Maternal Cardiovascular Dysregulation During Early Pregnancy After In Vitro Fertilization Cycles in the Absence of a Corpus Luteum.

Commonly used in vitro fertilization protocols produce pregnancies without a corpus luteum (CL), a major source of reproductive hormones. In vitro fertilization pregnancies without a CL showed deficient gestational increases of central (aortic) arterial compliance during the first trimester and were at increased risk for developing preeclampsia. Here, we investigated whether there was generalized impairment of cardiovascular adaptation in in vitro fertilization pregnancies without a CL compared with pregnancies conceived spontaneously or through ovarian stimulation, which lead to 1 and >1 CL, respectively (n=19-26 participants per cohort). Prototypical maternal cardiovascular adaptations of gestation were serially evaluated noninvasively, initially during the follicular phase before conception, 6× in pregnancy, and then, on average, 1.6 years post-partum. The expected increases of cardiac output, left atrial dimension, peak left ventricular filling velocity in early diastole (E wave velocity), peripheral/central arterial pulse pressure ratio, and global AC, as well as decrease in augmentation index were significantly attenuated or absent during the first trimester in women who conceived without a CL, when compared with the 1 and >1 CL cohorts, which were comparable. Thereafter, these cardiovascular measures showed recovery in the 0 CL group except for E wave velocity, which remained depressed. These results provided strong support for a critical role of CL factor(s) in the transformation of the maternal cardiovascular system in early gestation. Regimens that lead to the development of a CL or replacement of missing CL factor(s) may be indicated to improve cardiovascular function and reduce preeclampsia risk in in vitro fertilization pregnancies.

Increased Preeclampsia Risk and Reduced Aortic Compliance With In Vitro Fertilization Cycles in the Absence of a Corpus Luteum.

In vitro fertilization involving frozen embryo transfer and donor oocytes increases preeclampsia risk. These in vitro fertilization protocols typically yield pregnancies without a corpus luteum (CL), which secretes vasoactive hormones. We investigated whether in vitro fertilization pregnancies without a CL disrupt maternal circulatory adaptations and increase preeclampsia risk. Women with 0 (n=26), 1 (n=23), or >1 (n=22) CL were serially evaluated before, during, and after pregnancy. Because increasing arterial compliance is a major physiological adaptation in pregnancy, we assessed carotid-femoral pulse wave velocity and transit time. In a parallel prospective cohort study, obstetric outcomes for singleton livebirths achieved with autologous oocytes were compared between groups by CL number (n=683). The expected decline in carotid-femoral pulse wave velocity and rise in carotid-femoral transit time during the first trimester were attenuated in the 0-CL compared with combined single/multiple-CL cohorts, which were similar (group-time interaction: P=0.06 and 0.03, respectively). The blunted changes of carotid-femoral pulse wave velocity and carotid-femoral transit time from prepregnancy in the 0-CL cohort were most striking at 10 to 12 weeks of gestation ( P=0.01 and 0.006, respectively, versus 1 and >1 CL). Zero CL was predictive of preeclampsia (adjusted odds ratio, 2.73; 95% CI, 1.14-6.49) and preeclampsia with severe features (6.45; 95% CI, 1.94-25.09) compared with 1 CL. Programmed frozen embryo transfer cycles (0 CL) were associated with higher rates of preeclampsia (12.8% versus 3.9%; P=0.02) and preeclampsia with severe features (9.6% versus 0.8%; P=0.002) compared with modified natural frozen embryo transfer cycles (1 CL). In common in vitro fertilization protocols, absence of the CL perturbed the maternal circulation in early pregnancy and increased the incidence of preeclampsia.

Wave reflections and global arterial compliance during normal human pregnancy.

