Search

Background: Options for interventional therapy to lower blood pressure (BP) in patients with treatment-resistant hypertension include renal denervation and the creation of an arteriovenous anastomosis using the ROX coupler. It has been shown that BP response after renal denervation is greater in patients with combined hypertension (CH) than in patients with isolated systolic hypertension (ISH). We analyzed the effect of ROX coupler implantation in patients with CH as compared with ISH., Methods and Results: The randomized, controlled, prospective ROX Control Hypertension Study included patients with true treatment-resistant hypertension (office systolic BP ≥140 mm Hg, average daytime ambulatory BP ≥135/85 mm Hg, and treatment with ≥3 antihypertensive drugs including a diuretic). In a post hoc analysis, we stratified patients with CH (n=31) and ISH (n=11). Baseline office systolic BP (177±18 mm Hg versus 169±17 mm Hg, P=0.163) and 24-hour ambulatory systolic BP (159±16 mm Hg versus 154±11 mm Hg, P=0.463) did not differ between patients with CH and those with ISH. ROX coupler implementation resulted in a significant reduction in office systolic BP (CH: -29±21 mm Hg versus ISH: -22±31 mm Hg, P=0.445) and 24-hour ambulatory systolic BP (CH: -14±20 mm Hg versus ISH: -13±15 mm Hg, P=0.672), without significant differences between the two groups. The responder rate (office systolic BP reduction ≥10 mm Hg) after 6 months was not different (CH: 81% versus ISH: 82%, P=0.932)., Conclusions: Our data suggest that creation of an arteriovenous anastomosis using the ROX coupler system leads to a similar reduction of office and 24-hour ambulatory systolic BP in patients with combined and isolated systolic hypertension., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01642498., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

It has been shown previously that changes in brainstem neural activity correlate with changes in both mean arterial pressure (MAP) and muscle sympathetic nerve activity (MSNA) during static handgrip (SHG). However, the relationship between baseline MAP and brainstem neural activity is unclear. We investigated changes in blood oxygen level-dependent (BOLD) signal induced by SHG in 12 young adults using BOLD functional magnetic resonance imaging (FMRI). An estimation of the blood pressure response to SHG was obtained in seven subjects during a session outside the MRI scanner and was used to model the blood pressure response to SHG inside the scanner. SHG at 40% of maximum grip increased MAP (mean ± s.d.) at the end of the 180-s squeeze from 85 ± 6 mm Hg to 108 ± 15 mm Hg, P = 0.0001. The brainstem BOLD signal change associated with SHG was localised to the ventrolateral medulla. This regional BOLD signal change negatively correlated with baseline MAP, r = -0.61, P = 0.01. This relationship between baseline MAP and brainstem FMRI responses to forearm contraction is suggestive of a possible role for brainstem activity in the control of MAP and may provide mechanistic insights into neurogenic hypertension.

Background: Aortic dilatation is the main therapeutic target in patients with Marfan syndrome. Standard treatment with a β-blocker may not lower central pulse pressure - the major objective - because it does not do so in hypertension, unlike angiotensin-converting enzyme inhibitors and calcium-channel blockers. We therefore performed a prospective, randomised, double-blind, crossover trial to compare the effects of these three agents on large artery function and central aortic pressure in patients with Marfan syndrome., Methods and Results: Eighteen patients had applanation tonometry, pulse wave analysis and echocardiography, before and after atenolol 75 mg, perindopril 4 mg and verapamil 240 mg, each given for 4 weeks, in a random order, with 2 weeks between medications. Fourteen patients completed the study. Within-drug comparisons demonstrated that perindopril (-10·3 mmHg, P = 0·002), verapamil (-9·2 mmHg, P = 0·003) and atenolol (-7·1 mmHg, P = 0·01) all reduced central systolic pressure and brachial pressure; central changes were least, and peripheral changes greatest with atenolol but between-drug comparisons (analysis of covariance) were not significant. There was a trend for augmentation to be reduced by perindopril (-6·3%, P = 0·05), verapamil (-5·5%, P = 0·07) and atenolol (-3·2%, P = 0·09). Only atenolol reduced heart rate (by 16%) and delayed expansion in the arch and abdominal aorta (by 8% and 11%) (P < 0·001, P < 0·01 and P < 0·05, respectively, for between-drug comparisons)., Conclusions: Perindopril, verapamil and atenolol all reduced peripheral and central systolic pressure. As atenolol slowed heart rate and delayed aortic wave travel, β-blockade may have a continuing role in the treatment of patients with Marfan syndrome., (© 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.)

