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1. Genetic insights into resting heart rate and its role in cardiovascular disease.

Author

van de Vegte, Yordi, Eppinga, Ruben, van der Ende, M, Hagemeijer, Yanick, Mahendran, Yuvaraj, Salfati, Elias, Smith, Albert, Tan, Vanessa, Arking, Dan, Ntalla, Ioanna, Appel, Emil, Schurmann, Claudia, Brody, Jennifer, Rueedi, Rico, Polasek, Ozren, Sveinbjornsson, Gardar, Lecoeur, Cecile, Ladenvall, Claes, Zhao, Jing, Isaacs, Aaron, Wang, Lihua, Luan, Jianan, Hwang, Shih-Jen, Mononen, Nina, Auro, Kirsi, Jackson, Anne, Bielak, Lawrence, Zeng, Linyao, Shah, Nabi, Nethander, Maria, Campbell, Archie, Rankinen, Tuomo, Pechlivanis, Sonali, Qi, Lu, Zhao, Wei, Rizzi, Federica, Tanaka, Toshiko, Robino, Antonietta, Cocca, Massimiliano, Lange, Leslie, Müller-Nurasyid, Martina, Roselli, Carolina, Zhang, Weihua, Kleber, Marcus, Guo, Xiuqing, Lin, Henry, Pavani, Francesca, Galesloot, Tessel, Noordam, Raymond, Milaneschi, Yuri, Schraut, Katharina, den Hoed, Marcel, Degenhardt, Frauke, Trompet, Stella, van den Berg, Marten, Pistis, Giorgio, Tham, Yih-Chung, Weiss, Stefan, Sim, Xueling, Li, Hengtong, van der Most, Peter, Nolte, Ilja, Lyytikäinen, Leo-Pekka, Said, M, Witte, Daniel, Iribarren, Carlos, Launer, Lenore, Ring, Susan, de Vries, Paul, Sever, Peter, Linneberg, Allan, Bottinger, Erwin, Padmanabhan, Sandosh, Psaty, Bruce, Sotoodehnia, Nona, Kolcic, Ivana, Arnar, David, Gudbjartsson, Daniel, Holm, Hilma, Balkau, Beverley, Silva, Claudia, Newton-Cheh, Christopher, Nikus, Kjell, Salo, Perttu, Mohlke, Karen, Peyser, Patricia, Schunkert, Heribert, Lorentzon, Mattias, Lahti, Jari, Rao, Dabeeru, Cornelis, Marilyn, Faul, Jessica, Smith, Jennifer, Stolarz-Skrzypek, Katarzyna, Bandinelli, Stefania, Concas, Maria, Sinagra, Gianfranco, Meitinger, Thomas, Waldenberger, Melanie, and Sinner, Moritz

Subjects
Humans, Cardiovascular Diseases, Risk Factors, Heart Rate, Genetic Predisposition to Disease, Atrial Fibrillation, Mendelian Randomization Analysis, Genome-Wide Association Study, Polymorphism, Single Nucleotide
Abstract

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.

Published
2023

3. Association of Air Pollution with a Urinary Biomarker of Biological Aging and Effect Modification by Vitamin K in the FLEMENGHO Prospective Population Study

Author

Martens, Dries S., An, De-Wei, Yu, Yu-Ling, Chori, Babangida S., Wang, Congrong, Silva, Ana Ines, Wei, Fang-Fei, Liu, Chen, Stolarz-Skrzypek, Katarzyna, Rajzer, Marek, Latosinska, Agnieszka, Mischak, Harald, Staessen, Jan A., and Nawrot, Tim S.

Subjects
Urine -- Analysis, Medical research, Medicine, Experimental, Aging -- Health aspects, Environmentally induced diseases -- Risk factors -- Statistics, Vitamin K -- Health aspects, Air pollution -- Health aspects -- Statistics, Biological markers -- Research, Particles -- Health aspects -- Statistics, Environmental issues, Health
Abstract

