Changes In Pulse Wave Velocity Research Articles

Association of mid-regional pro-adrenomedullin with office and 24-h ambulatory blood pressure in a Swiss general population sample.

Adrenomedullin (ADM) is a potent vasodilator. The association between plasma ADM levels and blood pressure (BP) remains unclear. We assessed the association between mid-regional-pro-ADM (MR-proADM) and BP in a multicenter population- and family-based cohort. We used data from the Swiss Kidney Project on Genes in Hypertension (SKIPOGH). We included participants present at both baseline and 3-year follow-up (N = 843). We examined the association of baseline MR-proADM with baseline office and 24 h ambulatory BP as well as the 3-year change in office BP. In secondary analyses, we studied the association between baseline MR-proADM and 3-year changes in pulse wave velocity (PWV), renal resistive index (RRI) and augmentation index (AI). Mixed-effects linear regression models were used. In cross-sectional analyses, MR-proADM was negatively associated with office, 24-h and daytime diastolic BP (DBP). MR-proADM was positively associated with nighttime systolic BP (SBP). In longitudinal analyses, baseline MR-proADM was associated with an increase in office SBP and pulse pressure (PP) over 3 years [β (95% CI): 8.2 (0.4, 15.9) and β (95% CI): 6.4 (0.3, 12.4), respectively] but not with changes in PWV, RRI and AI. The cross-sectional negative association of MR-proADM with DBP is in line with known vasodilatory properties of ADM. The positive association between MR-proADM and nighttime SBP at baseline may reflect endothelial dysfunction believed to be part of the pathogenesis of nocturnal hypertension. The association of higher baseline MR-proADM levels with increased SBP and PP at 3-year follow-up suggests that ADM levels could be a marker of cardiovascular risk.

'Effects of dehydration on central blood pressure in young healthy adults'.

Brachial blood pressure (BP) is the current gold standard for BP assessment; however, measures of pulse wave velocity (PWV) and central blood pressure (CBP) may contribute uniquely to assessment of cardiovascular health status. As of yet, standards for assessment of CBP and PWV have not addressed the impact of hydration status on proper measurement. To understand the impact of hydration, PWV and CBP should be measured in a euhydrated and hypohydrated state. Forty-three young, healthy participants (21 ± 2 years) completed a dehydration protocol utilizing moderate aerobic activity until they lost 1%-2% of their body weight. PWV and CBP were measured before and following the dehydration protocol. Linear regression was utilized to assess change in hydration status and change in PWV and CBP. No significant relationships were observed between the change in hydration status (% body weight lost) and PWV (β = 0.05, p = 0.78) or central diastolic BP (β = -3.8, p = 0.10), however, a significant relationship was observed with central systolic BP (β = -5.0, p = 0.03). In conclusion, the assessment of hydration status before measurement of CBP or PWV may not be necessary in young, healthy individuals.

Haemodynamic Forces: Emerging Markers of Ventricular Remodelling in Multiple Myeloma Cardiovascular Baseline Risk Assessment.

Multiple myeloma (MM) affects a population with a high prevalence of cardiovascular (CV) disease. These patients benefit from an accurate CV risk evaluation in order to choose the safest drug regimen. Haemodynamic forces (HDFs) analysis allows for the earlier detection of myocardial damage compared with standard markers; the role played by MM in HDFs alteration, with or without the influence of hypertension, is yet to be studied. Therefore, we aimed to identify differences in HDFs analysis in patients with MM, hypertension or both versus normotensive non-oncologic subjects. A total of 173 patients (MM hypertensive patients, MMHT; MM normotensive patients, MMNT; non-oncologic hypertensive patients, CoHT; and non-oncologic normotensive patients, CoNT) underwent transthoracic echocardiography for HDFs analysis and pulse wave velocity (PWV) assessment. Hypertensive patients (MMHT, CoHT) showed decreased ejection fraction (EF), global longitudinal strain (GLS) and HDFs values compared with CoNT, whereas ventricular mass (LVMi) and PWV increased. MMNT displayed a significant reduction in systolic HDFs (p < 0.006) and systolic ejection HDFs (p < 0.008) compared with CoNT, without significant change in EF, GLS, LVMi or PWV. In conclusion, MM leads to ventricular remodelling regardless of hypertension; HDFs application for MM patients could help detect early myocardial damage, especially in patients receiving cardiotoxic drugs.

