Editors' review of 2006 and the BJCP prize.
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
James M Ritter
Publications and source records attributed to James M Ritter.
Acute reduction of blood pressure by nitroglycerin does not normalize large artery stiffness in essential hypertension.
Stiffness of large elastic arteries is elevated in subjects with hypertension, an effect that could potentially be explained by increased distending pressure. We examined effects of an acute change in blood pressure on carotid-femoral pulse wave velocity and carotid artery distensibility (inversely related to stiffness) in normotensive control subjects (n=20, mean age 42) with mean arterial pressure (MAP) 84+/-1.7 mm Hg (mean+/-SE) and subjects with essential hypertension (n=20, mean age 45, MAP 104+/-2.0 mm Hg). Normotensive subjects received intravenous nitroglycerin (NTG) and angiotensin II to lower/increase blood pressure. Hypertensive subjects received NTG to lower blood pressure. Pulse wave velocity was 24% (95% CI: 12% to 35%) higher and carotid distensibility 47% (95% CI: 32% to 63%) lower in hypertensive subjects compared with controls. In normotensive subjects, acute changes in blood pressure produced expected changes in stiffness. However, in hypertensive subjects, despite reducing MAP by 22 mm Hg to the same level as in normotensive subjects, there was no detectable reduction in arterial stiffness: pulse wave velocity remained 24% (95% CI: 10% to 38%) higher and carotid distensibility 48% (95% CI: 31% to 63%) lower in hypertensive compared with normotensive subjects. Because blood pressure-independent effects of NTG are, if anything, to reduce stiffness, these results indicate that elevated carotid and aortic stiffness in hypertensive subjects is not explained by elevated blood pressure but relates to structural change in the arterial wall.
Adult↗
The role of inheritance and environment in predisposition to vascular disease in people of African descent.
OBJECTIVES: This study sought to compare vascular reactivity and carotid intima media thickness (CIMT) between Afro-Caribbean people in the United Kingdom (UK) and the West Indies and Afro-Caribbean and Caucasian people in the UK. BACKGROUND: Attenuated vascular reactivity and increased CIMT in black patients is seen as evidence for predisposition to vascular disease, but no comparisons exist between Afro-Caribbean people in different settings, which can provide insight into non-inherited determinants of increased ethnic susceptibility. METHODS: A representative community sample of 81 healthy Afro-Caribbean people and 101 Caucasian people in the UK was compared with 197 matched Afro-Caribbean people in Jamaica. Small vessel reactivity was assessed by measuring the absolute change from baseline in the reflection index (RI) of the digital volume pulse during intravenous infusion of albuterol (5 microg/min, DeltaRI(ALB)) and glyceryl trinitrate (5 microg/min, DeltaRI(GTN)). The CIMT was measured ultrasonographically in the distal 1 cm of the common carotid artery. RESULTS: Mean DeltaRI(ALB) was 4.2 percentage points (95% confidence interval [CI], 2.3 to 6.1, p < 0.001) lower in UK Afro-Caribbean people compared with Jamaican Afro-Caribbean people and 2.6 percentage points (95% CI, 0.4 to 4.7, p = 0.02) lower compared with Caucasian people, after adjusting for vascular risk profile. Adjusted mean CIMT of UK Afro-Caribbean people was 0.13 mm (95% CI, 0.08 to 0.17, p < 0.001) greater compared with Jamaican Afro-Caribbean people and 0.05 mm (95% CI, 0.01 to 0.10, p = 0.02) greater compared with Caucasian people. CONCLUSIONS: Healthy UK Afro-Caribbean people have greater and Jamaican Afro-Caribbean people have less impairment of vascular reactivity and intima media thickness compared with UK Caucasian people, suggesting that potentially modifiable environmental interactions may contribute to excess vascular disease in Afro-Caribbean people.
Black People↗
Aldosterone and left ventricular hypertrophy in Afro-Caribbean subjects with low renin hypertension.