BACKGROUND: A recently developed urinary peptidomics biological aging clock can be used to study accelerated human aging. From 1990 to 2019, exposure to airborne particulate matter (PM) became the leading environmental risk factor worldwide. OBJECTIVES: This study investigated whether air pollution exposure is associated with accelerated urinary peptidomic aging, independent of calendar age, and whether this association is modified by other risk factors. METHODS: In a Flemish population, the urinary peptidomic profile (UPP) age (UPP-age) was derived from the urinary peptidomic profile measured by capillary electrophoresis coupled with mass spectrometry. UPP-age-R was calculated as the residual of the regression of UPP-age on chronological age, which reflects accelerated aging predicted by UPP-age, independent of chronological age. A high-resolution spatial-temporal interpolation method was used to assess each individual's exposure to P[M.sub.10], P[M.sub.2.5], black carbon (BC), and nitrogen dioxide (N[O.sub.2]). Associations of UPP-age-R with these pollutants were investigated by mixed models, accounting for clustering by residential address and confounders. Effect modifiers of the associations between UPP-age-R and air pollutants that included 18 factors reflecting vascular function, renal function, insulin resistance, lipid metabolism, or inflammation were evaluated. Direct and indirect (via UPP-age-R) effects of air pollution on mortality were evaluated by multivariable-adjusted Cox models. RESULTS: Among 660 participants (50.2% women; mean age: 50.7 y), higher exposure to P[M.sub.10], P[M.sub.2.5], BC, and N[O.sub.2] was associated with a higher UPP-age-R. Studying effect modifiers showed that higher plasma levels of desphospho-uncarboxylated matrix Gla protein (dpucMGP), signifying poorer vitamin K status, steepened the slopes of UPP-age-R on the air pollutants. In further analyses among participants with dpucMGP [greater than or equal to] 4.26 [micro]g/L (median), an interquartile range (IQR) higher level in P[M.sub.10], P[M.sub.2.5], BC, and N[O.sub.2] was associated with a higher UPP-age-R of 2.03 [95% confidence interval (CI): 0.60, 3.46], 2.22 (95% CI: 0.71, 3.74), 2.00 (95% CI: 0.56, 3.43), and 2.09 (95% CI: 0.77, 3.41) y, respectively. UPP-age-R was an indirect mediator of the associations of mortality with the air pollutants [multivariable-adjusted hazard ratios from 1.094 (95% CI: 1.000, 1.196) to 1.110 (95% CI: 1.007, 1.224)] in participants with a high dpucMGP, whereas no direct associations were observed. DISCUSSION: Ambient air pollution was associated with accelerated urinary peptidomics aging, and high vitamin K status showed a potential protective effect in this population. Current guidelines are insufficient to decrease the adverse health effects of airborne pollutants, including healthy aging trajectories. https://doi.org/10.1289/EHP13414, Introduction Over the past 20 y, global life expectancy at birth increased from 67.2 to 73.5 y. (1) In line with this remarkable increase in longevity, global exposure to harmful [...]

Published
2023
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5. OSTEO18, a novel urinary proteomic signature, associated with osteoporosis in heart transplant recipients

Author

Yu, Yu Ling, Huang, Qi Fang, An, De Wei, Raad, Julia, Martens, Dries S., Latosinska, Agnieszka, Stolarz-Skrzypek, Katarzyna, Van Cleemput, Johan, Feng, Ying Qing, Mischak, Harald, Allegaert, Karel, Verhamme, Peter, Janssens, Stefan, Nawrot, Tim S., Staessen, Jan A., Yu, Yu Ling, Huang, Qi Fang, An, De Wei, Raad, Julia, Martens, Dries S., Latosinska, Agnieszka, Stolarz-Skrzypek, Katarzyna, Van Cleemput, Johan, Feng, Ying Qing, Mischak, Harald, Allegaert, Karel, Verhamme, Peter, Janssens, Stefan, Nawrot, Tim S., and Staessen, Jan A.

Abstract

Background: Immunosuppressive treatment in heart transplant (HTx) recipient causes osteoporosis. The urinary proteomic profile (UPP) includes peptide fragments derived from the bone extracellular matrix. Study aims were to develop and validate a multidimensional UPP biomarker for osteoporosis in HTx patients from single sequenced urinary peptides identifying the parent proteins. Methods: A single-center HTx cohort was analyzed. Urine samples were measured by capillary electrophoresis coupled with mass spectrometry. Cases with osteoporosis and matching controls were randomly selected from all available 389 patients. In derivation case-control dataset, 1576 sequenced peptides detectable in ≥30 % of patients. Applying statistical analysis on these, an 18-peptide multidimensional osteoporosis UPP biomarker (OSTEO18) was generated by support vector modeling. The 2 replication datasets included 118 and 94 patients. For further validation, the whole cohort was analyzed. Statistical methods included logistic regression and receiver operating characteristic curve (ROC) analysis. Results: In derivation dataset, the AUC, sensitivity and specificity of OSTEO18 were 0.83 (95 % CI: 0.76–0.90), 74.3 % and 87.1 %, respectively. In replication datasets, results were confirmatory. In the whole cohort (154 osteoporotic patients [39.6 %]), the ORs for osteoporosis increased (p < 0.0001) across OSTEO18 quartiles from 0.39 (95 % CI: 0.25–0.61) to 3.14 (2.08–4.75). With full adjustment for known osteoporosis risk factors, OSTEO18 improved AUC from 0.708 to 0.786 (p = 0.0003) for OSTEO18 categorized (optimized threshold: 0.095) and to 0.784 (p = 0.0004) for OSTEO18 as continuously distributed classifier. Conclusion: OSTEO18 is a clinically meaningful novel biomarker indicative of osteoporosis in HTx recipients and is being certified as in-vitro diagnostic.

Published
2024

9. Isolated Diastolic Hypertension in the IDACO Study: An Age-Stratified Analysis Using 24-Hour Ambulatory Blood Pressure Measurements

Author

McEvoy, John W., Yang, Wen-Yi, Thijs, Lutgarde, Zhang, Zhen-Yu, Melgarejo, Jesus D., Boggia, José, Hansen, Tine W., Asayama, Kei, Ohkubo, Takayoshi, Dolan, Eamon, Stolarz-Skrzypek, Katarzyna, Malyutina, Sofia, Casiglia, Edoardo, Lind, Lars, Filipovský, Jan, Maestre, Gladys E., Li, Yan, Wang, Ji-Guang, Imai, Yutaka, Kawecka-Jaszcz, Kalina, Sandoya, Edgardo, Narkiewicz, Krzysztof, O’Brien, Eoin, Vanassche, Thomas, and Staessen, Jan A.

