Suchergebnisse

Background Stiffening and calcification of the large arteries are forerunners of cardiovascular complications. MGP (Matrix Gla protein), which requires vitamin K–dependent activation, is a potent locally acting inhibitor of arterial calcification. We hypothesized that the central hemodynamic properties might be associated with inactive desphospho‐uncarboxylated MGP (dp‐ucMGP). Methods and Results In 835 randomly recruited Flemish individuals (mean age, 49.7 years; 45.6% women), we measured plasma dp‐ucMGP, using an ELISA‐based assay. We derived central pulse pressure and carotid‐femoral pulse wave velocity (PWV) from applanation tonometry and calculated forward and backward pulse waves using an automated, pressure‐based wave separation analysis algorithm. Aortic PWV (n=657), central pulse pressure, forward pulse wave, and backward pulse wave mean±SD values were 7.34±1.64 m/s, 45.2±15.3 mm Hg, 33.2±10.2 mm Hg, and 21.8±8.6 mm Hg, respectively. The geometric mean plasma concentration of dp‐ucMGP was 4.09 μg/L. All hemodynamic indexes increased across tertiles of dp‐ucMGP distribution. In multivariable‐adjusted analyses, a doubling of dp‐ucMGP was associated with higher PWV (0.15 m/s; 95% CI, 0.01–0.28 m/s), central pulse pressure (1.70 mm Hg; 95% CI, 0.49–2.91 mm Hg), forward pulse wave (0.93 mm Hg; 95% CI, 0.01–1.84 mm Hg), and backward pulse wave (0.71 mm Hg; 95% CI, 0.11–1.30 mm Hg). Categorization of aortic PWV by tertiles of its distribution highlighted a decreasing trend of PWV at low dp‐ucMGP (<3.35 μg/L) and an increasing trend at high dp‐ucMGP (≥5.31 μg/L). Conclusions In people representative for the general population, higher inactive dp‐ucMGP was associated with greater PWV, central pulse pressure, forward pulse wave, and backward pulse wave. These observations highlight new avenues for preserving vascular integrity and preventing cardiovascular complications (eg, by improving a person's vitamin K status). ; This work was supported by the European Union (HEALTH‐F7‐305507‐HOMAGE), the European Research Council (Advanced Researcher Grant 2011‐294713‐EPLORE and Proof‐of‐Concept Grant 713601‐uPROPHET), and the European Research Area Net for Cardiovascular Diseases (JTC2017‐046‐PROACT); and the Research Foundation Flanders, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13 and 11Z0916N), supported the Studies Coordinating Center in Leuven, Belgium.

Background: Aortic pulse wave velocity (aPWV) predicts cardiovascular complications, but the association of central arterial properties with blood lead level (BL) is poorly documented. We therefore assessed their association with BL in 150 young men prior to occupational lead exposure, using baseline data of the Study for Promotion of Health in Recycling Lead (NCT02243904). Methods: Study nurses administered validated questionnaires and performed clinical measurements. Venous blood samples were obtained after 8-12h of fasting. The radial, carotid and femoral pulse waves were tonometrically recorded. We accounted for ethnicity, age, anthropometric characteristics, mean arterial pressure, heart rate, smoking and drinking, and total and high-density lipoprotein serum cholesterol, as appropriate. Results: Mean values were 4.14 mu g/dL for BL, 27 years for age, 108/79/28 mm Hg for central systolic/diastolic/pulse pressure, 100/10% for the augmentation ratio/index, 1.63 for pressure amplification, 5.94 m/s for a PWV, 27/11 mm Hg for the forward/backward pulse pressure height, and 43% for the reflection index. Per 10-fold BL increase, central diastolic pressure and the augmentation ratio were respectively 5.37 mm Hg (95% confidence interval [CI], 1.00-9.75) and 1.57 (CI, 0.20-2.94) greater, whereas central pulse pressure and the forward pulse pressure height were 3.74 mm Hg (CI, 0.60-6.88) and 3.37mm Hg (CI, 0.22-6.53) smaller (p <=.036 for all). The other hemodynamic measurements were unrelated to BL. The reflected pulse peak time was inversely correlated with diastolic pressure (r = -0.20; p <= .017). Conclusion: At the exposure levels observed in our current study, aPWV, the gold standard to assess arterial stiffness, was not associated with BL. Increased peripheral arterial resistance, as reflected by higher diastolic pressure, might bring reflection points closer to the heart, thereby moving the backward wave into systole and increasing the augmentation ratio in relation to BL. ; The European Union [HEALTH-F7-305507 HOMAGE] and the European Research Council [Advanced Researcher Grant 2011-294713-EPLORE and Proof-of-Concept Grant 713601-uPROPHET], the European Research Area Net for Cardiovascular Diseases [JTC2017-046-PROACT], and the Research Foundation Flanders, Ministry of the Flemish Community, Brussels, Belgium [G.0881.13] currently support the Research Unit Hypertension and Cardiovascular Research. An unrestricted grant from the International Lead Association (www.ila-lead.org) partially supports the data collection and analysis of the current data. The sponsors had no role in the preparation of this report.