BACKGROUND: Activity of the renin-angiotensin-aldosterone system is thought to play a major role in determining blood pressure (BP) and target organ damage such as left ventricular hypertrophy. In Afro-Caribbean subjects, however, hypertension tends to be more severe despite lower plasma renin activity. We investigated whether this might be due to a different relation between aldosterone and renin in Afro-Caribbean compared to white subjects. METHODS: Plasma aldosterone and renin activity were assessed in the morning after 15 min seated in 383 hypertensive subjects of Afro-Caribbean or white ethnicity (61% Afro-Caribbean, 83% on treatment) attending a hypertension clinic in London, UK. Left ventricular mass index (LVMI) was assessed by echocardiography in 276 subjects. RESULTS: Plasma renin activity was lower in Afro-Caribbean compared to white subjects (0.4 [0.3-1.0] v 1.4 [0.5-3.4] ng/mL/h, medians [interquartile range], P < .0001). Despite this, aldosterone was higher in Afro-Caribbean compared to white subjects (8.0 [6.1-12.6] v 7.4 [2.3-17.1] ng/dL, medians [interquartile range], P < .01). The LVMI corrected for sex and BP was higher in Afro-Caribbean than in white subjects. In Afro-Caribbean but not in white subjects LVMI was independently correlated with plasma aldosterone (standardized regression coefficient, beta= 0.25, P < .001). CONCLUSIONS: In Afro-Caribbean hypertensive subjects in London, plasma aldosterone is elevated despite lower renin and may contribute to increased severity of hypertension and left ventricular hypertrophy in Afro-Caribbean compared to white subjects.
Adult↗
Contour analysis of the photoplethysmographic pulse measured at the finger.
Analysis of the contour of the peripheral pulse to assess arterial properties was first described in the nineteenth century. With the recognition of the importance of arterial stiffness there has been a resurgence of interest in pulse wave analysis, particularly the analysis of the radial pressure pulse acquired using a tonometer. An alternative technique utilizes a volume pulse. This may conveniently be acquired optically from a finger (digital volume pulse). Although less widely used, this technique deserves further consideration because of its simplicity and ease of use. As with the pressure pulse, the contour of the digital volume pulse is sensitive to changes in arterial tone induced by vasoactive drugs and is influenced by ageing and large artery stiffness. Measurements taken directly from the digital volume pulse or from its second derivative can be used to assess these properties. This review describes the background to digital volume pulse contour analysis, how the technique relates to contour analysis of the pressure pulse, and current and future applications.
Blood Pressure↗
Elevation of plasma homocysteine by methionine loading increases the diastolic blood pressure response to exercise.
OBJECTIVE: Exercise blood pressure is elevated in conditions associated with endothelial dysfunction. To determine whether this is a causal association, we examined the effects of endothelial dysfunction induced by methionine loading, on exercise blood pressure. DESIGN: Healthy subjects (18-63 years) participated in randomized, double-blind, cross-over studies receiving methionine and placebo on separate occasions before exercise. METHODS: In study 1 (n = 32), subjects received placebo and methionine 100 mg/kg 4 h before exercise and, in study 2 (n = 11), placebo and methionine 200 mg/kg (given as 100 mg 20 and 12 h before exercise). A further study confirmed that methionine 100 mg/kg impaired brachial artery flow-mediated dilation. Blood pressure was measured by mercury sphygmomanometry at rest and during low workload bicycle ergometry. RESULTS: Plasma homocysteine increased after methionine compared to placebo (22.5 +/- 1.2 versus 7.7 +/- 0.7 mumol/l in study 1, and 50.2 +/- 7.6 versus 12.8 +/- 0.7 mumol/l in study 2, means +/- SE, each P < 0.0001). In both studies resting systolic and diastolic blood pressures and the increases in systolic blood pressure during exercise were similar after methionine and placebo. By contrast, exercise diastolic blood pressure responses (measured as the change from resting values) increased more after methionine than after placebo. In study 1, diastolic blood pressure responses increased relative to placebo by 3.5 +/- 1.0, 3.7 +/- 1.0 and 2.4 +/- 1.0 mmHg at 50, 75 and 100 W, respectively (P < 0.01). In study 2, diastolic blood pressure responses increased by 4.9 +/- 1.0, 5.4 +/- 2.1 and 6.1 +/- 1.1 mmHg at 50, 75 and 100 W, respectively (P < 0.001). CONCLUSION: Endothelial dysfunction produced by methionine loading is associated with an increased exercise diastolic blood pressure response.