Published
2021
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11. Serial echocardiographic evaluation of COVID-19 patients without prior history of structural heart disease: a 1-year follow-up CRACoV-HHS study

Author

Olszanecka, Agnieszka, primary, Wojciechowska, Wiktoria, additional, Bednarek, Agnieszka, additional, Kusak, Piotr, additional, Wizner, Barbara, additional, Terlecki, Michał, additional, Stolarz-Skrzypek, Katarzyna, additional, Klocek, Marek, additional, Drożdż, Tomasz, additional, Sładek, Krzysztof, additional, Bociąga-Jasik, Monika, additional, Garlicki, Aleksander, additional, Rewiuk, Krzysztof, additional, Matyja, Andrzej, additional, Małecki, Maciej, additional, Sydor, Wojciech, additional, Krzanowski, Marcin, additional, Grodzicki, Tomasz, additional, and Rajzer, Marek, additional

Published
2023
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12. Blood pressure and cardiovascular risk in relation to birth weight and urinary sodium: an individual-participant meta-analysis of European family-based population studies

Author

Yu, Yu-Ling, Moliterno, Paula, An, De-Wei, Raaijmakers, Anke, Martens, Dries S, Stolarz-Skrzypek, Katarzyna, Tikhonoff, Valerie, Malyutina, Sofia, Casiglia, Edoardo, Chori, Babangida, Filipovsky, Jan, Rajzer, Marek, Allegaert, Karel, Kawecka-Jaszcz, Kalina, Verhamme, Peter, Nawrot, Tim S, Staessen, Jan A, Boggia, Jose, Yu, Yu-Ling, Moliterno, Paula, An, De-Wei, Raaijmakers, Anke, MARTENS, Dries, Stolarz-Skrzypek, Katarzyna, Tikhonoff, Valérie, Malyutina, Sofia, Casiglia, Edoardo, Filipovský, Jan, CHORI, Babangida, Rajzer, Marek, Allegaert, Karel, Kawecka-Jaszcz, Kalina, Verhamme, Peter, NAWROT, Tim, Staessen, Jan A., and Boggia, José

Subjects
hypertension, urinary sodium excretion, HDL, interquartile range, Physiology, FLEMENGHO, high-density lipoprotein, European Project on Genes in Hypertension, Genes and Health Outcomes, 24-h urinary sodium excretion, BP, urinary sodium-to-potassium ratio, eGFR, Internal Medicine, BW, total mortality, EPOGH, UVNA, cardiovascular risks, IQR, birth weight, blood pressure, 95%CI, UNAK, 95%confidence interval, Cardiology and Cardiovascular Medicine, estimated glomerular filtration rate derived from serum creatinine, Flemish Study on Environment
Abstract

BACKGROUND: Although the relation of salt intake with blood pressure (BP) is linear, it is U-shaped for mortality and cardiovascular disease (CVD). This individual-participant meta-analysis explored whether the relation of hypertension, death or CVD with 24-h urinary sodium excretion (UVNA) or sodium-to-potassium (UNAK) ratio was modified by birth weight. METHODS: Families were randomly enrolled in the Flemish Study on Genes, Environment and Health Outcomes (1985-2004) and the European Project on Genes in Hypertension (1999-2001). Categories of birth weight, UVNA and UNAK (≤2500, >2500-4000, >4000 g; 4.6 g; and 2, respectively) were coded using deviation-from-mean coding and analyzed by Kaplan-Meier survival functions and linear and Cox regression. RESULTS: The study population was subdivided into the Outcome ( n = 1945), Hypertension ( n = 1460) and Blood Pressure cohorts ( n = 1039) to analyze the incidence of mortality and cardiovascular endpoints, hypertension and BP changes as function of UVNA changes. The prevalence of low/medium/high birth weight in the Outcome cohort was 5.8/84.5/9.7%. Over 16.7 years (median), rates were 4.9, 8 and 27.1% for mortality, CVD and hypertension, respectively, but were not associated with birth weight. Multivariable-adjusted hazard ratios were not significant for any endpoint in any of the birth weight, UVNA and UNAK strata. Adult body weight tracked with birth weight ( P

Published
2023

13. Association of Fatal and Nonfatal Cardiovascular Outcomes With 24-Hour Mean Arterial Pressure

Author

Melgarejo, Jesus D., Yang, Wen-Yi, Thijs, Lutgarde, Li, Yan, Asayama, Kei, Hansen, Tine W., Wei, Fang-Fei, Kikuya, Masahiro, Ohkubo, Takayoshi, Dolan, Eamon, Stolarz-Skrzypek, Katarzyna, Huang, Qi-Fang, Tikhonoff, Valérie, Malyutina, Sofia, Casiglia, Edoardo, Lind, Lars, Sandoya, Edgardo, Filipovský, Jan, Gilis-Malinowska, Natasza, Narkiewicz, Krzysztof, Kawecka-Jaszcz, Kalina, Boggia, José, Wang, Ji-Guang, Imai, Yutaka, Vanassche, Thomas, Verhamme, Peter, Janssens, Stefan, O’Brien, Eoin, Maestre, Gladys E., Staessen, Jan A., and Zhang, Zhen-Yu

Published
2021
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14. Cardiovascular End Points and Mortality Are Not Closer Associated With Central Than Peripheral Pulsatile Blood Pressure Components

