K. McNeill

Increased Wave Reflection Rather Than Central Arterial Stiffness Is the Main Determinant of Raised Pulse Pressure in Women and Relates to Mismatch in Arterial Dimensions A Twin Study

OBJECTIVES Our aim was to examine the relative contributions of the first systolic shoulder (P1) and augmentation pressure (DeltaP(aug)) to central pulse pressure (cPP), their relation to central arterial stiffness (pulse wave velocity [PWV]) and arterial diameters, and their respective heritability estimates. BACKGROUND cPP is augmented above P1 by DeltaP(aug) due to pressure waves reflected from the periphery of the circulation. METHODS Women (n = 496) from the Twins UK adult twin registry (112 monozygotic, 135 dizygotic pairs) age 21 to 81 years were studied. cPP, P1, and DeltaP(aug) were estimated using the SphygmoCor system (Atcor, West Ryde, Australia) from transformed radial waveforms. Carotid-femoral PWV was measured using the same system. Aortic and femoral artery diameters were measured by ultrasonography. Heritability was estimated using structural equation modeling. RESULTS P1 and DeltaP(aug) accounted for 22% and 76%, respectively, of the variance in cPP. After adjustment for mean arterial pressure and heart rate, P1 strongly independently positively correlated with PWV (standardized regression coefficient, beta = 0.4, p < 0.0001), whereas DeltaP(aug) did not independently correlate with PWV but independently negatively correlated with the ratio of the diameter of the femoral to that of the abdominal aorta (beta = -0.12, p < 0.001). Estimates of heritability (h(2)) of cPP, PWV, P1, and DeltaP(aug) were 0.43, 0.34, 0.31, and 0.62, respectively, after adjustment for mean arterial pressure and heart rate. CONCLUSIONS These results suggest that, in women, DeltaP(aug) is highly heritable, is associated with the ratio of distal to proximal arterial diameters, and, independent of PWV, is a major determinant of cPP.

Inhibitory effects of low-density lipoproteins from men with type II diabetes on endothelium-dependent relaxation

OBJECTIVES The object of the present study is to determine whether native (n) low-density lipoprotein (LDL) isolated from men with type II diabetes and abnormal endothelial function inhibits endothelium-dependent relaxation more than n-LDL isolated from nondiabetic control subjects. BACKGROUND Endothelium-dependent vasodilation is impaired in men with type II diabetes and this may result from qualitative rather than quantitative abnormalities of LDL. METHODS Forearm blood flow responses to brachial artery infusions of acetylcholine (endothelium-dependent vasodilator) and nitroprusside (endothelium-independent vasodilator) were measured in 10 men with uncomplicated type II diabetes and 10 nondiabetic men of similar age and with similar plasma concentrations of LDL cholesterol. Native LDL was isolated by discontinuous density gradient ultracentrifugation using EDTA to prevent oxidation. Preconstricted rabbit aortic ring bioassay was used to determine inhibitory properties of n-LDL on endothelium-dependent relaxation by measuring relaxation to acetylcholine (and nitroprusside) in the presence and absence of n-LDL. RESULTS Forearm blood flow responses to acetylcholine but not nitroprusside were significantly impaired (p < 0.01) in diabetic men compared with control subjects. Native LDL (10 and 100 microg protein/ml) from diabetic men inhibited relaxation to acetylcholine by 13.9 +/- 4.8% and 61.9 +/- 7.8% (mean inhibition for all doses +/- SE), respectively, whereas n-LDL from control subjects inhibited relaxation by 7.3 +/- 3.0% and 23.9 +/- 5.7% (p < 0.01 for a difference between diabetic and control n-LDL). Relaxation to nitroprusside was not significantly inhibited by n-LDL. CONCLUSIONS A qualitative abnormality of LDL may account for endothelial dysfunction in men with type II diabetes.

Divergent effects of vitamin C on relaxations of rabbit aortic rings to acetylcholine and NO-donors

Vitamin C may influence NO‐dependent relaxation independently of effects on oxidant stress. We investigated effects of vitamin C (0.1 – 10 mmol l−1) on relaxation of pre‐constricted rabbit aortic rings to acetylcholine (ACh), authentic NO and the NO‐donors glyceryl trinitrate (GTN), nitroprusside (NP) and S‐nitroso‐N‐acetyl‐penicillamine (SNAP). DETCA (2 – 6 mmol l−1), a cell permeable inhibitor of endogenous Cu‐Zn superoxide dismutase (SOD) was used to increase intracellular superoxide anion (O2−). Vitamin C reduced the response to ACh (71±7% inhibition of maximum relaxation at 10 mmol l−1) and inhibited relaxation to authentic NO. Vitamin C inhibited relaxation to GTN but potentiated relaxations to NP and SNAP, causing a parallel shift to a lower concentration range of the log dose‐response curve by approximately one log unit at the highest dose. Vitamin C increased the concentration of NO in bath solution (plus EDTA, 1.0 mmol l−1) following the addition of SNAP from 53±14 to 771±101 nmol l−1 over the range 0.1 – 3.0 mmol l−1. DETCA inhibited relaxation to ACh (71±9% inhibition of maximum relaxation). This inhibition was abolished by a cell permeable SOD mimetic, but not by vitamin C. DETCA inhibited relaxation to SNAP but not that to NP nor to GTN. Vitamin C inhibits endothelium‐dependent relaxations of rabbit aortic rings to ACh and authentic NO and does not reverse impaired relaxation resulting from increased intracellular oxidant stress. Vitamin C potentiates relaxation to the NO‐donors NP and SNAP by a mechanism that could involve release of NO from nitrosothiols.

Measurement of pulse wave velocity in children: comparison of volumetric and tonometric sensors, brachial-femoral and carotid-femoral pathways

Background: Pulse wave velocity (PWV), a measure of arterial stiffness strongly predictive of cardiovascular risk in adults, is usually measured by sequential ECG-referenced carotid and femoral tonometry. A simplified technique, more suitable for use in children, employs simultaneous volumetric recording from a sensor applied over the carotid artery and a cuff applied over the femoral artery or arm and thigh pressure cuffs applied over the brachial and femoral arteries. The purpose of this study was to compare PWV computed over the carotid-femoral path (PWVcf) with that over the brachial-femoral path (PWVbf) using a volumetric system (Vicorder) and to compare values of PWVcf obtained by the volumetric and a tonometric method (SphygmoCor) in children. Method: Vicorder PWVcf and PWVbf were compared in 156 children (3–18 years, 110 with chronic kidney disease), and PWVcf by Vicorder was compared to PWVcf by SphygmoCor in a subset of 122 patients. Results: PWVcf by Vicorder was moderately correlated with PWVcf by SphygmoCor (R = 0.50, P < 0.000). PWVbf and PWVcf Vicorder were more closely correlated (R = 0.75, P < 0.0001), but with a significant systematic difference. Applying a correction factor to PWVbf measurements gave results similar to those obtained over the carotid-femoral path. Within-patient coefficients of variation for repeated measures were 5.9, 7.8, and 8.5% for PWVbf (Vicorder), PWVcf (Vicorder) and PWVcf (SphygmoCor), respectively. All PWV values showed a similar relation to age. Conclusion: Volumetric methods appear reproducible and are easy to use in children, but values obtained by Vicorder and SphygmoCor are not interchangeable even when measured over the same pathway.