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Sex-specific features of optical coherence tomography detected plaque vulnerability related to clinical outcomes: insights from the CLIMA study

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Abstract

Purpose: To investigate the different impact of optical coherence tomography (OCT)-derived vulnerable plaque features on future adverse events (AEs) according to the biological sex. Methods: The prospective multicenter CLIMA study (ClinicalTrials.gov: NCT02883088) enrolled 1003 patients with OCT plaque analysis of non-treated coronary plaques located in the proximal left anterior descending artery. Sex-specific differences in plaque composition and vulnerable features were described. We investigated the incidence of AEs, including cardiac death, any myocardial infarction and target vessel revascularization at 1-year. Results: Among 1003 patients, 24.6% were women. Women were older and more frequently affected by chronic kidney disease. Dyslipidemia, prior MI and smoking habit were more common in men. At OCT analysis, women had shorter plaque length (p < 0.001), ticker fibrous cap (p = 0.001), smaller maximum lipid arc (p = 0.019), lower macrophage infiltration (p < 0.001) and intra-plaque layered tissue (p = 0.007). During follow-up, 65 AEs were registered. The presence of a thin fibrous cap and a large macrophage infiltration (> 67°) predicted AEs in both sexes. The presence of macrophages (HR 3.38, p = 0.018) and a small minimum lumen area (HR 4.97, p = 0.002) were associated with AEs in women but not in men, while a large lipid arc (> 180°) was associated with AEs in men (HR 2.56, p = 0.003) but not in women. Conclusion: This subanalysis of the CLIMA study investigated for the first-time sex-specific OCT features of plaque vulnerability associated with AEs. Local inflammation was associated with AEs in women and a large lipid arc was predictive in men. OCT may help develop sex-specific risk stratification strategies.

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Abbreviations

ACS:

acute coronary syndromes

CAD:

coronary artery disease

CI:

confidence interval

CRP:

C-reactive protein

FCT:

fibrous cap thickness

OR:

odds ratio

HR:

hazard ratio

IVUS:

intravascular ultrasound

LAD:

left anterior descending artery

MLA:

minimum lumen area

MI:

myocardial infarction

NIRS:

near infrared spectroscopy

NLRP3:

nucleotidebinding domain and leucine-rich repeat pyrin domain containing protein3

OCT:

optical coherence tomography

TFC:

thin fibrous cap

TVR:

target vessel revascularization

References

  1. Jernberg T, Hasvold P, Henriksson M, Hjelm H, Thuresson M, Janzon M (2015) Cardiovascular risk in post-myocardial infarction patients: nationwide real world data demonstrate the importance of a long-term perspective. Eur Heart J 36:1163–1170

    Article  PubMed  Google Scholar 

  2. Mauvais-Jarvis F, Bairey Merz N, Barnes PJ, Brinton RD, Carrero J-J, DeMeo DL et al (2020) Sex and gender: modifiers of health, disease, and medicine. Lancet (London England) 396:565–582

    Article  PubMed  Google Scholar 

  3. Marrugat J, Sala J, Masiá R, Pavesi M, Sanz G, Valle V et al (1998) Mortality differences between men and women following first myocardial infarction. JAMA 280:1405–1409

    Article  CAS  PubMed  Google Scholar 

  4. Collet JP, Thiele H, Barbato E, Barthélémy O, Bauersachs J, Bhatt DL et al (2020) 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation.European heart journal.

  5. Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C et al (2020) 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J 41:407–477

    Article  PubMed  Google Scholar 

  6. Hochman JS, Tamis JE, Thompson TD, Weaver WD, White HD, Van de Werf F et al (1999) Sex, clinical presentation, and outcome in patients with acute coronary syndromes. Global use of strategies to open occluded coronary arteries in Acute coronary syndromes IIb investigators. N Engl J Med 341:226–232

    Article  CAS  PubMed  Google Scholar 

  7. Erlinge D, Maehara A, Ben-Yehuda O, Bøtker HE, Maeng M, Kjøller-Hansen L et al (2021) Identification of vulnerable plaques and patients by intracoronary near-infrared spectroscopy and ultrasound (PROSPECT II): a prospective natural history study. Lancet (London England) 397:985–995

    Article  CAS  PubMed  Google Scholar 

  8. Prati F, Romagnoli E, Gatto L, La Manna A, Burzotta F, Ozaki Y et al (2020) Relationship between coronary plaque morphology of the left anterior descending artery and 12 months clinical outcome: the CLIMA study. Eur Heart J 41:383–391

    Article  PubMed  Google Scholar 

  9. Gatto L, Alfonso F, Paoletti G, Burzotta F, La Manna A, Budassi S et al (2022) Relationship betweeen the amount and location of macrophages and clinical outcome: subanalysis of the CLIMA-study. Int J Cardiol. 2022 Jan 1;346:8-12.