Author

Huang, Qi-Fang, Aparicio, Lucas S., Thijs, Lutgarde, Wei, Fang-Fei, Melgarejo, Jesus D., Cheng, Yi-Bang, Sheng, Chang-Sheng, Yang, Wen-Yi, Gilis-Malinowska, Natasza, Boggia, José, Niiranen, Teemu J., Wojciechowska, Wiktoria, Stolarz-Skrzypek, Katarzyna, Barochiner, Jessica, Ackermann, Daniel, Tikhonoff, Valérie, Ponte, Belen, Pruijm, Menno, Casiglia, Edoardo, Narkiewicz, Krzysztof, Filipovský, Jan, Czarnecka, Danuta, Kawecka-Jaszcz, Kalina, Jula, Antti M., Bochud, Murielle, Vanassche, Thomas, Verhamme, Peter, Struijker-Boudier, Harry A.J., Wang, Ji-Guang, Zhang, Zhen-Yu, Li, Yan, and Staessen, Jan A.

Published
2020
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15. Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial—First progress report

Author

Chori, Babangida S., An, De‐Wei, Martens, Dries S., Yu, Yu‐Ling, Gilis-Malinowska, Natasza, Abubakar, Sani M., Ibrahim, Etubi A., Ajanya, Ojonojima, Abiodun, Olugbenga O., Anya, Tina, Tobechukwu, Iyidobi, Isiguzo, Godsent, Cheng, Hao‐Min, Chen, Chen‐Huan, Liao, Chia‐Te, Mokwatsi, Gontse, Stolarz-Skrzypek, Katarzyna, Wojciechowska, Wiktoria, Narkiewicz, Krzysztof, Rajzer, Marek, Brguljan‐Hitij, Jana, Nawrot, Tim, Asayama, Kei, Reyskens, Peter, Mischak, Harald, Odili, Augustine N., Staessen, Jan A., CHORI, Babangida, An, De‐Wei, MARTENS, Dries, Yu, Yu‐Ling, Gilis‐Malinowska, Natasza, Abubakar, Sani M., Ibrahim, Etubi A., Ajanya, Ojonojima, Abiodun, Olugbenga O., Anya, Tina, Tobechukwu, Iyidobi, Isiguzo, Godsent, Cheng, Hao‐Min, Chen, Chen‐Huan, Liao, Chia‐Te, Mokwatsi, Gontse, Stolarz‐Skrzypek, Katarzyna, Wojciechowska, Wiktoria, Narkiewicz, Krzysztof, Rajzer, Marek, Brguljan‐Hitij, Jana, NAWROT, Tim, Asayama, Kei, Reyskens, Peter, Mischak, Harald, Odili, Augustine N., and Staessen, Jan A.

Subjects
left ventricular function, hypertension, Chronic kidney disease, diabetic nephropathy, home blood pressure telemonitoring, type-2 diabetes mellitus
Abstract

Background Hypertension and diabetes cause chronic kidney disease (CKD) and diastolic left ventricular dysfunction (DVD) as forerunners of disability and death. Home blood pressure telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling prevention. Methods UPRIGHT-HTM (Urinary Proteomics Combined with Home Blood Pressure Telemonitoring for Health Care Reform [NCT04299529]) is an investigator-initiated 5-year clinical trial with patient-centred design, which will randomise 1148 patients to be recruited in Europe, sub-Saharan Africa and South America. During the whole study, HTM data will be collected and freely accessible for patients and caregivers. The UPP, measured at enrolment only, will be communicated early during follow-up to 50% of patients and their caregivers (intervention), but only at trial closure in 50% (control). The hypothesis is that early knowledge of the UPP risk profile will lead to more rigorous risk factor management and result in benefit. Eligible patients, aged 55-75 years old, are asymptomatic, but have >= 5 CKD- or DVD-related risk factors, preferably including hypertension, type-2 diabetes, or both. The primary endpoint is a composite of new-onset intermediate and hard cardiovascular and renal outcomes. Demonstrating that combining UPP with HTM is feasible in a multicultural context and defining the molecular signatures of early CKD and DVD are secondary endpoints. Expected outcomes The expected outcome is that application of UPP on top of HTM will be superior to HTM alone in the prevention of CKD and DVD and associated complications and that UPP allows shifting emphasis from treating to preventing disease, thereby empowering patients. The authors gratefully acknowledge the enthusiasm of the patientsenrolled in UPRIGHT-HTM and the expert assistance of the consul-tants, residents and nursing staff supporting the trial at the clinicalsites. The Alliance for the Promotion of Preventive Medicine is anot-profitresearchinstitute(URL:www.appremed.org;Belgianregis-trationnumber,739849385),whichreceivedanon-bindinggrantfromOMRONHealthcareCo.Ltd.,Kyoto,Japan.UPRIGHT-HTMisaTopZprojectsupportedbyOMRONHealthcareCo.Ltd.,Kyoto,Japan

Published
2023

16. Opposing Age-Related Trends in Absolute and Relative Risk of Adverse Health Outcomes Associated With Out-of-Office Blood Pressure

Author

Li, Yan, Thijs, Lutgarde, Zhang, Zhen-Yu, Asayama, Kei, Hansen, Tine W., Boggia, José, Björklund-Bodegård, Kristina, Yang, Wen-Yi, Niiranen, Teemu J., Ntineri, Angeliki, Wei, Fang-Fei, Kikuya, Masahiro, Ohkubo, Takayoshi, Dolan, Eamon, Hozawa, Atsushi, Tsuji, Ichiro, Stolarz-Skrzypek, Katarzyna, Huang, Qi-Fang, Melgarejo, Jesus D., Tikhonoff, Valérie, Malyutina, Sofia, Casiglia, Edoardo, Nikitin, Yuri, Lind, Lars, Sandoya, Edgardo, Aparicio, Lucas, Barochiner, Jessica, Gilis-Malinowska, Natasza, Narkiewicz, Krzysztof, Kawecka-Jaszcz, Kalina, Maestre, Gladys E., Jula, Antti M., Johansson, Jouni K., Kuznetsova, Tatiana, Filipovský, Jan, Stergiou, George, Wang, Ji-Guang, Imai, Yutaka, OʼBrien, Eoin, and Staessen, Jan A.