Profound changes occur in the maternal circulation during pregnancy. Routine measures of arterial function - central systolic pressure (CSP) and augmentation index (AIx) - decline during normal human pregnancy. The objectives of this study were twofold: (1) explore wave reflection indices besides CSP and AIx that are not routinely reported, if at all, during normal human pregnancy; and (2) compare wave reflection indices and global arterial compliance (gAC) obtained from carotid artery pressure waveforms (CAPW) as a surrogate for aortic pressure waveforms (AOPW) versus AOPW synthesized from radial artery pressure waveforms (RAPW) using a generalized transfer function. To our knowledge, a comparison of these two methods has not been previously evaluated in the context of pregnancy. Ten healthy women with normal singleton pregnancies were studied using applanation tonometry (SphygmoCor) at pre-conception, and then during 10-12 and 33-35 gestational weeks. CSP and AIx declined, and gAC increased during pregnancy as previously reported. As a consequence of the rise in gAC, the return of reflected waves of lesser magnitude from peripheral reflection sites to the aorta was delayed that, in turn, reduced systolic duration of reflected waves, augmentation index, central systolic pressure, LV wasted energy due to reflected waves, and increased brachial-central pulse pressure. For several wave reflection indices, those derived from CAPW as a surrogate for AOPW versus RAPW using a generalized transfer function registered greater gestational increases of arterial compliance. This discordance may reflect imprecision of the generalized transfer function for some waveform parameters, though potential divergence of carotid artery and aortic pressure waveforms during pregnancy cannot be excluded.

All-Extremity Exercise Training Improves Arterial Stiffness in Older Adults.

Large elastic arteries stiffen with age, which predisposes older adults to increased risk for cardiovascular disease. Aerobic exercise training is known to reduce the risk for cardiovascular disease, but the optimal exercise prescription for attenuating large elastic arterial stiffening in older adults is not known. PURPOSE: The purpose of this randomized controlled trial was to compare the effect of all-extremity high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on aortic pulse wave velocity (PWV) and carotid artery compliance in older adults. METHODS: Forty-nine sedentary older adults (age = 64 ± 1 yr), free of overt major clinical disease, were randomized to HIIT (n = 17), MICT (n = 18), or nonexercise controls (CONT; n = 14). HIIT (4 × 4 min at 90% HRpeak interspersed with 3 × 3 min active recovery at 70% HRpeak) and isocaloric MICT (70% HRpeak) were performed on an all-extremity non-weight-bearing ergometer, 4 d·wk for 8 wk under supervision. Aortic (carotid to femoral PWV [cfPWV]) and common carotid artery compliance were assessed at pre- and postintervention. RESULTS: cfPWV improved by 0.5 m·s in MICT (P = 0.04) but did not significantly change in HIIT and CONT (P > 0.05). Carotid artery compliance improved by 0.03 mm·mm Hg in MICT (P = 0.001), but it remained unchanged in HIIT and CONT (P > 0.05). Improvements in arterial stiffness in response to MICT were not confounded by changes in aortic or brachial blood pressure, HR, body weight, total and abdominal adiposity, blood lipids, or aerobic fitness. CONCLUSION: All-extremity MICT, but not HIIT, improved central arterial stiffness in previously sedentary older adults free of major clinical disease. Our findings have important implications for aerobic exercise prescription in older adults.

Influence of the central-to-peripheral arterial stiffness gradient on the timing and amplitude of wave reflections.

In individuals with compliant aortas, peripheral muscular artery stiffness exceeds central elastic artery stiffness. With aging, central stiffness increases with little change in peripheral stiffness, resulting in a reversal of the normal stiffness gradient. This reversal may reduce the wave reflection amplitude due to the movement of the major 'effective' reflection site further from the heart. To test this phenomenon, we investigated the relationship among arterial stiffness gradients (normal and reversed), wave reflection amplitude and reflection site distance. Subjects aged ⩾50 years were recruited from the Anglo-Cardiff Collaborative Trial. Central stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV). In Study 1, peripheral PWV was also measured in the arm (carotid-radial pulse wave velocity) and, in Study 2, in the leg (femoral-dorsalis pedis). Reflection site distance was calculated from cfPWV and the reflected wave Tr. Subjects were dichotomized into those with a normal stiffness gradient (peripheral >central PWV) or a reversed gradient (peripheral

Accuracy of commercial devices and methods for noninvasive estimation of aortic systolic blood pressure a systematic review and meta-analysis of invasive validation studies.