Pulse Wave Velocity as a Tool for Cardiometabolic Risk Stratification in Individuals With Hypertensive Disorders of Pregnancy and Increased BMI

ObjectivesObesity is one of the most prevalent risk factors for hypertensive disorders of pregnancy (HDP); however, the role of pre-pregnancy cardiometabolic health in the development of these conditions is not well understood. Carotid-femoral pulse wave velocity (PWV) is an established measure of arterial stiffness and cardiovascular health and is validated in pregnancy. Our objective was to examine the obesity-related changes in PWV in pregnant individuals with and without HDP. MethodsOverall, 87 individuals with singleton pregnancies were recruited and classified into 2 groups: cases (HDP: including pre-existing/chronic hypertension, gestational hypertension, preeclampsia, or intrauterine growth restriction; n = 39) and normotensive controls (no HDP or intrauterine growth restriction; n = 48). Patient data, including BMI, were collected from patient charts. Measurements of PWV were performed weekly until discharge or delivery (gestational age 24–37 weeks) and placental growth factor (PlGF) was measured at routine blood draws. ResultsPWV did not significantly change over gestation for either group. Cases had significantly increased PWV and decreased PlGF compared to normotensive controls. An elevated BMI was associated with higher PWV in both cases and controls. Once grouped based on BMI, PWV was only significantly higher in cases with a BMI ≥25 kg/m2 compared to controls, whereas PlGF was less affected by BMI. As PWV increased, PlGF decreased; however, after controlling for BMI, there was no relationship between PWV and PlGF. ConclusionsPWV measurements in early pregnancy may be useful as an additional independent marker to PlGF for risk-stratifying for HDP, especially in individuals with increased BMI.

Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism.

Empagliflozin has been shown in clinical studies to lower the risk of adverse cardiovascular events. Using proteomics, the current study aims to determine whether empagliflozin reduces aortic alterations in obese mice and to investigate its molecular mechanism of action. We constructed obese mice and then treated them with empagliflozin. Changes in the weight of the mice were recorded. Blood glucose and lipid levels were measured in each group of mice, and changes in pulse wave velocity and aortic structure were recorded. In addition, changes in aortic protein expression were detected by proteomics and analyzed bioinformatically. Proteomics results showed that 507 differentially expressed proteins (DEPs) were identified in the comparison of normal and obese mice, while 90 DEPs were identified in the comparison of obese and empagliflozin-treated mice. Examination of these three groups revealed that DEPs were largely associated with the digestion of unsaturated fats. Among them, empagliflozin significantly reduced the expression of fatty acid synthase (FASN), acyl-CoA desaturase 3 (SCD3), ACSL1. and ACSL5 in the aorta of obesity-induced mice, and there was a close relationship between the four. Empagliflozin reduced the protein expression of FASN, SCD3, ACSL1, and ACSL5 in the aorta of obese mice and improved aortic fatty acid metabolism and reduced vascular stiffness for vasoprotective effects.

Advancing the Local Pulse Wave Velocity Measurement-Wave Confluence Decomposition Using a Double Gaussian Propagation Model.

Background Pulse wave velocity (PWV) is a marker of arterial stiffness and local measurements could facilitate its widescale clinical use. However, confluence of incident and early reflected waves leads to biased spatiotemporal PWV estimates. Objective We introduce the Double Gaussian Propagation Model (DGPM) to measure local PWV in consideration of wave confluence (PWV[Formula: see text]) and compare it against conventional spatiotemporal PWV (PWV[Formula: see text]), with Bramwell-Hill PWV (PWV[Formula: see text]) and blood pressure (BP) as reference measures. Methods Ten subjects ranging from normotension to hypertension were repeatedly measured at rest and with induced PWV changes. Carotid distension waveforms over a 19 mm wide segment were acquired from ultrasonography, simultaneously with noninvasive continuous BP. Per cardiac cycle, the 8-parameter DGPM (amplitude, centroid, width, and velocity, respectively of forward and backward propagating wave) was fitted to the distension waveforms' systolic foot and dicrotic notch complexes. Corresponding PWV[Formula: see text] was computed from linear fittings of respective feature timings and distances. Regression analyses were conducted with PWV[Formula: see text] and PWV[Formula: see text] as predictors, and various PWV and BP measures as response variables. Results Whereas PWV[Formula: see text] correlations were insignificant, PWV[Formula: see text] estimated the reference PWV[Formula: see text] with a significant reduction in errors (P < 0.001), explained up to 65% PWV[Formula: see text] variability at rest, demonstrated higher intra-method consistency and correlated significantly with all BP measures (P < 0.001). Conclusion The proposed DGPM measures local carotid PWV in consideration of wave confluence, showing significant correlations with Bramwell-Hill PWV and BP at two distinct waveform complexes. Thereby PWV[Formula: see text] outperforms the conventional PWV[Formula: see text] in all investigated respects, potentially enabling PWV assessment in routine clinical practice.