Published
2019
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17. Outcome-Driven Thresholds for Ambulatory Blood Pressure Based on the New American College of Cardiology/American Heart Association Classification of Hypertension

Author

Cheng, Yi-Bang, Thijs, Lutgarde, Zhang, Zhen-Yu, Kikuya, Masahiro, Yang, Wen-Yi, Melgarejo, Jesus D., Boggia, José, Wei, Fang-Fei, Hansen, Tine W., Yu, Cai-Guo, Asayama, Kei, Ohkubo, Takayoshi, Dolan, Eamon, Stolarz-Skrzypek, Katarzyna, Malyutina, Sofia, Casiglia, Edoardo, Lind, Lars, Filipovský, Jan, Maestre, Gladys E., Imai, Yutaka, Kawecka-Jaszcz, Kalina, Sandoya, Edgardo, Narkiewicz, Krzysztof, Li, Yan, O’Brien, Eoin, Wang, Ji-Guang, and Staessen, Jan A.

Published
2019
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19. Risk Stratification by Cross-Classification of Central and Brachial Systolic Blood Pressure

Author

Cheng, Yi-Bang, Thijs, Lutgarde, Aparicio, Lucas S., Huang, Qi-Fang, Wei, Fang-Fei, Yu, Yu-Ling, Barochiner, Jessica, Sheng, Chang-Sheng, Yang, Wen-Yi, Niiranen, Teemu J., Boggia, Jose, Zhang, Zhen-Yu, Stolarz-Skrzypek, Katarzyna, Gilis-Malinowska, Natasza, Tikhonoff, Valerie, Wojciechowska, Wiktoria, Casiglia, Edoardo, Narkiewicz, Krzysztof, Filipovsky, Jan, Kawecka-Jaszcz, Kalina, Wang, Ji-Guang, Li, Yan, and Staessen, Jan A.

Subjects
cardiovascular risk, Male, brachial blood pressure, hypertension, Brachial Artery, Physiology, central blood pressure, Blood Pressure, Blood Pressure Determination, Middle Aged, mortality, Risk Assessment, population science, Female, Humans, Hypertension, Internal Medicine, Cardiology and Cardiovascular Medicine
Abstract

Background: Whether cardiovascular risk is more tightly associated with central (cSBP) than brachial (bSBP) systolic pressure remains debated, because of their close correlation and uncertain thresholds to differentiate cSBP into normotension versus hypertension. Methods: In a person-level meta-analysis of the International Database of Central Arterial Properties for Risk Stratification (n=5576; 54.1% women; mean age 54.2 years), outcome-driven thresholds for cSBP were determined and whether the cross-classification of cSBP and bSBP improved risk stratification was explored. cSBP was tonometrically estimated from the radial pulse wave using SphygmoCor software. Results: Over 4.1 years (median), 255 composite cardiovascular end points occurred. In multivariable bootstrapped analyses, cSBP thresholds (in mm Hg) of 110.5 (95% CI, 109.1–111.8), 120.2 (119.4–121.0), 130.0 (129.6–130.3), and 149.5 (148.4–150.5) generated 5-year cardiovascular risks equivalent to the American College of Cardiology/American Heart Association bSBP thresholds of 120, 130, 140, and 160. Applying 120/130 mm Hg as cSBP/bSBP thresholds delineated concordant central and brachial normotension (43.1%) and hypertension (48.2%) versus isolated brachial hypertension (5.0%) and isolated central hypertension (3.7%). With concordant normotension as reference, the multivariable hazard ratios for the cardiovascular end point were 1.30 (95% CI, 0.58–2.94) for isolated brachial hypertension, 2.28 (1.21–4.30) for isolated central hypertension, and 2.02 (1.41–2.91) for concordant hypertension. The increased cardiovascular risk associated with isolated central and concordant hypertension was paralleled by cerebrovascular end points with hazard ratios of 3.71 (1.37–10.06) and 2.60 (1.35–5.00), respectively. Conclusions: Irrespective of the brachial blood pressure status, central hypertension increased cardiovascular and cerebrovascular risk indicating the importance of controlling central hypertension.

