Suchergebnisse

Background-Experimental studies have demonstrated that lead and cadmium have direct toxic effects on the myocardium, but the few human studies are limited by design, assessment of exposure, and use of heart failure as a late-stage endpoint. Methods and Results-In a prospective population study, we studied the association of left ventricular (LV) function with blood lead (BPb) and 24-hour urinary cadmium (UCd). In 179 participants randomly recruited from a Flemish population (50.3% women; mean age 39.1 years), geometric mean BPb and UCd at enrollment (1985-2000) were 0.20 mu mol/L and 6.1 nmol, respectively. We assessed systolic and diastolic LV function 11.9 years (median) later (2005-2010) by using Doppler imaging of the transmitral blood flow and the mitral annular movement and speckle tracking. In multivariable-adjusted linear regression, LV systolic function decreased with BPb. For a doubling of exposure, estimates were -0.392% for global longitudinal strain (P=0.034), -0.618% and -0.113 s (1) for regional longitudinal strain (P=0.028)and strain rate (P=0.008), and -0.056 s (1) for regional radial strain rate (P=0.050). Regional longitudinal strain rate (-0.066 s (1), P=0.009)and regional radial strain (-2.848%, P=0.015) also decreased with UCd. Models including both exposure indexes did not allow differentiating whether LV dysfunction was predominately related to BPb or UCd. Diastolic LV function was not associated with BPb or UCd (P=0.159). Conclusions-Although effect sizes were small, our results suggest that environmental exposure to lead, cadmium, or both might be a risk factor for systolic LV dysfunction, a condition often proceeding to heart failure. ; European Union [HEALTH-FP7-278249-EUMAS-CARA, HEALTH-F7-305507 HOMAGE]; European Union (European Research Council) [2011-294713-EPLORE]; European Union (Proof-of-Concept Grant) [713601-uPRO-PHET]; Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium [G.0881.13, G.0880.13]

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-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.