Left ventricular mechanics in late second trimester of healthy pregnancy.

OBJECTIVE: To evaluate left ventricular (LV) mechanics in the second trimester of healthy pregnancy and to determine the influence of underpinning hemodynamics (heart rate (HR), preload and afterload) on LV mechanics during gestation. METHODS: This was a cross-sectional study of 18 non-pregnant, 14 nulliparous pregnant (22-26 weeks' gestation) and 13 primiparous postpartum (12-16 weeks after delivery) women. All pregnant and postpartum women had uncomplicated, singleton gestations. Cardiac structure and function were assessed using echocardiography. LV mechanics, specifically longitudinal strain, circumferential strain and twist/untwist, were measured using speckle-tracking echocardiography. Differences between groups were identified using ANCOVA, with age, HR, end-diastolic volume (EDV) and systolic blood pressure (SBP) as covariates. Relationships between LV mechanics and hemodynamics were examined using Pearson's correlation. RESULTS: There were no significant differences in LV structure and traditional measurements of systolic and diastolic function between the three groups. Pregnant women, compared with non-pregnant ones, had significantly higher resting longitudinal strain (-22 ± 2% vs -17 ± 3%; P = 0.002) and basal circumferential strain (-23 ± 4% vs -16 ± 2%; P = 0.001). Apical circumferential strain and LV twist and untwist mechanics were similar between the three groups. No statistically significant relationships were observed between LV mechanics and HR, EDV or SBP within the groups. CONCLUSIONS: Compared to the non-pregnant state, pregnant women in the second trimester of a healthy pregnancy have significantly greater resting systolic function, as assessed by LV longitudinal and circumferential strain. Contrary to previous work, these data show that healthy pregnant women should not exhibit reductions in resting systolic function between 22 and 26 weeks' gestation. The enhanced myocardial contractile function during gestation does not appear to be related to hemodynamic load and could be the result of other physiological adaptations to pregnancy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Correlation between baseline blood pressure and the brainstem FMRI response to isometric forearm contraction in human volunteers: a pilot study.

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.

Randomized clinical trial of angiotensin-converting enzyme inhibitor, ramipril, in patients with intermittent claudication.

BACKGROUND: The aim was to investigate the effect of ramipril on clinical parameters in patients with peripheral arterial disease. METHODS: Patients with intermittent claudication were randomized to receive ramipril or placebo for 24 weeks in a double-blind study. Outcome measures were walking distance, arterial stiffness measurement and quality of life (QoL). RESULTS: A total of 33 patients were included (25 men; mean(s.d.) age 64.6(7.8) years); 14 received ramipril and 19 placebo. After 24 weeks, ramipril improved maximum treadmill walking distance by an adjusted mean (95 per cent confidence interval, c.i.) of 131 (62 to 199) m (P = 0·001), improved treadmill intermittent claudication distance by 122 (56 to 188) m (P = 0.001) and improved patient-reported walking distance by 159 (66 to 313) m (P = 0.043) compared with placebo. Ramipril reduced carotid femoral pulse wave velocity by -1.47 (95 per cent c.i. -2.40 to -0.57) m/s compared with placebo (P = 0.002). Resting ankle : brachial pressure index (ABPI) improved slightly in both ramipril and placebo groups (0.02 (95 per cent c.i. -0.08 to 0.11) versus 0.03 (-0.05 to 0.10); P = 0.830). Ramipril had a slight, non-significant effect on QoL physical domains compared with placebo. CONCLUSION: Ramipril improved walking distance in patients with claudication; however, this improvement was not related to improved ABPI but might have been due to ramipril reducing arterial stiffness. REGISTRATION NUMBER: NCT01037530 (http://www.clinicaltrials.gov).

Is fatty acid intake a predictor of arterial stiffness and blood pressure in men? Evidence from the Caerphilly Prospective Study.

