Cédric Collin

Arterial Remodeling Associates with CKD Progression

In CKD, large arteries remodel and become increasingly stiff. The greater pulsatile pressure reaching the glomerulus as a result of increased aortic stiffness could induce renal damage, suggesting that the stiffening and remodeling of large arteries could affect the progression of CKD. We measured carotid-femoral pulse wave velocity, aortic pressure and carotid remodeling and stiffness parameters in 180 patients with CKD (mean measured GFR, 32 ml/min per 1.73 m(2)) and followed them prospectively for a mean of 3.1 years. During follow-up, carotid stiffness significantly increased (+0.28 ± 0.05 m/s; P<0.0001) but aortic stiffness did not. Carotid intima-media thickness decreased significantly during follow-up and the internal diameter of the carotid increased, producing increased circumferential wall stress (+2.08 ± 0.43 kPa/yr; P<0.0001). In a linear mixed model, circumferential wall stress significantly associated with faster GFR decline after adjustment for risk factors of cardiovascular disease and progression of CKD. In a multivariable Cox model, carotid circumferential wall stress and pulse pressure independently associated with higher risk for ESRD. None of the arterial stiffness parameters associated with progression of CKD. In conclusion, maladaptive remodeling of the carotid artery and increased pulse pressure independently associate with faster decline of renal function and progression to ESRD.

Endothelial Function and Chronic Exposure to Air Pollution in Normal Male Subjects

Exposure to urban air pollution, ultrafine particles or gases, is associated with acute cardiovascular mortality and morbidity. We investigated the effect of ambient air pollution on endothelial function in 40 healthy white male nonsmokers spontaneously breathing ambient air in Paris, France. Air pollutant levels (nitrogen, sulfur and carbon oxides, and particulate matter) were averaged during the 5 days preceding arterial measurements. Brachial artery endothelium-dependent flow-mediated dilatation and reactive hyperemia induced by hand ischemia and endothelium-independent glyceryl trinitrate dilatation were measured using a radiofrequency-based echo-tracking device at 2-week intervals. Flow-mediated dilatation was independently and negatively correlated with the average levels of sulfur dioxide (P<0.001) and nitrogen monoxide (P<0.01). Sulfur dioxide levels explained 19% of the variance of flow-mediated dilatation. An increase in gaseous pollutants, 2 weeks apart, was significantly associated with a decreased in flow-mediated dilatation. No association was found between air pollutants and glyceryl trinitrate–induced vasodilatation. Reactive hyperemia was significantly and positively correlated with particulate matter with aerodynamic diameters <10 &mgr;m and <2.5 &mgr;m (P<0.0001 and P<0.001, respectively) and nitrogen dioxide (P<0.01). An increase in particulate matter, 2 weeks apart, was significantly correlated with an increase in reactive hyperemia. Endothelial function was impaired by ordinary levels of pollution in healthy young males, in an urban area, and may be reduced by 50% between the least and the most polluted day. Gaseous pollutants affect large artery endothelial function, whereas particulate matter exaggerates the dilatory response of small arteries to ischemia.

Long-term reduction in aortic stiffness: a 5.3-year follow-up in routine clinical practice.

Background Whether a direct blood pressure-independent reduction in aortic stiffness can occur after several years of antihypertensive treatment has never been unequivocally demonstrated. Method In this observational study, performed under conditions of routine clinical practice, we included 97 patients (age 63 ± 11 years) with treated essential hypertension who attended the outpatient hypertension clinic of a university hospital, had a significant blood pressure (BP) lowering under treatment before the first measurement of aortic stiffness, and had at least one additional measurement of aortic stiffness during follow-up. Aortic stiffness and carotid pulse pressure (PP) were determined through carotid–femoral pulse wave velocity (PWV) and applanation tonometry, respectively. Results A linear mixed model showed that the reduction in PWV (from 14.2 ± 4.2 to 11.0 ± 2.4 m/s; P < 0.0001) over a long follow-up (mean delay 5.3 ± 1.3 years) was associated with a significant reduction in central SBP (from 132 ± 22 to 122 ± 16 mmHg; P < 0.0001) and central PP (from 59 ± 22 to 54 ± 14; P < 0.001), contrasting with a smaller change in brachial SBP (from 132 ± 17 to 129 ± 16 mmHg; P < 0.02) and no change in brachial PP. In multivariate analysis, the decrease in PWV (−0.70 ± 0.07 m/s per year; P < 0.0001) was only slightly explained by the reduction in mean blood pressure. By contrast, the decrease in central PP (−0.83 ± 0.41 mmHg per year; P = 0.043) was largely explained by the reduction in PWV. Conclusion These results indicate that a large and sustained decrease in aortic stiffness can be obtained in treated hypertensive patients under conditions of routine clinical practice. These changes likely represent a delayed response to the long-term normalization of BP and cardiovascular risk factors, through arterial remodeling.

