Decrease In Augmentation Index Research Articles

Evaluation of the effectiveness of statin and spironolactone by the influence on indicators of vascular stiffness in patients with arterial hypertension

Abstract Introduction The possibility of slowing down vascular remodeling in hypertensive patients with the combined effect of antihypertensive drugs and statins has been studied in unitary studies. The effect of spironolactone on vascular stiffness in relation to the severity of the hypotensive effect in combination therapy has also been insufficiently studied. The aim of the research was to study the dynamics vascular stiffness parameters in hypertension patients of high/very high cardiovascular risk in addition rosuvastatin or spironolactone to combined two-component amlodipine and lisinopril therapy. Methods 90 patients (46 men and 44 women aged 51.6±8.5) with hypertension were randomized into groups: the first group received a fixed combination of amlodipine/lisinopril, the 2nd one followed the same regimen of therapy with addition of 20 mg rosuvastatin, the third - in addition to the combination of amlodipine / lisinopril received 25 mg of spironolactone. The office and ambulatory blood pressure (BP), central (aortic) BP, augmentation index (AIx), carotid-femoral and carotid-radial pulse wave velocity (PWV) were evaluated before and after a 24-week follow-up period. Results The office and average daily blood pressure decreased against the background of all therapy regimens (all p<0.0001). The degree of decrease in the above parameters was more pronounced under the influence of spironolactone, compared with taking a combination of amlodipine / lisinopril (office systolic BP (SBP) p=0.04 and diastolic BP (DBP) p=0.002, average daily SBP p=0.02 and DBP p=0.014) and office DBP in comparison with the group of additional administration of rosuvastatin (p=0.02). A decrease in central BP and AIx was noted in all groups. A more pronounced decrease in AIx occurred in the statin supplementation group relative to the standard treatment group (−5.8% and −9.0%, respectively, p=0.036). Carotid-femoral PWV significantly decreased in all groups (−0.9±1.5 m/s, −0.7±1.4 m/s, −2.2±2.6 m/s, respectively), in greater degree in the spironolactone addition group compared with the statin supplementation group (p=0.036). Carotid-radial PWV to the same extent significantly decreased only in the second (from 9.5±1.8 to 8.8±1.1 m/s (p=0.034)) and the third (from 9.8±1.3 to 8.4±1.3 m/s (p=0.0002)) groups. Conclusions The addition of a statin to a two-component combination of amlodipine / lisinopril in the treatment of hypertensive patients had an additional effect on the elastic properties of the aorta, in the form of a decrease in the augmentation index, and peripheral arteries, in the form of a decrease in PWV. The addition of spironolactone to standard therapy was accompanied by a significant increase in the antihypertensive effect and a decrease in aortic stiffness in the form of a more pronounced decrease in PWV in the carotid-femoral and carotid-radial areas. Funding Acknowledgement Type of funding sources: None.

Effect of long-term testosterone replacement therapy on arterial stiffness and systemic endothelial function in male patients with hypogonadism

Abstract Purpose The study aims at providing the long-term effect of testosterone replacement therapy on systemic endothelial function, aortic stiffness and wave reflections in men with testosterone deficiency (TD). Methods This is a randomized single-center double-blind placebo-controlled trial involving 24 men (aged 51±9 years) with erectile dysfunction (ED) and total testosterone (TT) levels below 3.5 ng/ml randomised to receive either intramuscular (i.m) testosterone undecanoate (TU) injections (1000 mg as a single 4 mL i.m. injection at 0, 6, 18, 30 and 42 weeks) or an identical placebo at similar time points. A TU /placebo 2:1 randomization list was generated and patients were centrally assigned to one of the two arms, consecutively. Central blood pressure (BP), augmentation index (AIx), carotid-femoral pulse wave velocity (PWV) and brachial flow mediated dilatation (FMD) were measured at baseline, and at 18, 24, 30 and 44 weeks. Results The changes in central systolic BP and pulse pressure were more potent in the TU group compared to placebo group, however the decreases in these parameters were not statistically significant in point-of-time and time and group interaction. Repeated measures ANOVA revealed that the in point-of-time decrease in AIx was statistically significant in the group receiving TU (P=0.029) compared to men receiving placebo (figure). The maximal response in AIx was observed at 18 and 24 weeks (by 4.2% and 5.0%, respectively, all P<0.05). The interaction of time and group was also statistically significant (P=0.012) indicating significant differences between the treatment groups and time. PWV in the TU therapy group decreases during the whole study period, however the in point-of-time change was not statistically significant (P>0.05, figure). In men receiving TU the change in PWV was marginally significant only at 24 weeks (reduction by 0.34 m/s, P=0.05), whereas there were no significant differences in PWV between baseline and all other assessment time points. TU minimally increased brachial FMD up to 24 weeks (increase by 0.15%, P=0.05) from the beginning of therapy and the in point of the time change was not statistically significant (P>0.05, figure). Conclusion The 44-week TU i.m therapy was associated with a beneficial sustained effect on central AIx wave reflections thorough the whole study period. PWV decreased, particularly at 24 weeks, however the change in aortic elastic properties during the whole study session was not significant. Systemic endothelial function minimally improved compared to placebo. Given that AIx is an independent marker of cardiovascular disease and predictor of the corresponding risk, these findings have important implications to assess the effect of testosterone replacement interventions on cardiovascular performance and the corresponding risk of patients with ED and TD. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Bayer Pharmaceuticals Figure 1. TU vs placebo Aix PWV and FMD changes