BACKGROUND: Although compelling evidence has established the physiological and clinical relevance of aortic SBP (a-SBP), no consensus exists regarding the validity of the available methods/techniques that noninvasively measure it. OBJECTIVES: The systematic review and meta-analysis aimed to determine the accuracy of commercial devices estimating a-SBP noninvasively, which have been validated by invasive measurement of a-SBP. Moreover their optimal mode of application, in terms of calibration, as well as specific technique and arterial site of pulse wave acquisition were further investigated. METHODS: The study was performed according to the PRISMA guidelines; 22 eligible studies were included, which validated invasively 11 different commercial devices in 808 study participants. RESULTS: Overall, the error in a-SBP estimation (estimated minus actual value) was -4.49 mmHg [95% confidence interval (CI): -6.06 to -2.92 mmHg]. The estimated (noninvasive) a-SBP differed from the actual (invasive) value depending on calibration method: by -1.08 mmHg (95% CI: -2.81, 0.65 mmHg) and by -5.81 mmHg (95% CI: -7.79, -3.84 mmHg), when invasively and noninvasively measured brachial BP values were used respectively; by -1.83 mmHg, (95% CI: -3.32, -0.34 mmHg), and by 7.78 mmHg (95% CI: -10.28, -5.28 mmHg), when brachial mean arterial pressure/DBP and SBP/DBP were used, respectively. CONCLUSION: Automated recording of waveforms, calibrated noninvasively by brachial mean arterial pressure/DBP values seems the most promising approach that can provide relatively more accurate, noninvasive estimation of a-SBP. It is still uncertain whether a specific device can be recommended as 'gold standard'; however, a consensus is currently demanding.

American Society of Hypertension position paper: central blood pressure waveforms in health and disease.

A number of devices are available which noninvasively estimate central aortic blood pressure using a variety of approaches such as tonometry or oscillometry. In this position paper, we discuss how the central pressure waveform is generated and measured, how central pressure waveforms appear in health and disease, the predictive value of central blood pressure measurements, the effects of interventions on waveforms, and areas of future need in this field of clinical and research endeavor.

Association of aortic stiffness and wave reflections with coronary flow reserve in women without obstructive coronary artery disease: An ancillary study from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).

BACKGROUND: Increased aortic stiffness and reduced coronary flow reserve (CFR) independently predict adverse outcomes. But information about relationships between arterial properties and CFR in subjects without obstructive coronary artery disease (CAD) is limited. METHODS: CFR was measured (Doppler flow wire and intracoronary adenosine) in 50 women (age 53 ± 11 years) with symptoms and signs of myocardial ischemia without obstructive CAD. Aortic pulse wave velocity (aPWV), a measure of aortic stiffness, was obtained via catheter pullback; radial artery pressure waves were measured by applanation tonometry and central aortic pressure synthesized. RESULTS: Overall, CFR (mean 2.61 ± 0.47) was significantly correlated with aPWV (r = -0.51), pulse wave amplification (r = 0.45), augmented pressure (r = -0.48), augmentation index (AIx, r = -0.44), aortic systolic pressure (r = -0.49), left ventricular wasted energy (LVEw, r = -0.47) (all P < .001), systolic pressure time index (r = -0.37, P < .008), and rate pressure product (r = -0.29, P < .04). In the multiple regression model including aPWV, CFR was still significantly correlated with aPWV (P < .008) and aortic systolic pressure (P < .01). No other measures contributed significant additional information. Women with CFR ≤2.5 versus those with CFR >2.5 had greater aPWV (894 ± 117 vs 747 ± 93 cm/s, P < .001), augmented pressure (14 ± 4.9 vs 11 ± 4.1 mmHg, P < .008), AIx (32 ± 6.6 vs 27 ± 6.6%, P < .003), LVEw (30 ± 12 vs 21 ± 10 dyne-s/cm(2) × 10(2), P < .02) and reduced pulse pressure amplification (1.20 ± .07 vs 1.26 ± .10, P < .008) and pressure wave travel time (133 ± 7.3 vs 138 ± 6.9 milliseconds, P < .04). CONCLUSIONS: Among symptomatic women without obstructive CAD, CFR was inversely related to aortic systolic pressure and indices of aortic stiffness. These changes in arterial properties increase left ventricular afterload requiring the ventricle to generate additional, but wasted, energy that increases indices of myocardial oxygen demand, reduces CFR and increases vulnerability to ischemia.