Carotid Plaque, Arterial Stiffness Gradient, and Remodeling in Hypertension

The analysis of plaque mechanics along the longitudinal axis (bending strain) may provide useful information because repetitive bending strain of an atherosclerotic plaque can fatigue the wall material and result in plaque rupture. Whether essential hypertension is associated with a specific pattern of bending strain has not yet been determined. The study included 92 patients with an atherosclerotic plaque on the common carotid artery: 66 patients with essential hypertension, either treated or not, and 26 normotensive patients. A novel noninvasive echotracking system (ArtLab; Esaote, The Netherlands) was used to measure intima-media thickness, diameter, and distensibility at 128 sites on a 4-cm-long carotid segment. Carotid plaque was either less elastic than adjacent carotid artery (inward strain) or more elastic (outward strain). Inward strain was more frequently associated with an inward plaque remodeling, whereas an outward strain was more frequently associated with an outer remodeling. In multivariate logistic regression analysis, patients with essential hypertension were more likely to exhibit an inward strain of carotid plaque (odds ratio=6.9 [1.4 to 34.9]; P<0.02), independently of 2 factors favoring inward strain: an outer remodeling (odds ratio=4.6 [1.7 to 13.4]; P<0.005) and the absence of renin-angiotensin system blockers (odds ratio=4.8 [1.1 to 20.4]; P<0.05). In conclusion, arterial wall material of hypertensive patients was less elastic at the site of the plaque than upstream, and carotid was inwardly strained in the zone affected by plaque. This may generate a high level of stress concentrations and fatigue, exposing the plaque to a greater risk of rupture.

Association of central and peripheral pulse pressure with intermediate cardiovascular phenoytpes

Objective We assessed the relationship between pulse pressure and intermediate cardiovascular phenotypes in a middle-aged cohort with high prevalence of hypertension. Background It has been suggested that central pulse pressure (cPP) is a better predictor of cardiovascular outcome than peripheral pulse pressure (pPP), particularly in the elderly. Yet, it is unclear if cPP provides additional prognostic information to pPP in younger individuals. Methods In 535 individuals we assessed cPP and pPP as well as the intermediate cardiovascular phenotypes pulse wave velocity (PWV; SphygmoCor, Complior, PulsePen), carotid intima-media thickness (C-IMT; carotid ultrasound), left-ventricular mass index (LVMI; echocardiography) and urinary albumin : creatinine ratio (ACR). cPP was derived noninvasively from brachial blood pressure by pulse wave analysis (PWA; SphygmoCor) based on radial pulse wave tonometry and a validated transfer function. Results The cohort contained 331 hypertensive participants of whom 84% were treated. The average age was 46 ± 16 years. When compared to pPP, cPP had stronger associations with PWV (r = 0.471 vs. r = 0.372; P < 0.01), C-IMT (r = 0.426 vs. r = 0.235; P < 0.01) and LVMI (r = 0.385 vs. r = 0.189; P < 0.01), but equal association with ACR (r = 0.236 vs. r = 0.226; P = n.s.). In contrast, after adjustment for age, mean arterial pressure, heart rate and hypertension status there was no significant difference between cPP and pPP for prediction of PWV (adjusted R2, 0.399 vs. 0.413; P = 0.066), C-IMT (adjusted R2, 0.399 vs. 0.413; P = 0.487) and LVMI (adjusted R2, 0.181 vs. 0.170; P = 0.094) in multivariate analysis. Conclusion In our middle-aged cohort with high prevalence of hypertension cPP is more closely correlated with cardiovascular phenotypes than pPP. When adjusted for relevant cofactors, however, cPP does not provide additional information beyond pPP.

