The Tip of The Iceberg: Non-Calcified Coronary Plague and Epicardial Adipose Tissue

Keywords
Adipose Tissue / pathology; Coronary Artery Disease; Calcium Signaling; Biomarkers / analysis; Radionuclide Imaging; Tomography, Emission Computed

To the Editor,

I have read with great interest the article entitled "Relationship between Calcium Score and Myocardial Scintigraphy in the Diagnosis of Coronary Disease" by Siqueira et al.,¹ recently published in Arquivos Brasileiros de Cardiologia 2016; 107:367-74. The investigators reported the possibility of removing extensive coronary artery disease (CAD) by means of a zero calcium score, or by indicating the presence of an extensive disease when it is severely increased, which justifies the use of this method in the initial or joint evaluation in asymptomatic patients with suspected CAD and in cardiovascular risk stratification. The evaluation of symptomatic low-risk patients, despite suggestive evidence, should be re-evaluated in upcoming guidelines.¹

Epicardial adipose tissue (EAT) is anatomically contiguous with the myocardium and several studies have shown it to be a potential contributing factor for coronary atherosclerosis.² EAT is a type of visceral adipose tissue with paracrine and endocrine effects.³ EAT serves as an energy source for the myocardium and it is known to secrete proatherogenic cytokines.³ Increased EAT is not only associated with a higher prevalence of CAD but it is also a prognostic parameter for future cardiovascular events, and, eventually, cardiovascular mortality.⁴ Hwang et al.⁵ have reported that a high epicardial fat volume index determined by computed tomography was an independent risk factor for the future development of non-calcified coronary plaque even after adjustment for traditional cardiovascular risk factors.

In the light of these findings, assessment of EAT by computed tomography might be beneficial as a part of further evaluation for future cardiovascular events.

References

• ¹
  Siqueira FP, Mesquita CT, Santos AA, Nacif MS. Relationship between calcium score and myocardial scintigraphy in the diagnosis of coronary disease. Arq Bras Cardiol. 2016;107(4):365-74.
• ²
  Lee HY, Després JP, Koh KK. Perivascular adipose tissue in the pathogenesis of cardiovascular disease. Atherosclerosis. 2013;230(2):177-84.
• ³
  Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, et al. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation. 2003;108(20):2460-6.
• ⁴
  Mahabadi AA, Berg MH, Lehmann N, Kälsch H, Bauer M, Kara K, et al. Association of epicardial fat with cardiovascular risk factors and incident myocardial infarction in the general population: the Heinz Nixdorf Recall Study. J Am Coll Cardiol. 2013;61(13):1388-95.
• ⁵
  Hwang IC, Park HE, Choi SY. Epicardial adipose tissue contributes to the development of non-calcified coronary plaque: a 5-year computed tomography follow-up study. J Atheroscler Thromb. 2016 Aug 9. [Epub ahead of print].

Reply

We would like to thank you for your interest and comments related to our recent article.¹ We believe the great scientific basis referent to coronary calcium quantification clearly demonstrates the importance of this method in the stratification of asymptomatic patients with low to intermediate cardiovascular risk.^2-7

Recent publications related to calcium score (CS) continue to point to flaws in clinical score classifications and reinforce their ability to distinguish the different cardiovascular events risk groups. The role of clinical score reclassification, when CS is implemented, is a warning to its clinical applicability.^2-7 Population studies with long periods of follow-up^2-7 have demonstrated that the use of CS is one of the best tools to determine cardiovascular risk, even when compared to other markers.⁷

The potential use of CS is not limited to cardiovascular risk evaluation, for it has proven to be a useful tool in the primary prevention and adequate treatment of sub-clinical forms of coronary artery disease.^8-15 The presence of a zero CS is indicative of a very low risk, often exempting the patient from early preventive treatment with statins.^8-11 On the other hand, in the presence of a CS that is not zero, and especially > 100 Agatston, therapeutic introduction may be recommended, even in patients who do not fit the indication of current guidelines for the use of statins and other medications, such as anti-hypertensives.^10-15

Important changes in the guidelines can already be seen, putting CS in the recommendation class I for some of its indications.¹⁶ However, there still are some discrepant recommendations,^17-20 such as in orientations about the beginning of treatment for cardiovascular risk reduction, that still do not include coronary calcification data, even with robust data that support this positioning.^21-22

Therefore, we believe that in the next few years, this method will take on a growing importance in clinical guidelines, aiding in a more adequate follow-up of low to intermediate risk patients.