Brachial systolic and pulse blood pressures (BPs) are better predictors of adverse cardiovascular (CV) events than diastolic BP in individuals older than 50 years. The principal cause of increased systolic and pulse BP is increased stiffness of the elastic arteries as a result of degeneration and hyperplasia of the arterial wall. Recent studies have shown that central BP, the pressure exerted on the heart, brain, and kidneys, is a better predictor of CV risk than brachial BP. As stiffness increases, reflected wave amplitude increases and augments pressure in late systole, producing an increase in left ventricular afterload and myocardial oxygen demand. Vasoactive drugs have little direct effect on large human elastic arteries but can markedly modify wave reflection by altering stiffness of the muscular arteries and changing pulse wave velocity of the reflected wave from the periphery to the heart. Vasodilators decrease the amplitude and increase the travel time (or delay) of the reflected wave, causing a generalized decrease in systolic BP. The decrease in systolic BP brought about by this mechanism is grossly underestimated when systolic BP is measured in the brachial artery.

In recent years, great emphasis has been placed on the role of arterial stiffness in the development of cardiovascular diseases. Indeed, the assessment of arterial stiffness is increasingly used in the clinical assessment of patients. Although several papers have previously addressed the methodological issues concerning the various indices of arterial stiffness currently available, and their clinical applications, clinicians and researchers still report difficulties in selecting the most appropriate methodology for their specific use. This paper summarizes the proceedings of several meetings of the European Network for Non-invasive Investigation of Large Arteries and is aimed at providing an updated and practical overview of the most relevant methodological aspects and clinical applications in this area.

Acromegaly is associated with increased cardiovascular risk. Although conventional risk factors such as glucose intolerance, hypertension, and dyslipidemia probably contribute, there may also be direct effects of GH/IGF-I excess on the vasculature. To study the effects of GH excess on the vasculature, we have assessed arterial stiffness in acromegalic subjects with and without active disease and have investigated the effects of Sandostatin LAR (OCT-LAR) on vascular function. Sixteen normotensive subjects with acromegaly (10 males and 6 females) and 8 healthy controls were studied. Of the acromegalic subjects, eight had active disease (group A), and eight were cured (GH < 2.5 mU/liter; group B). The three groups were age, sex, and blood pressure matched. Group A subjects were restudied after 3 and 6 months of OCT-LAR therapy. Arterial stiffness was assessed by analyzing central arterial pressure waveforms derived from measured radial artery waveforms. This allowed determination of the augmentation of central pressure and the augmentation index. Lipids, glucose, and IGF-I were also measured. Comparing the three groups (ANOVA; mean +/- SD), the augmentation index was higher in group A (28 +/- 12 vs. 12 +/- 13%; P < 0.01) but not in group B (22 +/- 7 vs. 12 +/- 13%; P = 0.60), compared with controls. IGF-I was higher in group A (50.3 +/- 21.2 nmol/liter; P < 0.01), compared with group B (22.5 +/- 8.9 nmol/liter) and controls (19.5 +/- 5.3 nmol/liter). On regression analysis, IGF-I concentration was identified as a strong independent predictor of the augmentation index (beta = 0.50; P = 0.007). There were no significant differences in aortic systolic pressure, aortic diastolic pressure, lipids, or glucose. Compared with baseline, OCT-LAR treatment resulted in a lowering of augmentation index at 3 months (20 +/- 15 vs. 28 +/- 12%; P < 0.05), but at 6 months (24 +/- 16%; P = 0.21) there was no significant change. IGF-I was reduced from 50.3 +/- 21.2 nmol/liter at baseline to 31.4 +/- 13.2 nmol/liter at 3 months (P < 0.05) and 26.6 +/- 15.8 nmol/liter at 6 months (P < 0.05). In conclusion, acromegaly is associated with changes in the central arterial pressure waveform, suggesting large artery stiffening. This may have important implications for cardiac morphology and performance in acromegaly as well as increasing the susceptibility to atheromatous disease. Large artery stiffness is reduced in cured acromegaly and partially reversed after pharmacological treatment of active disease.