BACKGROUND AND AIMS: Arterial stiffness is an independent predictor of cardiovascular disease (CVD) events and all-cause mortality and may be differentially affected by dietary fatty acid (FA) intake. The aim of this study was to investigate the relationship between FA consumption and arterial stiffness and blood pressure in a community-based population. METHODS AND RESULTS: The Caerphilly Prospective Study recruited 2398 men, aged 45-59 years, who were followed up at 5-year intervals for a mean of 17.8-years (n 787). A semi-quantitative food frequency questionnaire estimated intakes of total, saturated, mono- and poly-unsaturated fatty acids (SFA, MUFA, PUFA). Multiple regression models investigated associations between intakes of FA at baseline with aortic pulse wave velocity (aPWV), augmentation index (AIx), systolic and diastolic blood pressure (SBP, DBP) and pulse pressure after a 17.8-year follow-up--as well as cross-sectional relationships with metabolic markers. After adjustment, higher SFA consumption at baseline was associated with higher SBP (P = 0.043) and DBP (P = 0.002) and after a 17.8-year follow-up was associated with a 0.51 m/s higher aPWV (P = 0.006). After adjustment, higher PUFA consumption at baseline was associated with lower SBP (P = 0.022) and DBP (P = 0.036) and after a 17.8-year follow-up was associated with a 0.63 m/s lower aPWV (P = 0.007). CONCLUSION: This study suggests that consumption of SFA and PUFA have opposing effects on arterial stiffness and blood pressure. Importantly, this study suggests that consumption of FA is an important risk factor for arterial stiffness and CVD.

Aortic stiffness and vitamin D are independent markers of aortic calcification in patients with peripheral arterial disease and in healthy subjects.

OBJECTIVE: Arterial stiffness is a significant determinant of cardiovascular risk and is related to vascular calcification. Vitamin D may regulate arterial calcification and has been associated with cardiovascular survival benefits. However, data about the relationship between arterial stiffness, aortic calcification and vitamin D levels in patients with peripheral arterial disease (PAD) and in healthy subjects are limited. We examined the potential association between aortic calcification, arterial stiffness and vitamin D levels in patients with symptomatic PAD and in healthy individuals. METHODS: We studied 78 men with PAD (aged 63 ± 7 years) and 74 healthy men (aged 61 ± 10 years). Aortic pulse wave velocity (aPWV) was determined by applanation tonometry using the Sphygmocor device. Aortic calcification score (ACS) was quantified by computed tomography. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured using a radioimmune assay. RESULTS: ACS (4.9(2.3-8.9) vs. 0.2(0.03-1.6) (cm³); p < 0.01), aPWV (9.8 ± 2.4 vs. 8.2 ± 1.6 (m s⁻¹; p < 0.01) and 25(OH)D (15.1 ± 5.4 vs. 19.0 ± 5.9 (ng ml⁻¹); p < 0.01) were different in the patients compared with the controls. In multivariate analysis, ACS was independently determined by 25(OH)D, aPWV, calcium and age in patients with PAD (R² = 0.49; p < 0.001) and by 25(OH)D, aPWV, cholesterol/high-density lipoprotein (HDL) and age in the control group (R² = 0.55; p < 0.001). Increased aPWV and lower levels of 25(OH)D were associated with decreased ankle-brachial pressure index (p = 0.03). CONCLUSION: These results indicate that calcification of the aorta is independently associated with aortic stiffness and serum 25(OH)D level in patients with PAD and in healthy subjects. Aortic stiffness and abnormal vitamin D level may contribute to vascular calcification and are related to higher severity grade of atherosclerotic disease.

Increased augmentation index in patients with cystic fibrosis.