Adolescent↗
Sex differences in age-related stiffening of the aorta in subjects with type 2 diabetes.
Hypertension and type 2 diabetes are associated with increased aortic pulse wave velocity (PWV), a measure of aortic stiffness and a powerful risk factor for cardiovascular events. The association of hypertension with type 2 diabetes may obscure the degree to which diabetes rather than hypertension contributes to an elevated PWV. The objective of this study was to determine whether the presence of type 2 diabetes is associated with an elevated PWV compared with nondiabetic subjects matched for mean arterial blood pressure. PWV was determined by measuring carotid to femoral transit time using applanation tonometry in 186 subjects (104 women) with (n=93) and without (n=93) type 2 diabetes. Diabetic and nondiabetic subjects were matched for age and mean arterial pressure (to +/-5 years and 5 mm Hg, respectively). PWV was strongly correlated with age and mean arterial blood pressure (R=0.59 and 0.29 respectively, each P<0.0001). PWV increased significantly more with age in women with diabetes (slope of regression line+/-SE: 0.19+/-0.03 m x s(-1) x year(-1)) than in nondiabetic women (0.08+/-0.02 m x s(-1) x year(-1), P<0.01 for difference). In men, however, the age-related increase in PWV was similar in diabetic (0.15+/-0.03 m x s(-1) x year(-1)) and nondiabetic subjects (0.13+/-0.03 m. s(-1) x year(-1), P=NS). The interaction of diabetic status with age and with sex was significant (P=0.01). Type 2 diabetes is associated with a greater age-related stiffening of the aorta in women compared with men, and this is not explained by hypertension.
Adult↗
Reduced vascular complications after percutaneous coronary interventions with a nonmechanical suture device: results from the randomized RACE study.
The objective of this study was to evaluate the safety and efficacy of a novel nonmechanical percutaneous suture device, X-Press, after diagnostic catheterization and percutaneous coronary interventions (PCIs) in the setting of glycoprotein IIb/IIIa inhibitor usage. Current percutaneous vascular suture devices remain mechanically complex and expensive and have not been shown to reduce major vascular complications. Using a 2:1 randomization scheme (2:1 ratio, device vs. compression), 393 patients undergoing diagnostic catheterization (n = 133) or PCI (n = 260) were randomized in the prospective Rapid Ambulation After Closure (RACE) study and evaluated for time to ambulation, time to hemostasis, treatment success, and incidence of major vascular complications. Glycoprotein IIb/IIIa inhibitors were used in 52% of PCI patients. There was a significant reduction in the primary efficacy endpoint of median time to ambulation for device compared to control with both diagnostic (2.2 vs. 6.2 hr; P = 0.0001) and PCI patients (4.1 vs. 14.7 hr; P = 0.0001). Device malfunction occurred in 3.1% patients without clinical sequalae. Equivalence in the primary safety endpoint, the incidence of major complications (vascular repair, ultrasound-guided compression, transfusion, or infection) at 14 days, was observed with the X-Press device (1/261; 0.4%) compared to control (3/132; 2.3%; P = 0.11). In PCI patients, half of whom received glycoprotein IIb/IIIa inhibitors, there was a significant reduction in the incidence of vascular complications in patients using the device (0/172; 0%) compared to control (3/88; 3.4%; P = 0.037). In diagnostic catheterization and PCI, a novel nonmechanical suture device reduced the time to ambulation and demonstrated equivalence in major complications compared to conventional compression techniques. The incidence of major complications after PCI was reduced with the device.
Blood Vessels↗
Randomized double-blind placebo-controlled study of an angiotensin immunotherapeutic vaccine (PMD3117) in hypertensive subjects.
