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Objective: Obesity and hypertension share a well known association. However, the mechanisms underlying their relationship are not well understood. Our goal was to assess the feasibility of a longitudinal, interventional weight gain study with detailed cardiovascular measurements in humans., Methods: Sixteen healthy, normotensive, young, male volunteers (28 ± 7 years) were enrolled. Body composition, biochemical and cardiovascular data were obtained at baseline, and after an 8-week period of overfeeding (800-1000 kcal/day). Blood pressure (BP), cardiac output (CO) and peripheral vascular resistance (PVR) were determined, as were the minimum forearm vascular resistance (MFVR), forearm blood flow (FBF) response to mental stress and heart rate variability (HRV) parameters., Results: Overfeeding resulted in a median weight gain of 5.6 kg [interquartile range (IQR) 4.6-6.4 kg; P  < 0.001]. Seated systolic and diastolic BP were significantly increased by 10 ± 9 and 4 ± 6 mmHg, respectively, after weight gain ( P  < 0.001 and P  = 0.011, respectively). CO also increased and PVR decreased significantly as a result of weight gain ( P  = 0.032 and P  = 0.044, respectively). MFVR was also significantly decreased after weight gain ( P  = 0.023). The FBF response to mental stress was blunted significantly ( P  = 0.002), and sympathovagal balance and responsiveness to orthostatic challenge altered moderately after weight gain., Conclusion: Our overfeeding regimen resulted in moderate weight gain and significant increases in BP. An increase in CO is likely to be the dominant mechanism underlying the observed BP changes, with decreases in PVR partially compensating for these effects. Experimental weight gain, coupled with detailed cardiovascular phenotyping, is a feasible model to examine potential mechanisms underlying obesity-associated hypertension in young adults., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This review aims to summarize associations of the perinatal environment with arterial biophysical properties in childhood, to elucidate possible perinatal origins of adult cardiovascular disease (CVD)., Methods: A systematic search of PubMed database was performed (December 2020). Studies exploring associations of perinatal factors with arterial biophysical properties in children 12 years old or less were included. Properties studied included: pulse wave velocity; arterial stiffness or distensibility; augmentation index; intima-media thickness of aorta (aIMT) or carotids; endothelial function (laser flow Doppler, flow-mediated dilatation). Two reviewers independently performed study selection and data extraction., Results: Fifty-two of 1084 identified records were included. Eleven studies explored associations with prematurity, 14 explored maternal factors during pregnancy, and 27 explored effects of low birth weight, small-for-gestational age and foetal growth restriction (LBW/SGA/FGR). aIMT was consistently higher in offspring affected by LBW/SGA/FGR in all six studies examining this variable. The cause of inconclusive or conflicting associations found with other arterial biophysical properties and perinatal factors may be multifactorial: in particular, measurements and analyses of related properties differed in technique, equipment, anatomical location, and covariates used., Conclusion: aIMT was consistently higher in LBW/SGA/FGR offspring, which may relate to increased long-term CVD risk. Larger and longer term cohort studies may help to elucidate clinical significance, particularly in relation to established CVD risk factors. Experimental studies may help to understand whether lifestyle or medical interventions can reverse perinatal changes aIMT. The field could be advanced by validation and standardization of techniques assessing arterial structure and function in children., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The aim of this study was to investigate the effect of age and sex on nPWV and ndI in the ascending aorta of healthy humans., Background: Local pulse wave velocity (nPWV) and wave intensity (ndI) in the human ascending aorta have not been studied adequately, because of the need for invasive pressure measurements. However, a recently developed technique made the noninvasive determination of nPWV and ndI possible using measurements of flow velocity and arterial diameter., Methods: Diameter and flow velocity were measured at the level of the ascending aorta in 144 healthy participants (aged 20-77 years, 66 men), using MRI. nPWV, ndI parameters; forward (FCW); backward (BCW) compression waves, forward decompression wave (FDW), local aortic distensibility (nDs) and reflection index (nRI) were calculated., Results: nPWV increased significantly with age from 4.7 ± 0.3 m/s for those 20-30 years to 6.4 ± 0.2 m/s for those 70-80 years (P < 0.001) and did not differ between sexes. nDs decreased with age (5.3 ± 0.5 vs. 2.6 ± 0.2 10 1/Pa, P < 0.001) and nRI increased with age (0.17 ± 0.03 vs. 0.39 ± 0.06, P < 0.01) for those 20-30 and 70-80 years, respectively. FCW, BCW and FDW decreased significantly with age by 86.3, 71.3 and 74.2%, respectively (P < 0.001), all compared to the lowest age-band., Conclusion: In healthy humans, ageing results in stiffer ascending aorta, with increase in nPWV and decrease in nDs. A decrease in FCW and FDW indicates decline in left ventricular early and late systolic functions with age in healthy humans with no differences between sexes. nRI is more sensitive than BCW in establishing the effects of ageing on reflected waves measured in the ascending aorta.

