Tracking of serum lipid levels from childhood to adulthood: Systematic review and meta-analysis.

BACKGROUND AND AIMS: The utility of lipid screening in pediatric settings for preventing adult atherosclerotic cardiovascular diseases partly depends on the lifelong tracking of lipid levels. This systematic review aimed to quantify the tracking of lipid levels from childhood and adolescence to adulthood. METHODS: We systematically searched MEDLINE, Embase, Web of Science, and Google Scholar in March 2022. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; ID: CRD42020208859). We included cohort studies that measured tracking of lipids from childhood or adolescence (<18 years) to adulthood (≥18) with correlation or tracking coefficients. We estimated pooled correlation and tracking coefficients using random-effects meta-analysis. Risk of bias was assessed with a review-specific tool. RESULTS: Thirty-three studies of 19 cohorts (11,020 participants) were included. The degree of tracking from childhood and adolescence to adulthood differed among lipids. Tracking was observed for low-density lipoprotein cholesterol (pooled r = 0.55-0.65), total cholesterol (pooled r = 0.51-0.65), high-density lipoprotein cholesterol (pooled r = 0.46-0.57), and triglycerides (pooled r = 0.32-0.40). Only one study included tracking of non-high-density lipoprotein cholesterol (r = 0.42-0.59). Substantial heterogeneity was observed. Study risk of bias was moderate, mostly due to insufficient reporting and singular measurements at baseline and follow-up. CONCLUSIONS: Early-life lipid measurements are important for predicting adult levels. However, further research is needed to understand the tracking of non-high-density lipoprotein cholesterol and the stability of risk classification over time, which may further inform pediatric lipid screening and assessment strategies.

Relation of forward and backward traveling pressure waves with subclinical carotid artery wall remodeling and central pulse pressure.

Central pulse pressure (PP) is the sum of forward and backward traveling pressure waves that have been associated with cardiovascular disease (CVD) risk. However, previous studies have reported differential findings regarding the importance of the forward versus the backward wave for CVD risk. Therefore, we sought to determine the degree to which the forward and backward pressure waves are associated with subclinical carotid artery wall remodeling and central PP in healthy adults. Using applanation tonometry, carotid pressure waveforms were acquired in 308 healthy individuals (aged 45 ± 17 years, range 19-80 years, 61% women), from which the time integral of the forward (PfTI) and backward (PbTI) pressure waves were derived via pressure-only wave separation analysis. Common carotid artery intima-media thickness (cIMT), a biomarker of subclinical CVD risk, was derived via B-mode ultrasonography measured ∼2 cm from the carotid bulb. Both PfTI (r = 0.31, P < 0.001) and PbTI (r = 0.40, P < 0.001) were correlated with cIMT. However, further analysis revealed that PbTI mediated the relation between PfTI and cIMT (proportion mediated = 156%, P < 0.001). The association between PbTI and cIMT remained after adjusting for age, sex, body mass index, blood glucose, low-density lipoprotein cholesterol, heart rate, brachial systolic pressure, and aortic stiffness (B = 0.02, 95% confidence interval = 0.01, 2.77, P < 0.001). Both PfTI (r = -0.58, P < 0.001) and PbTI (r = -0.50, P < 0.001) were correlated with central PP, however, PfTI fully mediated the association between PbTI and central PP (proportion mediated = 124%, P < 0.001). Although PfTI is correlated with higher central PP, it is PbTI that is directly associated with carotid artery wall remodeling.NEW & NOTEWORTHY The present study contributes to the growing body of evidence highlighting the physiological and clinical insight provided by the pulsatile hemodynamic components of central artery pulse pressure. The notable findings of this study are: 1) The reflected (backward) pressure wave is associated with carotid intima-media thickness independent of traditional cardiovascular risk factors, including systolic blood pressure and aortic stiffness. 2) The incident (forward) pressure wave, and not the reflected pressure wave, is associated with greater central pulse pressure.

Sex-specific associations of reservoir-excess pressure parameters with age and subclinical vascular remodeling.