Increased large artery stiffness occurs in a range of inflammatory conditions indicating an ageing of the vasculature and additionally being an independent risk factor for cardiovascular events. We determined large artery parameters in adults with cystic fibrosis (CF). 50 clinically stable adult patients with CF (mean+/-sd age 28.0+/-8.2 yrs) and 26 controls matched for age, sex and body mass index were studied. Central aortic blood pressure, augmentation index (AIx) and aortic pulse wave velocity (PWV) were determined using applanation tonometry. Lung function, diabetic status and C-reactive protein (CRP) were also determined. Mean+/-sd AIx was greater in patients than controls, 8.5+/-11.1% and -1.8+/-13.1%, respectively (p<0.001), while PWV was similar. Although AIx was greatest in the sub-group with CF-related diabetes (CFRD), it was also increased in the non-CFRD sub-group when compared with controls. In patients, AIx was related to log(10) CRP (r = 0.33) and forced vital capacity (r = -0.34; both p<0.05), and CRP remained predictive in multiple regression. AIx is increased in adults with CF, in the presence of a normal blood pressure and independent of diabetic status. AIx was related to the systemic inflammatory status. These findings have implications for management and require further exploration so that cardiovascular health can be maintained.

Is arterial stiffening in Alström syndrome linked to the development of cardiomyopathy?

BACKGROUND: Alström syndrome (AS) is a rare autosomal recessive condition characterized by retinal degeneration, childhood obesity, and severe insulin resistance. Dilated cardiomyopathy of unknown aetiology is a well-recognized and potentially lethal complication. The aim of this study was to investigate the relationship between vascular function, hyperinsulinaemia and cardiac performance in AS. MATERIALS AND METHODS: Fifteen subjects with AS (mean age 21 years, range 10-35) were studied and compared with age-, sex-, and blood pressure-matched healthy controls. Large artery stiffness and wave reflections were assessed in both groups by measuring aortic and brachial pulse wave velocity (PWV) (carotid-femoral and carotid-radial) and augmentation index (AIX) (Sphygmocor). In AS subjects, left ventricular function was assessed by echocardiography and metabolic parameters including fasting insulin, glucose, lipids and brain natriuretic peptide were also measured. RESULTS: Comparing AS subjects vs. controls (mean +/- SD), AIX was elevated in AS subjects (18 +/- 9% vs. 3 +/- 11%, P < 0.0001). No significant changes in brachial PWV (8.1 +/- 1.3 m s(-1) vs. 7.3 +/- 1.1 m s(-1), P = 0.14) or aortic PWV (6.5 +/- 1.1 m s(-1) vs. 6.0 +/- 1.0 m s(-1), P = 0.26) were observed. AS subjects were hyperinsulinaemic and had disturbances in lipid profiles relative to controls. No correlations were observed between vascular, metabolic and echocardiographic parameters. CONCLUSIONS: In AS there are alterations in the shape of the central arterial pressure waveform associated with augmented aortic systolic pressure and indicative of increased wave reflection. Unfavourable central arterial haemodynamics in AS may contribute to the development of cardiomyopathy but other aetiological factors are probably involved.

Impaired vasoreactivity in bodybuilders using androgenic anabolic steroids.

BACKGROUND: Anabolic androgenic steroids are used by some bodybuilders to enhance performance. While the cardiovascular implications of supraphysiological androgen levels requires further clarification, use is associated with sudden death, left ventricular hypertrophy, thrombo-embolism and cerebro-vascular events. MATERIALS AND METHODS: To further understand the effect of androgenic anabolic steroid abuse on vascular function, this study assessed vascular stiffness (pulse-wave analysis) and cardiovascular risk factors in 28 male, bodybuilding subjects, of whom ten were actively receiving anabolic agents (group A; 26.4 +/- 7.2 years) and eight had undergone a 3-month "wash-out" period (group B; 32.1 +/- 7.1 years). The remaining ten bodybuilding subjects (group C; 24.4 +/- 4.4 years) denied any past use of anabolic steroids or other performance enhancing drugs. Comparisons were made with ten sedentary male controls (group D, 29.3 +/- 4.7 years). RESULTS: Endothelial independent dilatation in response to glycerol trinitrate was significantly impaired in the group currently using anabolic steroids (group A) compared with the other three groups [A (5.63 +/- 3.24%) versus; B (11.10 +/- 4.91%), C (17.88 +/- 9.2%) and D (14.46 +/- 3.9%), P < 0.0005, respectively], whereas no significant differences in endothelial-dependent dilatation were detected between the groups [A (5.0 +/- 3.0%), B (7.4 +/- 3.4%), C (9.6 +/- 4.5%) and D (8.2 +/- 3.3%), P < 0.059, respectively]. CONCLUSIONS: Previous studies described a decline in vascular reactivity occurring in bodybuilding subjects which is independent of anabolic steroid use and may result from smooth muscle hypertrophy with increased vascular stiffness. This study revealed impaired vascular reactivity associated with anabolic agents and that improvement in vascular function may occur following their discontinuation.