Long-term changes in arterial structure and function and left ventricular geometry after enzyme replacement therapy in patients affected with Fabry disease

Aims: Fabry disease is a lysosomal storage disorder due to deficient alpha-galactosidase A activity, characterised by glycosphingolipids deposition in tissues. Patients have a common arterial involvement and contract progressive renal and cardiac disease. Although short-term effects of enzyme replacement therapy (ERT) on target organs have been established, no data are available on the long-term outcome. Methods and results: We studied the effects of ERT (agalsidase beta, 1 mg/kg/14 days) on arterial and cardiac structure and function during a longitudinal study beginning in 1999, with 4.5 ± 0.4 years follow-up (four visits) in 30 patients (age: 33 ± 12 years). In addition, we studied 16 untreated Fabry patients during 2.6 ± 1.6 years (two visits). Aortic stiffness was determined by carotid-femoral pulse wave velocity, central pulse pressure by aplanation tonometry, and carotid and radial intima-media thickness and diameter by high definition echotracking device. Left ventricular mass was determined by MRI. A significant decrease in aortic stiffness (−0.56 ± 0.13 m/s/yr, p = 0.0002) was observed after ERT whereas central pulse pressure did not change. Carotid intima-media thickness (IMT) increased (+18 ± 6 µm/yr; p < 0.005) whereas radial IMT remained stable. Radial artery diameter decreased (−50 ± 20 µm/years, p < 0.05) whereas carotid diameter did not change. Carotid circumferential wall stress was reduced (−1.7 ± 0.6 kPa/yrs, p < 0.01). Left ventricular mass index significantly decreased (−7.8 ± 2.3 g/m2/yr, p < 0.005). Conclusion: A sustained reduction in aortic stiffness and left ventricular hypertrophy, and a limited radial artery wall thickening were observed after long-term enzyme replacement therapy. There was no significant benefit of treatment on carotid hypertrophy.

Age-independent association between arterial and bone remodeling in mild-to-moderate chronic kidney disease

BACKGROUND Damages to large arteries are related to bone disease in end-stage renal disease and contribute to cardiovascular mortality. An outward remodeling and stiffening of carotid artery already exist at an earlier stage of chronic kidney disease (CKD). We made the hypothesis that bone disease could be associated with the carotid outward remodeling in parallel with the decline of renal function in this population. METHODS One hundred and seven patients (60.4 +/- 14.6 years) with CKD (mean glomerular filtration rate = 34 +/- 17 mL/min/1.73 m(2)) were included in this cross-sectional study. Common carotid artery diameter, intima-media thickness and carotid stiffness were determined with an echotracking system. Bone evaluation was performed by bone densitometry and the measurement of a bone-remodeling marker, bone-specific alkaline phosphatase (BSALP). RESULTS After adjustment for age, sex, mean blood pressure, carotid pulse pressure and glomerular filtration rate, bone mineral densities measured at the radius, hip and lumbar spine were significantly and negatively correlated with carotid internal diameter (P = 0.0001, P = 0.0003, P = 0.01, respectively). This association exists only in patients with glomerular filtration rate < or =38 mL/min/ 1.73 m(2). BSALP was independently and positively correlated with carotid internal diameter and explained 13% of the variance. CONCLUSIONS Bone mineral density and serum marker of bone remodeling are independently correlated with arterial remodeling in CKD patients suggesting a crosstalk between kidney, arterial wall and bone.