Fixed combination of ramipril and indapamide in patients with hypertension and non-alcoholic fatty liver disease: focus on the large arteries

Objective.To assess the effect of antihypertensive therapy with ramipril and indapamide on the elasticity of the vascular wall of the large arteries in relation to insulin resistance and chronic low-intensity inflammation in patients with hypertension (HTN) and non-alcoholic fatty liver disease (NAFLD).Design and methods.An open prospective controlled study was conducted: 30 patients with HTN stage I–II in combination with NAFLD (Fatty Liver Index (FLI) > 60) at the age of 45–65 years were included. Washout period was scheduled 5–7 days before the baseline examination, followed by the prescription of one of the fixed combinations of ramipril (2,5/5 mg/day) and indapamide (0,625/1,25 mg), depending on the required dosage (Konsilar-D 24 VERTEX AO, Russia) and were given recommendations on lifestyle changes and weight loss. A clinical examination was carried out, indicators of daily blood pressure (BP) monitoring and central aortic pressure (CAP), pulse wave velocity (PWV), lipid and carbohydrate metabolism, chronic low-intensity inflammation and the severity of insulin resistance before and after treatment were analyzed.Results.After 24-week therapy with a fixed combination of ramipril and indapamide at an average dosage of 4,04 ± 1,24 and 1,01 ± 0,31 mg, respectively, 100% of patients with HTN and NAFLD achieved target BP levels. According to 24-hour BP monitoring data, a significant decrease in systolic BP (SBP) and diastolic BP (DBP) was observed, both in the daytime (Δ12 mm Hg, р = 0,0001; Δ5,5 mm Hg, р = 0,0019, respectively), and at night (Δ13,5 mm Hg, р = 0,0006; Δ5,5 mm Hg, р = 0,0054, respectively). In addition, there was a significant decrease in CAP in the daytime (SBPao p = 0,0011, DBPao p = 0,0022) and night hours (SBPao p = 0,0015, DBPao p = 0,00124), and a statistically significant decrease in augmentation index (day p = 0,0460, night p = 0,0182). When evaluating clinical data and bioimpedance measurements, a decrease in waist circumference (p = 0,0000), hip circumference (p = 0,0001), the proportion of subcutaneous (p = 0,0134) and visceral (p = 0,0019) fat was found, which may indicate a decrease in the severity of visceral obesity. Also, during treatment, there is a decrease in the severity of insulin resistance (and the concentration of tumor necrosis factor alpha (TNF-α) (p < 0,0001) and CRP (p = 0,0002) in blood plasma. Finally, fixed combination of ramipril and indapamide led to a significant decrease in vascular stiffness (p = 0,0166) and a decrease in the proportion of patients with PWV paradoxical test (p = 0,0320). Correlation analysis showed that increased stiffness of the large arteries in patients with HTN and NAFLD is closely related to insulin resistance and lipid metabolism. At the same time, after 24-week therapy by a fixed combination of ramipril and indapamide, a decrease in the vascular stiffness in patients with HTN and NAFLD significantly correlated with the TNF-α concentration.Conclusions.A 24-week therapy by the fixed combination of ramipril and indapamide iin patients with HTN and NAFLD is associated with the persistent decrease in BP and CAP, both during the day and at night. There was a decrease in the vascular rigidity in muscular arteries. The treatment and recommendations for changing the lifestyle are associated with the decrease in the severity of abdominal obesity and insulin resistance, as well as the decrease in the severity of low-intensity systemic inflammation in patients with HTN and NAFLD, and a significant correlation was established between a decrease in TNF-α and an increase in the vascular elasticity of muscle and elastic type arteries.

The effect of left ventricular contractility on arterial hemodynamics: A model-based investigation.