OBJECTIVE: Central artery reservoir pressure and excess pressure (XSP) are associated with cardiovascular disease (CVD) events and mortality. However, sex differences in the trajectory of central reservoir pressure and XSP with advancing age and their relations with vascular markers of subclinical CVD risk are incompletely understood. Therefore, we tested the hypothesis that central reservoir pressure and XSP would be positively associated with advancing age and vascular markers of subclinical CVD risk in men and women. METHOD: Healthy adults ( n  = 398; aged 18-80 years, 60% female individuals) had central (carotid) artery pressure waveforms acquired by applanation tonometry. Reservoir pressure and XSP peaks and integrals were derived retrospectively from carotid pressure waveforms using custom written software. Carotid artery intimal-medial thickness (IMT) was measured by ultrasonography, and aortic stiffness was determined from carotid-femoral pulse wave velocity (cfPWV). RESULTS: Reservoir pressure peak, reservoir pressure integral and XSP integral were higher with age in both men and women ( P  < 0.05), whereas XSP peak was lower with age in men ( P  < 0.05). In women, both reservoir pressure peak ( ß â€Š= 0.231, P  < 0.01) and reservoir pressure integral ( ß â€Š= 0.254, P  < 0.01) were associated with carotid artery IMT, and reservoir pressure peak was associated with cfPWV ( ß â€Š= 0.120, P  = 0.02) after adjusting for CVD risk factors. CONCLUSION: Central artery reservoir pressure and XSP were higher with advancing age in men and women, and reservoir pressure peak was associated with both carotid artery wall thickness and aortic stiffness in women but not men. Central reservoir pressure peak may provide some insight into sex differences in vascular remodeling and subclinical CVD risk with advancing age in healthy adults.

Comparison between cuff-based and invasive systolic blood pressure amplification.

OBJECTIVE: Accurate measurement of central blood pressure (BP) using upper arm cuff-based methods is associated with several factors, including determining the level of systolic BP (SBP) amplification. This study aimed to determine the agreement between cuff-based and invasively measured SBP amplification. METHODS: Patients undergoing coronary angiography had invasive SBP amplification (brachial SBP - central SBP) measured simultaneously with cuff-based SBP amplification using a commercially available central BP device (device 1: Sphygmocor Xcel; n = 171, 70% men, 60 ±â€Š10 years) and a now superseded model of a central BP device (device 2: Uscom BP+; n = 52, 83% men, 62 ±â€Š10 years). RESULTS: Mean difference (±2SD, limits of agreement) between cuff-based and invasive SBP amplification was 4 mmHg (-12, +20 mmHg, P < 0.001) for device 1 and -2 mmHg (-14, +10 mmHg, P = 0.10) for device 2. Both devices systematically overestimated SBP amplification at lower levels and underestimated at higher levels of invasive SBP amplification, but with stronger bias for device 1 (r = -0.68 vs. r = -0.52; Z = 2.72; P = 0.008). Concordance of cuff-based and invasive SBP amplification across quartiles of invasive SBP amplification was low, particularly in the lowest and highest quartiles. The root mean square errors from regression between cuff-based central SBP and brachial SBP were significantly lower (indicating less variability) than from invasive regression models (P < 0.001). CONCLUSIONS: Irrespective of the difference from invasive measurements, cuff-based estimates of SBP amplification showed evidence of proportional systematic bias and had less individual variability. These observations could provide insights on how to improve the performance of cuff-based central BP.

Aortic pressure-only wave separation analysis in adolescents: accuracy and associations with left ventricular mass index.

Early-life exposure to high blood pressure (BP) is associated with cardiovascular target organ damage but not all BP-related risk is attributable to systolic and diastolic BP alone. In adolescence, aortic wave separation (WS) parameters are associated with increased left ventricular mass index (LVMI) but this approach is limited by the requirement for aortic flow measurements. Several methods for estimating the aortic flow waveform from pressure waveforms have emerged, but their accuracy and associations with LVMI have never been tested in adolescents, which was the aim of our study. Carotid pressure waveforms were acquired by tonometry from 58 adolescents (age 16 ± 1.5 years, 59% female). Measured (aortic) flow and LVMI were acquired via 2D echocardiography. Three pressure-only approximations of aortic flow were synthesized, including triangular, excess, and individualized-physiologic flow. A 4th aortic flow (average flow) was approximated from the average of all 58 measured flow waveforms. Forward (Pf) and backward (Pb) pressure and reflection magnitude (Rm) were derived from WS analysis. The individualized-physiologic flow produced the best approximations of Pf (mean difference ± SD, -0.15 ± 2.38 mmHg), Pb (0.14 ± 0.25 mmHg), and Rm (0.01 ± 0.02 mmHg). Pf derived using measured, individualized-physiologic, and average flow, was similarly associated with LVMI adjusting for age, brachial systolic BP, cardiac output, and BMI (P ≤ 0.03 all). Pb derived using all flow waveforms was associated with LVMI and all associations yielded similar effect estimates. Of the estimated flow waveforms, individualized-physiologic flow yielded the best approximation of WS parameters and may provide important physiological and clinical insight among adolescents.