: Whether isolated systolic hypertension in the young (ISHY) implies a worse outcome and needs antihypertensive treatment is still a matter for dispute. ISHY is thought to have different mechanisms than systolic hypertension in the elderly. However, findings from previous studies have provided inconsistent results. From the analysis of the literature, two main lines of research and conceptualization have emerged. Simultaneous assessment of peripheral and central blood pressure led to the identification of a condition called pseudo or spurious hypertension, which was considered an innocent condition. However, an increase in pulse wave velocity has been found by some authors in about 20% of the individuals with ISHY. In addition, obesity and metabolic disturbances have often been documented to be associated with ISHY both in children and young adults. The first aspect to consider whenever evaluating a person with ISHY is the possible presence of white-coat hypertension, which has been frequently found in this condition. In addition, assessment of central blood pressure is useful for identifying ISHY patients whose central blood pressure is normal. ISHY is infrequently mentioned in the guidelines on diagnosis and treatment of hypertension. According to the 2013 European Guidelines on the management of hypertension, people with ISHY should be followed carefully, modifying risk factors by lifestyle changes and avoiding antihypertensive drugs. Only future clinical trials will elucidate if a benefit can be achieved with pharmacological treatment in some subgroups of ISHY patients with associated risk factors and/or high central blood pressure.

Objective: The inverse association between socioeconomic status (SES) and cardiovascular disease (CVD) risk is well documented. Aortic stiffness assessed by aortic pulse wave velocity (PWV) is a strong predictor of CVD events. However, no previous study has examined the effect of SES on arterial stiffening over time. The present study examines this association, using several measures of SES, and attained education level in a large ageing cohort of British men and women., Methods: Participants were drawn from the Whitehall II study. The sample was composed of 3836 men and 1406 women who attended the 2008-2009 clinical examination (mean age = 65.5 years). Aortic PWV was measured in 2008-2009 and in 2012-2013 by applanation tonometry. A total of 3484 participants provided PWV measurements on both occasions. The mean difference in 5-year PWV change was examined according to household income, education, employment grade, and father's social class, using linear mixed models., Results: PWV increase [mean: confidence interval (m/s)] over 5 years was higher among participants with lower employment grade (0.38: 0.11-0.65), household income (0.58, 95%: 0.32-0.85), and education (0.30: 0.01, 0.58), after adjusting for sociodemographic variables, BMI, alcohol consumption, smoking, and other cardiovascular risk factors, namely SBP, mean arterial pressure, heart rate, cholesterol, diabetes, and antihypertensive use., Conclusion: The present study supports the presence of robust socioeconomic disparities in aortic stiffness progression. Our findings suggest that arterial aging could be an important pathophysiological pathway explaining the impact of lower SES on CVD risk.

