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1. Exploring the Therapeutic Potential of Bromelain: Applications, Benefits, and Mechanisms.

Author

Kansakar, Urna, Trimarco, Valentina, Manzi, Maria V., Cervi, Edoardo, Mone, Pasquale, and Santulli, Gaetano

Abstract

Bromelain is a mixture of proteolytic enzymes primarily extracted from the fruit and stem of the pineapple plant (Ananas comosus). It has a long history of traditional medicinal use in various cultures, particularly in Central and South America, where pineapple is native. This systematic review will delve into the history, structure, chemical properties, and medical indications of bromelain. Bromelain was first isolated and described in the late 19th century by researchers in Europe, who identified its proteolytic properties. Since then, bromelain has gained recognition in both traditional and modern medicine for its potential therapeutic effects. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Intima-media thickness at the near or far wall of the common carotid artery in cardiovascular risk assessment

Author

Seekircher, Lisa, primary, Tschiderer, Lena, additional, Lind, Lars, additional, Safarova, Maya S, additional, Kavousi, Maryam, additional, Ikram, M Arfan, additional, Lonn, Eva, additional, Yusuf, Salim, additional, Grobbee, Diederick E, additional, Kastelein, John J P, additional, Visseren, Frank L J, additional, Walters, Matthew, additional, Dawson, Jesse, additional, Higgins, Peter, additional, Agewall, Stefan, additional, Catapano, Alberico, additional, de Groot, Eric, additional, Espeland, Mark A, additional, Klingenschmid, Gerhard, additional, Magliano, Dianna, additional, Olsen, Michael H, additional, Preiss, David, additional, Sander, Dirk, additional, Skilton, Michael, additional, Zozulińska-Ziółkiewicz, Dorota A, additional, Grooteman, Muriel P C, additional, Blankestijn, Peter J, additional, Kitagawa, Kazuo, additional, Okazaki, Shuhei, additional, Manzi, Maria V, additional, Mancusi, Costantino, additional, Izzo, Raffaele, additional, Desvarieux, Moise, additional, Rundek, Tatjana, additional, Gerstein, Hertzel C, additional, Bots, Michiel L, additional, Sweeting, Michael J, additional, Lorenz, Matthias W, additional, and Willeit, Peter, additional

Published
2023
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4. Intima-media thickness at the near or far wall of the common carotid artery in cardiovascular risk assessment

Author

Seekircher, Lisa, Tschiderer, Lena, Lind, Lars, Safarova, Maya S., Kavousi, Maryam, Ikram, M. Arfan, Lonn, Eva, Yusuf, Salim, Grobbee, Diederick E., Kastelein, John J.P., Visseren, Frank L.J., Walters, Matthew, Dawson, Jesse, Higgins, Peter, Agewall, Stefan, Catapano, Alberico, De Groot, Eric, Espeland, Mark A., Klingenschmid, Gerhard, Magliano, Dianna, Olsen, Michael H., Preiss, David, Sander, Dirk, Skilton, Michael, Zozulińska-Ziółkiewicz, Dorota A., Grooteman, Muriel P.C., Blankestijn, Peter J., Kitagawa, Kazuo, Okazaki, Shuhei, Manzi, Maria V., Mancusi, Costantino, Izzo, Raffaele, Desvarieux, Moise, Rundek, Tatjana, Gerstein, Hertzel C., Bots, Michiel L., Sweeting, Michael J., Lorenz, Matthias W., Willeit, Peter, Seekircher, Lisa, Tschiderer, Lena, Lind, Lars, Safarova, Maya S., Kavousi, Maryam, Ikram, M. Arfan, Lonn, Eva, Yusuf, Salim, Grobbee, Diederick E., Kastelein, John J.P., Visseren, Frank L.J., Walters, Matthew, Dawson, Jesse, Higgins, Peter, Agewall, Stefan, Catapano, Alberico, De Groot, Eric, Espeland, Mark A., Klingenschmid, Gerhard, Magliano, Dianna, Olsen, Michael H., Preiss, David, Sander, Dirk, Skilton, Michael, Zozulińska-Ziółkiewicz, Dorota A., Grooteman, Muriel P.C., Blankestijn, Peter J., Kitagawa, Kazuo, Okazaki, Shuhei, Manzi, Maria V., Mancusi, Costantino, Izzo, Raffaele, Desvarieux, Moise, Rundek, Tatjana, Gerstein, Hertzel C., Bots, Michiel L., Sweeting, Michael J., Lorenz, Matthias W., and Willeit, Peter