Relative Contribution of Blood Pressure in Childhood, Young- and Mid-Adulthood to Large Artery Stiffness in Mid-Adulthood.

Background Blood pressure associates with arterial stiffness, but the contribution of blood pressure at different life stages is unclear. We examined the relative contribution of childhood, young- and mid-adulthood blood pressure to mid-adulthood large artery stiffness. Methods and Results The sample comprised 1869 participants from the Cardiovascular Risk in Young Finns Study who had blood pressure measured in childhood (6-18 years), young-adulthood (21-30 years), and mid-adulthood (33-45 years). Markers of large artery stiffness were pulse wave velocity and carotid distensibility recorded in mid-adulthood. Bayesian relevant life course exposure models were used. For each 10-mm Hg higher cumulative systolic blood pressure across the life stages, pulse wave velocity was 0.56 m/s higher (95% credible interval: 0.49 to 0.63) and carotid distensibility was 0.13%/10 mm Hg lower (95% credible interval: -0.16 to -0.10). Of these total contributions, the highest contribution was attributed to mid-adulthood systolic blood pressure (relative weights: pulse wave velocity, childhood: 2.6%, young-adulthood: 5.4%, mid-adulthood: 92.0%; carotid distensibility, childhood: 5.6%; young-adulthood: 10.1%; mid-adulthood: 84.3%), with the greatest individual contribution coming from systolic blood pressure at the time point when pulse wave velocity and carotid distensibility were measured. The results were consistent for diastolic blood pressure, mean arterial pressure, and pulse pressure. Conclusions Although mid-adulthood blood pressure contributed most to mid-adulthood large artery stiffness, we observed small contributions from childhood and young-adulthood blood pressure. These findings suggest that the burden posed by arterial stiffness might be reduced by maintaining normal blood pressure levels at each life stage, with mid-adulthood a critical period for controlling blood pressure.

Postpartum ambulatory and home blood pressure monitoring in women with history of preeclampsia: Diagnostic agreement and detection of masked hypertension.

Women with a history of preeclampsia (hxPE) are at a four-fold higher risk for chronic hypertension after pregnancy compared with healthy pregnancy, but 'masked' hypertension cases are missed by clinical assessment alone. Twenty-four hour ambulatory blood pressure monitoring (ABPM) is the reference-standard for confirmation of hypertension diagnoses or detection of masked hypertension outside of clinical settings, whereas home blood pressure monitoring (HBPM) may represent a well-tolerated and practical alternative to ABPM in the postpartum period. The objectives of this study were to 1) assess concordance between ABPM and HBPM postpartum in women with a hxPE compared with healthy pregnancy controls and 2) evaluate HBPM in the detection of masked postpartum hypertension. Young women with a hxPE (N = 26) and controls (N = 36) underwent in-office, 24-h ABPM and 7-day HBPM 1-4 years postpartum. Chronic hypertension was more prevalent among women with a hxPE by all three blood pressure measures, but the prevalence of masked postpartum hypertension did not differ (36% vs 37%, P = 0.97). HBPM showed excellent agreement with ABPM (systolic: r = 0.78, intraclass coefficient [ICC] = 0.83; diastolic: r = 0.82, ICC = 0.88) and moderate concordance in classification of hypertension (κ = 0.54, P < 0.001). HBPM identified 21% of masked postpartum hypertension cases without false-positive cases, and HBPM measures among those with normotensive in-office readings could detect ABPM-defined masked hypertension (area under the curve [AUC] = 0.88 ± 0.06, P < 0.0001). The findings of the present study indicate that HBPM may be a useful screening modality prior or complementary to ABPM in the detection and management of postpartum hypertension.

Physiological and clinical insights from reservoir-excess pressure analysis.