Background: Rheumatoid arthritis (RA) is associated with increased cardiovascular mortality for reasons which are insufficiently understood. Chronic inflammation may impair vascular function and lead to an increase of arterial stiffness, an important determinant of cardiovascular risk., Objective: To investigate the augmentation index (AIx) as a measure of arterial stiffness in patients with RA, free of cardiovascular disease or risk factors, by means of a matched cohort pilot study., Method: Patients with a diagnosis of RA, aged 50 years or younger, were screened for the absence of clinical cardiovascular disease and risk factors, such as smoking, hypercholesterolaemia, hypertension, and excessive systemic steroid use. Suitable subjects were assessed by non-invasive radial pulse wave analysis to determine their AIx. These data were compared with those from healthy controls, matched closely for sex, age, mean peripheral blood pressure, heart rate, and height., Results: 14 suitable patients (11 female; mean (SD) age 42 (6) years, mean RA duration 11 (6) years; mean C reactive protein 19 (15) mg/l, no clinical systemic rheumatoid vasculitis) and matched controls were identified. The RA group had a higher mean (SD) AIx and mean (SD) central blood pressure (BP) than the control group: AIx 26.2 (6.7) v 18.9 (10.8)%, p=0.028; mean central BP 91.3 (7.8) v 88.2 (8.9) mm Hg, p<0.0001, by two tailed, paired t test., Conclusions: This preliminary study suggests that RA is associated with increased arterial stiffness and central BP, independently of clinically manifest cardiovascular disease or risk factors. This may contribute to the increased cardiovascular mortality in RA.

Pulse pressure rather than diastolic pressure is the best predictor of coronary heart disease risk in older subjects, but the converse is true in younger subjects. We hypothesized that this disparity results from an age-related difference in pressure amplification from the aorta to brachial artery. Data from 212 subjects age < 50 years and 230 subjects age > or =50 years were abstracted from a community database. All subjects were free from cardiovascular disease, diabetes, and medication. Peripheral blood pressure was assessed by sphygmomanometry. Radial artery waveforms recorded noninvasively by applanation tonometry were used to derive central blood pressure. Pressure amplification (peripheral/central pulse pressure ratio) was linearly related to age (r=0.7; P<0.001). There was an inverse, linear relationship between amplification and diastolic pressure in the younger group (r=0.3; P<0.001) but not in older subjects (r=0.1; P=0.2). There was no relationship in either group when the amplification ratio was calculated with nonaugmented central pressure. Amplification is reduced in older subjects because of enhanced wave reflection. In younger, but not older, subjects, amplification declines as diastolic pressure rises. Therefore, peripheral pulse pressure underestimates the effect that diastolic pressure has on central pulse pressure in younger subjects. This may explain why diastolic pressure is a better predictor of risk in this age group and suggests that assessment of central pressure may improve risk stratification further.

Peripheral pulse pressure provides a surrogate measure of arterial stiffness. Analysis of the central pressure waveform allows assessment of central pulse pressure and arterial stiffness. The aim of the present study was to assess the effect of vasoconstrictor drugs on pulse pressure amplification and arterial stiffness in vivo. Eight healthy male subjects (mean age 30 years) received an infusion of angiotensin II (1, 3, 6 and 10 ng kg(-1) min(-1)), noradrenaline (10, 30, 60 and 100 ng kg(-1) min(-1)) and matching placebo, in random order, on separate occasions. Peripheral blood pressure and cardiac index were recorded non-invasively. Pulse wave analysis was used to determine augmentation index (AIx), which provides a measure of systemic arterial stiffness, aortic stiffness and central arterial pressure. Infusion of both active drugs resulted in a significant increase in peripheral mean arterial pressure (PMAP), peripheral vascular resistance, AIx, aortic stiffness and central pulse pressure, but only angiotensin II reduced cardiac index. Peripheral pulse pressure was unaffected by infusion of angiotensin II but increased with noradrenaline, which also produced a greater reduction in pulse pressure amplification than angiotensin II. However, the linear relationship of PMAP with both AIx and aortic stiffness did not differ significantly between drugs. These results demonstrate that intravenous infusion of angiotensin II and noradrenaline increase aortic and systemic arterial stiffness. Despite a similar effect on both parameters, for a given change in PMAP, the two drugs had divergent effects on peripheral pulse pressure and pulse pressure amplification. These data reveal that assessment of peripheral pulse pressure does not always reliably predict changes in central pulse pressure or arterial stiffness.