Abstract

Aims: Current guidelines recommend measuring carotid intima-media thickness (IMT) at the far wall of the common carotid artery (CCA). We aimed to precisely quantify associations of near vs. far wall CCA-IMT with the risk for atherosclerotic cardiovascular disease (CVD, defined as coronary heart disease or stroke) and their added predictive values. Methods and results: We analysed individual records of 41 941 participants from 16 prospective studies in the Proof-ATHERO consortium {mean age 61 years [standard deviation (SD) = 11]; 53% female; 16% prior CVD}. Mean baseline values of near and far wall CCA-IMT were 0.83 (SD = 0.28) and 0.82 (SD = 0.27) mm, differed by a mean of 0.02 mm (95% limits of agreement: -0.40 to 0.43), and were moderately correlated [r = 0.44; 95% confidence interval (CI): 0.39-0.49). Over a median follow-up of 9.3 years, we recorded 10 423 CVD events. We pooled study-specific hazard ratios for CVD using random-effects meta-analysis. Near and far wall CCA-IMT values were approximately linearly associated with CVD risk. The respective hazard ratios per SD higher value were 1.18 (95% CI: 1.14-1.22; I² = 30.7%) and 1.20 (1.18-1.23; I² = 5.3%) when adjusted for age, sex, and prior CVD and 1.09 (1.07-1.12; I² = 8.4%) and 1.14 (1.12-1.16; I²=1.3%) upon multivariable adjustment (all P < 0.001). Assessing CCA-IMT at both walls provided a greater C-index improvement than assessing CCA-IMT at one wall only [+0.0046 vs. +0.0023 for near (P < 0.001), +0.0037 for far wall (P = 0.006)]. Conclusions: The associations of near and far wall CCA-IMT with incident CVD were positive, approximately linear, and similarly strong. Improvement in risk discrimination was highest when CCA-IMT was measured at both walls.

Published
2023

5. Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque:Individual Participant Data Meta-Analysis of 20 Prospective Studies

Author

Tschiderer, Lena, Seekircher, Lisa, Izzo, Raffaele, Mancusi, Costantino, Manzi, Maria V., Baldassarre, Damiano, Amato, Mauro, Tremoli, Elena, Veglia, Fabrizio, Tuomainen, Tomi Pekka, Kauhanen, Jussi, Voutilainen, Ari, Iglseder, Bernhard, Lind, Lars, Rundek, Tatjana, Desvarieux, Moise, Kato, Akihiko, de Groot, Eric, Aşçi, Gülay, Ok, Ercan, Agewall, Stefan, Beulens, Joline W.J., Byrne, Christopher D., Calder, Philip C., Gerstein, Hertzel C., Gresele, Paolo, Klingenschmid, Gerhard, Nagai, Michiaki, Olsen, Michael H., Parraga, Grace, Safarova, Maya S., Sattar, Naveed, Skilton, Michael, Stehouwer, Coen D.A., Uthoff, Heiko, van Agtmael, Michiel A., van der Heijden, Amber A., Zozulińska-Ziółkiewicz, Dorota A., Park, Hyun Woong, Lee, Moo Sik, Bae, Jang Ho, Beloqui, Oscar, Landecho, Manuel F., Plichart, Matthieu, Ducimetiere, Pierre, Empana, Jean Philippe, Bokemark, Lena, Bergström, Göran, Schmidt, Caroline, Castelnuovo, Samuela, Calabresi, Laura, Norata, Giuseppe D., Grigore, Liliana, Catapano, Alberico, Zhao, Dong, Wang, Miao, Liu, Jing, Ikram, M. Arfan, Kavousi, Maryam, Bots, Michiel L, Sweeting, Michael J., Lorenz, Matthias W., Willeit, Peter, Tschiderer, Lena, Seekircher, Lisa, Izzo, Raffaele, Mancusi, Costantino, Manzi, Maria V., Baldassarre, Damiano, Amato, Mauro, Tremoli, Elena, Veglia, Fabrizio, Tuomainen, Tomi Pekka, Kauhanen, Jussi, Voutilainen, Ari, Iglseder, Bernhard, Lind, Lars, Rundek, Tatjana, Desvarieux, Moise, Kato, Akihiko, de Groot, Eric, Aşçi, Gülay, Ok, Ercan, Agewall, Stefan, Beulens, Joline W.J., Byrne, Christopher D., Calder, Philip C., Gerstein, Hertzel C., Gresele, Paolo, Klingenschmid, Gerhard, Nagai, Michiaki, Olsen, Michael H., Parraga, Grace, Safarova, Maya S., Sattar, Naveed, Skilton, Michael, Stehouwer, Coen D.A., Uthoff, Heiko, van Agtmael, Michiel A., van der Heijden, Amber A., Zozulińska-Ziółkiewicz, Dorota A., Park, Hyun Woong, Lee, Moo Sik, Bae, Jang Ho, Beloqui, Oscar, Landecho, Manuel F., Plichart, Matthieu, Ducimetiere, Pierre, Empana, Jean Philippe, Bokemark, Lena, Bergström, Göran, Schmidt, Caroline, Castelnuovo, Samuela, Calabresi, Laura, Norata, Giuseppe D., Grigore, Liliana, Catapano, Alberico, Zhao, Dong, Wang, Miao, Liu, Jing, Ikram, M. Arfan, Kavousi, Maryam, Bots, Michiel L, Sweeting, Michael J., Lorenz, Matthias W., and Willeit, Peter