There is a growing body of evidence indicating that reservoir-excess pressure model parameters provide physiological and clinical insights above and beyond standard blood pressure (BP) and pulse waveform analysis. This information has never been collectively examined and was the aim of this review. Cardiovascular disease is the leading cause of mortality worldwide, with BP as the greatest cardiovascular disease risk factor. However, brachial systolic and diastolic BP provide limited information on the underlying BP waveform, missing important BP-related cardiovascular risk. A comprehensive analysis of the BP waveform is provided by parameters derived via the reservoir-excess pressure model, which include reservoir pressure, excess pressure, and systolic and diastolic rate constants and Pinfinity. These parameters, derived from the arterial BP waveform, provide information on the underlying arterial physiology and ventricular-arterial interactions otherwise missed by conventional BP and waveform indices. Application of the reservoir-excess pressure model in the clinical setting may facilitate a better understanding and earlier identification of cardiovascular dysfunction associated with disease. Indeed, reservoir-excess pressure parameters have been associated with sub-clinical markers of end-organ damage, cardiac and vascular dysfunction, and future cardiovascular events and mortality beyond conventional risk factors. In the future, greater understanding is needed on how the underlying physiology of the reservoir-excess pressure parameters informs cardiovascular disease risk prediction over conventional BP and waveform indices. Additional consideration should be given to the application of the reservoir-excess pressure model in clinical practice using new technologies embedded into conventional BP assessment methods.

Identifying Isolated Systolic Hypertension From Upper-Arm Cuff Blood Pressure Compared With Invasive Measurements.

Isolated systolic hypertension (ISH) is the most common form of hypertension and is highly prevalent in older people. We recently showed differences between upper-arm cuff and invasive blood pressure (BP) become greater with increasing age, which could influence correct identification of ISH. This study sought to determine the difference between identification of ISH by cuff BP compared with invasive BP. Cuff BP and invasive aortic BP were measured in 1695 subjects (median 64 years, interquartile range [55-72], 68% male) from the INSPECT (Invasive Blood Pressure Consortium) database. Data were recorded during coronary angiography among 29 studies, using 21 different cuff BP devices. ISH was defined as ≥130/<80 mm Hg using cuff BP compared with invasive aortic BP as the reference. The prevalence of ISH was 24% (n=407) according to cuff BP but 38% (n=642) according to invasive aortic BP. There was fair agreement (Cohen κ, 0.36) and 72% concordance between cuff and invasive aortic BP for identifying ISH. Among the 28% of subjects (n=471) with misclassification of ISH status by cuff BP, 20% (n=96) of the difference was due to lower cuff systolic BP compared with invasive aortic systolic BP (mean, -16.4 mm Hg [95% CI, -18.7 to -14.1]), whereas 49% (n=231) was from higher cuff diastolic BP compared with invasive aortic diastolic BP (+14.2 mm Hg [95% CI, 11.5-16.9]). In conclusion, compared with invasive BP, cuff BP fails to identify ISH in a sizeable portion of older people and demonstrates the need to improve cuff BP measurements.

Association of Non-High-Density Lipoprotein Cholesterol Measured in Adolescence, Young Adulthood, and Mid-Adulthood With Coronary Artery Calcification Measured in Mid-Adulthood.

Importance: Elevated non-high-density lipoprotein cholesterol (non-HDL-C) is associated with the presence of coronary artery calcification (CAC), a marker of heart disease in adulthood. However, the relative importance of non-HDL-C levels at specific life stages for CAC remains unclear. Objective: To identify the relative association of non-HDL-C measured at distinct life stages (adolescence, young adulthood, mid-adulthood) with the presence of CAC measured in mid-adulthood. Design, Setting, and Participants: The Cardiovascular Risk in Young Finns Study is a population-based prospective cohort study that started in 1980 with follow-up over 28 years. Participants from 3 population centers (Kuopio, Tampere, and Turku in Finland) represent a convenience sample drawn from the 3 oldest cohorts at baseline (aged 12-18 years in 1980). Data were collected from September 1980 to August 2008. Analysis began February 2020. Exposures: Non-HDL-C levels were measured at 3 life stages including adolescence (aged 12-18 years), young adulthood (aged 21-30 years), and mid-adulthood (aged 33-45 years). Main Outcomes and Measures: In 2008, CAC was determined from computed tomography and dichotomized as 0 (no CAC, Agatston score = 0) and 1 (presence of CAC, Agatston score ≥1) for analysis. Using a bayesian relevant life course exposure model, the relative association was determined between non-HDL-C at each life stage and the presence of CAC in mid-adulthood. Results: Of 589 participants, 327 (56%) were female. In a model adjusted for year of birth, sex, body mass index, systolic blood pressure, blood glucose level, smoking status, lipid-lowering and antihypertensive medication use, and family history of heart disease, cumulative exposure to non-HDL-C across all life stages was associated with CAC (odds ratio [OR], 1.50; 95% credible interval [CrI], 1.14-1.92). At each life stage, non-HDL-C was associated with CAC and exposure to non-HDL-C during adolescence had the strongest association (adolescence: OR, 1.16; 95% CrI, 1.01-1.46; young adulthood: OR, 1.14; 95% CrI, 1.01-1.43; mid-adulthood: OR, 1.12; 95% CrI, 1.01-1.34). Conclusions and Relevance: These data suggest that elevated non-HDL-C levels at all life stages are associated with coronary atherosclerosis in mid-adulthood. However, adolescent non-HDL-C levels showed the strongest association with the presence of CAC in mid-adulthood, and greater awareness of the importance of elevated non-HDL-C in adolescence is needed.

