Laure Joly

Pulse Pressure Amplification: A Mechanical Biomarker of Cardiovascular Risk

OBJECTIVESnThe aim of this study was to determine whether the carotid/brachial (C/B) ratio is an independent predictor of cardiovascular (CV) risk.nnnBACKGROUNDnBrachial and carotid pulse pressure (PP) are independent predictors of CV risk, mainly in elderly patients. Because PP is physiologically lower at the brachial than at the carotid arterial site, PP amplification is represented by the C/B ratio and could independently predict CV risk.nnnMETHODSnIn a Paris population (n = 834), brachial and carotid PP were measured from sphygmomanometry and pulse wave analysis. With stepwise multiple regression, carotid PP was calculated from a nomogram including age, sex, body height, brachial PP, and plasma glucose. This model was applied to 125,151 subjects, followed for 12 years, during which 3,997 deaths occurred (735 of CV origin). With Cox regression analysis, multi-adjusted hazard ratios (HRs) were calculated for 1 SD increase of brachial PP, calculated carotid PP, and C/B ratio.nnnRESULTSnBrachial PP was significantly associated with both CV and all-cause mortality (HR: 1.16, 95% confidence interval [CI]: 1.13 to 1.19, and HR: 1.13, 95% CI: 1.10 to 1.17, respectively). Calculated carotid PP predicted a similar risk (HR: 1.21, 95% CI: 1.15 to 1.28, and HR: 1.18, 95% CI: 1.12 to 1.25, respectively). Finally, the C/B ratio was a strong risk predictor (HR: 1.22, 95% CI: 1.12 to 1.32, and HR: 1.41, 95% CI: 1.14 to 1.73, respectively). Addition of drug treatment and other confounding variables did not statistically modify the results.nnnCONCLUSIONSnBrachial PP, calculated carotid PP, and C/B PP amplification all predict CV mortality. In contrast to brachial and carotid PP, the C/B ratio is less dependent on blood pressure calibration and thus can be directly applicable to large population studies.

Heart rate as a risk factor for cardiovascular disease.

Almost all the epidemiological studies that aimed to answer the question of the relationship between heart rate and all-cause or cardiovascular morbidity and mortality reported that a high heart rate was associated with a higher risk of all-cause mortality and cardiovascular events. This relationship has been found to be generally stronger in men than among women. The increase in the cardiovascular risk, associated with the acceleration of heart rate, was comparable to the increase in risk observed with high blood pressure. It has been shown that an increase in heart rate by 10 beats per minute was associated with an increase in the risk of cardiac death by at least 20%, and this increase in the risk is similar to the one observed with an increase in systolic blood pressure by 10 mm Hg. It has also been shown that heart rate recorded in elderly men has a strong predictive value in survival to a very old age. Taken together, these results indicate that the risk associated with accelerated heart rate is not only statistical significant but also clinically relevant and that it should be taken into account in the evaluation of the patients. Although the association between elevated heart rate and cardiovascular morbidity and mortality has been demonstrated in a large number of epidemiological studies, tachycardia has remained a neglected cardiovascular risk factor until very recently. For the first time, the recent guidelines of the European Society of Cardiology and the European Society of Hypertension indicate than an accelerated heart rate is considered as an independent risk factor and potentially as a target for pharmacologic therapies, especially in high-risk patients.

Aortic inflammation, as assessed by hybrid FDG-PET/CT imaging, is associated with enhanced aortic stiffness in addition to concurrent calcification

PurposeTo analyse the relationship between: (i) aortic pulse wave velocity (PWV), an index of aortic stiffness with strong prognostic significance, and (ii) aortic calcification and inflammation, which were quantified by hybrid imaging with X-ray computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET).MethodsCentral aortic (carotid-femoral) and peripheral (carotid-brachial and femoral-tibial) PWV were recorded in 26 patients, who had been routinely referred for dual FDG-PET/CT imaging.ResultsIn univariate analyses, central aortic PWV was strongly linked to the volume of calcifications (VCa) and an enhanced FDG activity, when determined by averaging standardized uptake values (SUVmax). By multivariate stepwise analysis including age and gender, both VCa (pu2009<u20090.0001) and SUVmax (pu2009<u20090.01) were significant determinants of PWV explaining 61% and 11% of its variability.ConclusionAortic inflammation, assessed by hybrid FDG-PET/CT imaging, is associated with an enhanced aortic stiffness, in addition to the concurrent impact of calcifications.