Objectives: The positive association between adiposity and hypertension is well recognized. However, not all overweight individuals have elevated blood pressure (BP). Moreover, different factors may be associated with high BP in normal-weight versus overweight individuals. The aim of the current study was to examine the influence of adiposity on the relationship between SBP and underlying haemodynamic mechanisms in young adults., Method: Data from 2502 patients were available from the Enigma study. Detailed demographic, biochemical, and haemodynamic data were obtained in all individuals. Data were analysed between lower and upper tertiles of BMI and SBP, separately for each sex., Results: In normal-weight individuals, cardiac output (CO) was elevated in those with higher SBP, independently of body size. Moreover, higher CO was associated with an increased stroke volume in men (P < 0.001), but an increased heart rate in women (P = 0.002). In contrast, in overweight individuals, peripheral vascular resistance (PVR) was elevated in men with higher SBP (P = 0.02) and those with lower SBP had the lowest PVR of all groups. In linear regression analyses, there was a stronger association between SBP and CO in normal-weight individuals, but a stronger association between SBP and PVR in overweight individuals., Conclusion: Different haemodynamic mechanisms are associated with elevated SBP in young adults, depending on body size and sex. These data suggest the need for differential approaches to the identification and management of young adults with elevated BP.

Objective: Our objective was to investigate the extent of changes in maternal cardiovascular function, lipids and renal function during normal pregnancy from preconception to postpartum period., Methods: In this prospective study of 54 normal pregnancies, detailed hemodynamics were performed preconception, at 6, 23 and 33 weeks during pregnancy and 16 weeks postpartum., Results: Although the greatest reduction of blood pressures (BPs) and augmentation index occurred in early pregnancy (Δbrachial systolic: 4 ± 7  mmHg, Δcentral systolic: 7 ± 7  mmHg; P < 0.001), the peripheral vascular resistance reached a nadir (Δ: 222 ± 215 dynes.s.cm; P < 0.001) by the second trimester. The greatest increase in cardiac output occurred by the second trimester (Δ: 0.6 ± 1 l/min, P < 0.001), whereas the heart rate increased maximally by the third trimester (Δ: 13 ± 11  bpm; P = 0.001). The unadjusted aortic pulse wave velocity decreased in the second trimester (P < 0.001), however, when adjusted for mean arterial pressure this was not significant (P = 0.06). BPs were lower (Δ brachial systolic: 5 ± 8  mmHg; P < 0.001) and augmentation index higher (Δ: 2.5 ± 7%; P = 0.01) postpartum than preconception. The cholesterol:high-density lipoprotein ratio, serum low density lipoprotein and serum creatinine all fell (P < 0.001) in the first trimester., Conclusion: We have shown that normal pregnancy, irrespective of parity, is associated with significant changes commencing very early in pregnancy, continuing throughout pregnancy, and some of these changes persisted postpartum. Therefore, first trimester or postpartum baselines will underestimate the true extent of pregnancy-related changes. Prospective studies of cardiovascular function from preconception to postpartum will provide more reliable estimates of the influence of cardiovascular maladaptation during pregnancy complications and their effect on longer term cardiovascular function.

Background: Carotid-femoral pulse wave velocity, a predictor of cardiovascular outcome, is conventionally measured using a tonometer sequentially placed upon the carotid and femoral arteries, gated using an electrocardiogram. Leg cuff detection of the femoral pulse removes the need for signal gating, reduces the time required for a single measurement, but gives different pulse wave velocity values to tonometric analysis. A novel algorithm to correct for the transit time and distance related to the additional femoral segment was applied to the cuff-based approach in this study., Method: Eighty-eight individuals were recruited across four centres and carotid-femoral pulse wave velocity measured in triplicate using two operators with both a tonometer-based device and a device using an inflated thigh cuff with and without the use of the novel algorithm. Comparison was made by Bland-Altman and regression analysis., Results: The unadjusted cuff-based approach gave lower pulse wave velocity values than the tonometer-based approach (6.11 ± 1.27 and 7.02 ± 1.88 m/s, P < 0.001). With application of the algorithm, the cuff-based device gave similar pulse wave velocity values (7.04 ± 1.72 m/s) as the tonometer-based approach (P = 0.86). Analysis of covariance with age showed a difference between the tonometer and cuff-based methods (P < 0.001), with a dependence upon age (P = 0.004). The adjusted cuff-based method gave similar results to the tonometer-based method (P = 0.94), with no dependence upon age (P = 0.46)., Conclusion: This study provided validation of a cuff-based assessment of carotid-femoral pulse wave velocity against the universally accepted tonometric method. Adjusting the cuff-based method for the additional femoral segment measured gives results comparable to the tonometer-based method, for which the majority of population data exist to date.