Excess pressure as an analogue of blood flow velocity.

INTRODUCTION: Derivation of blood flow velocity from a blood pressure waveform is a novel technique, which could have potential clinical importance. Excess pressure, calculated from the blood pressure waveform via the reservoir-excess pressure model, is purported to be an analogue of blood flow velocity but this has never been examined in detail, which was the aim of this study. METHODS: Intra-arterial blood pressure was measured sequentially at the brachial and radial arteries via fluid-filled catheter simultaneously with blood flow velocity waveforms recorded via Doppler ultrasound on the contralateral arm (n = 98, aged 61 ±â€Š10 years, 72% men). Excess pressure was derived from intra-arterial blood pressure waveforms using pressure-only reservoir-excess pressure analysis. RESULTS: Brachial and radial blood flow velocity waveform morphology were closely approximated by excess pressure derived from their respective sites of measurement (median cross-correlation coefficient r = 0.96 and r = 0.95 for brachial and radial comparisons, respectively). In frequency analyses, coherence between blood flow velocity and excess pressure was similar for brachial and radial artery comparisons (brachial and radial median coherence = 0.93 and 0.92, respectively). Brachial and radial blood flow velocity pulse heights were correlated with their respective excess pressure pulse heights (r = 0.53, P < 0.001 and r = 0.43, P < 0.001, respectively). CONCLUSION: Excess pressure is an analogue of blood flow velocity, thus affording the opportunity to derive potentially important information related to arterial blood flow using only the blood pressure waveform.

Self-directed multimedia process for delivering participant informed consent.

OBJECTIVE: Obtaining informed consent is a cornerstone requirement of conducting ethical research. Traditional paper-based consent is often excessively lengthy and may fail to achieve the desired participant understanding of study requirements. Multimedia tools including video and audio may be a useful alternative. This study aimed to determine the efficacy, usability and acceptability of self-directed multimedia delivery of participant consent. DESIGN: It is a single-centre, randomised, prospective study to determine the efficacy, usability and acceptability of a self-directed multimedia consent process (intervention) compared with the traditional paper-based approach (control). The intervention was free of research staff, with computer-based finger-signed consent. SETTING: Pathology blood collection services in Tasmania, Australia. PARTICIPANTS: 298 participants (63±8 years; 51% female individuals) referred from general practice were randomised to intervention (n=146) and control (n=152). OUTCOME MEASURES: Efficacy, usability and acceptability of the allocated consent process were assessed by a questionnaire. RESULTS: All participants successfully completed the allocated interventions. Efficacy parameters were higher among intervention participants, including a better understanding of study requirements compared with controls (p<0.05 all). Intervention participants were more likely to engage with the study information and spend more time on the consent process (p=<0.001 and p=0.006, respectively). Both groups reported similar levels of acceptability, although more control participants reported that the study information was too long (24% vs 14%; p=0.020). CONCLUSION: A self-directed multimedia consent process is effective for achieving participant understanding and obtaining consent free of research staff. Thus, multimedia represents a viable method to reduce the burden on researchers, meet participant needs and achieve informed consent in clinical research.

Validation Study to Determine the Accuracy of Central Blood Pressure Measurement Using the Sphygmocor Xcel Cuff Device.