Ventricular-arterial coupling is a major determinant of cardiovascular performance, however, there are still inherent difficulties in distinguishing ventricular from vascular effects on arterial pulse phenotypes. In the present study, we employed an extensive mathematical model of the cardiovascular system to investigate how sole changes in cardiac contractility might affect hemodynamics. We simulated two physiologically relevant cases of high and low contractility by altering the end-systolic elastance, Ees, (3 versus 1 mmHg/mL) under constant cardiac output and afterload, and subsequently performed pulse wave analysis and wave separation. The aortic forward pressure wave component was steeper for high Ees, which led to the change of the total pressure waveform from the characteristic Type A phenotype to Type C, and the decrease in augmentation index, AIx (-2.4% versus +18.1%). Additionally, the increase in Ees caused the pulse pressure amplification from the aorta to the radial artery to rise drastically (1.86 versus 1.39). Our results show that an increase in cardiac contractility alone, with no concomitant change in arterial properties, alters the shape of the forward pressure wave, which, consequently, changes central and peripheral pulse phenotypes. Indices based on the pressure waveform, like AIx, cannot be assumed to reflect only arterial properties.

Acute and Long-Term Effects of Aortic Compliance Decrease on Central Hemodynamics: A Modeling Analysis

Aortic compliance is an important determinant of cardiac afterload and a contributor to cardiovascular morbidity. In the present study, we sought to provide in silico insights into the acute as well as long-term effects of aortic compliance decrease on central hemodynamics. To that aim, we used a mathematical model of the cardiovascular system to simulate the hemodynamics (a) of a healthy young adult (baseline), (b) acutely after banding of the proximal aorta, (c) after the heart remodeled itself to match the increased afterload. The simulated pressure and flow waves were used for subsequent wave separation analysis. Aortic banding induced hypertension (SBP 106 mmHg at baseline versus 152 mmHg after banding), which was sustained after left ventricular (LV) remodeling. The main mechanism that drove hypertension was the enhancement of the forward wave, which became even more significant after LV remodeling (forward amplitude 30 mmHg at baseline versus 60 mmHg acutely after banding versus 64 mmHg after remodeling). Accordingly, the forward wave’s contribution to the total pulse pressure increased throughout this process, while the reflection coefficient acutely decreased and then remained roughly constant. Finally, LV remodeling was accompanied by a decrease in augmentation index (AIx 13% acutely after banding versus −3% after remodeling) and a change of the central pressure wave phenotype from the characteristic Type A (“old”) to Type C (“young”) phenotype. These findings provide valuable insights into the mechanisms of hypertension and provoke us to reconsider our understanding of AIx as a solely arterial parameter.

Drug Correction of Vascular Remodeling in Patients with Hypertension: Results of 52-Week Prospective Study ARTERIA-AG

Aim. To study the long-term dynamics of vascular remodeling in patients with hypertension and high and very high cardiovascular risk when statin is added to antihypertensive therapy with a fixed combination of calcium antagonist and angiotensin converting enzyme (ACE) inhibitor.Material and methods. Hypertensive patients (n=75) with high and very high cardiovascular risk (age 51.5 [44;58] years) were included in the study. Patients were randomized into two groups. The first group (n=36) received a fixed combination of amlodipine and lisinopril in starting dose of 5/10 mg/day. The second group (n=39) received the same antihypertensive therapy and additionally rosuvastatin (20 mg/day). The follow-up period was 52 weeks. The effect of therapy on the following parameters was evaluated: level of office and average daily blood pressure (BP), central BP in the aorta, augmentation index (AIx), pulse wave velocity (PWV), endothelium-dependent brachial artery vasodilation, carotid intima-media complex thickness, carotid arteries plaque height, and blood lipid profile indicators.Results. A significant decrease in office and average daily BP was found in both groups: from 171.5 (152;194)/104.5 (97;112) to 140.0 (129;154)/87.0 (83;95) mm Hg and from 142.1 (135;153)/86.7 (83;97) to 124.6 (119;133)/76.5 (73;80) mm Hg, respectively, in the 1st group; from 169.5 (160;190)/103.5 (95;109) to 135.0 (125;141)/83.0 (77;88) mm Hg and from 139.9 (136;152)/86.2 (80;92) to 125.1 (118;134)/74.0 (70;81) mm Hg, respectively, in the 2nd group (p<0.001 for all changes). The frequency of reaching the target office BP level was higher in the 2nd group (p=0.031). Significant decrease in total cholesterol by 33.1% and low-density lipoprotein cholesterol by 50.0% was observed in the group 2. Central BP in the aorta decreased in both groups; the degree of central BP reduction did not differ significantly. AIx decreased from 36.5 (24;41)% to 25.0 (15;36)% (p=0.04) in the 1st group and from 36.0 (30;41)% to 24.0 (20;32)% in the 2nd group (p<0.0001) with a more pronounced decrease in AIx after 24 weeks of therapy (-4.8% and -9.4%, respectively, p=0.036). This trend continued at the end of the observation (-6.4% and -10.8%, respectively, p=0.08). Carotid-femoral and carotid-radial PWV decreased only in the 2nd group from 9.5 (8.2;10.7) to 8.3 (7.6;8.9) m/s (p=0.003) and from 9,6 (8.5;10.6) to 8.4 (7.9;9.3) m/s (p=0.01), respectively. A significant decrease in the thickness of the intima-media from 1.08 (1.0;1.2) to 1.02 (0.9;1.1) cm (p<0.0001) and the height of the plaque from 2.2 (2,2;1.7) to 2.1 (2.1;1.7) mm (p=0.001) was found in the 2nd group.Conclusion. Addition of rosuvastatin to the fixed combination of amlodipine and lisinopril in treatment of hypertensive patients with high and very high cardiovascular risk was accompanied by a more frequent (compared with amlodipine and lisinopril only) achievement of the target office BP level and more pronounced reduction in the following indicators: augmentation index, carotid-femoral and carotid-radial PWV, intima-media thickness, plaque height, total cholesterol and low density lipoprotein cholesterol blood levels.