Objectives: The Vicorder is a new brachial cuff-based device that estimates central blood pressure (cBP) using a brachial-to-aortic transfer function. The aim of this study was to evaluate cBP estimated by the Vicorder., Methods: During cardiac angiography, cBP estimated by the Vicorder and the SphygmoCor was evaluated against simultaneous invasive cBP in 50 patients. The two devices were also compared noninvasively in a separate group of 90 healthy individuals., Results: Central SBP (cSBP) obtained with each device satisfied the American Association for the Advancement of Medical Instrumentation accuracy criteria when peripheral waveforms were calibrated to invasive mean arterial pressure (MAP)/DBP: estimated - invasive cSBP difference, -4.0 ± 7.4 mmHg, Vicorder, P < 0.001; -1.4 ± 7.9 mmHg, SphygmoCor, P = 0.21. When oscillometric brachial SBP/DBP was used for peripheral waveform calibration, cSBP was underestimated by Vicorder (Δ -6.4 ± 7.4 mmHg, P < 0.001 versus invasive) and more so by SphygmoCor (Δ -11.9 ± 7.2 mmHg, P < 0.001 versus invasive). Conversely, cSBP was more closely estimated by SphygmoCor when waveforms were calibrated to brachial MAP/DBP (Δ -2.8 ± 9.4 mmHg, P = 0.04 versus invasive). In the noninvasive study, Vicorder cSBP correlated well with SphygmoCor cSBP when SphygmoCor waveforms were calibrated to brachial MAP/DBP (121 ± 16 versus 121 ± 17 mmHg, P = 0.2) but not when brachial SBP/DBP was used for calibration (115 ± 19 mmHg, P < 0.001)., Conclusion: The Vicorder and SphygmoCor devices provide reliable estimates of cSBP when calibrated to invasive pressure. When calibrated to brachial BP, both devices underestimated cSBP, although this was attenuated when SphygmoCor was calibrated to brachial MAP/DBP. Vicorder may be a simple alternative to tonometry-based methods for noninvasive assessment of cBP.

Objective: Our aim was to assess changes in maternal cardiovascular haemodynamics, including central blood pressure (BP), wave reflections and aortic stiffness, from pre-pregnancy to very early pregnancy., Methods: Fifty-six healthy nulliparous or women with previous uncomplicated pregnancy were studied prior to conception and in very early pregnancy. Assessments of brachial and central BPs, pulse wave reflection quantified by augmentation index (AIx), aortic stiffness using carotid femoral pulse wave velocity (aPWV) and cardiac output (CO) were performed., Results: Pregnancy measurements were obtained at median gestational age of 6.3 weeks [interquartile range (IQR) 6-6.5 weeks] from the last menstrual period. Whilst heart rate (HR) increased from 67  ±  10 to 71  ±  10  bpm. (P  =  0.001), brachial SBP, DBP and central SBP were all lower than the pre-pregnancy values (109  ±  10 to 104  ±  7 mmHg, 72  ±  8 to 65  ±  6 mmHg and 99  ±  10 to 92  ±  7 mmHg, respectively; P  <  0.001 for all). AIx adjusted for HR fell (19  ±  10 to 13  ±  9%; P  =  0.001) as did peripheral vascular resistance (PVR; 1234 ± 229 to 1128  ±  280 dynes/s/cm; P = 0.003). aPWV adjusted for mean arterial pressure (MAP) was unchanged (5.3  ±  0.6 to 5.1  ±  0.6m/s; P  =  0.2)., Conclusion: Significant changes occur in brachial and central BP, AIx and PVR in successful, ongoing pregnancies, by about 6-7 weeks gestation; much earlier than has hitherto been assumed. Using late first trimester data as 'baseline' cannot be relied on to estimate the extent of cardiovascular changes in normal pregnancy. Future studies of cardiovascular changes in pregnancy should, therefore, have a pre-pregnancy starting point.