Background-Stiffening and calcification of the large arteries are forerunners of cardiovascular complications. MGP (Matrix Gla protein), which requires vitamin K-dependent activation, is a potent locally acting inhibitor of arterial calcification. We hypothesized that the central hemodynamic properties might be associated with inactive desphospho-uncarboxylated MGP (dp-ucMGP). Methods and Results-In 835 randomly recruited Flemish individuals (mean age, 49.7 years; 45.6% women), we measured plasma dp-ucMGP, using an ELISA-based assay. We derived central pulse pressure and carotid-femoral pulse wave velocity (PWV) from applanation tonometry and calculated forward and backward pulse waves using an automated, pressure-based wave separation analysis algorithm. Aortic PWV (n 657), central pulse pressure, forward pulse wave, and backward pulse wave mean +/- SD values were 7.34 +/- 1.64 m/s, 45.2 +/- 15.3 mm Hg, 33.2 +/- 10.2 mm Hg, and 21.8 +/- 8.6 mm Hg, respectively. The geometric mean plasma concentration of dp-ucMGP was 4.09 mu g/L. All hemodynamic indexes increased across tertiles of dp-ucMGP distribution. In multivariable-adjusted analyses, a doubling of dp-ucMGP was associated with higher PWV (0.15 m/s; 95% CI, 0.01-0.28 m/s), central pulse pressure (1.70 mm Hg; 95% CI, 0.49-2.91 mm Hg), forward pulse wave (0.93 mm Hg; 95% CI, 0.01-1.84 mm Hg), and backward pulse wave (0.71 mm Hg; 95% CI, 0.11-1.30 mm Hg). Categorization of aortic PWV by tertiles of its distribution highlighted a decreasing trend of PWV at low dp-ucMGP (= 5.31 mu g/L). Conclusions-In people representative for the general population, higher inactive dp-ucMGP was associated with greater PWV, central pulse pressure, forward pulse wave, and backward pulse wave. These observations highlight new avenues for preserving vascular integrity and preventing cardiovascular complications (eg, by improving a person's vitamin K status). ; This work was supported by the European Union (HEALTH-F7-305507-HOMAGE), the European Research Council (Advanced Researcher Grant 2011-294713-EPLORE and Proof-of-Concept Grant 713601-uPROPHET), and the European Research Area Net for Cardiovascular Diseases (JTC2017-046-PROACT); and the Research Foundation Flanders, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13 and 11Z0916N), supported the Studies Coordinating Center in Leuven, Belgium.

Purpose: Arterial stiffness predicts cardiovascular complications. The association between arterial stiffness and blood lead (BL) remains poorly documented. We aimed to assess the association of central hemodynamic measurements, including pulse wave velocity (aPWV), with blood lead in a Flemish population. Materials and Methods: In this Flemish population study (mean age, 37.0 years; 48.3% women), 267 participants had their whole BL and 24-h urinary cadmium (UCd) measured by electrothermal atomic absorption spectrometry in 1985-2005. After 9.4 years (median), they underwent applanation tonometry to estimate central pulse pressure (cPP), the augmentation index (AI), pressure amplification (PA), and aPWV. The amplitudes of the forward (Pf) and backward (Pb) pulse waves and reflection index (RI) were derived by a pressure-based wave separation algorithm. Results: BL averaged 2.93 mu g/dL (interquartile range, 1.80-4.70) and UCd 4.79 mu g (2.91-7.85). Mean values were 45.0 +/- 15.2 mm Hg for cPP, 24.4 +/- 12.4% for AI, 1.34 +/- 0.21 for PA, 7.65 +/- 1.74 m/s for aPWV, 32.7 +/- 9.9 mm Hg for Pf, 21.8 +/- 8.4 mm Hg for Pb, and 66.9 +/- 18.4% for RI. The multivariable-adjusted association sizes for a 2-fold higher BL were: +3.03% (95% confidence interval, 1.56, 4.50) for AI; -0.06 (-0.08, -0.04) for PA; 1.02 mm Hg (0.02, 2.02) for Pb; and 3.98% (1.71, 6.24) for RI (p <= .045). In 206 participants never on antihypertensive drug treatment, association sizes were +2.59 mm Hg (0.39, 4.79) for cPP and +0.26 m/s (0.03, 0.50) for aPWV. Analyses adjusted for co-exposure to cadmium were consistent. Conclusion: In conclusion, low-level environmental lead exposure possibly contributes to arterial stiffening and wave reflection from peripheral sites. ; The European Union [HEALTH-F7-305507 HOMAGE] and the European Research Council [Advanced Researcher Grant 2011-294713-EPLORE and Proof-of-Concept Grant 713601-uPROPHET], the European Research Area Net for Cardiovascular Diseases [JTC2017-046-PROACT], and the Research Foundation Flanders, Ministry of the Flemish Community, Brussels, Belgium [G.0881.13] supported the Research Unit Hypertension and Cardiovascular Research. ; Staessen, JA (reprint author), Univ Leuven, Studies Coordinating Ctr, KU Leuven Dept Cardiovasc Sci, Res Unit Hypertens & Cardiovasc Epidemiol, Campus Sint Rafael,Kapucijnenvoer 35,Box 7001, BE-3000 Leuven, Belgium jan.staessen@med.kuleuven.be