ADDITIONAL ANGIOPROTECTION AND METAbOLIC DISORDERS CORRECTION IN TREATMENT OF ARTERIAL HYPERTENSION PATIENTS REACHED TARGET bLOOD PRESSURE LEVELS, WITH FIxED COMbINATION OF PERINDOPRIL AND INDAPAMIDE

Aim. Evaluation of the ability of fixed combination of perindopril and indapamide (Noliprel Bi Forte) to achieve additional angioprotection in patients with arterial hypertension already reached target blood pressure (BP) at previous antihypertension therapy with losartan and hydrochlorothiazide (HCT).Material and methods. To open observational study, lasting 12 weeks, 25 patients included, those who had been taking losartan+HCT 100/12,5 mg. Results. During the study, all patients underwent 24 hour BP monitoring, applanation tonometry (augmentation index assessment and of central BP), measurement of pulse wave velocity (PWV), laboratory tests (lipids, fasting glucose, HOMA index, homocystein, leptin, adiponectin, high-sensitive C-reactive protein (hsCRP), vascular age assessment). After shifting the therapy with losartan and HCT to combination perindopril and indapamide, BP decreased additionally by 3,9%, and diastolic BP — 5,4% (p<0,05). There was decrease of augmentation index by 9,4% and vascular age by 6,0% (p<0,05). There was also decrease of leptin level by 14,5%, hsCRP by 11,0%, and increase of adiponectin by 9,9% (p<0,05).Conclusion. The fixed combination perindopril and indapamide does have advantages for losartan and HCT combination in BP control, vascular elasticity improvement, and facilitates the decrease of body mass index, insulin resistance and non-infectious inflammation.

Myocardial preload alters central pressure augmentation through changes in the forward wave.

Augmentation index (AIx) is often used to quantify the contribution of wave reflection to central pulse pressure. Recent studies have challenged this view by showing how contractility-induced changes in the forward pressure wave can markedly impact AIx. We hypothesized that changes in preload will also affect AIx through changes in the forward wave and studied this in two experiments. Noninvasively obtained aortic pressure was used to study central haemodynamics and wave morphology. In the first experiment, we examined the effects of head-up tilt with and without unilateral thigh cuff in 12 young healthy volunteers (mean age 26 years, 50% men). In the second experiment, we examined the effects of active standing in 31 middle-aged patients (mean age 57 years, 65% men) before and after phlebotomy. Head-up tilt or active standing significantly decreased AIx [-17.7 ± 10.4 percentage point (pp) in the young population, -4.7 ± 12.3 pp in the middle-aged population, both P < 0.05]. The fall in AIx was associated with increases in HR, diastolic pressure and systemic vascular resistance and a decrease in stroke volume (all P < 0.05). Inflation of a unilateral thigh cuff reduced the decrease in AIx by 10.7 pp, whereas 500 ml of blood loss augmented the fall in AIx by 5.9 pp (both P < 0.05). The changes in AIx were related to a preload-induced change in forward pressure wave shape (earlier peaking and steeper downstroke). Next to inotropic and chronotropic effects, preload emerges as another myocardial factor that obscures the relation between wave reflection and AIx.