Association of current weight and birth weight with blood pressure levels in saharan and European teenager populations

BACKGROUNDnThe Saharan adult population is characterized by a high prevalence of hypertension. The aim of the present study was to compare blood pressure (BP) levels in Saharan Arab-origin teenagers, in relationship with Europeans of the same age, and to assess the association with birth weight, body weight, and other anthropometric measurements.nnnMETHODSnBP values, heart rate (HR), clinical parameters, and anthropometric measurements were determined in 2,057 teenagers ages 15-19, 1,122 Algerians (388 boys) and 935 Italians (407 boys). Birth weight was obtained from obstetrical records in 568 Algerians and 735 Italians.nnnRESULTSnThe European teenagers were significantly taller and heavier than their Algerian counterparts. In the Algerian population, systolic BP (SBP) was higher in boys (P < 0.01) and lower in girls (P < 0.0001) compared to the Italians, whereas diastolic BP (DBP) was higher in Italians (P < 0.001). Both SBP and DBP were higher in boys than in girls independently of geographic origin (P < 0.001). In all four gender and ethnic groups, both SBP and DBP were strongly correlated with weight or body mass index (BMI). Influence of body weight was stronger on SBP than on DBP; in all four groups, those with the highest weight or BMI quartiles had higher SBP levels by 6-12 mm Hg as compared to those individuals in the lowest quartiles. No correlation was found between birth weight, and SBP or DBP.nnnCONCLUSIONSnIn Algerian and Italian teenagers, both male and female, current weight but not birth weight was found to be a strong determinant of BP levels.

Glomerular filtration rate estimated by Cockcroft-Gault formula better predicts anti-Xa levels than modification of the diet in renal disease equation in older patients with prophylactic enoxaparin.

OBJECTIVESnOlder people have an increased risk of low molecular weight heparin accumulation leading to an increased bleeding risk. The objective of this study was to assess whether reduced glomerular filtration rate (GFR), estimated by the Cockcroft-Gault or modification of the diet in renal disease (MDRD) equations, indicates drug accumulation by increased anti-Xa levels in older subjects receiving prophylactic enoxaparin treatment.nnnDESIGNnCohort study.nnnSETTINGnAcute geriatric units in Nancy Hospital.nnnPARTICIPANTSnNinety-two consenting consecutive patients, 65 and older, confined to bed for an acute medical condition requiring enoxaparin for prevention of venous thromboembolism, and hospitalized for at least six days were enrolled.nnnMEASUREMENTSnSerum creatinine and peak plasma anti-Xa levels 3 to 4 hours after the daily injection of enoxaparin were measured at days 3, 6, 9 and 12 (first dose of enoxaparin at day one). Analyses of variance for repeated measures were used to evaluate significant predictors of peak anti-Xa activity in univariate and multivariate analyses.nnnRESULTSnA significant correlation was observed between anti-Xa activity and GFR estimated with the Cockcroft formula r=0.43. Following univariate analysis, the three factors associated with higher anti-Xa levels were a lower Cockcroft-Gault GFR (p=0.0002), female gender (p=0.0003) and a lower bodyweight (p<.0001). No significant association between anti-Xa levels and MDRD GFR (p=0.33) was observed. Following multivariate analysis, female gender (p=0.02), bodyweight (p=0.04) and Cockcroft GFR (p=0.05) remained independent determinants of anti-Xa levels.nnnCONCLUSIONnIn hospitalized patients older than 65 years old, the Cockcroft-Gault equation, in contrast to the MDRD equation, is able to predict the risk of higher anti-Xa levels.

Influence of Thoracic Aortic Inflammation and Calcifications on Arterial Stiffness and Cardiac Function in Older Subjects.

BackgroundVascular aging is accompanied by gradual remodeling affecting both arterial and cardiac structure and mechanical properties. Hypertension is suggested to exert pro-inflammatory actions enhancing arterial stiffness.ObjectivesTo determine the influence of thoracic aortic inflammation and calcifications on arterial stiffness and cardiac function in hypertensive and normotensive older subjects.DesignA prospective study.SettingAn acute geriatrics ward of the University Hospital of Nancy in France.SubjectsThirty individuals ≥ 65 years were examined, including 15 hypertensive subjects and 15 controls well-matched for age and sex.MeasurementsApplanation tonometry was used to measure aortic pulse wave velocity (AoPWV) and carotid/brachial pulse pressure amplification (PPA). Left ventricular parameters were measured with magnetic resonance imaging. Local thoracic aortic inflammation and calcification were measured by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Biomarkers of low-grade inflammation were also quantified.ResultsAoPWV was higher in elderly hypertensive subjects comparatively to normotensive controls (15.5±5.3 vs. 11.9±2.5, p=0.046), and hypertensives had a higher calcification volume. In the overall population, calcifications of the thoracic descending aorta and inflammation of the ascending aorta accounted for respectively 18.1% (p=0.01) and 9.6% (p=0.07) of AoPWV variation. Individuals with high levels of calcifications and/or inflammation had higher AoPWV (p=0.003). Inflammation had a negative effect on PPA explaining 13.8% of its variation (p<0.05).ConclusionsThis study highlights the importance of local ascending aortic inflammation as a potential major actor in the determination of PPA while calcifications and hypertension are more linked to AoPWV. Assessment of PPA in the very elderly could provide complementary information to improve diagnostic and therapeutic strategies targeting ascending aortic inflammation.