Abstract

Background The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid p

Published
2023

6. Intima-media thickness at the near or far wall of the common carotid artery in cardiovascular risk assessment

Author

Global Health, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Interne Geneeskunde Vasculaire, Nefro Vasculaire Geneeskunde, Cardiovasculaire Epi Team 5, Cardiovasculaire Epidemiologie, Seekircher, Lisa, Tschiderer, Lena, Lind, Lars, Safarova, Maya S., Kavousi, Maryam, Ikram, M. Arfan, Lonn, Eva, Yusuf, Salim, Grobbee, Diederick E., Kastelein, John J.P., Visseren, Frank L.J., Walters, Matthew, Dawson, Jesse, Higgins, Peter, Agewall, Stefan, Catapano, Alberico, De Groot, Eric, Espeland, Mark A., Klingenschmid, Gerhard, Magliano, Dianna, Olsen, Michael H., Preiss, David, Sander, Dirk, Skilton, Michael, Zozulińska-Ziółkiewicz, Dorota A., Grooteman, Muriel P.C., Blankestijn, Peter J., Kitagawa, Kazuo, Okazaki, Shuhei, Manzi, Maria V., Mancusi, Costantino, Izzo, Raffaele, Desvarieux, Moise, Rundek, Tatjana, Gerstein, Hertzel C., Bots, Michiel L., Sweeting, Michael J., Lorenz, Matthias W., Willeit, Peter, Global Health, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Interne Geneeskunde Vasculaire, Nefro Vasculaire Geneeskunde, Cardiovasculaire Epi Team 5, Cardiovasculaire Epidemiologie, Seekircher, Lisa, Tschiderer, Lena, Lind, Lars, Safarova, Maya S., Kavousi, Maryam, Ikram, M. Arfan, Lonn, Eva, Yusuf, Salim, Grobbee, Diederick E., Kastelein, John J.P., Visseren, Frank L.J., Walters, Matthew, Dawson, Jesse, Higgins, Peter, Agewall, Stefan, Catapano, Alberico, De Groot, Eric, Espeland, Mark A., Klingenschmid, Gerhard, Magliano, Dianna, Olsen, Michael H., Preiss, David, Sander, Dirk, Skilton, Michael, Zozulińska-Ziółkiewicz, Dorota A., Grooteman, Muriel P.C., Blankestijn, Peter J., Kitagawa, Kazuo, Okazaki, Shuhei, Manzi, Maria V., Mancusi, Costantino, Izzo, Raffaele, Desvarieux, Moise, Rundek, Tatjana, Gerstein, Hertzel C., Bots, Michiel L., Sweeting, Michael J., Lorenz, Matthias W., and Willeit, Peter

Published
2023

7. Reply

Author

Manzi, Maria V., primary, James, Stefan, additional, Sarno, Giovanna, additional, and Buccheri, Sergio, additional

Published
2023
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11. Low mechano-energetic efficiency is associated with future left ventricular systolic dysfunction in hypertensives

Author

Maria V. Manzi, Costantino Mancusi, Maria Lembo, Giovanni Esposito, Maria A.E. Rao, Giovanni de Simone, Carmine Morisco, Valentina Trimarco, Raffaele Izzo, Bruno Trimarco, Manzi, Maria V, Mancusi, Costantino, Lembo, Maria, Esposito, Giovanni, Rao, Maria A E, de Simone, Giovanni, Morisco, Carmine, Trimarco, Valentina, Izzo, Raffaele, and Trimarco, Bruno

Subjects
Arterial hypertension, Ventricular Dysfunction, Left, Systolic dysfunction, Hypertension, Humans, Heart failure, Stroke Volume, Cardiology and Cardiovascular Medicine, Carotid Intima-Media Thickness, Ventricular Function, Left, Mechano-energetic efficiency
Abstract