Numerous devices purport to measure central (aortic) blood pressure (BP) as distinct from conventional brachial BP. This validation study aimed to determine the accuracy of the Sphygmocor Xcel cuff device (AtCor Medical, CardieX, Sydney, Australia) for measuring central BP. 296 patients (mean age 61±12 years) undergoing coronary angiography had simultaneous measurement of invasive central BP and noninvasive cuff-derived central BP using the Xcel cuff device (total n=558 individual comparisons). A subsample (n=151) also had invasive brachial BP measured. Methods were undertaken according to the Artery Society recommendations, and several calibration techniques to derive central systolic BP (SBP) were examined. Minimum acceptable error was ≤5±≤8 mm Hg. Central SBP was significantly underestimated, and with wide variability, when using the default calibration of brachial-cuff SBP and diastolic BP (DBP; mean difference±SD, -7.7±11.0 mm Hg). Similar variability was observed using other calibration methods (cuff 33% form-factor mean arterial pressure and DBP, -4.4±11.5 mm Hg; cuff 40% form-factor mean arterial pressure and DBP, 4.7±11.9 mm Hg; cuff oscillometric mean arterial pressure and DBP, -18.2±12.1 mm Hg). Only calibration with invasive central integrated mean arterial pressure and DBP was within minimal acceptable error (3.3±7.5 mm Hg). The difference between brachial-cuff SBP and invasive central SBP was 3.3±10.7 mm Hg. A subsample analysis to determine the accuracy of central-to-brachial SBP amplification showed this to be overestimated by the Xcel cuff device (mean difference 4.3±9.1 mm Hg, P=0.02). Irrespective of cuff calibration technique, the Sphygmocor Xcel cuff device does not meet the Artery Society accuracy criteria for noninvasive measurement of central BP.

Associations of Reservoir-Excess Pressure Parameters Derived From Central and Peripheral Arteries With Kidney Function.

BACKGROUND: Central artery reservoir-excess pressure parameters are clinically important but impractical to record directly. However, diastolic waveform morphology is consistent across central and peripheral arteries. Therefore, peripheral artery reservoir-excess pressure parameters related to diastolic waveform morphology may be representative of central parameters and share clinically important associations with end-organ damage. This has never been determined and was the aim of this study. METHODS: Intra-arterial blood pressure (BP) waveforms were measured sequentially at the aorta, brachial, and radial arteries among 220 individuals (aged 61 ± 10 years, 68% male). Customized software was used to derive reservoir-excess pressure parameters at each arterial site (reservoir and excess pressure, systolic and diastolic rate constants) and clinical relevance was determined by association with estimated glomerular filtration rate (eGFR). RESULTS: Between the aorta and brachial artery, the mean difference in the diastolic rate constant and reservoir pressure integral was -0.162 S-1 (P = 0.08) and -0.772 mm Hg s (P = 0.23), respectively. The diastolic rate constant had the strongest and most consistent associations with eGFR across aortic and brachial sites (ß = -0.20, P = 0.02; ß = -0.20, P = 0.03, respectively; adjusted for traditional cardiovascular risk factors). Aortic, but not brachial peak reservoir pressure was associated with eGFR in adjusted models (aortic ß = -0.48, P = 0.02). CONCLUSIONS: The diastolic rate constant is the most consistent reservoir-excess pressure parameter, in both its absolute values and associations with kidney dysfunction, when derived from the aorta and brachial artery. Thus, the diastolic rate constant could be utilized in the clinical setting to improve BP risk stratification.

Brachial and Radial Systolic Blood Pressure Are Not the Same.

Radial intra-arterial blood pressure (BP) is sometimes used as the reference standard for validation of brachial cuff BP devices. Moreover, there is an emerging wearables market seeking to measure BP at the wrist. However, radial systolic BP may differ when compared with brachial; yet some authors have labeled these differences as a fictional Popeye phenomenon. Indeed, differences between brachial and radial systolic BP have never been accurately quantified, and this was the aim of this study. Intra-arterial BP was measured consecutively at the brachial and radial artery in 180 participants undergoing coronary angiography (aged 61±10 years; 69% men). On average, radial systolic BP was 5.5 mm Hg higher than brachial systolic BP. Only 43% of participants had radial systolic BP within ±5 mm Hg of brachial. Additionally, 46%, 19%, and 13% of participants had radial systolic BP >5, between 5 and 10, and between 10 and 15 mm Hg higher than brachial respectively. A further 14% of participants had radial systolic BP >15 mm Hg higher than brachial, representing the so-called Popeye phenomenon. Finally, 11% of participants had radial systolic BP >5 mm Hg lower than brachial. In conclusion, radial systolic BP is not representative of brachial systolic BP, with most participants having a radial systolic BP >5 mm Hg higher than brachial and many with differences >15 mm Hg. Therefore, validation testing of BP devices utilizing intra-arterial BP as the reference standard should use intra-arterial BP measured at the same site as the brachial cuff or wearable device.