Published
2022

20. Derivation of an Outcome-Driven Threshold for Aortic Pulse Wave Velocity: An Individual-Participant Meta-Analysis.

Author

De-Wei An, Hansen, Tine W., Aparicio, Lucas S., Chori, Babangida, Qi-Fang Huang, Fang-Fei Wei, Yi-Bang Cheng, Yu-Ling Yu, Chang-Sheng Sheng, Gilis-Malinowska, Natasza, Boggia, José, Wojciechowska, Wiktoria, Niiranen, Teemu J., Tikhonoff, Valérie, Casiglia, Edoardo, Narkiewicz, Krzysztof, Stolarz-Skrzypek, Katarzyna, Kawecka-Jaszcz, Kalina, Jula, Antti M., and Wen-Yi Yang

Abstract

BACKGROUND: Aortic pulse wave velocity (PWV) predicts cardiovascular events (CVEs) and total mortality (TM), but previous studies proposing actionable PWV thresholds have limited generalizability. This individual-participant meta-analysis is aimed at defining, testing calibration, and validating an outcome-driven threshold for PWV, using 2 populations studies, respectively, for derivation IDCARS (International Database of Central Arterial Properties for Risk Stratification) and replication MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease Health Survey - Copenhagen). METHODS: A risk-carrying PWV threshold for CVE and TM was defined by multivariable Cox regression, using stepwise increasing PWV thresholds and by determining the threshold yielding a 5-year risk equivalent with systolic blood pressure of 140 mm Hg. The predictive performance of the PWV threshold was assessed by computing the integrated discrimination improvement and the net reclassification improvement. RESULTS: In well-calibrated models in IDCARS, the risk-carrying PWV thresholds converged at 9 m/s (10 m/s considering the anatomic pulse wave travel distance). With full adjustments applied, the threshold predicted CVE (hazard ratio [CI]: 1.68 [1.15-2.45]) and TM (1.61 [1.01-2.55]) in IDCARS and in MONICA (1.40 [1.09-1.79] and 1.55 [1.23-1.95]). In IDCARS and MONICA, the predictive accuracy of the threshold for both end points was ≈-0.75. Integrated discrimination improvement was significant for TM in IDCARS and for both TM and CVE in MONICA, whereas net reclassification improvement was not for any outcome. CONCLUSIONS: PWV integrates multiple risk factors into a single variable and might replace a large panel of traditional risk factors. Exceeding the outcome-driven PWV threshold should motivate clinicians to stringent management of risk factors, in particular hypertension, which over a person's lifetime causes stiffening of the elastic arteries as waypoint to CVE and death. [ABSTRACT FROM AUTHOR]

Published
2023
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23. Erratum: Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author

Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F., Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W., Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H., Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I. W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid, Dietrich, Andrea, Ehret, George B., Ellinor, Patrick T., Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G. J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A., Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C., Lin, Henry J., Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F., Siscovick, David, Smit, Johannes H., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu-Ming, Zonderman, Alan B, Cusi, Daniele, Evans, Michele K., Greiser, Halina K., van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J., Oldehinkel, Albertine J., Penninx, Brenda, Reiner, Alexander P., Riese, Harriëtte, van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G. M., Asselbergs, Folkert W., Brundel, Bianca J. J.M, Heckbert, Susan R., Whitsel, Eric A., den Hoed, Marcel, Snieder, Harold, and de Geus, Eco J. C.

Published
2017
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25. Predictive power of 24-h ambulatory pulse pressure and its components for mortality and cardiovascular outcomes in 11 848 participants recruited from 13 populations

Author

Gavish, Benjamin, Bursztyn, Michael, Thijs, Lutgarde, Wei, Dong-Mei, Melgarejo, Jesus D., Zhang, Zhen-Yu, Boggia, Jose, Hansen, Tine W., Asayama, Kei, Ohkubo, Takayoshi, Kikuya, Masahiro, Yang, Wen-Yi, Stolarz-Skrzypek, Katarzyna, Malyutina, Sofia, Casiglia, Edoardo, Lind, Lars, Li, Yan, Kawecka-Jaszcz, Kalina, Filipovsky, Jan, Tikhonoff, Valerie, Gilis-Malinowska, Natasza, Dolan, Eamon, Sandoya, Edgardo, Narkiewicz, Krzysztof, Wang, Ji-Guang, Imai, Yutaka, Maestre, Gladys E., O'Brien, Eoin, Staessen, Jan A., Gavish, Benjamin, Bursztyn, Michael, Thijs, Lutgarde, Wei, Dong-Mei, Melgarejo, Jesus D., Zhang, Zhen-Yu, Boggia, Jose, Hansen, Tine W., Asayama, Kei, Ohkubo, Takayoshi, Kikuya, Masahiro, Yang, Wen-Yi, Stolarz-Skrzypek, Katarzyna, Malyutina, Sofia, Casiglia, Edoardo, Lind, Lars, Li, Yan, Kawecka-Jaszcz, Kalina, Filipovsky, Jan, Tikhonoff, Valerie, Gilis-Malinowska, Natasza, Dolan, Eamon, Sandoya, Edgardo, Narkiewicz, Krzysztof, Wang, Ji-Guang, Imai, Yutaka, Maestre, Gladys E., O'Brien, Eoin, and Staessen, Jan A.