    Article  PubMed  Google Scholar 

  10. Xing L, Higuma T, Wang Z, Aguirre AD, Mizuno K, Takano M et al (2017) Clinical significance of lipid-rich plaque detected by Optical Coherence Tomography: a 4-Year Follow-Up study. J Am Coll Cardiol 69:2502–2513

    Article  PubMed  Google Scholar 

  11. Hoshino M, Yonetsu T, Usui E, Kanaji Y, Ohya H, Sumino Y et al (2019) Clinical significance of the Presence or absence of lipid-rich plaque underneath intact fibrous Cap Plaque in Acute Coronary Syndrome. J Am Heart Association 8:e011820

    Article  Google Scholar 

  12. Waksman R, Di Mario C, Torguson R, Ali ZA, Singh V, Skinner WH et al (2019) Identification of patients and plaques vulnerable to future coronary events with near-infrared spectroscopy intravascular ultrasound imaging: a prospective, cohort study. Lancet (London England) 394:1629–1637

    Article  CAS  PubMed  Google Scholar 

  13. Schuurman AS, Vroegindewey M, Kardys I, Oemrawsingh RM, Cheng JM, de Boer S et al (2018) Near-infrared spectroscopy-derived lipid core burden index predicts adverse cardiovascular outcome in patients with coronary artery disease during long-term follow-up. Eur Heart J 39:295–302

    Article  PubMed  Google Scholar 

  14. Man JJ, Beckman JA, Jaffe IZ (2020) Sex as a Biological Variable in Atherosclerosis. Circul Res 126:1297–1319

    Article  CAS  Google Scholar 

  15. Lansky AJ, Ng VG, Maehara A, Weisz G, Lerman A, Mintz GS et al (2012) Gender and the extent of coronary atherosclerosis, plaque composition, and clinical outcomes in acute coronary syndromes. JACC Cardiovasc imaging 5:S62–72

    Article  PubMed  Google Scholar 

  16. Qian J, Maehara A, Mintz GS, Margolis MP, Lerman A, Rogers J et al (2009) Impact of gender and age on in vivo virtual histology-intravascular ultrasound imaging plaque characterization (from the global virtual histology Intravascular Ultrasound [VH-IVUS] registry). Am J Cardiol 103:1210–1214

    Article  PubMed  Google Scholar 

  17. Ten Haaf ME, Rijndertse M, Cheng JM, de Boer SP, Garcia-Garcia HM, van Geuns RM et al (2017) Sex differences in plaque characteristics by intravascular imaging in patients with coronary artery disease. EuroIntervention: J EuroPCR Collab Working Group Interventional Cardiol Eur Soc Cardiol 13:320–328

    Article  Google Scholar 

  18. Johnson TW, Räber L, di Mario C, Bourantas C, Jia H, Mattesini A et al (2019) Clinical use of intracoronary imaging. Part 2: acute coronary syndromes, ambiguous coronary angiography findings, and guiding interventional decision-making: an expert consensus document of the European Association of Percutaneous Cardiovascular Interventions. Eur Heart J 40:2566–2584

    Article  PubMed  Google Scholar 

  19. Kataoka Y, Puri R, Hammadah M, Duggal B, Uno K, Kapadia SR et al (2016) Sex differences in Nonculprit Coronary Plaque Microstructures on frequency-domain Optical Coherence Tomography in Acute Coronary Syndromes and stable coronary artery disease.Circulation Cardiovascular imaging. ; 9

  20. Mariani L, Burzotta F, Aurigemma C, Romano A, Niccoli G, Leone AM et al (2017) Frequency-domain optical coherence tomography plaque morphology in stable coronary artery disease: sex differences. Coron Artery Dis 28:472–477

    Article  PubMed  Google Scholar 

  21. Wendorff C, Wendorff H, Pelisek J, Tsantilas P, Zimmermann A, Zernecke A et al (2015) Carotid plaque morphology is significantly Associated with Sex, Age, and history of neurological symptoms. Stroke 46:3213–3219

    Article  PubMed  Google Scholar 

  22. Bonaventura A, Mach F, Roth A, Lenglet S, Burger F, Brandt KJ et al (2016) Intraplaque expression of C-Reactive protein predicts Cardiovascular events in patients with severe atherosclerotic carotid artery stenosis. Mediat Inflamm 2016:9153673

    Article  Google Scholar 

  23. Budassi S, Biccirè FG, Paoletti G, Marco V, Boi A, Romagnoli E et al (2022) The Role of the Association between serum C-Reactive protein levels and coronary plaque macrophage Accumulation in Predicting clinical events - results from the CLIMA Registry. J Cardiovasc Transl Res. 2022 Dec;15(6):1377-1384.

    Article  PubMed  Google Scholar 

  24. Kubo T, Ino Y, Mintz GS, Shiono Y, Shimamura K, Takahata M et al (2021) Optical coherence tomography detection of vulnerable plaques at high risk of developing acute coronary syndrome.European heart journal Cardiovascular Imaging.