Background: Accumulating evidence suggests that low birth weight is associated with increased cardiovascular risk. However, the relationship between birth weight, blood pressure, arterial stiffness and wave reflections as putative mechanisms is controversial., Method: Data from 882 participants (mean age 21 years) were analysed. Participants underwent a detailed physiological assessment, including anthropometric measurement, blood pressure, aortic pulse wave velocity, augmentation index (AIx) and cardiac output (CO). Analyses were conducted in men and women separately, according to birth weight quartiles and categories referenced to UK birth weight percentiles., Results: In men, those in the lowest birth weight quartile had higher brachial SBP (P = 0.04), central pulse pressure (PP; P = 0.03) and AIx (P = 0.02). Further analysis of the low birth weight spectrum revealed that central PP (P = 0.03), AIx (P = 0.03) and peripheral vascular resistance index (P = 0.01) were higher in those in the lowest birth weight percentile, although the association with AIx disappeared after adjustment for adult height. In women, analysis by birth weight quartiles and categories referenced to UK birth weight percentiles revealed a significant positive association between birth weight and CO (P = 0.04, P = 0.02) and stroke volume (P = 0.03, P = 0.002); although these associations disappeared when body size was taken into account. There was no association between birth weight and aortic pulse wave velocity in either men or women., Conclusion: These data suggest that although lower birth weight is associated with altered haemodynamics in young adulthood, the associations are predominantly driven by other factors such as adult body size, rather than intrinsic structural changes within the large elastic arteries.

Objectives: The long-term consequences of extreme prematurity are becoming increasingly important, given recent improvements in neonatal intensive care. The aim of the current study was to examine the cardiovascular consequences of extreme prematurity in 11-year-olds born at or before 25 completed weeks of gestation., Methods: Age and sex-matched classmates were recruited as controls. Information concerning perinatal and maternal history was collected, and current anthropometric characteristics were measured in 219 children born extremely preterm and 153 classmates. A subset of the extremely preterm children (n = 68) and classmates (n = 90) then underwent detailed haemodynamic investigations, including measurement of supine blood pressure (BP), aortic pulse wave velocity (aPWV, a measure of aortic stiffness) and augmentation index (AIx, a measure of arterial pressure wave reflections)., Results: Seated brachial systolic and diastolic BP were not different between extremely preterm children and classmates (P = 0.3 for both), although there was a small, significant elevation in supine mean and diastolic BP in the extremely preterm children (P < 0.05 for both). Arterial pressure wave reflections were significantly elevated in the extremely preterm children (P < 0.001) and this persisted after adjusting for confounding variables. However, aortic stiffness was not different between the groups (P = 0.1)., Conclusions: These data suggest that extreme prematurity is associated with altered arterial haemodynamics in children, not evident from the examination of brachial BP alone. Moreover, the smaller, preresistance and resistance vessels rather than large elastic arteries appear to be most affected. Children born extremely preterm may be at increased future cardiovascular risk.