The effect of time-restricted eating on arterial stiffness indices in men with metabolic syndrome: study protocol for a randomized controlled trial

BackgroundTime-restricted eating (TRE) has been shown to be associated with improvements in some aspects of the metabolic syndrome. Nevertheless, only a few studies have addressed the effect of TRE on pulse wave velocity (PWV). We thus propose a randomized controlled trial to compare the effects of TRE with standard dietary advice on PWV and thereby present the protocol.MethodsForty-eight participants will be assigned to either TRE or control groups using simple randomization. The TRE group will consume their meals during a 10-h period and experience 14 h of fasting. They will also be advised to consume their last meal no later than 20:00. Both groups will receive standard dietary advice. The participants will be followed for 6 weeks. The primary outcome will be changes in PWV. Laboratory measurements, including lipid profile, liver enzyme tests, fasting blood glucose (FBG), insulin concentrations, and insulin resistance, as well as anthropometric data, blood pressure, basal metabolic rate, appetite status, physical activity level, sleep quality, cognitive function, quality of life, and calorie intake, will be evaluated throughout the study.DiscussionThe outcomes of this study will allow a comparison of the effects of TRE and standard dietary recommendations on PWV and other cardiometabolic factors in individuals with metabolic syndrome (MetS).Trial registrationIranian Registry of Clinical Trials; code: IRCT20201230049889N1; registered on August 14, 2022. The registration of the trial is accessible at: https://www.IRCT.ir/trial/64485?revision=281341.

Prognostic value of brachial-ankle pulse wave velocity changes post-transcatheter aortic valve replacement.

Transcatheter aortic valve replacement (TAVR) offers a solution, especially for high-risk aortic stenosis (AS) patients. However, patient outcomes post-TAVR show variability, highlighting the need for reliable prognostic indicators. Brachial-ankle pulse wave velocity (baPWV), a measure of arterial stiffness, may predict outcomes post-TAVR. This study aims to explore baPWV's prognostic value in relation to all-cause mortality post-TAVR. This study prospectively enrolled 212 severe AS patients undergoing TAVR between September 2015 and December 2021, focusing on pre- and post-TAVR baPWV measurements to explore associations with all-cause mortality. Of the 212 patients (119 females, 93 males, mean age 85years), post-TAVR baPWV increased significantly from 1589 ± 376 to 2010 ± 521cm/s (p < 0.001). Aortic valve (AV) peak velocity and mean pressure gradient decreased, while AV area increased, indicating procedural success. Despite this, 88% of patients experienced an increase in baPWV, with higher pre-procedure AV peak velocity and mean pressure gradient identified as predictors of increased baPWV post-TAVR. Over 23months, 29 patients (14%) reached the primary endpoint of all-cause mortality. Notably, changes in baPWV, rather than baseline values, were significantly associated with event-free survival (HR: 0.64 per 1SD increase, p = 0.009). The study highlights the prognostic value of baPWV changes post-TAVR in predicting patient outcomes. Elevated baPWV post-TAVR may reflect a beneficial adaptation to altered hemodynamics, suggesting the need for individualized patient evaluation and the integration of baPWV measurements into clinical practice for improved post-TAVR management.

Association between blood-brain barrier permeability and changes in pulse wave velocity following a recent small subcortical infarct.