Aortic arch stiffness in Fabry disease

Results Aortic arch PWV was significantly increased in FD patients (6.5±3.1vs 5.0 ±1.5 m/s, p<0.01) Compared to control subjects, patients with FD had also markedly decreased distensibility (2.73±1.14 vs 3.45±1.13 10-2 kPa-1, p<0.01) and increased stiffness index beta (9.4 ±6.7.10-2 vs 5.9±2.7.10-2, p<0.001) in the ascending aorta. Descending aortic stiffness parameters were also impaired with a trend for decreased distensibility (2.26±1.15 vs 3.15 ±1.0 10-2 kPa-1, P=0.06) and significant increased for b-index stiffness (8.5 ±3.9 .10-2 vs 2.9±0.9.10-2, p<0.0001).

Ascending aorta dilatation common feature which correlate with left ventricular hypertrophy in fabry disease

Methods and results Fourty-four adult males with FD (age: 38.1±11.3 years) and 44 healthy male controls matched for age were included. The diameters of the ascending and descending aorta were measured by magnetic resonance imaging (MRI) at the level of the sinuses of Valsalva, sinotubular jonction, tubular portion, aortic arch and descending aorta. Cardiac geometry and properties were also assessed by MRI. Dilatation of the ascending aorta was found in 40.9% of the patients with FD and was predominantly located at the sinuses of Valsalva (38.2±4.6 vs. 32.4 ±3.1 mm, P<0.0001). The dilatation was associated with increased left ventricular mass (LVM), independently of age and presence of hypertension. In multivariate analysis, LVM was the main determinant of the sinus diameter (R=13.6%, P<0.05). When assessing the regional remodelling of the ascending aorta by a mean diameter estimated at three different levels, both LVM (R=30.4%, P=0.0001) and renal failure (R=7.3%, P=0.0297) were independently associated with aortic dilatation.

ELEVATED AORTIC PULSE WAVE VELOCITY IS ASSOCIATED WITH A HIGHER RISK OF EXTEND PERIVENTRICULAR WHITE MATTER LESIONS IN ELDER MALES: 3B.04

Purpose: White matter lesions (WMLs) are detected on brain MRI of elderly people and are suggested to be predictive of stroke and cognitive decline. Arterial stiffness is a major cause of systolic hypertension and of increase in central pulse pressure and might predict cardiovascular events. This study aimed to examine the relationships between arterial stiffness parameters and WMLs severity in a large noninstitutionalized French cohort. Methods: In a sample of 931 subjects belonging to 3C-Dijon study, vascular and brain MRI measurements were performed. WMLs were detected and measured, using automated software from which total, periventricular and deep WMLs volumes were estimated. Central systolic blood pressure (SBP) and aortic stiffness (carotid-to-femoral Pulse Wave Velocity, PWV) were assessed by tonometry using Shygmocor® device (Atcor, Australia). Due differences in vascular profile, all analyses were performed stratified by gender. Associations between tertiles of WMLs and Central SBP and PWV were studied using multivariate polytomic logistic regression. Results: 349 males and 582 females (respectively 75.0 ± 3.7 and 75.4 ± 3.8yrs) were included. Males had higher cardiovascular risk factors: hypertension (69.3% vs. 61.5 for females, P < 0.0005) and diabetes (11.8 vs. 5.5% for females, P < 0.001). Mean Total WMLs volumes were similar between males and females (5.8 ± 0.2 vs. 5.6 ± 0.2 mm3, NS) but PWV was higher in males (15.2 ± 3.3 vs. 14.3 ± 3.1 m/s in females). In multivariable analyses adjusted for age, total brain volume, MBP, heart rate and diabetes, aortic stiffness was significantly related to higher periventricular WMLs volume only in males (odds ratio of being in 3rd tertile of WML volume [per 1 SD increase in PWV]: 1.48; 95% CI: 1.10 to 2.02; P < 0.05) but not in females (OR: 1.04, P = 0.71). In contrast, in females, a higher central SBP was significantly associated with a greater volume of deep WMLs (OR: 1.27; P < 0.05) but not in males (OR: 0.94, P = 0.44). Conclusion: These data suggest that the relationships between aortic stiffness, central systolic blood pressure and white matter lesions might differ by gender.