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Plasma levels of the arterial wall protein fibulin-1 are associated with carotid-femoral pulse wave velocity: a cross-sectional study.

ABSTRACT: The arterial system in diabetic patients is characterized by generalized non-atherosclerotic alterations in the vascular extracellular matrix causing increased arterial stiffness compared with subjects without diabetes. The underlying pathophysiology remains elusive. The elastin-associated extracellular matrix protein, fibulin-1, was recently found in higher concentrations in the arterial wall and in plasma in patients with long duration type 2 diabetes. Furthermore, plasma fibulin-1 independently predicted total mortality and was associated with pulse pressure, an indirect measure of arterial stiffness. Whether plasma fibulin-1 is associated with arterial stiffness at earlier phases of type 2 diabetes has not been determined.In this cross-sectional study, we examined 90 patients with recently diagnosed type 2 diabetes (< 5 years) and 90 gender- and age-matched controls. Plasma fibulin-1 was measured immunochemically. Arterial stiffness was assessed by carotid-femoral Pulse Wave Velocity (PWV). Differences in means were assessed by t-tests. Associations were assessed by multivariate regression analyses.Plasma fibulin-1 levels were lower in the diabetic group compared with the control group, 93?±?28 vs 106?±?30 ?g/mL, p?=?0.005. In unadjusted analysis of the total study sample, plasma fibulin-1 was not associated with PWV, p?=?0.46. However, with adjustment for the confounders age, gender, mean blood pressure, heart rate, body mass index, diabetes and glomerular filtration rate, a 10 ?g/mL increase in plasma fibulin was associated with 0.09?±?0.04 m/s increase in PWV, p?

SUBMITTER: Laugesen E

PROVIDER: S-EPMC3722025 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Plasma levels of the arterial wall protein fibulin-1 are associated with carotid-femoral pulse wave velocity: a cross-sectional study.

Laugesen Esben E Høyem Pernille P Christiansen Jens Sandahl JS Knudsen Søren Tang ST Hansen Klavs Würgler KW Argraves W Scott WS Hansen Troels Krarup TK Poulsen Per Løgstrup PL Rasmussen Lars Melholt LM

Cardiovascular diabetology 20130718

<h4>Background</h4>The arterial system in diabetic patients is characterized by generalized non-atherosclerotic alterations in the vascular extracellular matrix causing increased arterial stiffness compared with subjects without diabetes. The underlying pathophysiology remains elusive. The elastin-associated extracellular matrix protein, fibulin-1, was recently found in higher concentrations in the arterial wall and in plasma in patients with long duration type 2 diabetes. Furthermore, plasma fi ...[more]

PMID: 23866070

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Project description:BACKGROUND:In end-stage renal disease (ESRD) patients, increased arterial stiffness detected by carotid-femoral pulse wave velocity (cf-PWV) is associated with fatal cardiovascular events and all-cause mortality. Since cf-PWV is an operator-dependent technique, poor reproducibility may be a source of bias in the estimation of arterial stiffness. OBJECTIVES:We assessed the week-to-week reproducibility of cf-PWV and radial artery pulse wave analysis in healthy subjects and ESRD patients. We also determined the extent of patient eligibility, enrollment, acceptance, and comfort. METHODS:In a cohort study design, independent tonometric examinations of carotid, femoral, and radial arteries were conducted in 20 healthy subjects and 15 ESRD patients attending chronic hemodialysis treatments according to a randomized sequence by two operators on 2 days scheduled 1-week apart. cf-PWV, augmentation index (AIx@HR75) and central pulse pressure (CPP) were the outcome measures. Patients were tested at mid-week and prior to dialysis treatment. The variability on the distance measured between the suprasternal notch and femoral site using two different methods (standard vs direct) was compared. A post-examination survey assessed acceptance and comfort associated with examinations. Reproducibility was evaluated by intra-class correlations (ICCs). RESULTS:The mean age for healthy subjects and ESRD patients was 45?±?12 and 63?±?16 years, respectively. ESRD patients had higher cf-PWV (p?=?0.0002), elevated AIx@HR75 (p?=?0.003), and increased CPP (p?=?0.001) compared to healthy subjects. The mean inter-visit differences for all stiffness indices were non-significant (p?>?0.05), but the mean inter-operator differences for the cf-PWV were significant only in the healthy subject group (-0.7 m/s; p?=?0.02). The ICCs between operators and visits were higher for the ESRD group compared to the healthy subjects (between operators, 0.870 vs 0.461; between visits, 0.830 vs 0.570). Distances were longer (p?<?0.001), but less variable with the standard method compared to the direct method (healthy subjects, p?=?0.036; ESRD, p?=?0.39). There was a high rate of patient acceptance and minimal discomfort. CONCLUSIONS:Week-to-week measurements of cf-PWV and pulse wave analysis are highly reproducible in ESRD patients prior to hemodialysis treatment. The high reproducibility and minimal test-to-test variations encourage use of cf-PWV to monitor changes in arterial stiffness and the efficacy of interventions in ESRD patients. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02196610.

Dataset Information

Plasma levels of the arterial wall protein fibulin-1 are associated with carotid-femoral pulse wave velocity: a cross-sectional study.

Publications

Plasma levels of the arterial wall protein fibulin-1 are associated with carotid-femoral pulse wave velocity: a cross-sectional study.

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