Hyperhomocystinemia is a risk factor for cardiovascular disease, and acute elevation of plasma homocysteine after methionine loading impairs endothelial function in healthy subjects. Interestingly, pretreatment with vitamin C can ameliorate this effect. We have already shown that acute oral vitamin C administration reduces arterial stiffness in healthy subjects, and the aim of the present study was to investigate the effect of methionine loading on arterial stiffness with and without concomitant vitamin C using the noninvasive technique of pulse wave analysis. Eight healthy male subjects (mean age, 29 years; range, 20-42 years) were studied on three occasions at weekly intervals. In a double-blind, double-dummy, randomized order they received orally either 100 mg/kg methionine, 100 mg/kg methionine plus 2 g of vitamin C, or matching placebos. Peripheral and central blood pressure, heart rate, cardiac index, arterial stiffness, and plasma homocysteine levels were assessed at baseline and 6 hours after dosing. Compared with placebo, there was no significant change in any of the hemodynamic parameters, including arterial stiffness, after oral methionine, although plasma homocysteine did increase from 11.5 +/- 1.6 to 28.7 +/- 4.4 microM (mean +/- SEM; p < 0.001). Combined methionine and vitamin C led to a similar increase in plasma homocysteine but significantly reduced augmentation index by 10.5 +/- 3.2% (p = 0.02). Acute hyperhomocystinemia does not significantly alter arterial stiffness, as assessed by pulse wave analysis, whereas a combination of methionine and vitamin C leads to a similar reduction in augmentation index to that previously described after vitamin C alone. These data reinforce evidence that vitamin C reduces arterial stiffness but do not indicate any important interaction with oral methionine.

Primary hyperparathyroidism (PHPT) is associated with increased cardiovascular risk, although the mechanisms involved remain unclear. Recent evidence has shown increased pulse pressure to be a powerful predictor of cardiovascular events. As increases in pulse pressure are due largely to arterial stiffening, we measured arterial stiffness in 21 subjects with PHPT (18 women and 3 men; 46-71 yr old) and 21 age- and sex-matched healthy controls using pulse wave analysis, a technique that measures peripheral arterial pressure waveforms and generates corresponding central aortic waveforms. This allows determination of the augmentation of central pressure resulting from wave reflection and augmentation index, a measure of vessel stiffness. Metabolic parameters were also measured. The serum calcium level among PHPT subjects was (mean +/- SD) 2.74+/-0.14 mmol/L. pulse wave analysis showed that both augmentation and the augmentation index were significantly higher in the PHPT group vs. controls [16+/-5 vs. 10+/-4 mm Hg (P < 0.001) and 36+/-9% vs. 25+/-6% (P < 0.001)] despite comparable brachial systolic pressures between groups (136+/-13 vs. 134+/-18 mm Hg). Patients with PHPT had higher fasting serum insulin levels [median (range), 15.8 (7.4-39.4) vs. 11.6 (5.1-23) mU/L; P < 0.05] and triglyceride (1.6+/-0.6 vs. 1.2+/-0.4 mmol/L; P < 0.05), but lower high density lipoprotein cholesterol (1.4+/-0.4 vs. 1.6+/-0.3 mmol/L; P < 0.05). These data indicate that subjects with mild PHPT (calcium, <3.0 mmol/L) have increased arterial stiffness, as evidenced by higher augmentation of central aortic pressures. Enhanced vessel stiffness may arise from a combination of structural and functional vascular changes due to hypercalcemia and/or metabolic abnormalities. Increased vascular stiffness in subjects with PHPT may account in part for the increased cardiovascular risk in this group.

Arterial stiffness is an important determinant of cardiovascular risk. Augmentation index (AIx) is a measure of systemic arterial stiffness derived from the ascending aortic pressure waveform. The aim of the present study was to assess the effect of heart rate on AIx. We elected to use cardiac pacing rather than chronotropic drugs to minimize confounding effects on the systemic circulation and myocardial contractility. Twenty-two subjects (13 male) with a mean age of 63 years and permanent cardiac pacemakers in situ were studied. Pulse wave analysis was used to determine central arterial pressure waveforms, non-invasively, during incremental pacing (from 60 to 110 beats min-1), from which AIx and central blood pressure were calculated. Peripheral blood pressure was recorded non-invasively from the brachial artery. There was a significant, inverse, linear relationship between AIx and heart rate (r = -0.76; P < 0.001). For a 10 beats min-1 increment, AIx fell by around 4 %. Ejection duration and heart rate were also inversely related (r = -0. 51; P < 0.001). Peripheral systolic, diastolic and mean arterial pressure increased significantly during incremental pacing. Although central diastolic pressure increased significantly with pacing, central systolic pressure did not. There was a significant increase in the ratio of peripheral to central pulse pressure (P < 0.001), which was accounted for by the observed change in central pressure augmentation. These results demonstrate an inverse, linear relationship between AIx and heart rate. This is likely to be due to alterations in the timing of the reflected pressure wave, produced by changes in the absolute duration of systole. Consideration of wave reflection and aortic pressure augmentation may explain the lack of rise in central systolic pressure during incremental pacing despite an increase in peripheral pressure.