Cross-sectional variations of white and grey matter in older hypertensive patients with subjective memory complaints

Mild cognitive impairment and Alzheimers dementia involve a grey matter disease, quantifiable by 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET), but also white matter damage, evidenced by diffusion tensor magnetic resonance imaging (DTI), which may play an additional pathogenic role. This study aimed to determine whether such DTI and PET variations are also interrelated in a high-risk population of older hypertensive patients with only subjective memory complaints (SMC). Sixty older hypertensive patients (75 ± 5 years) with SMC were referred to DTI and FDG-PET brain imaging, executive and memory tests, as well as peripheral and central blood pressure (BP) measurements. Mean apparent diffusion coefficient (ADCmean) was determined in overall white matter and correlated with the grey matter distribution of the metabolic rate of glucose (CMRGlc) using whole-brain voxel-based analyses of FDG-PET images. ADCmean was variable between individuals, ranging from 0.82 to 1.01.10− 3 mm2 sec− 1, and mainly in relation with CMRGlc of areas involved in Alzheimers disease such as internal temporal areas, posterior associative junctions, posterior cingulum but also insulo-opercular areas (global correlation coefficient: − 0.577, p < 0.001). Both the ADCmean and CMRGlc of the interrelated grey matter areas were additionally and concordantly linked to the results of executive and memory tests and to systolic central BP (all p < 0.05). Altogether, our findings show that cross-sectional variations in overall white brain matter are linked to the metabolism of Alzheimer-like cortical areas and to cognitive performance in older hypertensive patients with only subjective memory complaints. Additional relationships with central BP strengthen the hypothesis of a contributing pathogenic role of hypertension.