The Acute Arterial Stiffness Response to Interval vs. Continuous Exercise in Postmenopausal Women

High Intensity Interval Exercise (HIIE) has been associated with greater reductions in cardiovascular disease (CVD) risk factors when compared to continuous moderate exercise. Arterial stiffness (AS) is an independent risk factor for CVD that increases exponentially in women following menopause. PURPOSE: The current research was designed to investigate the acute AS response to a single bout of HIIE versus a single bout of moderate continuous endurance exercise (MCE) in postmenopausal women. METHODS: A total of 13 women (age = 60.85 ± 4.41 years) completed the study. Subjects completed both a HIIE and a MCE treadmill protocol on separate occasions. Time of the MCE intervention was adjusted to match for the average number of heart beats obtained during the HIIE intervention. Pulse wave velocity (PWV), augmentation index (AIx), central systolic blood pressure (CSBP), and central diastolic blood pressure (CDBP) were measured pre exercise, 15 min post exercise, and 30 min post exercise to assess arterial stiffness. RESULTS: No significant interaction (p > .05) between exercise intervention and time was determined for PWV, AIx, CSBP, or CDBP. No change in PWV was found from pre to post exercise (p = .109). A trend was found for a greater decrease in AIx following HIIE compared to the decrease in AIx following MCE (p = .086). A significant decrease in AIx was found from pre exercise to 15 min post exercise (p = .002; Mpre = 33.91, M15post = 27.40) and from pre exercise to 30-min post exercise (p = .035; Mpre = 33.91, M30post = 28.67). CONCLUSION: The results of this study indicate that whether postmenopausal women perform MCT or HIIE, the acute response of central arterial stiffness does not differ. No change in PWV from pre to post exercise was found for either exercise intervention.

PP.26.08] THE ENDOTHELIAL FUNCTION AND ARTERIAL STIFFNESS DYNAMICS UNDER THE EFFECT OF ROSUVASTATIN ADDED TO A STANDARD ANTIHYPERTENSIVE THERAPY

Objective: We studied the influence of rosuvastatin added to a standard therapy on endothelial dependent vasodilatation (EDVD) and arterial stiffness markers in patients with uncontrolled hypertension. Design and method: 56 patients (40 men and 16 women aged 51.19.1) with uncontrolled hypertension were randomized into two groups. Group 1 included 30 patients who received a fixed combination of 10 mg/day lisinopril and 5 mg/day amlodipine. Group 2 consisted of 26 patients who followed the same regimen of therapy with addition of 20 mg/day of rosuvastatin. The office and central (aortic) BP, augmentation index (AIx), carotid-femoral and carotid-radial pulse wave velocity (PWV) as well as EDVD by cuff occlusion test were evaluated before and after a 24-week follow-up period. Results: The office systolic/diastolic BP decreased in both groups from 172.424.3/105.413.5 to 136.712,8/88.19.4 mmHg (p < 0.001) in the 1st group and from 170.820.0/104.014.3 to 131.09.1/83.37.7 mmHg (p < 0.001) in the 2nd one. Central BP also decreased in both groups from 153.622.1/100.513.2 to 118.610.5/82.48.5 mmHg (p < 0.001) in the 1st group and from 154.220.3/98.810.0 to 118.311.9/81.26.8 mmHg (p < 0.001) in the other. The extent of office and central BP decline did not differ. AIx decreased from 30.614.0 to 25.814.6% (p = 0.05) in the 1st group and from 34.38.3% to 24.712.6% in the 2nd group (p < 0.001) with more prominent AIx decrease in the latter (-4.8% and -9.6% respectively, p = 0.035). Mean carotid-femoral PWV decreased statistically only in the 1st group from 9.22.0 to 8.11.3 m/s (p < 0.005). The carotid-radial PWV did not change in both groups. The level of EDVD was equally more pronounced in the 1st group from −1.35.2% to 4.24.9% (p < 0.001) vs -0.56.4% to 3.95.9% (p = 0.01) in the 2nd group. Conclusions: Addition of rosuvastatin to a fixed lisinopril/amlodipine combination in treatment of patients with uncontrolled hypertension resulted in a more pronounced decline of augmentation index, but was beneficial neither for decrease of carotid-femoral pulse wave velocity nor endothelial dependent vasodilatation increase.