Epidemiological data suggest that insulin may have direct effects on large-vessel function, but thus far insulin has only been shown, after prolonged infusions, to slowly decrease peripheral vascular resistance by increasing muscle blood flow. We determined whether physiological doses of insulin affect function of large arteries, before any changes in peripheral blood flow, in vivo using pulse wave analysis. Nine normal men were studied on 2 occasions: once during a 6-hour infusion of saline and once under normoglycemic hyperinsulinemic conditions (sequential 2-hour insulin infusions of 1, 2, and 5 mU/kg. min). Central aortic pressure waves were synthesized from those recorded in the periphery with the use of applanation tonometry and a validated reverse transfer function every 30 minutes. This allowed determination of central aortic augmentation (the pressure difference between early and late systolic pressure peaks) and augmentation index (augmentation expressed as a percentage of pulse pressure). Both augmentation and augmentation index decreased significantly within 1 hour after administration of insulin (P<0.001) but not saline. Systolic and diastolic blood pressure and heart rate remained unchanged for the first 2 hours. A significant increase in peripheral (forearm) blood flow was not observed until 2.5 hours after start of the insulin infusion. These data demonstrate that insulin, in normal subjects, rapidly decreases wave reflection in the aorta. This beneficial effect is consistent with increased distensibility or vasodilatation of large arteries. In contrast to the effect of insulin on peripheral blood flow, this action of insulin is observed under conditions in which both the insulin dose and duration of insulin exposure are physiological. Resistance to this action of insulin could provide a mechanism linking insulin resistance and conditions such as hypertension at the level of large arteries.

Objective: To compare effects of N(G)-monomethyl-L-arginine (L-NMMA; a NO synthase inhibitor) and L-arginine (a NO synthase substrate) on haemodynamics in healthy men at rest and during exercise., Methods: We infused L-NMMA and saline placebo intravenously in two groups of eight healthy men. Each group underwent a two-phase, randomized, single-blind crossover study. Men in one group received 3 mg/kg L-NMMA and men in the other group received 6 mg/kg L-NMMA. Haemodynamic measurements were performed before, during and after a 12 min stepped exercise protocol starting 6 min after the intravenous infusion. A further six men received, according to the same study design, 30 g L-arginine over 30 min and saline placebo before exercise. Blood pressure was measured by sphygmomanometry and cardiac output by bioimpedance, allowing computation of total systemic vascular resistance index (SVRI)., Results: Infusion of 6 mg/kg L-NMMA into men at rest produced modest increases (compared with effect of saline placebo) in systolic and diastolic blood pressures of 4.1 +/- 1.1 and 12.6 +/- 3.5%, respectively (means +/- SEM, P < 0.01 for both comparisons) and a marked increase in SVRI of 39.2 +/- 5.2% (P < 0.01). Cardiac index and heart rate were 22.0 +/- 3.3 and 17.0 +/- 4.4% lower after administration of L-NMMA (P < 0.01 for each comparison) than after infusion of saline placebo. During exercise there was no significant difference between total SVRI after infusions of L-NMMA and saline (difference not significant, diminished with increasing exercise). Six minutes into recovery the difference between total SVRI after infusions of L-NMMA and saline reappeared with SVRI 25 +/- 6.9% higher after infusion of L-NMMA than after infusion of saline (P < 0.01). Administration of L-arginine had no significant effect on haemodynamics in men at rest, during exercise and during recovery., Conclusions: Effects of L-NMMA on total systemic vascular resistance during exercise are less marked than are those on subjects at rest, probably because vasodilatation of resistance vessels of skeletal muscle during exercise is mediated mainly by factors other than NO. Our results also suggest that NO synthesis in healthy men is not substrate limited either at rest or during exercise.

