evaluate the related factors of PATV. Multivariable logistic regression was used to analyze the risk factors of CAD.ResultsLeft ventricular fat volume, right ventricular fat volume, body mass index, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were significant and independent risk factors of enlargement of PATV. Increased PATV was identified as an independent risk factor of CAD, and increased pulse pressure was also independently and positively correlated with CAD.ConclusionsPATV is significantly correlated with the classic risk factors of CAD. Pulse pressure is also correlated with PATV. PATV is an independent risk factor of CAD, and pericardial adipose tissue may alternatively be used in non-invasive diagnostic examination of CAD.

P0164AMBULATORY BLOOD PRESSURE MONITORING AND CLINICAL SIGNIFICANCE IN PATIENTS WITH GASTROESOPHAGIAL REFLUX DISEASE

Abstract Background and Aims The patients with gastro-esophageal reflux disease (GERD) have distortion of sympathetic and parasympathetic components of the autonomic nervous system. The increase in sympathetic activity results in hyperkinetic circulation with peripheral vasoconstrictor and tachycardia and also regulates blood pressure with increase of renin in kidneys. We aimed to elucidate the patterns of pulse pressure in GERD patients, and also to investigate possible relationship between patterns of pulse pressure and laboratory/urinary parameters in adults Method The ambulatory blood pressure measuring was performed in all cases. Fifty patients in the reflux group and fifty individuals in the control group were included. Blood and urine specimens were examined. The individuals with cardiovascular disease, hypertension, malignancy, asthma disease, gastric peptic ulcer, hepatitis disease, tuberculosis, gastrointestinal disease excluding reflux, cerebrovascular disease, vasculitic disease, chronic alcohol usage, drugs with affect on autonomic system usage were excluded from study. Results We found lower diastolic blood pressure and increased pulse pressure values in reflux group and these were significant statistically. When patients were evaluated separately as men and women, this situation was found to be more pronounced in women. The decrease in serum potassium, chloride levels and the increase in serum LDL cholesterol, triglyceride levels in reflux group considered as statistically significant. Urinary parameters were similar in both groups. Non-dipper pattern found more common in reflux group, but considered as insignificant. The results were summarized in Table 1 and Table 2. Conclusion This study supports the hypothesis that increased vascular risk may be present in patients with GERD. Thus, perhaps a new population at risk for cardiovascular disease will be identified and mortality rates will able to decrease with early clinical evaluation.

Артеріальна гіпертензія і серцева недостатність у загальнолікарській практиці

The Framingham study demonstrated that myocardial infarction (25% of cases) and arterial hypertension (AH) (75% of cases) caused the development of chronic heart failure (CHF). The most significant predictor of CHF development was an increase in systolic blood pressure (SBP) and pulse pressure and each increase in SBP by 20 mm Hg and pulse blood pressure by 16 mm Hg led to an increase in the incidence of CHF by 52% and 55%, respectively. The presented clinical case of a patient with CHF, developed due to long-term hypertension, considered the mechanisms of CHF development, as well as the issue of pharmacotherapy of AH in combination with chronic heart failure with systolic dysfunction. The key mechanisms that directly lead to the development of CHF in AH are hemodynamic overload, reduction of myocardial contractility, left ventricular hypertrophy (LVH). The likelihood of CHF development in patients with AH is by 4 times higher, whilst in patients with LVH it is by 15 times higher. Along with LVH, one of the early manifestations of LV remodeling in AH is the development of diastolic dysfunction, which precedes the development of systolic abnormalities in AH and LVH. Antihypertensive therapy resulted in reduction of the incidence of CHF by approximately 52% compared to patients who did not receive adequate therapy. The decrease in the incidence of CHF was linearly dependent on the decrease in SBP: each decrease of SBP by 10 mm Hg led to a 26% reduction in the relative risk in CHF development. It has been established that AH is not only one of the leading etiological factors in CHF development, but also have similar key links in pathogenesis. The strategy for the selection of pathogenetic pharmacotherapy should be determined taking into account the above circumstance. Currently, the European Society of Cardiology recommends prescribing beta-blockers to all patients with stable CHF Class II–IV as a standard treatment in combination with ACE inhibitors and diuretics in the absence of contraindications. In addition to RAAS blockers, medications for patients with AH in combination with systolic CHF can be supplemented with thiazide or loop diuretics, as well as mineralocorticoid receptor ant agonists (MRA).