B3. Reproducibility and assessment of longitudinal confounders in the measurement of maternal haemodynamics in women with chronic hypertension in pregnancy

Introduction: To assess the reproducibility of Tensiomed Arteriograph measurements taken as part of a longitudinal cohort study of women with chronic hypertension (CHT).Methods/Results: chartPulse wave velocity (PWV) and augmentation index (AIX) were measured three times (lying and sitting) per visit at 4–8 weekly intervals from 10 to 34 weeks gestation. Three hundred and ninety-one observations were available from 40 women. PWV and AIX were obtained in 95.4% and 94.6% of attempts. Intraclass coefficients (ICC) were calculated across six gestation windows. The median PWV ICC was 0.71 (range 0.22–0.92), improving to 0.84 (0.78–0.88) for readings with standard deviation <1.5m/s (79.6% of readings). Corresponding AIX ICCs were 0.88 (0.54–0.93) and 0.94 (0.92–0.97). For lying and sitting position measurements, PWV ICC was 0.82 (0.71–0.89) and AIX 0.81 (0.57–0.87). A 10 beat increase in HR was associated with 4.1–5.2% decrease in AIX, adjustment for HR reduced the gestational effect (Figure 1). The effects of HR and gestation on PWV were smaller, but statistically significant.Figure 1. Mixed level regression models (with 95% CI) assessing the interaction between HR, gestation and haemodynamic measurements (fixed effects), adjusted for individual and visit number (random effects).Discussion: PWV and AIX have acceptable reproducibility for use in clinical practice. Changes AIX attributable to HR are consistent with non-pregnant studies and interact with the gestational effect. Reproducibility was unaffected by maternal position, but unacceptable in 20% of readings and additional measures of haemodynamic status may therefore be required.

Stiffness of the Arterial Wall and Central Hemodynamics During Long-Term Combination Antihypertensive Therapy

Aim of the METR study - to assess effect of antihypertensive therapy with fixed combination of angiotensin converting enzyme inhibitor lisinopril (10 mg) and calcium antagonist amlodipine (5 mg) on parameters of arterial wall stiffness and central hemodynamics in patients with stage I-II essential hypertension (EH) and functional class II-III ischemic heart disease. Combination therapy was associated with persistent lowering of central arterial pressure, decrease of augmentation index and other parameters of arterial wall stiffness, and reduction of left ventricular myocardial mass. These changes have a potential to lower risk of cardiovascular complications and improve prognosis of patients with EH.

The effect of vitamin D supplementation on arterial stiffness in an elderly community–based population

Vitamin D deficiency may lead to impaired vascular function and abnormalities in central arterial stiffness. We compared the effects of two different doses of vitamin D3 on arterial stiffness in an elderly population with deficient serum 25–hydroxy–vitamin D levels. A total of 119 known vitamin D deficient (<50 nmol/L) subjects were randomized to receive either 50,000 international units (IU) or 100,000 IU single intramuscular vitamin D3. In the group that received 100,000 IU vitamin D, median pulse wave velocity decreased from 12.2 m/s (range, 5.1–40.3 m/s) to 11.59 m/s (range, 4.3–14.9 m/s) after 8 weeks (P = .22). A mean decrease of 3.803 ± 1.7 (P = .032) in augmentation index (a measure of systemic stiffness) was noted. Only 3/51 (5.8%) who received 100,000 IU vitamin D reached levels of sufficiency (>75 nmol/L). A significant decrease in augmentation index was seen in the group that received 100,000 IU vitamin D. Serum levels of 25–hydroxy–vitamin D were still deficient at 8 weeks in the majority of patients, which may be attributable to impaired bioavailability.

Effects of renin-angiotensin-aldosterone system inhibitors and beta-blockers on markers of arterial stiffness

Antihypertensive agents may, even within the same class, exert variable effects on arterial stiffness variables. Nebivolol could have a better impact than atenolol on arterial stiffness, by increasing the bioavailability of endothelium-derived nitric oxide. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) increase plasma renin activity (enhancing the production of angiotensin II via non-ACE-related pathways) whereas aliskiren does not, potentially affecting central hemodynamics differently. We compared the effects of two renin-angiotensin-aldosterone system (RAAS) inhibitors (quinapril and aliskiren) and 2 beta-blockers (atenolol and nebivolol) on arterial stiffness variables. Treatment-naïve patients (n = 72; 68.1% males; age, 47.6 ± 10.6 years) with uncomplicated stage I-II essential hypertension were randomly assigned to quinapril, aliskiren, atenolol, or nebivolol for 10 weeks. Central systolic and diastolic blood pressure (BP), central pulse pressure (PP), augmentation index (AIx), and pulse wave velocity (PWV) were measured at baseline, 2, and 10 weeks. The same measurements were performed in 20 normotensive subjects (65.0% males; age, 40.0 ± 8.9 years). Peripheral and central systolic and diastolic BP, peripheral PP, and PWV were significantly and similarly reduced by all agents. However, PWV continued to decline between the second and last visit in patients on quinapril and aliskiren but did not change in those on nebivolol or atenolol. Central PP and AIx decreased in patients on quinapril, aliskiren, and nebivolol but did not change in those taking atenolol. The decrease in central PP and AIx did not differ between patients on quinapril, aliskiren, and nebivolol. Despite similar reductions in peripheral BP, atenolol is less effective than nebivolol and RAAS inhibitors in improving central pulsatile hemodynamics. Aliskiren exerts similar effects on markers of arterial stiffness as quinapril. The clinical relevance of these differences remains to be established.