Cerebral small vessel disease (cSVD) is associated with increased blood-brain barrier (BBB) permeability. We sought to evaluate whether arterial stiffness might be associated with BBB permeability in patients with cSVD. We assessed BBB permeability using Dynamic Contrast-Enhanced MRI (DCE-MRI) in 29 patients that had suffered a recent small subcortical infarct (RSSI). BBB permeability in the whole brain (WB), gray matter (GM) and white matter (WM) was assessed with the parameter Ktrans. We used ambulatory blood pressure monitoring to measure 24-h systolic blood pressure (24-h SBP), diastolic blood pressure (24-h DBP), and pulse wave velocity (24-h PWV) both after stroke and following a 2-year follow-up. The differences between both measurements were calculated as Δ24-h SBP, Δ24-h DBP and Δ24-h PWV. DCE-MRI was acquired at a median (IQR) of 24 (19-27) months after stroke. Median age was 66.7 (9.7) years, and 24 (83%) patients were men. Median (IQR) Δ24-h PWV was 0.3 (-0.1, 0.5) m/s. WB-Ktrans, GM-Ktrans, and WM-Ktrans were associated with Δ24-h PWV (Spearman's, r [95% CI], WB 0.651 [0.363-0.839]; GM 0.657 [0.373-0.845], WM 0.530[0.197-0.777]) but not with Δ24-h SBP or Δ24-h DBP. These associations remained significant after adjustment with linear regression models, controlling for age, sex, body mass index, and Δ24-h SBP (b[95% CI], WB 0.725[0.384-1.127], GM 0.629 [0.316-1.369], WM 0.865 [0.455-0.892]) or Δ24-h DBP (b[95% CI], WM 0.707 [0.370-1.103], GM 0.643 [0.352-1.371], WM 0.772 [0.367-0.834]). Our results suggest that an increment on arterial stiffness in the months following a RSSI might increase BBB permeability.

Effects of a medium cut-off dialyzer on inflammation and cardiac and vascular function in hemodialysis patients with heart failure.

Expanded hemodialysis (HDx) could provide clearance of larger middle-molecule uremic toxins. We compared the effect of hemodialysis with medium cut-off membranes and high-flux (HFHD) membranes regarding changes in inflammation and vascular and left ventricular function. This was a single-center, prospective, parallel-group comparative study. Patients were divided into two groups (HDx: 25 patients and HFHD: 26 patients). All measurements were performed at baseline and 12 weeks. Serum c-reactive protein, interkelukin-18, pentraxin-3, β-2 microglobulin, and brain natriuretic peptide were measured. We used pulse wave velocity and augmentation index to assess arterial stiffness and echocardiography to evaluate left and right ventricular function. We enrolled 51 patients. Although serum c-reactive protein, interkelukin-18, pentraxin 3, and β-2 microglobulin were significantly decreased in the HDx group (p = 0.02, p < 0.001, p = 0.002, and p = 0.02, respectively), there was no significant change in HFHD group at 12th week. Serum c-reactive protein and interkelukin-18were significantly lower in the HDx group compared to the HFHD group in the 12th week (p = 0.007 and p = 0.03, respectively). We observed a significant decrease in pulse wave velocity in the HDx group at the end of the study (p = 0.03). Although there was no significant change in pulse wave velocity in the HFHD group, pulse wave velocity was similar between the HDx and HFHD groups in the 12th week. We detected a significant decrease in the mean isovolumetric relaxation time in the HDx group (p = 0.006). However, there was no significant difference in isovolumetric relaxation time between the HDx and HFHD groups in the 12th week. HDx provides better clearance of middle molecular uremic toxins and inflammatory biomarkers, and it may be associated with better central hemodynamic parameters and diastolic functions.

Is GFR decline induced by SGLT2 inhibitor of clinical importance?

BackgroundUse of sodium-glucose-cotransporter-2 (SGLT2) inhibitors often causes an initial decline in glomerular filtration rate (GFR). This study addresses the question whether the initial decline of renal function with SGLT2 inhibitor treatment is related to vascular changes in the systemic circulation.MethodsWe measured GFR (mGFR) and estimated GFR (eGFR) in 65 patients with type 2 diabetes (T2D) at baseline and after 12 weeks of treatment randomized either to a combination of empagliflozin and linagliptin (SGLT2 inhibitor based treatment group) (n = 34) or metformin and insulin (non-SGLT2 inhibitor based treatment group) (n = 31). mGFR was measured using the gold standard clearance technique by constant infusion of inulin. In addition to blood pressure (BP), we measured pulse wave velocity (PWV) under standardized conditions reflecting vascular compliance of large arteries, as PWV is considered to be one of the most reliable vascular parameter of cardiovascular (CV) prognosis.ResultsBoth mGFR and eGFR decreased significantly after initiating treatment, but no correlation was found between change in mGFR and change in eGFR in either treatment group (SGLT2 inhibitor based treatment group: r=-0.148, p = 0.404; non-SGLT2 inhibitor based treatment group: r = 0.138, p = 0.460). Noticeably, change in mGFR correlated with change in PWV (r = 0.476, p = 0.005) in the SGLT2 inhibitor based treatment group only and remained significant after adjustment for the change in systolic BP and the change in heart rate (r = 0.422, p = 0.018). No such correlation was observed between the change in eGFR and the change in PWV in either treatment group.ConclusionsOur main finding is that after initiating a SGLT2 inhibitor based therapy an exaggerated decline in mGFR was related with improved vascular compliance of large arteries reflecting the pharmacologic effects of SGLT2 inhibitor in the renal and systemic vascular bed. Second, in a single patient with T2D, eGFR may not be an appropriate parameter to assess the true change of renal function after receiving SGLT2 inhibitor based therapy.Trial registrationclinicaltrials.gov (NCT02752113).