Yours truly,

Fabio Paiva Rossini Siqueira,

Claudio Tinoco Mesquita,

Alair Augusto Sarmet M. Damas dos Santos,

Marcelo Souto Nacif

References

• ¹
  Siqueira FP, Mesquita CT, Santos AA, Nacif MS. Relationship between calcium score and myocardial scintigraphy in the diagnosis of coronary disease. Arq Bras Cardiol. 2016;107(4):365-74.
• ²
  Valenti V, Ó Hartaigh B, Heo R, Cho I, Schulman-Marcus J, Gransar H, et al. A 15-year warranty period for asymptomatic individuals without coronary artery calcium: a prospective follow-up of 9,715 individuals. JACC Cardiovasc Imaging. 2015;8(8):900-9.
• ³
  Shaw LJ, Giambrone AE, Blaha MJ, Knapper JT, Berman DS, Bellam N, et al. Long-term prognosis after coronary artery calcification testing in asymptomatic patients: a cohort study. Ann Intern Med. 2015;163(1):14-21.
• ⁴
  McClelland RL, Jorgensen NW, Budoff M, Blaha MJ, Post WS, Kronmal RA, et al. 10-year coronary heart disease risk prediction using coronary artery calcium and traditional risk factors: derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) with validation in the HNR (Heinz Nixdorf Recall) Study and the DHS (Dallas Heart Study). J Am Coll Cardiol. 2015;66(15):1643-53.
• ⁵
  Blaha MJ, Cainzos-Achirica M, Greenland P, McEvoy JW, Blankstein R, Budoff MJ, et al. Role of coronary artery calcium score of zero and other negative risk markers for cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2016;133(9):849-58.
• ⁶
  Diederichsen AC, Mahabadi AA, Gerke O, Lehmann N, Sand NP, Moebus S, et al. Increased discordance between HeartScore and coronary artery calcification score after introduction of the new ESC prevention guidelines. Atherosclerosis. 2015;239(1):143-9.
• ⁷
  Joshi PH, Patel B, Blaha MJ, Berry JD, Blankstein R, Budoff MJ, et al. Coronary artery calcium predicts cardiovascular events in participants with a low lifetime risk of cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2016;246:367-73.
• ⁸
  Pursnani A, Massaro JM, D'Agostino RB, O'Donnell CJ, Hoffmann U. Guideline-based statin eligibility, coronary artery calcification, and cardiovascular events. JAMA. 2015;314(2):134-41.
• ⁹
  Nasir K, Bittencourt MS, Blaha MJ, Blankstein R, Agatson AS, Rivera JJ, et al. Implications of coronary artery calcium testing among statin candidates according to American College of Cardiology/American Heart Association Cholesterol Management Guidelines: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol. 2015;66(15):1657-68.
• ¹⁰
  Isma'eel H, Min D, Al-Shaar L, Hachamovitch R, Halliburton S, Gentry J, et al. Assessing Level of Agreement for Atherosclerotic Cardiovascular Disease Risk Categorization Between Coronary Artery Calcium Score and the American College of Cardiology/American Heart Association Cardiovascular Prevention Guidelines and the Potential Impa. Am J Cardiol. 2016;118(10):1480-5.
• ¹¹
  Waheed S, Pollack S, Roth M, Reichek N, Guerci A, Cao JJ. Collective impact of conventional cardiovascular risk factors and coronary calcium score on clinical outcomes with or without statin therapy: The St Francis Heart Study. Atherosclerosis. 2016;255:193-9.
• ¹²
  Martin SS, Blaha MJ, Blankstein R, Agatston A, Rivera JJ, Virani SS, et al. Dyslipidemia, coronary artery calcium, and incident atherosclerotic cardiovascular disease: implications for statin therapy from the multi-ethnic study of atherosclerosis. Circulation. 2014;129(1):77-86.
• ¹³
  McEvoy JW, Martin SS, Dardari ZA, Miedema MD, Sandfort V, Yeboah J, et al. Coronary artery calcium to guide a personalized risk-based approach to initiation and intensification of antihypertensive therapy. Circulation. 2017;135(2):153-65.
• ¹⁴
  Miedema MD, Duprez DA, Misialek JR, Blaha MJ, Nasir K, Silverman MG, et al. Use of coronary artery calcium testing to guide aspirin utilization for primary prevention: estimates from the multi-ethnic study of atherosclerosis. Circ Cardiovasc Qual Outcomes. 2014;7(3):453-60.
• ¹⁵
  Darabian S, Luo Y, Homat A, Khosraviani K, Wong N, Zeb I, et al. CAC score as a possible criterion for administration of angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers: the MultiEthnic Study of Atherosclerosis. Coron Artery Dis. 2015;26(8):678-85.
• ¹⁶
  Sara L, Szarf G, Tachibana A, Shiozaki AA, Villa AV, de Oliveira AC, et al; Sociedade Brasileira de Cardiologia; Colégio Brasileiro de Radiologia. [II Guidelines on Cardiovascular Magnetic Resonance and Computed Tomography of the Brazilian Society of Cardiology and the Brazilian College of Radiology]. Arq Bras Cardiol. 2014;103(6 Suppl 3):1-86.
• ¹⁷
  Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016;37(29):2315-81.
• ¹⁸
  Mahabadi AA, Möhlenkamp S, Lehmann N, Kälsch H, Dykun I, Pundt N, et al; Heinz Nixdorf Recall Study Investigators. CAC score improves coronary and CV risk assessment above statin indication by ESC and AHA/ACC Primary Prevention Guidelines. JACC Cardiovasc Imaging. 2017;10(2):143-53.
• ¹⁹
  Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB Sr, Gibbons R, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2935-59. Erratum in: J Am Coll Cardiol. 2014;63(25 Pt B):3026.
• ²⁰
  Wolk MJ, Bailey SR, Doherty JU, Douglas PS, Hendel RC, Kramer CM, et al; American College of Cardiology Foundation Appropriate Use Criteria Task Force. ACCF/AHA/ASE/ASNC/HFSA/HRS/SCAI/SCCT/SCMR/STS 2013 multi- modality appropriate use criteria for the detection and risk assessment of stable ischemic heart disease: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2014;63(4):380-406.
• ²¹
  Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2889-934. Erratum in: J Am Coll Cardiol. 2015;66(24):2812; J Am Coll Cardiol. 2014;63(25 Pt B):3024-5.
• ²²
  Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J. 2016;37(39):2999-3058.

Publication Dates

• Publication in this collection
  Apr 2017

History

• Received
  28 Oct 2016
• Reviewed
  19 Jan 2017
• Accepted
  19 Jan 2017