Background: The oral contraceptive pill (OCP) is widely prescribed throughout the world. Although it is associated with a small but significant increase in blood pressure, the influence of the OCP on large artery stiffness and wave reflection is unclear. The aim of this study was to determine the relationship between use of the OCP and aortic stiffness and wave reflections in a young, healthy cohort of women., Methods: Participants were drawn from the ENIGMA study, which examines the natural history of blood pressure in young adults. A detailed medical history and lifestyle questionnaire, including OCP details were taken. Blood pressure was measured according to the British Hypertension Society guidelines. Aortic pulse wave velocity (aPWV) was measured together with augmentation index (AIx). Stroke volume (SV) and cardiac output (CO) were also assessed., Results: Women taking the OCP (n = 225) had a higher SBP and pulse pressure compared with nonusers (n = 660; 112 ± 12 vs. 110 ± 11 and 43 ± 8 vs. 42 ± 8 mmHg, respectively, P < 0.05 for both). CO and SV were also higher (6.6 ± 1.5 vs. 6.3 ± 1.5 l/min, P < 0.01 and 81 ± 16 vs. 78 ± 19 ml, P < 0.05) as was aPWV (5.5 ± 0.7 vs. 5.4 ± 0.7 m/s, P < 0.05). However, there was no difference in DBP (68 ± 9 vs. 69 ± 9 mmHg), mean arterial pressure (81 ± 10 vs. 81 ± 10 mmHg) or AIx (2 ± 12 vs. 3 ± 13%) between the groups., Conclusion: Use of the OCP is associated with elevated pulse pressure and SV and a small increase in aPWV in young women. The longer term implications of these effects require further investigation.

Background: Recent evidence suggests that central aortic blood pressure may be a better predictor of cardiovascular risk than peripheral blood pressure. The central SBP (cSBP) can be estimated from the late systolic shoulder of the radial pulse waveform. We compared the second systolic peak of the radial waveform (pSBP(2)) with the central systolic pressure derived by a generalized transfer function in a large cohort, across a wide age range, of patients from the Anglo-Cardiff Collaborative Trial. We also compared pSBP(2) with the true cSBP measured by cardiac catheterization [invasively measured cSBP (cSBPi)]., Methods: Noninvasive measurements were made by applanation tonometry using the SphygmoCor device. The aortic pressure waveform was derived from the radial waveform using a validated transfer function. Invasive measures of cSBPi were carried out in a group of 38 patients undergoing diagnostic cardiac angiography, and radial artery pressure waveforms were simultaneously recorded using the SphygmoCor device., Results: Overall, there was a strong correlation (r = 0.99, P<0.001) and good agreement between pSBP(2) and the derived cSBP (mean difference +/- SD 1 +/- 4 mmHg). However, there was a systematic bias with a greater difference between these measures at lower average pressures. There was also a strong correlation and good agreement between the invasively measured cSBPi and pSBP(2) (r = 0.92, P<0.001, mean difference 2 +/- 6 mmHg)., Conclusion: The second systolic shoulder of the peripheral pressure waveform approximates the cSBP in a large cohort of patients across a wide age range, but this may be inaccurate at low SBP values.

Objectives: Some beta-blockers are less effective in reducing central blood pressure than other antihypertensive drugs, which may explain the higher rate of events in subjects randomized to atenolol in recent trials. We hypothesized that nebivolol, a mixed beta-blocker/nitro-vasodilator, would be more effective than atenolol in reducing central blood pressure and augmentation index (AIx). The aim of the present study was to test this in a double-blind, randomized, cross-over study, in a cohort of subjects with isolated systolic hypertension., Methods: Following a 2-week placebo run-in, 16 never-treated hypertensive subjects received atenolol (50 mg), nebivolol (5 mg) and placebo, each for 5 weeks, in a random order. Seated brachial blood pressure and heart rate were measured. Aortic blood pressure, AIx and pulse wave velocity (PWV) were assessed non-invasively., Results: The placebo-corrected fall in brachial pressure was similar between nebivolol and atenolol, as was the reduction in PWV (mean change +/- SEM: -1.0 +/- 0.3 and -1.2 +/- 0.2 m/s; P = 0.2). However, there was less reduction in heart rate (-19 +/- 2 versus -23 +/- 2 beats/min; P < 0.01) and increase in AIx (+6 +/- 1 versus +10 +/- 1%; P = 0.04), following nebivolol. Aortic pulse pressure was significantly lower (50 +/- 2 versus 54 +/- 2 mmHg; P = 0.02) after nebivolol. N-terminal pro-B-type natriuretic peptide (proBNP) rose on both drugs (100 +/- 33 versus 75 +/- 80 pg/ml; P < 0.01 for both, NS for comparison)., Conclusions: Nebivolol and atenolol have similar effects on brachial blood pressure and aortic stiffness. However, nebivolol reduces aortic pulse pressure more than atenolol, which may be related to a less pronounced rise in AIx and bradycardia. Whether this will translate into differences in clinical outcome requires further investigation.