AB0393 Increased in serum soluble receptor for advanced glycation end products levels are associated with improvement in augmentation index in patients with early rheumatoid arthritis- a prospective observational study

BackgroundReceptor for advanced glycation end products (RAGE) is a member of the immunoglobulin super family of cell surface molecules that is expressed in a variety of cell lines. The interaction...

A High-Fat SFA, MUFA, or n3 PUFA Challenge Affects the Vascular Response and Initiates an Activated State of Cellular Adherence in Lean and Obese Middle-Aged Men

BMI and fatty acid type affect postprandial metabolic TG responses, but whether these factors also affect vascular, inflammatory, and leukocyte adherence responses remains unclear. We therefore compared those postprandial responses between lean and obese men after 3 high-fat challenges differing in fatty acid composition. In a crossover double-blind study, 18 lean (BMI: 18–25 kg/m2) and 18 obese (BMI >29 kg/m2) middle-aged men received 3 isocaloric high-fat milkshakes containing 95 g fat (88% of energy), either high in SFAs (54% of energy/total fat), MUFAs (83% of energy/total fat), or n3 (omega-3) PUFAs (40% of energy/total fat). Hemodynamics, augmentation index (AIX), leukocyte cell surface adhesion markers, and plasma cytokines involved in vascular adherence, coagulation, and inflammation were measured before and after consumption of the milkshakes. In both groups and after all shakes were consumed, AIX decreased; plasma soluble intercellular adhesion molecule (sICAM) 1, sICAM3, soluble vascular cell adhesion molecule (sVCAM) 1, and interleukin-8 increased; monocyte CD11a, CD11b, and CD621 expression increased; neutrophil CD11a, CD11b, and CD621 expression increased; and lymphocyte CD62l expression increased (P < 0.05). Lymphocyte CD11a and CD11b expression decreased in lean participants after consumption of all shakes but did not change in obese participants (P < 0.05). Obese participants had a less pronounced decrease in heart rate after the consumption of all shakes (P < 0.05). MUFA consumption induced a more pronounced decrease in blood pressure and AIX compared with the other milkshakes in both lean and obese participants (P < 0.05). High-fat consumption initiates an activated state of cellular adherence and an atherogenic milieu. This response was independent of fatty acid type consumed or of being lean or obese, despite the clear differences in postprandial TG responses between the groups and different milkshakes. These findings suggest that in addition to increased TGs, other mechanisms are involved in the high-fat consumption–induced activated state of cellular adherence.

Evidence that cranberry juice may improve augmentation index in overweight men

The stiffening of arteries is a key step in atherogenesis leading to cardiovascular disease. It has been suggested that dietary polyphenols may be cardioprotective through possible favorable effects on oxidative stress and vascular function. The present study was undertaken in order to examine the effect of consuming low-calorie cranberry juice cocktail (CJC), a source of polyphenols, on arterial stiffness in abdominally obese men. We hypothesize that regular CJC consumption will reduce circulating oxidized low-density lipoproteins concentrations and have a beneficial impact on endothelial function. Thirty-five men (mean age ± SD: 45 ± 10 years) were randomly assigned to drink 500 mL CJC/day (27% juice) or 500 mL placebo juice (PJ)/day for 4 weeks in a double-blind crossover design. Augmentation index (AIx), an index of arterial stiffness, was measured by applanation tonometry of the radial artery and the cardiometabolic profile was assessed in each participant before and after each phase of the study. We found no significant difference in AIx changes between men who consumed CJC or PJ for 4 weeks (P = .5820). Furthermore, there was no between-treatment difference in changes in AIx responses to salbutamol (P = .6303) and glyceryl trinitrate (P = .4224). No significant difference was noted in other cardiometabolic variables between men consuming PJ or CJC. However, a significant within group decrease in AIx (mean decrease ± SE; -14.0 ± 5.8%, P = .019) was noted following the consumption of 500 mL CJC/day for 4 weeks. Our results indicate that the effect of chronic consumption of CJC on AIx was not significantly different from changes associated with the consumption of PJ. However, the significant within-group decrease in AIx following CJC consumption in abdominally obese men may deserve further investigation.

