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 The heart ejects in the central elastic arteries. No previous study in workers described the diurnal profile of central blood pressure (BP) or addressed the question whether electrocardiogram (ECG) indexes are more closely associated with central than peripheral BP. METHODS In 177 men (mean age, 29.1 years), we compared the associations of ECG indexes with brachial and central ambulatory BP, measured over 24 hours by the validated oscillometric Mobil-O-Graph 24h PWA monitor. RESULTS From wakefulness to sleep, as documented by diaries, systolic/diastolic BP decreased by 11.7/13.1 mm Hg peripherally and 9.3/13.6 mm Hg centrally, whereas central pulse pressure (PP) increased by 4.3 mm Hg (P < 0.0001). Over 24 hours and the awake and asleep periods, the peripheral-minus-central differences in systolic/diastolic BPs averaged 11.8/-1.6, 12.7/-1.8, and 10.3/-1.2 mm Hg, respectively (P < 0.0001). Cornell voltage and index averaged 1.18 mV and 114.8 mV.ms. Per 1-SD increment in systolic/diastolic BP, the Cornell voltages were 0.104/0.086 mV and 0.082/0.105 mV higher in relation to brachial 24-hour and asleep BP and 0.088/0.90 mV and 0.087/0.107 mV higher in relation to central BP. The corresponding estimates for the Cornell indexes were 9.6/8.6 and 8.2/10.5 mV.ms peripherally and 8.6/8.9 and 8.8/10.7 mV.ms centrally. The regression slopes (P = 0.067) and correlation coefficients (P = 0.088) were similar for brachial and central BP. Associations of ECG measurements with awake BP and PP were not significant. CONCLUSIONS Peripheral and central BPs run in parallel throughout the day and are similarly associated with the Cornell voltage and index. ; The authors acknowledge the expert clerical assistance of Vera De Leebeeck, Yvette Piccart, and Renilde Wolfs. ILZRO supports SPHERL by an unrestricted research grant. 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) and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13) currently support the Studies Coordinating Centre in Leuven.

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.

Background-The metabolic signature associated with subclinical diastolic left ventricular (LV) dysfunction in the population remains ill defined. Methods and Results-In 711 randomly recruited Flemish (50.8% women; mean age, 50.8 years), we assessed echocardiographic Doppler indexes of diastolic LV function in relation to 44 circulating metabolites determined by nuclear magnetic resonance spectroscopy. In multivariable-adjusted regression analysis with Bonferroni correction of significance levels applied, peak a' decreased (P <= 0.048) and e'/a' increased (P <= 0.044) with circulating tyrosine, high-density lipoprotein apolipoproteins, glucose+glutamine, and an unidentified molecule. Effect sizes expressed per 1-SD increment in the metabolite ranged from -0.277 to -0.203 cm/s for peak a' and from +0.047 to +0.054 for e'/a'. In addition, peak a' decreased (P <= 0.031) with glucose+2-aminobutyrate (-0.261 cm/s) and glucose+2-phosphoglycerate (-0.209 cm/s). In partial least square discriminant analysis (PLS-DA), metabolites associated with normal diastolic LV function (n=538) included glucose+glutamine, glucose+2-aminobutyrate, and glucose+2-phosphoglycerate, whereas those siding with abnormal function encompassed 4-aminobutyrate, 4-hydroxybutyrate, creatinine, and phosphocholine. In receiver operating characteristics plots, adding 3 latent factors identified by PLS-DA to prohormone brain natriuretic peptide increased (P<0.0001) the area under the curve from 0.64 (95% CI, 0.58-0.68) to 0.73 (0.68-0.78). Conclusions-In a general population, circulating metabolites indicative of energy substrate utilization and protection against oxidative stress differentiated normal from abnormal diastolic LV function. These findings improve our understanding of the pathophysiology underlying deterioration of diastolic LV function and potentially point to new targets for prevention and treatment of this condition. ; The European Union (grants HEALTH-2011.2.4.2-2-EU-MASCARA, HEALTH-F7-305507 HOMAGE, and the European Research Council Advanced Researcher Grant-2011-294713-EPLORE) gave support to the Studies Coordinating Centre (Leuven, Belgium). The Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community (Brussels, Belgium; G.0881.13, G.0880.13, and 11Z0916N) also supported the FLEMENGHO study.

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

This project has received funding from the Covid-19-Fund KU Leuven / University Hospitals Leuven, the COVID-19 call of the Research Foundation - Flanders (FWO) (grant G0G4820N), the European Union's Horizon 2020 research and innovation program (Grant 101,003,627, Swift COronavirus therapeutics REsponse project) and the Bill and Melinda Gates Foundation (Grant INV-00,636). LLi is member of the Institute of Tropical Medicine's Outbreak Research Team which is financially supported by the Department of Economy, Science and Innovation (EWI) of the Flemish government. BV is supported by a research grant of the Frans Van de Werf Fund for Clinical Cardiovascular Research. P. Verhamme, TV, P. Vermeersch are senior clinical investigators of the FWO. We thank Johnson & Johnson for determining drug concentrations in hamster samples and for providing. guidance on the dosing. We thank Lindsey Bervoets, Carolien De Keyzer, Elke Maas and Jasper Rymentants for the technical support with the animal experiments. TNDD is funded by the Horizon 2020 grant OrganoVIR 812,673 on the project 'Organoids for Virus Research - An innovative training-ITN programme'. XW and XZ received funding of the China Scholarship Council (CSC) (grant number 201,806,170,087 and 201,906,170,033). Part of this research work was performed using the 'Caps-It' research infrastructure (project ZW13 02) that was financially supported by the Hercules Foundation (FWO) and Rega Foundation, KU Leuven.