Objectives: Exercise brachial blood pressure (BP) is predictive of cardiovascular events. As a result of the amplification of pulse pressure, central BP (a stronger cardiovascular risk factor) differs significantly from peripheral measures. Pulse pressure amplification is reduced with increasing age and hypercholesterolemia at rest, but the effect of exercise on central pressure in these populations is unknown. This study aimed to assess the central and peripheral BP response to exercise with aging and hypercholesterolemia., Methods: Twenty healthy younger (aged 29 +/- 5 years; mean +/- SD), 20 healthy older (aged 57 +/- 5 years) and 12 matched older (aged 59 +/- 7 years) men with hypercholesterolemia exercised (bicycle ergometer) at 60% of their predicted maximal heart rate. Central BP and augmentation index (AIx), a marker of systemic arterial stiffness, were obtained non-invasively using pulse wave analysis. Pulse pressure amplification was defined as the ratio of peripheral to central pulse pressure., Results: The resting haemodynamics of the older men were not significantly different from those with hypercholesterolemia. During exercise, amplification was significantly lower (P < 0.001), and the augmentation index significantly higher (P < 0.001) in the hypercholesterolemic individuals. Younger men had significantly increased amplification (P < 0.01) and reduced AIx (P < 0.001) at rest and during exercise compared with older men. In multiple regression analysis, exercise pulse pressure amplification was independently predicted by age (beta = -0.48; P < 0.001) and total cholesterol (beta = -0.28; P = 0.03)., Conclusion: With increasing age, exercise pulse pressure amplification is significantly attenuated because of increased wave reflection. These effects are exacerbated by hypercholesterolemia and may contribute to cardiovascular risk by mechanisms associated with central hypertension.

Objective: Arterial stiffness is an independent determinant of cardiovascular risk, and there is evidence that it has a strong genetic component. Fibrillin-1 (FBN-1) is the disease gene for Marfan's syndrome and an FBN-1 polymorphism has been associated with large artery stiffening and elevated pulse pressure (PP) in patients with cardiovascular disease. The aim of this study was to investigate the possible influence of the common FBN-1 genotypes on arterial stiffness in a large cohort of healthy individuals., Subjects and Methods: A total of 742 individuals free from cardiovascular disease or risk factors were studied. Aortic pulse wave velocity (PWV) and augmentation index (AIx), blood pressure, lipids and glucose were assessed. Genomic DNA was extracted, and genotyping for the FBN-1 variable nucleotide tandem repeat (VNTR) was performed using a CEQ 8000 sequencer., Results: The mean age (+/- SEM) of the cohort was 49 +/- 1 years. The three common VNTR genotypes accounted for 87.1% of the population frequency. Their frequencies were: 52.3%, 2-2; 16.3%, 2-3; 18.5% 2-4. There were no significant differences in the blood pressure, AIx, PWV, lipids or body mass index among the common genotypes. Moreover, the FBN-1 genotype was not associated with either aortic PWV or other measures of stiffness after correction for other confounding factors., Conclusion: These data do not support the hypothesis that aortic PWV or PP are influenced by the FBN-1 VNTR genotype. Although we cannot exclude small effects, this negative finding also suggests that there is not a major allele for stiffness or blood pressure in apparently healthy individuals linked to this VNTR.