Aortic stiffness is associated with changes in retinal arteriole flow pulsatility mediated by local vasodilation in healthy young/middle-age adults

Aortic stiffness is associated with augmented pressure pulsatility in large conduit arteries and remodeling of the microcirculation. However, studies in humans examining the relation between aortic stiffness and end-organ microvascular flow pulsatility are limited. Therefore, we used the retinal microvasculature as an end-organ in vivo model to examine the hypothesis that aortic stiffness would be positively associated with microvascular flow pulsatility index (PI) (flow pulse amplitude/mean flow) in humans. In 40 young/middle-age healthy adults (25-60 yr old, 50% women), aortic stiffness (carotid-femoral pulse wave velocity, CFPWV) and retinal arteriole flow (laser speckle flowgraphy) were examined at rest and during metabolic vasodilation (light flicker). CFPWV and related increases in central pulse pressure (PP) were inversely correlated with arteriole lumen diameter independent of age (CFPWV: R = -0.52, P = 0.001; Central PP: R = -0.39, P = 0.014). Accordingly, microvascular resistance was positively related to CFPWV independent of age (R = 0.35, P = 0.031). Multiple linear regression showed that CFPWV was not a significant determinant of resting arteriole flow PI (β = -0.10, P = 0.64). However, during reduced retinal microvascular resistance using light flicker (P < 0.001), CFPWV was a significant determinant of the percent change in arteriole flow PI (β = 0.58, P = 0.046), but not mean flow (β = -0.17, P = 0.54), where reductions in arteriole flow PI were associated with lower CFPWV. In summary, our findings suggest that higher aortic stiffness and the related increase in central PP in healthy young/middle-age adults are associated with retinal arteriole narrowing and smaller reductions in arteriole flow pulsatility in response to dynamic conditions such as local metabolic vasodilation.NEW & NOTEWORTHY By using the human retinal microvasculature as an end-organ in vivo model, we confirm that aortic stiffness and related increases in central pulse pressure are inversely correlated with retinal arteriole lumen diameter and increased microvascular resistance among heathy young/middle-age adults. Additionally, higher aortic stiffness is not associated with excessive flow pulsatility in the retinal microvasculature under tonic conditions but may be related to limited reductions in retinal arteriole flow pulsatility in response to local vasodilation.

Arterial Hypertension and Heart Failure in General Practice

The Framingham study demonstrated that myocardial infarction (25% of cases) and arterial hypertension (AH) (75% of cases) caused the development of chronic heart failure (CHF). The most significant predictor of CHF development was an increase in systolic blood pressure (SBP) and pulse pressure and each increase in SBP by 20 mm Hg and pulse blood pressure by 16 mm Hg led to an increase in the incidence of CHF by 52% and 55%, respectively. The presented clinical case of a patient with CHF, developed due to long-term hypertension, considered the mechanisms of CHF development, as well as the issue of pharmacotherapy of AH in combination with chronic heart failure with systolic dysfunction. The key mechanisms that directly lead to the development of CHF in AH are hemodynamic overload, reduction of myocardial contractility, left ventricular hypertrophy (LVH). The likelihood of CHF development in patients with AH is by 4 times higher, whilst in patients with LVH it is by 15 times higher. Along with LVH, one of the early manifestations of LV remodeling in AH is the development of diastolic dysfunction, which precedes the development of systolic abnormalities in AH and LVH. Antihypertensive therapy resulted in reduction of the incidence of CHF by approximately 52% compared to patients who did not receive adequate therapy. The decrease in the incidence of CHF was linearly dependent on the decrease in SBP: each decrease of SBP by 10 mm Hg led to a 26% reduction in the relative risk in CHF development. It has been established that AH is not only one of the leading etiological factors in CHF development, but also have similar key links in pathogenesis. The strategy for the selection of pathogenetic pharmacotherapy should be determined taking into account the above circumstance. Currently, the European Society of Cardiology recommends prescribing beta-blockers to all patients with stable CHF Class II–IV as a standard treatment in combination with ACE inhibitors and diuretics in the absence of contraindications. In addition to RAAS blockers, medications for patients with AH in combination with systolic CHF can be supplemented with thiazide or loop diuretics, as well as mineralocorticoid receptor antagonists (MRA).

The Relation between Immune Cell Mitochondrial Respiration and Brachial Artery Pulse Pressure in Humans