Characterization of the flow of anisotropic colloidal particles using energy-dispersive X-ray diffraction.

The technique of energy-dispersive X-ray diffraction to study the orientation of microscopic crystalline particles dispersed in a liquid has been described recently. This complements previous neutron diffraction studies by permitting measurements at higher spatial resolution. Work with synchrotron radiation and high-energy X-rays has allowed studies on liquid dispersions flowing in pipes with a thickness of about 1 cm and a spatial resolution of 100 mum. Kaolinite is often found as a dispersion of monocrystalline, microscopic plates. The crystallographic layer structure is commensurate with the particle shape: the 00l direction is normal to the plane of the plates. Measurements of diffraction of the flowing liquid dispersion in a pipe oriented in various directions to the incident beam can be used to deduce the average orientation and order parameters of the particles. The competing effects of alignment with walls and in flow fields were observed. Further work has measured the orientation near a bend in a pipe.

The effect of exercise on large artery haemodynamics in healthy young men.

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 (T(R)), 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-P(1) (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.

Perindopril: the reasonable choice in patients with coronary artery disease.

Recent studies in patients with coronary artery disease (CAD) have suggested that angiotensin-converting enzyme (ACE) inhibitors may have benefits beyond blood pressure reduction alone. Increased arterial stiffness, itself an emerging risk factor for CAD, adversely influences ventricular vascular interaction, leading to an increased central aortic pulse pressure. A number of recent studies have demonstrated a clear relationship between central pulse pressure and angiographic CAD. Furthermore, aortic stiffness also correlates with CAD. These studies are consistent with the hypothesis that central aortic stiffness may promote the development of CAD and that therapeutic intervention targeted at reducing arterial stiffness may be of benefit in patients with CAD. The ACE inhibitor, perindopril, has been shown to decrease arterial stiffness, largely independently of any effect on peripheral blood pressure. Results of the recent REASON study demonstrate that perindopril, in combination with indapamide, reduces central systolic and pulse pressure to a greater degree than the beta-blocker atenolol and that this effect is due to improved arterial stiffness and decreased wave reflection. In addition to its other beneficial effects, such as improved endothelial function and decreased inflammation, these haemodynamic effects of perindopril may therefore have contributed to the decrease in cardiovascular events seen in patients in the EUROPA study. Overall, perindopril, in addition to lowering peripheral blood pressure, decreases arterial stiffness and central pulse pressure. In individuals with CAD, perindopril would thus appear to be a very reasonable choice.

Cardiovascular implications of exposure to traffic air pollution during exercise.

Regular aerobic exercise is recommended by physicians to improve health and longevity. However, individuals exercising in urban regions are often in contact with air pollution, which includes particles and gases associated with respiratory disease and cancer. We describe the recent evidence on the cardiovascular effects of air pollution, and the implications of exercising in polluted environments, with a view to informing clinicians and other health professionals. There is now strong evidence that fine and ultra fine particulate matter present in air pollution increases cardiovascular morbidity and mortality. The main mechanisms of disease appear to be related to an increase in the pathogenic processes associated with atherosclerosis. People exercising in environments pervaded by air contaminants are probably at increased risk, due to an exercise-induced amplification in respiratory uptake, lung deposition and toxicity of inhaled pollutants. We make evidence-based recommendations for minimizing exposure to air-borne toxins while exercising, and suggest that this advice be passed on to patients where appropriate.