Immunization against components of the renin-angiotensin system offers a potential alternative to daily medication in some patients with hypertension or heart failure. Our primary objective was to determine whether a sustained antibody titre to Ang I (angiotensin I) can be achieved in hypertensive patients. The secondary objective was to determine whether the antibodies block the renin system. Patients (n=27) with essential hypertension responsive to an ACEi (angiotensin-converting enzyme inhibitor) or ARB (angiotensin blocker) were randomly assigned to receive three or four injections of the Ang I vaccine PMD3117 or aluminium hydroxide (Alhydrogel trade mark ) over a 6 week period. Antibody titre was measured prior to each injection and every 30 days until disappearance. Indices of renin blockade were changes in renin and aldosterone (blood and urine) and a within-patient comparison of the pre- and post-vaccination rise in 24 h ambulatory blood pressure after 2 weeks of withdrawal of ACEi or ARB. The anti-(Ang I) antibody titre rose from the second injection in both regimes and peaked on day 64. Median half-life was 85 (95% CI, 44 and 153) days (where CI is confidence interval). Vaccination did not influence blood pressure, but significantly blunted the fall in plasma renin following withdrawal of ACEi or ARB. At 42 days after the first injection, aldosterone excretion was decreased by PMD3117 to 6 (95% CI, 1 and 31)% of values in patients receiving Alhydrogel trade mark (P=0.012). In patients with essential hypertension, PMD3117 generated a prolonged antibody response to Ang I. Biochemical measurements show evidence of blockade of the renin system, but higher titres will be required to achieve a decrease in blood pressure.
Adolescent↗
Cardiovascular risk factors and endothelial dysfunction.
Endothelial dysfunction is a feature of atherosclerosis and is associated with CHD (coronary heart disease) risk factors. This study aimed to determine the relationship between the degree of endothelial dysfunction and calculated cardiovascular risk. Endothelial function, as determined by the ACh/NP (acetycholine/sodium nitroprusside response) ratio on brachial plethysmography, was compared with cardiovascular risk as calculated from the Framingham, PROCAM (Prospective Cardiovascular Munster) and MRFIT (Multiple Risk Factor Intervention Trial) algorithms in 246 (187 male) patients, including 44 (22%) with established CHD. Endothelial dysfunction correlated with the total number of risk factors (r2=0.22; P=0.002) and was related to LDL (low-density lipoprotein)-cholesterol in men and triacylglycerols (triglycerides) in women. The ACh/NP ratio correlated with the occurrence of diabetes, CHD and the LDL-cholesterol concentration (r2=0.58; P<0.001). Endothelial dysfunction was associated with presence of CHD on receiver-operating characteristic plot analysis (area=0.706+/-0.04; P=0.001). There was no correlation between ACh/NP ratio and CHD risk calculated with the Framingham algorithm in men, although both ACh and NP response correlated separately with risk in women. The endothelial ACh/NP ratio correlated with absolute risk in the PROCAM algorithm (r2=0.41; P<0.005). Intermediate results were obtained with MRFIT. Individual risk factors make different contributions to endothelial dysfunction compared with their role in risk calculators. The stronger relationship of endothelial dysfunction with PROCAM risk reflects the contribution of male sex, LDL-cholesterol and triacylglycerols to risk calculated by this algorithm.
Adult↗
Effects of inhibition of basal nitric oxide synthesis on carotid-femoral pulse wave velocity and augmentation index in humans.
Aortic stiffness, as measured by carotid-femoral pulse wave velocity (PWV), is a powerful, independent predictor of vascular risk. PWV in muscular arteries is influenced by basal nitric oxide (NO) release. It is not known whether NO also influences carotid-femoral PWV. We examined the effects of an NO synthase inhibitor, NG-monomethyl-l-arginine (L-NMMA), on carotid-femoral PWV and aortic augmentation index (AIx, an indirect measure of arterial stiffness). To control for effects of L-NMMA on distending pressure, we used doses of norepinephrine and dobutamine that caused similar changes in mean arterial blood pressure (MAP). Healthy men (32 to 48 years old, n=8) were studied on 4 occasions and received, in random order, vehicle, L-NMMA (3 mg x kg(-1) by intravenous bolus followed by 3 mg x kg(-1) x h(-1)), norepinephrine (50 ng x kg(-1) x min(-1)), and dobutamine (2.5 to 10 microg x kg(-1) x min(-1)), each for 30 minutes. PWV and AIx were measured by carotid-femoral PWV and radial tonometry, respectively. L-NMMA and norepinephrine increased MAP by 7.8+/-1.7 and 9.7+/-2.1 mm Hg, respectively (each P<0.05 vs vehicle) and increased PWV by 0.7+/-0.2 and 1.0+/-0.3 m x s(-1) (each P<0.01 vs vehicle). Dobutamine, at doses that produced a similar increase in MAP (9.6+/-2.9 mm Hg), increased PWV by 0.8+/-0.2 m x s(-1) (P<0.01 vs vehicle). Changes in PWV caused by the 3 pressor agents were closely correlated with changes in MAP (R>0.99, P<0.0001). L-NMMA and norepinephrine increased AIx, but dobutamine decreased AIx (P<0.01 vs norepinephrine and L-NMMA). Effects of inhibition of basal NO release on carotid-femoral PWV can be explained by the change in MAP that this causes rather than any specific effect of NO inhibition within the aorta.