Abstract

Background: The role of pulse pressure (PP) 'widening' at older and younger age as a cardiovascular risk factor is still controversial. Mean PP, as determined from repeated blood pressure (BP) readings, can be expressed as a sum of two components: 'elastic PP' (elPP) and 'stiffening PP' (stPP) associated, respectively, with stiffness at the diastole and its relative change during the systole. We investigated the association of 24-h ambulatory PP, elPP, and stPP ('PP variables') with mortality and composite cardiovascular events in different age classes. Method: Longitudinal population-based cohort study of adults with baseline observations that included 24-h ambulatory BP. Age classes were age 40 or less, 40-50, 50-60, 60-70, and over 70 years. Co-primary endpoints were total mortality and composite cardiovascular events. The relative risk expressed by hazard ratio per 1SD increase for each of the PP variables was calculated from multivariable-adjusted Cox regression models. Results: The 11 848 participants from 13 cohorts (age 53 +/- 16 years, 50% men) were followed for up for 13.7 +/- 6.7 years. A total of 2946 participants died (18.1 per 1000 person-years) and 2093 experienced a fatal or nonfatal cardiovascular event (12.9 per 1000 person-years). Mean PP, elPP, and stPP were, respectively, 49.7, 43.5, and 6.2 mmHg, and elPP and stPP were uncorrelated (r = -0.07). At age 50-60 years, all PP variables displayed association with risk for almost all outcomes. From age over 60 years to age over 70 years, hazard ratios of of PP and elPP were similar and decreased gradually but differently for pulse rate lower than or higher than 70 bpm, whereas stPP lacked predictive power in most cases. For age 40 years or less, elPP showed protective power for coronary events, whereas stPP and PP predicted stroke events. Adjusted and unadjusted hazard ratio variations were similar over the entire age range. Conclusion: This study provides a new basis for associating PP components wit

Published
2022
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32. Urinary peptidomic profiles to address age-related disabilities: a prospective population study

Author

Martens, Dries S, primary, Thijs, Lutgarde, additional, Latosinska, Agnieszka, additional, Trenson, Sander, additional, Siwy, Justyna, additional, Zhang, Zhen-Yu, additional, Wang, Congrong, additional, Beige, Joachim, additional, Vlahou, Antonia, additional, Janssens, Stefan, additional, Mischak, Harald, additional, Nawrot, Tim S, additional, Staessen, Jan A, additional, Asayama, Kei, additional, Bochud, Murielle, additional, Boggia, José, additional, Brguljan-Hitij, Jana, additional, Feng, Ying-Mei, additional, Gu, Yu-Mei, additional, Hara, Azusa, additional, Huang, Qi-Fang, additional, Jin, Yu, additional, Seidlerová, Jitka, additional, Liu, Yan-Ping, additional, Melgarejo, Jesus, additional, Moliterno, Paula, additional, Odili, Augustine N, additional, Petit, Thibault, additional, Raaijmakers, Anke, additional, Schutte, Rudolph, additional, Stolarz-Skrzypek, Katarzyna, additional, Tikhonoff, Valérie, additional, Wang, Ji-Guang, additional, Wei, Fangfei, additional, Wei, Dongmei, additional, Yang, Wen-Yi, additional, Yu, Yuling, additional, Zhang, Zhenyu, additional, Martens, Dries S, additional, Roels, Harry A, additional, Willum-Hansen, Tine, additional, and Maestre, Gladys E, additional

Published
2021
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33. Impact of Arterial Hypertension and Use of Antihypertensive Pharmacotherapy on Mortality in Patients Hospitalized due to COVID-19: The CRACoV-HHS Study.

Author

Wojciechowska, Wiktoria, Terlecki, Michał, Klocek, Marek, Pac, Agnieszka, Olszanecka, Agnieszka, Stolarz-Skrzypek, Katarzyna, Jastrzębski, Marek, Jankowski, Piotr, Ostrowska, Aleksandra, Drożdż, Tomasz, Prejbisz, Aleksander, Dobrowolski, Piotr, Januszewicz, Andrzej, Krzanowski, Marcin, Małecki, Maciej T., Grodzicki, Tomasz, Kreutz, Reinhold, Rajzer, Marek, and CRACoV-HHS Investigators†

Abstract

Background: Cardiovascular diseases including arterial hypertension are common comorbidities among patients hospitalized due to COVID-19. We assessed the influence of preexisting hypertension and its pharmacological treatment on in-hospital mortality in patients hospitalized with COVID-19.Methods: We studied all consecutive patients who were admitted to the University Hospital in Krakow, Poland, due to COVID-19 between March 2020 and May 2021. Data of 5191 patients (mean age 61.9±16.7 years, 45.2% female) were analyzed.Results: The median hospitalization time was 14 days, and the mortality rate was 18.4%. About a quarter of patients had an established cardiovascular disease including coronary artery disease (16.6%) or stroke (7.6%). Patients with hypertension (58.3%) were older and had more comorbidities than patients without hypertension. In multivariable logistic regression analysis, age above median (64 years), male gender, history of heart failure or chronic kidney disease, and higher C-reactive protein level, but not preexisting hypertension, were independent risk factors for in-hospital death in the whole study group. Patients with hypertension already treated (n=1723) with any first-line antihypertensive drug (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, or thiazide/thiazide-like diuretics) had a significantly lower risk of in-hospital death (odds ratio, 0.25 [95% CI, 0.2-0.3]; P<0.001) compared to nontreated hypertensives (n=1305).Conclusions: Although the diagnosis of preexisting hypertension per se had no significant impact on in-hospital mortality among patients with COVID-19, treatment with any first-line blood pressure-lowering drug had a profound beneficial effect on survival in patients with hypertension. These data support the need for antihypertensive pharmacological treatment during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Published
2022
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37. Relative and Absolute Risk to Guide the Management of Pulse Pressure, an Age-Related Cardiovascular Risk Factor