Aims: In a hypertensive population with optimal blood pressure control with a long-term follow-up, we aimed at analysing possible predictors of left ventricular (LV) ejection fraction (LVEF) reduction, including indexed mechano-energetic efficiency (MEEi), a well-recognized echo-derived parameter of LV performance. Methods and results: The study population included 5673 hypertensive patients from the Campania Salute Network with a long-term follow-up, normal baseline LVEF (≥50%), and no prevalent cardiovascular (CV) disease. Patients developing LVEF impairment (LVEF

Published
2022

12. Potential effects of the hydrostatic pressure gradient on hyperemic and nonhyperemic pressure ratios.

Author

Florie NHM, Eerdekens R, Manzi MV, Heinrichs E, van 't Veer M, van Royen N, Tonino PAL, and van Nunen LX

Subjects
Humans, Cardiac Catheterization methods, Coronary Angiography methods, Coronary Vessels, Hydrostatic Pressure, Predictive Value of Tests, Severity of Illness Index, Clinical Studies as Topic, Coronary Stenosis, Fractional Flow Reserve, Myocardial, Hyperemia
Abstract

When measuring hyperemic and nonhyperemic pressure ratios with traditional sensor-tipped wires, the inevitable hydrostatic pressure gradient (HPG) may influence treatment decisions. This study aimed to simulate and analyze the effect of a hydrostatic pressure gradient on different indices of functional lesion severity. A hypothetical P d -P a height difference and subsequent hydrostatic pressure gradient based on previous literature was applied to the pressure measurements from the CONTRAST study. The effect on three indices of functional lesion severity (FFR, P d /P a , and dPR) was assessed and possible reclassifications in functional significance by the different indices were analyzed. In 602 pressure tracings, simulated hydrostatic pressure gradients led to an absolute change in P d of 3.18 ± 1.30 mmHg, resulting in an overall increase in FFR, P d /P a, and dPR of 0.02 ± 0.04 for all indices ( P = 0.69). Reclassification due to the hydrostatic pressure gradient when using dichotomous cutoff values occurred in 13.4, 22.3, and 20.6% for FFR, P d /P a , and dPR, respectively. The effect of hydrostatic pressure gradient correction differed among the coronary arteries and was most pronounced in the left anterior descending. When considering the gray zone for the different functional indices, the hydrostatic pressure gradient resulted in reclassification in only one patient out of the complete patient population (1/602; 0.17%). The hydrostatic pressure gradient can influence functional lesion assessment when using dichotomous cutoff values. When taking the gray zone into account, its effect is limited. NEW & NOTEWORTHY This study systematically simulated the effect of hydrostatic pressure gradients (HPG) on real-world hyperemic and nonhyperemic pressure ratios, showing correction for HPG leads to reclassification in functional significance from 13.4 to 22.3% for different functional indices. This was most pronounced in nonhyperemic pressure ratios. A new pressure guidewire (Wirecath) is unaffected by HPG. The ongoing PW-COMPARE study (NCT04802681) prospectively analyzes the magnitude and importance of HPG by simultaneous FFR measurements.

Published
2023
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13. Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta-Analysis of 20 Prospective Studies.

Author

Tschiderer L, Seekircher L, Izzo R, Mancusi C, Manzi MV, Baldassarre D, Amato M, Tremoli E, Veglia F, Tuomainen TP, Kauhanen J, Voutilainen A, Iglseder B, Lind L, Rundek T, Desvarieux M, Kato A, de Groot E, Aşçi G, Ok E, Agewall S, Beulens JWJ, Byrne CD, Calder PC, Gerstein HC, Gresele P, Klingenschmid G, Nagai M, Olsen MH, Parraga G, Safarova MS, Sattar N, Skilton M, Stehouwer CDA, Uthoff H, van Agtmael MA, van der Heijden AA, Zozulińska-Ziółkiewicz DA, Park HW, Lee MS, Bae JH, Beloqui O, Landecho MF, Plichart M, Ducimetiere P, Empana JP, Bokemark L, Bergström G, Schmidt C, Castelnuovo S, Calabresi L, Norata GD, Grigore L, Catapano A, Zhao D, Wang M, Liu J, Ikram MA, Kavousi M, Bots ML, Sweeting MJ, Lorenz MW, and Willeit P

Subjects
Humans, Female, Middle Aged, Male, Carotid Intima-Media Thickness, Prospective Studies, Risk Factors, Carotid Artery, Common diagnostic imaging, Plaque, Atherosclerotic, Carotid Artery Diseases diagnostic imaging, Carotid Artery Diseases epidemiology
Abstract

Background The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I 2 =63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I 2 =59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I 2 =57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.

Published
2023
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