1. The effects of intravenous and intra-arterial infusion of the peptides derived from prepro-vasoactive intestinal peptide, vasoactive intestinal peptide, peptide histidine methionine and peptide histidine valine, were examined in six healthy volunteers. 2. Vasoactive intestinal peptide given intravenously caused a significant increase in heart rate and a decrease in diastolic, but not systolic, blood pressure, whereas peptide histidine valine caused an increase in heart rate alone, despite higher achieved circulating peptide concentrations. Peptide histidine methionine did not affect heart rate or blood pressure. Forearm blood flow was increased by vasoactive intestinal peptide and peptide histidine valine when infused locally intra-arterially, although vasoactive intestinal peptide was more potent than peptide histidine valine. 3. Plasma concentrations of cardiodilatin (the N-terminal peptide derived from pro-atrial natriuretic peptide) were increased by intravenous infusion of vasoactive intestinal peptide, but were unaffected by peptide histidine methionine or peptide histidine valine. Circulating plasma concentrations of adrenaline and noradrenaline did not change during infusion of vasoactive intestinal peptide, peptide histidine methionine or peptide histidine valine. 4. Peptide histidine valine had a long half-life when compared with peptide histidine methionine and vasoactive intestinal peptide. 5. We conclude that peptide histidine valine is active in the human cardiovascular system and has a similar, though less potent, vasodilating action to vasoactive intestinal peptide. The higher circulating levels of peptide histidine valine found in man suggest that it may be important in modulating vascular tone.

Background Brachial blood pressure predicts cardiovascular outcome at rest and during exercise. However, because of pulse pressure amplification, there is a marked difference between brachial pressure and central (aortic) pressure. Although central pressure is likely to have greater clinical importance, very little data exist regarding the central haemodynamic response to exercise. The aim of the present study was to determine the central and peripheral haemodynamic response to incremental aerobic exercise. Materials and methods Twelve healthy men aged 31 ± 1 years (mean ± SEM) exercised at 50%, 60%, 70% and 80% of their maximal heart rate (HRmax) on a bicycle ergometer. Central blood pressure and estimated aortic pulse wave velocity, assessed by timing of the reflected wave (TR), were obtained noninvasively using pulse wave analysis. Pulse pressure amplification was defined as the ratio of peripheral to central pulse pressure and, to assess the influence of wave reflection on amplification, the ratio of peripheral pulse pressure to nonaugmented central pulse pressure (PPP : CDBP-P1) was also calculated. Results During exercise, there was a significant, intensity-related, increase in mean arterial pressure and heart rate ( P < 0·001). There was also a significant increase in pulse pressure amplification and in PPP : CDBP-P1 ( P < 0·001), but both were independent of exercise intensity. Estimated aortic pulse wave velocity increased during exercise ( P < 0·001), indicating increased aortic stiffness. There was also a positive association between aortic pulse wave velocity and mean arterial pressure ( r = 0·54; P < 0·001). Conclusions Exercise significantly increases pulse pressure amplification and estimated aortic stiffness. [ABSTRACT FROM AUTHOR]

Individuals whose platelets are resistant to the antiaggregatory effects of insulin in vitro are also resistant to the antiaggregatory effects of nitroglycerin (GTN). We have previously shown that insulin acutely diminishes central wave reflection in large arteries and that this action of insulin is blunted in insulin-resistant subjects. However, as yet, no studies have compared the haemodynamic effects of insulin and GTN on large arterial function in the same group of subjects. The aim of this study was to determine whether resistance to the haemodynamic effects of insulin is a defect specific to insulin or whether individuals resistant to the vascular actions of insulin are also resistant to GTN. Dose–response characteristics of insulin and GTN on the aortic waveform were determined using applanation tonometry and pulse wave analysis (PWA) in seven healthy men (age 26 ± 1 year, BMI 25 ± 2 kg m−2). Three doses of sublingual GTN (500 µg for 1, 3 or 5 min) and insulin (0·5, 1 or 2 mU kg−1 min−1 for 120 min) were administered on three separate occasions. Both agents dose-dependently decreased central pulse pressure and the augmentation index (AIx) without changing brachial artery blood pressure. We next compared responses to insulin (2 mU kg−1 min−1 for 120 min) and sublingual GTN (500 µg for 5 min) in 20 nondiabetic subjects (age 50 ± 2 year, BMI 21·0–36·3 kg m−2). Again, both agents significantly decreased AIx. Although the vascular effects of insulin and GTN vascular were positively correlated [Spearman's r = 0·92 (95% confidence interval 0·81–0·97), P < 0·0001], the time-course for the action GTN was faster than that of insulin. Brachial systolic blood pressure remained unchanged during the insulin infusion (122 ± 3 vs. 121 ± 3 mmHg, 0 vs. 120 min) but aortic systolic blood pressure decreased significantly by 30 min (111 ± 3 vs. 107 ± 3 mmHg, 0 vs. 30 min, P < 0·01). Similarly, GTN decreased aortic systolic blood pressure from 119 ± 4 to maximally 112 ± 3 mmHg ( P < 0·001) without significantly decreasing systolic blood pressure in the brachial artery. The effects of insulin and GTN on large arterial haemodynamics are dose-dependent and significantly correlated. The exact mechanisms and sites of action of insulin and GTN in subjects with insulin resistance remain to be established. Eur J Clin Invest 2004; 34 (1): 1–8 [ABSTRACT FROM AUTHOR]