Comparison of in vivo effects of nitroglycerin and insulin on the aortic pressure waveform.

BACKGROUND: 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. DESIGN AND RESULTS: 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 microg 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 microg 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. CONCLUSIONS: 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.

The effects of depot long-acting somatostatin analog on central aortic pressure and arterial stiffness in acromegaly.

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.

Arterial stiffness and central blood pressure, as determined by pulse wave analysis, in rheumatoid arthritis.

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.

Effects of GH replacement on endothelial function and large-artery stiffness in GH-deficient adults: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: Hypopituitary adults with growth hormone deficiency (GHD) have an increased cardiovascular mortality, although the mechanisms remain unclear. Endothelial dysfunction, characterized by reduced nitric oxide (NO) bioavailability, is a key early event in atherogenesis and is associated with increased vascular smooth muscle tone and arterial stiffening. DESIGN AND PATIENTS: In a randomized, double-blind, placebo-controlled study, we investigated the effects of GH replacement on endothelial function and large-artery stiffness in 32 GHD adults (19 males, 13 females) (age range 19-64 years) over a 6-month period. Thirty-two age- and sex-matched healthy controls were also studied. MEASUREMENTS: Endothelial function was assessed using ultrasonic wall tracking to measure flow-mediated dilatation (FMD) of the brachial artery. Large artery stiffness was assessed by pulse wave analysis of the radial artery pressure waveform, allowing determination of the corresponding central arterial pressure waveform and derivation of the augmentation index. Fasting lipid profiles, glucose and insulin were also measured. RESULTS: At baseline, FMD (mean +/- SD) was impaired in GH-deficient subjects vs. controls (3.4 +/- 2.3 vs. 5.7 +/- 2.0%, P < 0.0001), although endothelium-independent dilatation was similar. The augmentation index was higher in GH-deficient subjects vs. controls (23 +/- 12 vs. 14 +/- 14%, P < 0.01). GH-deficient subjects had higher LDL cholesterol (4.1 +/- 0.8 vs. 3.5 +/- 0.8 mmol/l, P < 0.01) and lower HDL cholesterol (1.1 +/- 0.3 vs. 1.4 +/- 0.4 mmol/l, P < 0.01). In GH-deficient subjects, there were inverse correlations between LDL cholesterol and FMD (r = -0.40, P < 0.05) and between FMD and the augmentation index (r = - 0.58, P < 0.01). Regression analysis identified FMD as an independent predictor of the augmentation index (P < 0.0001). In comparison with baseline, GH replacement resulted in an increase in FMD (5.0 +/- 2.6 vs. 2.8 +/- 1.9%, P < 0.01). There were decreases in central aortic systolic pressure (117 +/- 15 vs. 123 +/- 17 mmHg, P < 0.01), diastolic pressure (82 +/- 10 vs. 86 +/- 8 mmHg, P < 0.01) and the augmentation index (22 +/- 8% vs. 26 +/- 10%, P < 0.05) despite unchanged brachial pressure indices. LDL cholesterol also decreased (3.5 +/- 0.8 vs. 4.2 +/- 0.8 mmol/l, P < 0.01). There were no significant changes in the placebo group. CONCLUSIONS: Adult GHD is associated with endothelial dysfunction and increased large-artery stiffness. An improvement in endothelial function and a reduction in arterial stiffness following GH replacement suggests an important therapeutic role for GH in reducing cardiovascular risk associated with adult GHD.

Pressure amplification explains why pulse pressure is unrelated to risk in young subjects.

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.