#2570 Non-invasive blood pressure monitoring in dialysis patients using pulse wave velocity

Abstract Background and Aims Dialysis patients are at high risk of circulatory dysregulation and hypotension during treatment. Intradialytic hypotension (IDH) is a potentially life-threatening complication. The main causes are high ultrafiltration volumes and high ultrafiltration rates when patients tend to gain a lot of weight between dialysis treatments. A lack of patient compliance with regard to drinking volumes and a lack of residual diuresis are risk factors for this. Close circulatory monitoring and therapy settings to avoid absolute or relatively high UF rates to prevent IDH are frequently used. These are primarily the frequent non-invasive measurement of blood pressure using cuffs, the measurement of relative blood volume and the adjustment of ultrafiltration rates to these values. Prophylactically, the dialysis time can be extended, ultrafiltration profiles or ultrafiltration breaks can be planned, the dialysate temperature can be lowered and the composition of the dialysate can be adjusted. Despite all attempts, however, the incidence of IDH in everyday clinical practice is too high. The non-invasive measurements with cuffs are not carried out frequently enough, the measurement of the relative blood volume only covers a partial range, sudden changes in vascular tension or cardiac output are not recorded. Method The pulse wave velocity (PWV) is a well-known parameter for describing the propagation of the pressure wave after ejection of the heart beat volume in the arteries. The PWV is dependent on blood pressure, vessel wall tension and cardiac output. Changes in blood pressure can therefore be recognised by measuring the PWV. With the help of a measuring device (PESAS) for the ECG signal and peripheral pulse plethysmography, PWV can be measured non-invasively, continuously, for every heartbeat and, above all, hardly noticed by the patient. The PESAS allows the time-synchronised measurement of ECG and peripheral plethysmography curves and thus the determination of PWV. It is an experimental device. We would like to present a study showing the use of a measuring device (PESAS) in 15 prevalent dialysis patients for the detection of IDH. All study participants were examined during 3 dialysis treatments. Results The measurement of PWV in chronic dialysis patients during treatment is technically feasible. The measurement is tolerated by the patients. Changes in PWV could be detected in the patients during the course of dialysis; these were also dependent on the ultrafiltration rates. Individual patient reactions to volume withdrawal varied, with both increases and decreases in PWV being demonstrated. An acute change in PWV was usually associated with a drop in blood pressure. Continuous measurement allowed IDH events to be detected earlier than intermittent blood pressure measurement with cuffs. Sudden drops in blood pressure could be detected better and earlier with the PESAS system than by measuring the relative blood volume. Conclusion The PESAS system is suitable for monitoring dialysis patients to prevent IDH. Further adjustments and optimisation of the evaluation algorithms are necessary.

Influence of Blood Pressure Reduction on Pulse Wave Velocity in Primary Hypertension: A Meta-Analysis and Comparison With an Acute Modulation of Transmural Pressure.

Increased arterial stiffness and pulse wave velocity (PWV) of the aorta and large arteries impose adverse hemodynamic effects on the heart and other organs. Antihypertensive treatment reduces PWV, but it is unknown whether this results from an unloading of stiffer elements in the arterial wall or is due to an alternate functional or structural change that might differ according to class of antihypertensive drug. We performed a systematic review and meta-analysis of the effects of different antihypertensive drug classes and duration of treatment on PWV with and without adjustment for change in mean arterial blood pressure (BP; study 1) and compared this to the change in PWV after an acute change in transmural pressure, simulating an acute change in BP (study 2). A total of 83 studies involving 6200 subjects were identified. For all drug classes combined, the reduction of PWV was 0.65 (95% CI, 0.46-0.83) m/s per 10 mm Hg reduction in mean arterial BP, a change similar to that induced by an acute change in transmural pressure in a group of hypertensive subjects. When adjusted for change in mean arterial BP, the reduction in PWV after treatment with beta-blockers or diuretics was less than that after treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists or calcium channel antagonists. Reduction in PWV after antihypertensive treatment is largely explained by the reduction in BP, but there are some BP-independent effects. These might increase over time and contribute to better outcomes over the long term, but this remains to be demonstrated in long-term clinical trials.