Baseline predictors of central aortic blood pressure: a PEAR substudy.

Elevated central systolic blood pressure (BP) increases the risk of cardiovascular events and appears superior to peripheral BP for long term risk prediction. The objective of this study was to identify demographic and clinical factors associated with central pressures in patients with uncomplicated hypertension. We prospectively examined peripheral BP, central aortic BP, and arterial wall properties and wave reflection in 57 subjects with uncomplicated essential hypertension in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) Study. Significant predictors of central SBP included height, smoking status, heart rate (HR), and peripheral systolic BP (SBP), while central diastolic BP (DBP) was explained by peripheral DBP and HR. These variables accounted for nearly all of the variability in central SBP and central DBP (R(2) = 0.94 and R(2) = 0.98, respectively). Central pulse pressure variability was largely explained by gender, ex-smoking status, HR, peripheral SBP, and peripheral DBP (R(2) = 0.94). Central augmented pressure had a direct relationship with smoking status, peripheral SBP, and duration of hypertension, whereas it was indirectly related to height, HR, and peripheral DBP. Easily obtainable demographic and clinical factors are associated with central pressures in essential hypertensive persons. These relationships should be considered in future studies to improve assessment of BP to reduce cardiovascular risk and mortality.

Validity of a novel wristband tonometer for measuring central hemodynamics and augmentation index.

BACKGROUND: Central hemodynamic and augmentation indices are independent predictors of cardiovascular events and all-cause mortality that can be estimated noninvasively by pulse wave analysis. The purpose of this study was to assess the reliability and validity of a newly engineered wristband tonometer for acquiring radial artery pressure waveforms. METHODS: Radial artery pulse pressure waveforms were evaluated with an established pencil-type and a novel wristband tonometer in 31 participants (aged 30.2±9.5 years) resting in a supine position. Pulse wave analysis was executed using the same validated generalized transfer function (SphygmoCor) for both tonometers. RESULTS: A significant difference in time to data acquisition between tonometers was observed (-70.2±147.7 s; P < 0.05; wristband faster). The wristband tonometer had significantly lower within-subject coefficients of variation (CV) compared with the pencil-type tonometer in aortic pulse wave height (-2.67% ± 5.51%; P < 0.05) and time to reflection (-2.26% ± 6.16%; P < 0.01). No other differences in CV were observed. Slight but statistically significant mean differences between tonometers were observed in aortic systolic blood pressure (ASBP; 0.43±1.08 mm Hg; P < 0.05; wristband lower), aortic pulse pressure (APP; 0.43±0.96 mm Hg; P < 0.05; wristband lower), and round-trip travel time of the reflected pressure wave (Δtp; 3.58±12.86 ms; P < 0.05; wristband higher). However, ASBP, APP, and Δtp measurements were highly correlated (r = 0.9970, r = 0.9953, and r = 0.8838, respectively, P <0.0001) between tonometers; within-subject and between tonometer significant mean differences were within clinical ranges. CONCLUSIONS: This novel, hands-free platform may be interchangeable with the commonly used pencil-type tonometer, heralding new directions in noninvasive in vivo vascular research and clinical application.

Role of mineralocorticoid receptors in arterial stiffness in human aging.