Adult↗
Pressure wave reflection assessed from the peripheral pulse: is a transfer function necessary?
Synthesis of the aortic pressure waveform by application of a transfer function to the radial pulse allows the estimation of aortic systolic blood pressure and aortic augmentation index, an index of pressure wave reflection derived from the early systolic component of the waveform. The accuracy of this approach for determining the aortic augmentation index has been questioned, however, and it may be possible to derive similar information without using a transfer function. We compared aortic systolic blood pressure and the aortic augmentation index obtained from carotid and radial arteries with the use of transfer functions. We examined the correlation between the aortic augmentation index and a radial augmentation index obtained without use of a transfer function. Arterial tonometry (Sphygmocor) was performed in 84 subjects including healthy volunteers (n=30), subjects with essential hypertension (n=30), and patients with coronary artery disease (n=24). Effects of nitroglycerine and norepinephrine on aortic and radial augmentation index were examined in 12 healthy volunteers. Values of aortic systolic pressure obtained from radial and carotid arteries by using transfer functions were in acceptable agreement (R=0.98, difference=-0.9+/-4.6 mm Hg; mean+/-SD, n=84), but those of aortic augmentation index differed especially in control subjects (R=0.47, difference=-3.8+/-12.4%). Aortic augmentation index was, however, closely correlated with radial augmentation index (R=0.96, n=84). Nitroglycerine and norepinephrine produced parallel changes in the aortic and radial augmentation index. Our findings question the use of a transfer function to obtain the aortic augmentation index but suggest that similar information on central pressure wave reflection can be obtained directly from the radial pulse.
Adult↗
The vascular impact of aging and vasoactive drugs: comparison of two digital volume pulse measurements.
BACKGROUND: Indices of pressure wave reflection (RI(DVP)) and large artery stiffness (SI(DVP)) can be derived from the digital volume pulse (DVP). Indices obtained from the second derivative of the DVP have also been proposed to characterize vascular aging and effects of vasoactive drugs. METHODS: We compared RI(DVP) and SI(DVP) with the indices a/b, a/c, a/d, and a/e calculated from sequential peaks of the second derivative of the DVP in 124 healthy men. The DVP was obtained by measuring infrared light transmission through the finger. In 10 men measurements were obtained at baseline and during intravenous infusion of glyceryl trinitrate (GTN, 3 to 300 microg/min) and, on separate occasions, angiotensin II (AII, 75 to 300 microg/min) and saline vehicle. RESULTS: SI(DVP) was strongly associated with age (R = 0.63, P <.001) but little influenced by AII or GTN. RI(DVP) was weakly associated with age but showed a consistent dose-dependent increase during AII and a decrease during GTN. d/a was strongly associated with age (R = -0.66, P <.001), influenced by vasoactive drugs but did not change in a dose-dependent manner during GTN. Other second derivative indices were less strongly correlated with age and showed an inconsistent response to vasoactive drugs. Within subject standard deviations of SI(DVP) and d/a for measurements on different occasions were 2.1 and 5.4 "years of vascular aging" respectively. CONCLUSIONS: In healthy men, RI(DVP) may be a more reliable index of the effects of vasoactive drugs than d/a. SI(DVP) is similarly associated with age as is d/a, but less variable and may thus be a better index of vascular aging.