INFLUENCE OF STATINS ON ARTERIAL STIFFNESS AND BLOOD PRESSURE CONTROL IN PATIENTS WITH SEVERE ARTERIAL HYPERTENSION

Objective: In some studies, there was well established a statin influence on arterial stiffness. It was suggested statins could decrease the blood pressure too. Pulse wave velocity (PWV), a gold standard for arterial stiffness measurement, depends on blood pressure (BP). The aim of study was to evaluate the influence of statins on PWV changes in dependency on normalization of the 24-h BP. Design and method: In study, there were included 46 patients (mean age 55.6 ±1.07, f/male 47.8/52.2%) with systolic (SBP)/diastolic (DBP) BP &gt;/=180/110 mmHg, who were treated in specialized unit. Baseline and at the 6th month of combination therapy (mean medicines - 3.8±1.2), we provided office/ambulatory BP and PWV measurements. Results: At 6th month, only 39.1% had 24-h BP &lt;130/80. PWV changes under treatment are present in tab. In statin treatment group we noted significant PWV lowering in spite of BP control. In patients without statins, PWV decreased significantly only in subgroup with achieved the target 24-h BP. In statin group 66.7% achieved target 24-h BP compared to 33.3% in statin (-) group (p=0.048). Conclusions: The statin therapy is able to improve the arterial stiffness (independently to BP control) and helps to achieve the target BP.

Abstract MP60: A Randomized Placebo-Controlled Trial of Pitavastatin Calcium to Treat Combined Dyslipidemia of Obesity in Adolescents - The Pediatric Heart Network Dyslipidemia of Obesity Intervention in Teens (Do It!) Trial

Background: Combined dyslipidemia of obesity (CDO) is prevalent in ~20% of youth and characterized by high numbers of atherogenic small LDL (sLDL) particles associated with stiffer arteries. The safety and impact of statin therapy is not known. Methods: A 2-year masked trial of pitavastatin calcium 4 mg/day versus placebo for participants ages 10-19 years with body mass index (BMI) ≥85 th %ile and CDO defined as non-HDL-C ≥120 mg/dL and either low HDL-C or high triglyceride (TG):HDL-C ratio. The primary outcome was change in carotid-femoral pulse wave velocity (PWV) and carotid measures assessed at baseline, 6, 12, 18, and 24 months. Secondary outcomes included safety and lipid measures. Results: Across 18 sites, 59 participants were randomized to pitavastatin and 60 to placebo. Demographic (mean age 13.5±1.2 yrs; 55% males), anthropomorphic (BMI %ile 98±3; waist/height ratio 0.66±0.08), lipid (non-HDL-C 167±29 mg/dL, LDL-C 127±25 mg/dL, HDL-C 37±7 mg/dL, TG/HDL ratio 6.4±4.7, sLDL number 866±419 nmol/L), vascular (PWV 5.0±0.7 m/sec) and safety measures were similar at baseline between groups. There were 28 early terminations (11 pitavastatin, 17 placebo). Significant reductions with pitavastatin versus placebo were noted in non-HDL-C (median -25% vs +3% at 6 months, p&lt;0.001), LDL-C (-29% vs +7%, p&lt;0.001), and apolipoprotein B (-26% vs 0%, p&lt;0.001). An early reduction relative to placebo in sLDL particle number was not sustained (FIGURE A), and there were no significant changes or trends for PWV (FIGURE B) or carotid measures in either group. There was one serious adverse event (placebo), and no significant differences in liver enzymes, muscle toxicity, glucose homeostasis, or somatic growth, including adiposity. Conclusions: Over 2 years, treatment of CDO in adolescents with pitavastatin calcium resulted in significant improvement in dyslipidemia with no safety concerns. No change in PWV in either group may be due to lower-than-expected baseline PWV, insufficient magnitude of impact on CDO, or lack of change in adiposity.

Natural Autoantibodies in Biologic-Treated Rheumatoid Arthritis and Ankylosing Spondylitis Patients: Associations with Vascular Pathophysiology.