Arterial stiffness, an independent predictor of cardiovascular disease, is increased in aging, but the underlying mechanisms are not completely understood. Mineralocorticoid receptors (MR) may contribute to oxidative stress and arterial stiffness in healthy older adults. To test the hypothesis that short-term MR blockade may reduce oxidative stress and improve arterial stiffness, we conducted a randomized, double blind, crossover study using the selective MR blocker Eplerenone or placebo in 23 older adults (age, 64±1 years; mean±SE) free from overt cardiovascular and other clinical disease (e.g, diabetes, renal and liver disease). In response to MR blockade, brachial and carotid blood pressure decreased (P≤0.01). However, MR blockade had no effect on oxidative stress (oxidized LDL, 61.2±6.8 vs. 62.4±7.4 U/L, P=0.9; placebo vs. Eplerenone) and arterial stiffness (aortic pulse wave velocity (PWV), 9.17±1.19 vs. 8.92±1.19 m/s, P=0.5; leg PWV, 13.45±0.45 vs. 12.81±0.47 m/s, P=0.3; arm PWV, 11.43±0.62 vs. 11.73±0.68 m/s, P=0.7; carotid artery compliance, 0.150±0.013 vs. 0.149±0.014 mm(2)/mmHg, P=0.8; distensibility, 23.1±1.8 vs. 23.3±1.7 10(-3)/kPa, P=0.8; ß stiffness index, 3.5±0.3 vs. 3.6±0.3, P=0.6; and augmentation index, 16.0±2.2 vs. 15.6±2.8%, P=0.8). These results provide the first evidence that MR do not appear to contribute to oxidative stress in human aging and that short-term MR blockade does not result in reduced oxidative stress and improved arterial stiffness.

Increased wave reflection and ejection duration in women with chest pain and nonobstructive coronary artery disease: ancillary study from the Women's Ischemia Syndrome Evaluation.

OBJECTIVE: Wave reflections augment central aortic SBP and increase systolic pressure time integral (SPTI) thereby increasing left ventricular (LV) afterload and myocardial oxygen (MVO2) demand. When increased, such changes may contribute to myocardial ischemia and angina pectoris, especially when aortic diastolic time is decreased and myocardial perfusion pressure jeopardized. Accordingly, we examined pulse wave reflection characteristics and diastolic timing in a subgroup of women with chest pain (Women's Ischemia Syndrome Evaluation, WISE) and no obstructive coronary artery disease (CAD). METHODS: Radial artery BP waveforms were recorded by applanation tonometry, and aortic BP waveforms derived. Data from WISE participants were compared with data from asymptomatic women (reference group) without chest pain matched for age, height, BMI, mean arterial BP, and heart rate. RESULTS: Compared with the reference group, WISE participants had higher aortic SBP and pulse BP and ejection duration. These differences were associated with increased augmentation index and reflected pressure wave systolic duration. These modifications in wave reflection characteristics were associated with increased SPTI and wasted LV energy (Ew) and a decrease in pulse pressure amplification, myocardial viability ratio, and diastolic pressure time fraction. CONCLUSION: WISE participants with no obstructive CAD have changes in systolic wave reflections and diastolic timing that increase LV afterload, MVO2 demand, and Ew with the potential to reduce coronary artery perfusion. These alterations in cardiovascular function contribute to an undesirable mismatch in the MVO2 supply/demand that promotes ischemia and chest pain and may contribute to, or increase the severity of, future adverse cardiovascular events.

Carvedilol reduces aortic wave reflection and improves left ventricular/vascular coupling: a comparison with atenolol (CENTRAL Study).

Blood pressure (BP) characteristics, such as central aortic pressure and arterial stiffness, independently predict cardiovascular events. The effects of pharmacologically dissimilar ß-blockers on these properties have not been fully elucidated. Patients with essential hypertension and without significant concomitant cardiovascular disease were randomly assigned to controlled-release carvedilol, force-titrated to 80 mg (n=22), or atenolol, force-titrated to 100 mg (n=19); each was given once daily for 4 weeks. Baseline characteristics were similar. At the end of week 4, atenolol and carvedilol reduced central and brachial systolic and diastolic BP to a similar extent. Central augmentation index was increased in atenolol-treated patients but not carvedilol-treated patients (atenolol 4.47% vs carvedilol -0.68%; P=.04). Mean augmented central aortic pressure increased slightly during atenolol treatment (+1.1 mm Hg) but decreased slightly during carvedilol treatment (-1.1 mm Hg), although the difference in these changes was not statistically significant (P=.23). Pulse pressure amplification was reduced more with atenolol at week 4 (atenolol -10.7% vs carvedilol -1.8%; P=.02). Therefore, we conclude that carvedilol results in more favorable pulse pressure amplification and augmentation index by increasing arterial compliance and reducing the magnitude of wave reflection, respectively, compared with atenolol.