Adult↗
Barium reduces resting blood flow and inhibits potassium-induced vasodilation in the human forearm.
BACKGROUND: Increasing extracellular K+ concentration within and just above the physiological range hyperpolarizes and relaxes vascular smooth muscle in vitro. These actions involve inwardly rectifying potassium channels (K(IR)) and Na+/K+ ATPase, which are inhibited, respectively, by Ba2+ and ouabain. The role (if any) of K(IR) in controlling human resistance vessel tone is unknown, and we investigated this in the forearm. METHODS AND RESULTS: Blood flow was measured by plethysmography in healthy men. Drugs and electrolytes were infused through the brachial artery. BaCl2 (4 micromol/min, also used in subsequent experiments) increased Ba2+ plasma concentration in the infused forearm to 50+/-0.8 micromol/L (mean+/-SEM) and reduced blood flow by 24+/-4% (n=8, P<0.001) without causing systemic effects. Ouabain (2.7 nmol/min), alone and with BaCl2, reduced flow by 10+/-2% and 28+/-3%, respectively (n=10). Incremental infusions of KCl (0.05, 0.1, and 0.2 mmol/min) increased flow from baseline by 1.0+/-0.2, 2.0+/-0.4, and 4.2+/-0.5 mL/min per deciliter forearm, respectively. Responses to KCl (0.2 mmol/min) were inhibited by BaCl2, alone and plus ouabain, by 60+/-9% and 88+/-6%, respectively (both P< or =0.01). In control experiments, norepinephrine (240 pmol/min) reduced blood flow by 24+/-2% but had no significant effect on K+-induced vasodilation. BaCl2, alone or with ouabain, did not significantly influence responses to verapamil or nitroprusside. CONCLUSIONS: Ba2+ increases forearm vascular resistance. K+-induced vasodilation is selectively inhibited by Ba2+ and almost abolished by Ba2+ plus ouabain, suggesting a role for K(IR) and Na+/K+ ATPase in controlling basal tone and in K+-induced vasorelaxation in human forearm resistance vessels.
Adult↗
Acute haemodynamic effects of lipolysis-induced increase of free fatty acids in healthy men.
Circulating free fatty acids (FFA) are elevated in subjects with insulin resistance and Type II diabetes, and increase during myocardial ischaemia, but their haemodynamic effects are incompletely understood. During an investigation of the effects of FFA on endothelial function, we administered lipid emulsion (150 mg x min(-1) of soybean oil) with heparin (0.2 unit x kg(-1) x min(-1)) intravenously to eight healthy men for 2 h. This increased circulating FFA to 3.1+/-0.5 mmol/l. Forearm blood flow was measured by venous occlusion plethysmography during brachial artery infusions of saline, acetylcholine and nitroprusside before, and at 1 and 2 h. Lipid/heparin infusion had no significant effect on vasodilation to nitroprusside but progressively increased responses to acetylcholine (from 6.3+/-2.0 during 30 microg x min(-1) before-lipid infusion to 7.9+/-1.3 at 1 h and 12.2+/-1.1 ml x min(-1) x 100 ml(-1) at 2 h, P<0.001). Basal flow increased from 2.7+/-0.7 to 4.7+/-0.8 ml x min(-1) x 100 ml(-1) from 0 to 2 h. We performed a second study to clarify this effect on basal blood flow. Healthy men (n=8) received, on separate occasions, 4 h intravenous infusions of lipid emulsion with heparin and, as a control, saline with heparin. Lipid with heparin increased mean arterial blood pressure (maximum increment 8.2+/-2.7 mm Hg, P<0.01 compared with saline/heparin control) and forearm blood flow (from 1.7+/-0.2 to 2.9+/-0.3 ml x min(-1) x 100 ml(-1), P<0.01) without a significant effect on heart rate, and reduced calculated forearm vascular resistance (from 49.1+/-5.4 to 31.3+/-3.9 arbitrary units, P<0.01). In conclusion, acute elevation of FFA in healthy men increases arterial blood pressure and reduces vascular resistance. These haemodynamic changes could be clinically relevant.
Adult↗