Cardiovascular (CV) morbidity and mortality have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Natural autoantibodies (nAAb) are involved in innate immunity, as well as autoimmunity, inflammation, and atherosclerosis. There have not been any studies assessing the effects of biologics on nAAbs in RA and AS, also in relation to vascular pathophysiology. Fifty-three anti-TNF-treated RA and AS patients were included in a 12-month follow-up study. Anti-citrate synthase (CS) and anti-topoisomerase I fragment 4 (TOPO-F4) IgM and IgG levels were determined by ELISA. Ultrasonography was performed to assess brachial artery flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT), and arterial pulse-wave velocity (PWV). Other variables were also evaluated at baseline and 6 and 12 months after treatment initiation. Anti-TNF therapy improved FMD in RA and PWV in AS and stabilized ccIMT. TNF inhibition increased anti-CS IgM and IgG, and possibly also anti-TOPO-F4 IgG levels. Various correlation analyses revealed that nAAbs might be independently involved in autoimmunity as well as changes in inflammation and vascular pathology over time in biologic-treated patients (p < 0.05). We also found associations between anti-TOPO-F4 IgG and anti-Hsp60 IgG (p < 0.05). Baseline nAAb levels or nAAb level changes might determine changes in CRP, disease activity, FMD, PWV, and ccIMT over time (p < 0.05). The interplay between arthritis and inflammatory atherosclerosis, as well as the effects of anti-TNF biologics on these pathologies, might independently involve nAAbs.

Volume overload is a major characteristic in primary aldosteronism: a 3-year follow-up study.

We examined haemodynamics, focusing on volume balance and forward and backward wave amplitudes, before and after 2.8 years of targeted treatment of primary aldosteronism. Patients with essential hypertension and normotensive individuals were examined for comparison ( n = 40 in each group). Recordings were performed using radial artery pulse wave analysis and whole-body impedance cardiography. Unilateral aldosteronism was treated with adrenalectomy ( n = 20), bilateral aldosteronism with spironolactone-based medication ( n = 20), and essential hypertension with standard antihypertensive agents. Aortic SBP and DBP, forward and backward wave amplitudes, and systemic vascular resistance were equally elevated in primary aldosteronism and essential hypertension. All these haemodynamic variables were similarly reduced by the treatments. Primary aldosteronism presented with 1 litre (∼10%) extracellular water excess ( P < 0.001) versus the other groups, and this excess was normalized by treatment. Initial pulse wave velocity (PWV) was similarly increased in primary aldosteronism and essential hypertension, but final values remained higher in primary aldosteronism ( P < 0.001). In regression analyses, significant explanatory factors for treatment-induced forward wave amplitude reduction were decreased systemic vascular resistance ( β = 0.380) and reduced extracellular water volume ( β = 0.183). Explanatory factors for backward wave amplitude reduction were changes in forward wave amplitude ( β = 0.599), heart rate ( β = -0.427), and PWV ( β = 0.252). Compared with essential hypertension, the principal haemodynamic difference in primary aldosteronism was higher volume load. Volume excess elevated forward wave amplitude, which was subsequently reduced by targeted treatment of primary aldosteronism, along with normalization of volume load. We propose that incorporating extracellular water evaluation alongside routine diagnostics could enhance the identification and diagnosis of primary aldosteronism.

Effects of melatonin on blood pressure, arterial stiffness and quality of life in postmenopausal women: A randomized controlled trial

ObjectivesStudies suggest that melatonin may promote cardiovascular protection. Previous trials have primarily been performed on co-morbid patients. Little information exist on the effect in postmenopausal women with general good health. Design, participants and interventionIn a double-blinded placebo-controlled study, we randomized 41 postmenopausal women to either 10 mg melatonin per day or placebo for 3 months. Outcome measuresOutcomes of the trial was changes in blood pressure, pulse wave velocity (PWV), and quality of sleep evaluated by Pittsburgh Sleep Quality Index (PSQI). ResultsThirty-nine women completed the study. Mean age was 63 years (range 55–75 years). Over the 3 months of the trial, PWV did not differ between groups: Placebo 1.1% (IQR −2.1;9.9) vs. melatonin 0.0% (IQR-9.8;4.1), p = 0.43). The were no significant differences in blood pressure bewteen melatonin and placebo group. Both groups had a pour quality of sleep at baseline (placebo: PSQI 6.0 (IQR 3.3; 8.8) vs. melatonin PSQI 6.0 (IQR 3.0; 10.0), p = 0.94), which did not change in response to treatment. ConclusionIn healthy postmenopausal women, supplementation with 10 mg melatonin was well-tolerated, but we did not observe any significant improvements in pulse wave velocity, blood pressure or quality of sleep compared with placebo.