Author

Melgarejo, Jesus D., Thijs, Lutgarde, Wei, Dong-Mei, Bursztyn, Michael, Yang, Wen-Yi, Li, Yan, Asayama, Kei, Hansen, Tine W., Kikuya, Masahiro, Ohkubo, Takayoshi, Dolan, Eamon, Stolarz-Skrzypek, Katarzyna, Cheng, Yi-Bang, Tikhonoff, Valerie, Malyutina, Sofia, Casiglia, Edoardo, Lind, Lars, Sandoya, Edgardo, Filipovsky, Jan, Narkiewicz, Krzysztof, Gilis-Malinowska, Natasza, Kawecka-Jaszcz, Kalina, Boggia, Jose, Wang, Ji-Guang, Imai, Yutaka, Verhamme, Peter, Trenson, Sander, Janssens, Stefan, O'Brien, Eoin, Maestre, Gladys E., Gavish, Benjamin, Staessen, Jan A., Zhang, Zhen-Yu, Melgarejo, Jesus D., Thijs, Lutgarde, Wei, Dong-Mei, Bursztyn, Michael, Yang, Wen-Yi, Li, Yan, Asayama, Kei, Hansen, Tine W., Kikuya, Masahiro, Ohkubo, Takayoshi, Dolan, Eamon, Stolarz-Skrzypek, Katarzyna, Cheng, Yi-Bang, Tikhonoff, Valerie, Malyutina, Sofia, Casiglia, Edoardo, Lind, Lars, Sandoya, Edgardo, Filipovsky, Jan, Narkiewicz, Krzysztof, Gilis-Malinowska, Natasza, Kawecka-Jaszcz, Kalina, Boggia, Jose, Wang, Ji-Guang, Imai, Yutaka, Verhamme, Peter, Trenson, Sander, Janssens, Stefan, O'Brien, Eoin, Maestre, Gladys E., Gavish, Benjamin, Staessen, Jan A., and Zhang, Zhen-Yu

Abstract

BACKGROUND Pulse pressure (PP) reflects the age-related stiffening of the central arteries, but no study addressed the management of the PP-related risk over the human lifespan. METHODS In 4,663 young (18-49 years) and 7,185 older adults (>= 50 years), brachial PP was recorded over 24 hours. Total mortality and all major cardiovascular events (MACEs) combined were coprimary endpoints. Cardiovascular death, coronary events, and stroke were secondary endpoints. RESULTS In young adults (median follow-up, 14.1 years; mean PP, 45.1 mm Hg), greater PP was not associated with absolute risk; the endpoint rates were <= 2.01 per 1,000 person-years. The adjusted hazard ratios expressed per 10-mm Hg PP increments were less than unity (P <= 0.027) for MACE (0.67; 95% confidence interval [CI], 0.47-0.96) and cardiovascular death (0.33; 95% CI, 0.11-0.75). In older adults (median follow-up, 13.1 years; mean PP, 52.7 mm Hg), the endpoint rates, expressing absolute risk, ranged from 22.5 to 45.4 per 1,000 person-years and the adjusted hazard ratios, reflecting relative risk, from 1.09 to 1.54 (P < 0.0001). The PP-related relative risks of death, MACE, and stroke decreased >3-fold from age 55 to 75 years, whereas absolute risk rose by a factor 3. CONCLUSIONS From 50 years onwards, the PP-related relative risk decreases, whereas absolute risk increases. From a lifecourse perspective, young adulthood provides a window of opportunity to manage risk factors and prevent target organ damage as forerunner of premature death and MACE. In older adults, treatment should address absolute risk, thereby extending life in years and quality.

Published
2021
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43. Increased Blood Pressure Variability May Herald Cognitive Decline and Dementia.

Author

UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Service de pathologie cardiovasculaire, Guimarães Cunha, Pedro, Stolarz-Skrzypek, Katarzyna, Persu, Alexandre, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Service de pathologie cardiovasculaire, Guimarães Cunha, Pedro, Stolarz-Skrzypek, Katarzyna, and Persu, Alexandre

Abstract

A 68-year-old patient with well-controlled hypertension, asymptomatic since many years suddenly complains of vertigo, dizziness, and subtle loss of memory in daily life. Self-blood pressure (BP) measurement followed by 24-hour ambulatory BP measurement shows impressive BP variability. BP measurements on subsequent consultations vary from very high to low BP without an obvious explanation. Six months later, the patient’s cognitive status worsens and he is diagnosed with dementia. [...]

Published
2020

45. Significance of White-Coat Hypertension in Older Persons With Isolated Systolic Hypertension: A Meta-Analysis Using the International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes Population

Author

Franklin, Stanley S., Thijs, Lutgarde, Hansen, Tine W., Li, Yan, Boggia, José, Kikuya, Masahiro, Björklund-Bodegård, Kristina, Ohkubo, Takayoshi, Jeppesen, Jørgen, Torp-Pedersen, Christian, Dolan, Eamon, Kuznetsova, Tatiana, Stolarz-Skrzypek, Katarzyna, Tikhonoff, Valérie, Malyutina, Sofia, Casiglia, Edoardo, Nikitin, Yuri, Lind, Lars, Sandoya, Edgardo, Kawecka-Jaszcz, Kalina, Imai, Yutaka, Wang, Jiguang, Ibsen, Hans, OʼBrien, Eoin, and Staessen, Jan A.

Published
2012
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