Elevated pulse pressure (PP) occurs with advancing age due to stiffening of the elastic arteries and is an important risk factor for cardiovascular disease (CVD), even among normotensive adults. Mitochondrial function declines with aging and may contribute to the increase in PP through a mechanism involving oxidative stress and chronic inflammation; two important hallmarks of arterial aging. Emerging evidence indicates that mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) is negatively associated with risk factors for CVD in heart failure; however, the role of impaired mitochondrial function on cardiovascular function in healthy adults is not known. We hypothesized that mitochondrial function would be negatively associated with brachial PP. Twenty‐two healthy adults free of overt CVD (12 M/10 F; age: 56 ± 21 years; age range: 22–78 years; blood pressure, BP: 123 ± 15/72 ± 10 mmHg; PP: 51 ± 11 mmHg) were included in this analysis. PP was determined from brachial artery BP assessed in triplicate in the non‐dominant arm using an automated BP monitor. PBMCs were isolated by density dependent centrifugation and used to assess mitochondrial function by respirometry using an Agilent Seahorse XFp Analyzer. Primary outcome measures included the oxygen consumption rate (OCR) at baseline (basal respiration; BASERESP) and following three serial injections of oligomycin, FCCP and rotenone/antimycin A into the respirometer to determine maximal respiration (MAXRESP). Spare respiratory capacity (SRC), an indicator of how well the cell can respond to an increased energetic demand, ATP‐linked oxygen consumption (ATPO2), and coupling efficiency, which is how well ATPO2 is matched to BASERESP, were also measured. The associations between mitochondrial function and PP were analyzed using multi‐linear regressions correcting for age. PP was not associated with BASERESP (p=0.89, R2=0.10, β=0.01), coupling efficiency (p=0.20, R2=0.18, β= −8.5), or ATPO2 (p=0.33, R2=0.15, β= −0.10). However, PP was inversely associated with MAXRESP (p=0.05, R2=0.28, β= − 0.03) and SRC (PP; p=0.02, R2=0.33, β=−0.04). These data suggest that the impaired mitochondrial respiration may be an important contributor to CVD risk through increases in pulse pressure. Future studies should explore whether these associations are mediated by increases in oxidative stress and inflammatory cytokines.Support or Funding InformationFunding Sources: P20GM113125, K01AG054731

Human Angiotensin‐(1‐12) [Ang‐(1‐12)] is a Hypertension and Cardiac Disease Biomarker

BackgroundAng‐(1‐12) is a primary non‐renin dependent substrate for direct tissue angiotensin II (Ang II) formation by chymase. This discovery challenges conventional thinking and explains the large residual risk of cardiovascular events in patients medicated with blockers of the renin angiotensin system (RAS). Here we report the first demonstration of circulating Ang‐(1‐12) as a biomarker of essential hypertension (EH) and cardio‐renal remodeling.MethodsThe cohort of patients from Olmsted County MN included 52 healthy adult volunteers (21 females), age 54 ± 8 years, and 23 essential hypertensive (EH) patients (14 females) age 61 ± 8 years with systolic blood pressure (SBP) ≥140 mm Hg prior to recruitment. Clinical examination, standardized BP measurements, and venous blood were obtained for measurements of plasma concentrations of angiotensinogen (AGT), Ang‐(1‐12), Ang II, aldosterone, renin activity, N‐terminal pro–B‐type natriuretic peptide (NT‐proBNP) and atrial and brain natriuretic peptides (ANP and BNP, respectively). All values are Means ± SD. Data were analyzed by 2‐way ANOVA for sex and hypertension.ResultsPlasma Ang‐(1‐12) levels in EHs [SBP: 134 ± 14 mm Hg; Ang‐(1‐12): 1,463 ± 446] were higher than normotensives [SBP: 117 ± 13 mm Hg; Ang‐(1‐12): 1,353 ± 379 fmol/mL, hypertension effect: P&lt;0.05], irrespective of sex. Hypertension associated with increases in pulse pressure, PRA, and plasma AGT and NT‐proBNP concentrations (see Figure ). The elevation in circulating NT‐proBNP levels with hypertension was accounted for by a 4.6‐fold increase in hypertensive males (165 ± 134 pg/mL) while the 1.5‐fold rise in plasm NT‐proBNP did reach significance (134 ± 127 pg/mL, p&gt; 0.05).ConclusionsWe show for the first time that Ang‐(1‐12) circulates in humans and its concentrations are elevated by chronic hypertension. We further demonstrate a sexual dimorphic pattern in hypertensives with respect to NT‐proBNP, the latter a biomarker for cardiac remodeling. Whether this represents a natriuretic system‐related compensatory mechanism, or worsening pathology, due to an elevated noncanonical RAS specific to male hypertensives remains to be studied. Further investigation to fully define the role of Ang‐(1‐12) as a cardiac disease biomarker in a larger, gender and ethnic diverse population and its relationship to hypertension and myocardial structure is warranted.Support or Funding InformationSupported by grant HL‐051952 from the NHLBI of the NIHLines are means ± SDFigure 1

Mechanisms of Arterial Stiffening: From Mechanotransduction to Epigenetics.

Arterial stiffness is a major independent risk factor for cardiovascular complications causing isolated systolic hypertension and increased pulse pressure in the microvasculature of target organs. Stiffening of the arterial wall is determined by common mechanisms including reduced elastin/collagen ratio, production of elastin cross-linking, reactive oxygen species-induced inflammation, calcification, vascular smooth muscle cell stiffness, and endothelial dysfunction. This brief review will discuss current biological mechanisms by which other cardiovascular risk factors (eg, aging, hypertension, diabetes mellitus, and chronic kidney disease) cause arterial stiffness, with a particular focus on recent advances regarding nuclear mechanotransduction, mitochondrial oxidative stress, metabolism and dyslipidemia, genome mutations, and epigenetics. Targeting these different molecular pathways at different time of cardiovascular risk factor exposure may be a novel approach for discovering drugs to reduce arterial stiffening without affecting artery strength and normal remodeling.