Progressive resistance training might improve vascular function in older women but not in older men

ObjectivesResistance exercise training increases strength and muscle mass in older adults however there is no consensus for its effect on arterial health. The aim of this study was to determine the effect of community based resistance training versus flexibility training on indicators of arterial stiffness and central blood pressure in healthy older adults and to test whether the effects of training are gender specific. DesignA randomised crossover intervention study. MethodsForty-nine healthy elderly participants (23 males) aged 66.7±4.3 years (mean±SD) participated in this study which involved undertaking 16 weeks of resistance training and 16 weeks of flexibility training in a random order separated by a four week washout period of usual activity. Prior to and following each training protocol period, participants underwent testing of arterial stiffness as augmentation index; and central blood pressure. ResultsWhen all participants were compared no changes in any measure of arterial stiffness or central blood pressure following resistance training compared to flexibility training were found. When male and female participants were analysed separately, a statistically significant decrease in augmentation index was observed in females (−5.28%; 95% CI: −10.29 to −0.26; p=0.04) but not males (+1.72%; 95% CI: −3.04 to 6.48; p=0.48). ConclusionsCommunity based resistance exercise training does not adversely affect vascular function in apparently healthy older adults and may actually improve arterial function in females.

The Effect of a High-Fat Meal on Postprandial Arterial Stiffness in Men with Obesity and Type 2 Diabetes

Postprandial dysmetabolism is emerging as an important cardiovascular risk factor. Augmentation index (AIx) is a measure of systemic arterial stiffness and independently predicts cardiovascular outcome. The objective of this study was to assess the effect of a standardized high-fat meal on metabolic parameters and AIx in 1) lean, 2) obese nondiabetic, and 3) subjects with type 2 diabetes mellitus (T2DM). Male subjects (lean, n = 8; obese, n = 10; and T2DM, n = 10) were studied for 6 h after a high-fat meal and water control. Glucose, insulin, triglycerides, and AIx (radial applanation tonometry) were measured serially to determine the incremental area under the curve (iAUC). AIx decreased in all three groups after a high-fat meal. A greater overall postprandial reduction in AIx was seen in lean and T2DM compared with obese subjects (iAUC, 2251 +/- 1204, 2764 +/- 1102, and 1187 +/- 429% . min, respectively; P < 0.05). The time to return to baseline AIx was significantly delayed in subjects with T2DM (297 +/- 68 min) compared with lean subjects (161 +/- 88 min; P < 0.05). There was a significant correlation between iAUC AIx and iAUC triglycerides (r = 0.50; P < 0.05). Obesity is associated with an attenuated overall postprandial decrease in AIx. Subjects with T2DM have a preserved, but significantly prolonged, reduction in AIx after a high-fat meal. The correlation between AIx and triglycerides suggests that postprandial dysmetabolism may impact on vascular dynamics. The markedly different response observed in the obese subjects compared with those with T2DM was unexpected and warrants additional evaluation.

Low-fat versus low-carbohydrate weight reduction diets: effects on weight loss, insulin resistance, and cardiovascular risk: a randomized control trial.

OBJECTIVELow-fat hypocaloric diets reduce insulin resistance and prevent type 2 diabetes in those at risk. Low-carbohydrate, high-fat diets are advocated as an alternative, but reciprocal increases in dietary fat may have detrimental effects on insulin resistance and offset the benefits of weight reduction.RESEARCH DESIGN AND METHODSWe investigated a low-fat (20% fat, 60% carbohydrate) versus a low-carbohydrate (60% fat, 20% carbohydrate) weight reduction diet in 24 overweight/obese subjects ([mean ± SD] BMI 33.6 ± 3.7 kg/m2, aged 39 ± 10 years) in an 8-week randomized controlled trial. All food was weighed and distributed, and intake was calculated to produce a 500 kcal/day energy deficit. Insulin action was assessed by the euglycemic clamp and insulin secretion by meal tolerance test. Body composition, adipokine levels, and vascular compliance by pulse-wave analysis were also measured.RESULTSSignificant weight loss occurred in both groups (P < 0.01), with no difference between groups (P = 0.40). Peripheral glucose uptake increased, but there was no difference between groups (P = 0.28), and suppression of endogenous glucose production was also similar between groups. Meal tolerance–related insulin secretion decreased with weight loss with no difference between groups (P = 0.71). The change in overall systemic arterial stiffness was, however, significantly different between diets (P = 0.04); this reflected a significant decrease in augmentation index following the low-fat diet, compared with a nonsignificant increase within the low-carbohydrate group.CONCLUSIONSThis study demonstrates comparable effects on insulin resistance of low-fat and low-carbohydrate diets independent of macronutrient content. The difference in augmentation index may imply a negative effect of low-carbohydrate diets on vascular risk.