Genetic and biomarker modulation of arterial stiffness change in the SardiNIA population cohort.

Arterial stiffness (AS), quantified by pulse wave velocity (PWV), arises due to impaired arterial elastic tissue and smooth muscle dysfunction. We aimed to examine the longitudinal association of genetic, lipid and inflammation biomarkers with PWV and how these associations may change with aging. We utilized genotype and four time-point biomarker data from the SardiNIA cohort [n = 6,301; mean baseline age 43.3 (SD 17.3); 58% females]. To investigate the association of PWV with genetic variants, lipid, and inflammation biomarkers, we employed linear mixed modeling, using age as the time scale. Biomarkers exhibiting significant longitudinal associations were categorized into tertiles and individuals within the second tertile or those with heterozygous alleles were excluded, leaving a cohort of 2,000 individuals. This cohort was further divided into four risk groups: low genetic and low biomarker (L-L), low genetic and high biomarker (L-H), high genetic and low biomarker (H-L), and high genetic and high biomarker risk (H-H). Subsequent analyses focused on these risk groups to assess their association to PWV with time. Using the complete dataset, we found a significant longitudinal association of total cholesterol (TC), triglycerides (TG), fibrinogen (FGN), and total white blood cell count (TWBC) with PWV, all with p < 3.33 × 10-3. After grouping, individuals with homogeneous risk alleles of SNP rs3742207 and high baseline TG levels (H-H group) exhibited a 1.39-fold higher PWV (m/s) (95% CI, 1.17-1.64, p = 1.21 × 10-4) compared to the L-L group. Similarly, individuals in the H-H group of rs3742207-TWBC combination showed 1.75 times higher PWV (95% CI, 1.48-0.2.07, p = 1.01 × 10-10) compared to the L-L group. Similar patterns were observed for groups based on SNP rs7152623-TWBC risk. Furthermore, these associations became more pronounced with increasing age (p < 3.33 × 10-3). The longitudinal association of TG and TWBC biomarkers with PWV varied by SNPs rs3742207 and rs7152623 genotype. Further studies are warranted to investigate the function of genetics, lipids, and inflammation biomarkers on PWV change.

Effects of metformin on arterial elasticity and pro-inflammatory markers in black diabetes patients.

Pro-inflammatory markers are linked with the development and progression of type 2 diabetes mellitus and arterial stiffening. Pulse Wave Velocity (PWV) and Augmentation Index (Aix) are non-invasive standard markers of arterial elasticity and predictors of cardiovascular mortality and morbidity. To investigate the effects of metformin alone and in combination with glimepiride on arterial elasticity, pro-inflammatory cytokines in black type 2 diabetes mellitus patients. Participants were enrolled from Sefako Makgatho Health Sciences University community, Gauteng, South Africa. PWV and Aix were measured using the AtCor SphygmoCor® system (AtCor Medical, Inc., Sydney, Australia). Cytokines levels were measured using Multiplexing with Bio-Plex Pro™ human inflammation panel I assay. Treatment naïve type 2 diabetes participants were divided into two groups: metformin (M) (n = 10) and metformin glimepiride (MS) (n = 14). The study participants were followed up at 4 and 8 months after treatment initiation. In the M and MS, IL-1β increased significantly at four months (58.19 ± 0.03 pg/ml, 58.35 ± 0.30 pg/ml) when compared to baseline (33.05 ± 18.56 pg/ml, 34.79 ± 18.77 pg/ml) then decreased significantly at eight months (29.25 ± 11.64 pg/ml, 32.54 ± 14.26 pg/ml) when compared to four months (58.19 ± 0.03 pg/ml, 58.35 ± 0.3 pg/ml) (p < 0.05). There were no significant changes in PWV, Aix, IL-1ra, IL-2, IL-6, IL-8, TNF-α and hs-CRP levels at both treatment intervals. Metformin alone or in combination with glimepiride did not improve arterial elasticity and did not reduce pro-inflammatory cytokines levels in T2DM black South African patients. The context-based knowledge generated by the current study is expected to enhance the continuum of care for T2DM patients.