  25. Fairweather D (2014) Sex differences in inflammation during atherosclerosis. Clin Med Insights Cardiol 8:49–59

    PubMed  Google Scholar 

  26. Bermudez EA, Rifai N, Buring J, Manson JE, Ridker PM (2002) Interrelationships among circulating interleukin-6, C-reactive protein, and traditional cardiovascular risk factors in women. Arteriosclerosis, thrombosis, and vascular biology. 22:1668–1673

  27. Chen S, Markman JL, Shimada K, Crother TR, Lane M, Abolhesn A et al (2020) Sex-specific Effects of the Nlrp3 inflammasome on atherogenesis in LDL receptor-deficient mice. JACC Basic to translational science 5:582–598

    Article  PubMed  PubMed Central  Google Scholar 

  28. Jiang X, Wang F, Wang Y, Gisterå A, Roy J, Paulsson-Berne G et al (2019) Inflammasome-driven Interleukin-1α and Interleukin-1β production in atherosclerotic plaques relates to Hyperlipidemia and Plaque Complexity. 4:304–317JACC Basic to translational science

  29. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C et al (2017) Antiinflammatory therapy with Canakinumab for atherosclerotic disease. N Engl J Med 377:1119–1131

    Article  CAS  PubMed  Google Scholar 

  30. Ridker PM, Rane M (2021) Interleukin-6 signaling and anti-interleukin-6 therapeutics in Cardiovascular Disease. Circul Res 128:1728–1746

    Article  CAS  Google Scholar 

  31. Minami Y, Hou J, Xing L, Jia H, Hu S, Vergallo R et al (2016) Serial optical coherence tomography and intravascular Ultrasound analysis of gender difference in changes of Plaque phenotype in response to lipid-lowering therapy. Am J Cardiol 117:1890–1895

    Article  PubMed  Google Scholar 

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Acknowledgements

We acknowledge the work of all CLIMA study investigators.

Funding

Supported by a grant from the Centro per la Lotta contro l’Infarto – Fondazione Onlus, Rome, Italy.

Author information

Authors and Affiliations

  1. Centro per la Lotta Contro L’Infarto - CLI Foundation, Rome, Italy

    Flavio Giuseppe Biccirè, Caterina Debelak, Giuseppe Varricchione, Simone Budassi, Laura Gatto, Riccardo Di Pietro, Emanuele Sammartini, Valeria Marco, Giulia Paoletti & Francesco Prati

  2. Sapienza University of Rome, Rome, Italy

    Flavio Giuseppe Biccirè & Daniele Pastori

  3. Cardiovascular Sciences Department, San Giovanni Addolorata Hospital, Rome, Italy

    Giuseppe Varricchione, Simone Budassi, Laura Gatto, Riccardo Di Pietro & Francesco Prati

  4. Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy

    Giuseppe Varricchione

  5. Departement of Cardiovascular and Thoracic Sciences, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy

    Enrico Romagnoli & Francesco Burzotta

  6. UniCamillus - Saint Camillus International University of Health Sciences, Rome, Italy

    Giulia Paoletti & Francesco Prati

  7. Department of Cardiology, Fujita Health University Hospital, Toyoake, Japan

    Yukio Ozaki

  8. Department of Cardiology, Hospital Universitario de La Princesa, Madrid, Spain

    Fernando Alfonso

  9. Centre for Inherited Cardiovascular Diseases, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy

    Eloisa Arbustini

  10. Cardiovascular Department Interventional Cardiology Unit, San Giovanni Addolorata Hospital, Via dell’Amba Aradam, 8, 00184, Rome, Italy

    Francesco Prati

Authors
  1. Flavio Giuseppe Biccirè
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  2. Caterina Debelak
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  3. Giuseppe Varricchione
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  4. Simone Budassi
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  5. Laura Gatto
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  6. Enrico Romagnoli
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  7. Riccardo Di Pietro
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  8. Emanuele Sammartini
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  9. Valeria Marco
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  10. Giulia Paoletti
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  11. Francesco Burzotta
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  12. Yukio Ozaki
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  13. Daniele Pastori
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  14. Fernando Alfonso
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  15. Eloisa Arbustini
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  16. Francesco Prati
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Contributions

F.G.B. and F.P. conceptualized the paper and wrote the main manuscript text. Data collection was performed by L.G., E.R., V.M., G.P., F.B., Y.O., F.A., E.A., F.P. Formal analysis was performed by F.G.B., F.P. and D.P. Validation, review and editing were performed by Y.O., F.A., E.A. The first draft of the manuscript was written by F.G.B. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Francesco Prati.

Ethics declarations

Ethics approval

The CLIMA study was performed in line with the principles of the Declaration of Helsinki. Ethics approval was reported in the main paper (European heart journal. 2020;41:383 − 91; https://doi.org/10.1093/eurheartj/ehz520).

Conflict of interest

Dr Francesco Burzotta received speaker’s fees from Terumo, Abiomed, Abbott, Medtronic. Other Authors declare that they have no conflicts of interest. The other authors report no conflicts.

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Biccirè, F.G., Debelak, C., Varricchione, G. et al. Sex-specific features of optical coherence tomography detected plaque vulnerability related to clinical outcomes: insights from the CLIMA study. Int J Cardiovasc Imaging 39, 873–881 (2023). https://doi.org/10.1007/s10554-022-02775-w

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