Increased arterial stiffness is associated with an increased risk of stroke in the general population. Despite recent technological improvements, left ventricle assist device (LVAD) patients retained a high risk of stroke. In this study, we aimed to investigate whether increased arterial stiffness is associated with a higher risk of stroke in LVAD patients. We prospectively studied 28 patients who underwent HeartMate II (HMII) LVAD implantation between November 2011 and June 2018 at a single large-volume center. 24-hour blood pressure was recorded using the Mobil-O-Graph device, an ambulatory blood pressure monitor validated in HMII patients that can reliably estimate central blood pressure. Augmentation Index @ 75, an established index of arterial stiffness, was calculated by means of a generalized transfer function utilizing frequency-domain methods. Four (14%) patients experienced a stroke (all ischemic stroke) during LVAD support. Baseline demographics, LVAD parameters, and mean 24-hour blood pressure values are presented in Table 1. All patients with stroke had a prior history of pump thrombosis compared to 9 (38%) patients without stroke (P=0.035). Diurnal augmentation index @ 75 was not different between the two groups (26 [19-29] vs 25 [18-29], P=0.874), while nocturnal augmentation index @ 75 was higher in patients with stroke vs without (35 [25-44] vs 25 [16-29], P=0.05). Nocturnal augmentation index @75 was significantly associated with a higher rate of stroke (HR= 1.125; 95% CI 1.007-1.256). Increased nocturnal arterial stiffness is associated with a higher risk of stroke in LVAD patients. Further studies are warranted to validate our findings, investigate their prognostic implications and, eventually, test the impact of medical interventions on arterial stiffness in LVAD patients. [ABSTRACT FROM AUTHOR]

Lack of nocturnal blood pressure (BP) reduction (BP dipping) has been associated with cerebrovascular and cardiovascular events in the general population. However, the effect of a deranged circadian BP variability between day and night has never been studied in patients on left ventricular assist device (LVAD) support, where stroke still represents a major complication. We hypothesized that decreased BP dipping significantly increases the risk of stroke in patients on LVAD support. HeartMate II (HMII) outpatients were prospectively studied with an ambulatory BP monitor (Mobil-O-Graph) previously validated in this patient population. Systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) were recorded every 30 minutes during the day and every hour during the night for 24 hours. Circadian patterns, expressed as the percentage of nocturnal SBP, DBP, and MAP reduction from daytime values, were assessed in Cox regression models with stroke as primary endpoint. 29 patients were studied (age 59 ±15 yrs, 76% male, 38% ischemic, 69% DT). 6 patients (20%) experienced a stroke 879±591 days post LVAD implant. Nocturnal reductions of SBP, DBP, and MAP were 5.0 ± 6.1%, 5.0 ± 5.6% and 5.0 ± 5.5%, respectively. Preserved nocturnal reductions of SBP (HR 0.790 [95% CI 0.658 - 0.949]), DBP (HR 0.707 [95% CI 0.559 - 0.894]) and MAP (HR 0.703 [95% CI 0.554 - 0.894]) were associated with a decreased risk of stroke. When patients were grouped by the median nocturnal reduction in MAP (5.4%), patients with reduced dipping had a significantly greater risk of stroke (Figure 1). This study is the first to indicate that reduced BP dipping at night increases the risk of stroke in patients on HMII support. Further studies are warranted to investigate, mechanistically, the relationship between reduced BP dipping and sympathetic nervous system activation, and, clinically, its association with the risk of stroke in patients on HM3 support. [ABSTRACT FROM AUTHOR]