Aortic-to-brachial artery stiffness gradient is not blood pressure independent.

Aortic stiffness predicts cardiovascular mortality but is limited as a risk marker because it is dependent on blood pressure (BP). A potential solution is provided from the ratio of aortic-to-brachial artery stiffness (ab-ratio), which has been shown to be a BP-independent risk marker among patients with renal dysfunction (RD). We sought to determine the BP independence of the ab-ratio in patients with disease, including RD, and healthy populations. The ab-ratio (aortic/brachial pulse wave velocity) and mean arterial pressure (MAP) were recorded in patients with RD (n = 119, aged 65 ± 7 years), hypertension (n = 140, aged 62 ± 9 years), type 2 diabetes mellitus (n = 77, aged 60 ± 9 years) and healthy subjects (n = 99, aged 51 ± 8 years). Multiple-regression analysis was performed to test the independent association of MAP with the ab-ratio adjusted for age, sex, body mass index, glucose and heart rate. There was no significant relationship between the ab-ratio and MAP in patients with RD (ß = 0.08, p = 0.34), hypertension (ß = 0.04, p = 0.62) or diabetes (ß = 0.22, p = 0.11). However, among healthy subjects the ab-ratio was significantly and independently associated with MAP (ß = 0.31, p = 0.003). There was a significant difference in the strength of association between the ab-ratio and MAP between patients with disease and healthy subjects (z > 2.2, p < 0.05 all). Although ab-ratio is purported to be a risk marker that is independent of BP, this was observed only among patient populations, and not among healthy subjects. As a result, the ab-ratio has limited potential as a screening tool for the clinical assessment of arterial stiffness in otherwise healthy individuals.

Three members of a peptide family are differentially distributed and elicit differential state-dependent responses in a pattern generator-effector system.

C-type allatostatins (AST-Cs) are pleiotropic neuropeptides that are broadly conserved within arthropods; the presence of three AST-C isoforms, encoded by paralog genes, is common. However, these peptides are hypothesized to act through a single receptor, thereby exerting similar bioactivities within each species. We investigated this hypothesis in the American lobster, Homarus americanus, mapping the distributions of AST-C isoforms within relevant regions of the nervous system and digestive tract, and comparing their modulatory influences on the cardiac neuromuscular system. Immunohistochemistry showed that in the pericardial organ, a neuroendocrine release site, AST-C I and/or III and AST-C II are contained within distinct populations of release terminals. Moreover, AST-C I/III-like immunoreactivity was seen in midgut epithelial endocrine cells and the cardiac ganglion (CG), whereas AST-C II-like immunoreactivity was not seen in these tissues. These data suggest that AST-C I and/or III can modulate the CG both locally and hormonally; AST-C II likely acts on the CG solely as a hormonal modulator. Physiological studies demonstrated that all three AST-C isoforms can exert differential effects, including both increases and decreases, on contraction amplitude and frequency when perfused through the heart. However, in contrast to many state-dependent modulatory changes, the changes in contraction amplitude and frequency elicited by the AST-Cs were not functions of the baseline parameters. The responses to AST-C I and III, neither of which is COOH-terminally amidated, are more similar to one another than they are to the responses elicited by AST-C II, which is COOH-terminally amidated. These results suggest that the three AST-C isoforms are differentially distributed in the lobster nervous system/midgut and can elicit distinct behaviors from the cardiac neuromuscular system, with particular structural features, e.g., COOH-terminal amidation, likely important in determining the effects of the peptides. NEW & NOTEWORTHY Multiple isoforms of many peptides exert similar effects on neural circuits. In this study we show that each of the three isoforms of C-type allatostatin (AST-C) can exert differential effects, including both increases and decreases in contraction amplitude and frequency, on the lobster cardiac neuromuscular system. The distribution of effects elicited by the nonamidated isoforms AST-C I and III are more similar to one another than to the effects of the amidated AST-C II.