MRI AORTIC THORACIC ELASTIC PROPERTIES ASSESSMENT COMPARED TO ARTERIAL STIFFNESS ASSESSMENT BY TRANSCUTANEOUS DEVICES

s 165 PWV was assessed in all patients first by a fast PC cine sequence of magnetic resonance imaging (MRI) between the ascending aorta and the descending thoracic aorta under the diaphragm and second by Pulsepen and Complior II between right carotid and femoral sites. Results: Aortic MRI PWV value was 8.00 2.66 m.s-1. Complior II PWV values were significantly lower than those obtained with Pulsepen, respectively 7.88 1.38 m.s-1 vs 9.01 1.64 m.s-1, p< 0.0001. There was a good correlation between Pulsepen PWV and aortic MRI PWV (p Z 0.005, r Z 0.47) and between Complior II PWV and aortic MRI PWV (p Z 0.01, r Z 0.43). Conclusion: This is the first study to show the reliability of PWV assessment by transcutaneous devices in comparison to MRI PWV measurements in obese patients. P6.05 MRI AORTIC THORACIC ELASTIC PROPERTIES ASSESSMENT COMPARED TO ARTERIAL STIFFNESS ASSESSMENT BY TRANSCUTANEOUS DEVICES L. Joly , A. Kearney-Schwartz , P. Salvi , D. Mandry , P. Rossignol , G. Karcher , P. Y. Marie , F. Zannad , A. Benetos 1 Service de Geriatrie, CHU Nancy, Nancy, France Service de Radiologie, CHU Nancy, Nancy, France CIC, CHU Nancy, Nancy, France Service de Medecine Nucleaire, Nancy, France Background: Aortic elasticity properties (aortic distensibility, compliance, elastic modulus, and stiffness index) can be evaluated by cross-sectional thoracic aorta areas measurements at 2 times of the cardiac cycle (peak systolic and end-diastolic phases) with PC-cine MRI series. Pulse wave velocity (PWV) measurement between carotid and femoral sites is considered as the gold standard measurement of aortic stiffness and elastic properties of aorta. Obesity is a difficult feature to assess aortic elasticity properties because of methodological problems due to the use of transcutaneous devices. The aim of this study was to assess aortic elasticity properties with PC MRI and to compare the results with PWV assessed by two transcutaneous devices (Pulse pen and Complior II) in 32 consecutive patients presenting an isolated abdominal obesity defined by a waist circumference >102 cm in men and >88 cm in women (27< BMI< 35). Results: Aortic cross-sectional compliance assessed with MRI was inversely correlated with: Pulse Pen PWV (p Z 0.01, r Z -0.44), with the same trend for Complior PWV (p Z 0.07, r Z -0.32). Positive relationship was found between the above 2 PWV measurements and aortic stiffness index computed by MRI. Relationship was stronger for PWV assessed by MRI (p Z 0.02, r Z 0.41) and Pulse Pen (p Z 0.03, r Z 0.38). The relationship between aortic stiffness index and Complior PWV did not reach statistical significance (p Z 0.12, r Z 0.28). Conclusion: In clinical difficult situation like obesity, aortic elasticity can be measured by PC MRI with a good correlation with peripheral PWV assessments. P6.06 CAN WE LEARN ANYMORE ABOUT ARTERIAL FUNCTION FROM THE VALSALVA MANOEUVRE? WAVE INTENSITY ANALYSIS CAN INFORM US ABOUT RESERVOIR FUNCTION A. J. Baksi, J. E. Davies, N. Hadjiloizou, R. Baruah, B. Unsworth, R. A. Foale, K. H. Parker, D. P. Francis, J. Mayet, A. D. Hughes International Centre for Circualtory Health & Imperial College London, London, United Kingdom Background: The Valsalva manoeuvre (VM) is a physiological manoeuvre capable of generating profound changes in venous return. Although its physiology has been extensively described, the predominant focus has been on dynamic effects on cardiac preload with subsequent impact on cardiac output. However, analysis of the dramatic changes seen in arterial pressure and flow during this manoeuvre offers valuable insight into arterial function. Methods: In 11 patients (9male, mean age 64 years), invasive measurement of pressure & Doppler flow velocity were made in the proximal aorta using sensor-tipped intra-arterial wires. Whilst recording, patients performed a controlled VM by blowing into a syringe. Calculation of pressure, aortic reservoir function and wave intensity were performed offline. Results: Peak systolic blood pressure fell on average by 24% during sustained VM (157 43mmHg to 122 48mmHg, p< 0.0001). The peak reservoir pressure fell by an average of 65% (55 17mmHg to 20 13mmHg, p< 0.0001). The aortic pressure waveform during sustained VM assumes that morphology typically seen peripherally (Figure). Conclusion: Prolonged VM is able to dramatically reduce both measured pressure and reservoir pressure in the proximal aorta and appears to produce a loss of this normal ‘cushioning’ effect. Is this simply a consequence of decreased stroke volume or are there other mechanisms involved? Pressure waveform recorded invasively in proximal aorta during sustained Valsalva manoeuvre. P6.07 METHODOLOGICAL ASPECT OF BRACHIAL FLOW MEDIATED DILATION: IMPROVEMENT OF REPRODUCIBILITY F. Faita , V. Gemignani , E. Bianchini , F. Stea , M. Demi , L. Ghiadoni 2 Institute of Clinical Physiology, Pisa, Italy Department of Internal Medicine, University of Pisa, Pisa, Italy Brachial artery flow-mediated dilation (FMD) is the most widely used technique for assessing endothelial function in humans. FMD is reduced in the presence of cardiovascular risk factors and diseases and it is an independent predictor of events. However, its major limitation is the relatively low reproducibility. One of the main challenge is to maintain a stable scan plane during examinations, especially when the forearm cuff is inflated/deflated. The aim of this study was to evaluate the FMD reproducibility when resting diameter is calculated as the mean value measured from 8th to 9th minute after reactive hyperemia, when the vasodilation is concluded (BAS_POST), and to compare the results with those obtained with a standard assessment of resting diameter over 1 minute before cuff inflation (BAS_PRE). Thirty healthy subjects (age 25-45 years) underwent two FMD examinations 30 minutes apart. FMD to 5 minutes forearm ischemia was assessed by one trained operator using a clamp to hold the ultrasound probe in the same position and calculated as maximum percentage increase in diameter with respect to BAS_PRE and BAS_POST, by a real-time automatic edge-detection system (FMD Studio, Institute of Clinical Physiology, Pisa, Italy). FMD% variability was assessed as intra-session coefficients of variation (CV). Diameter was 3.56 + 0.66 mm in BAS_PRE and 3.57 + 0.66 mm in the BAS_POST. FMD% was 7.4 + 3.8% with BAS_PRE and 7.1 + 3.7% with BAS_POST. CV of FMD% was 15.61 + 10.9% in BAS PRE and 9.22 + 5.93% with BAS_POST calculation. These results suggest that FMD% calculated with BAS_POST can ensure a more reproducible measure of conduit artery endothelial function.