Asymptomatic coronary artery disease in a Norwegian cohort with type 2 diabetes: a prospective angiographic study with intravascular ultrasound evaluation

Satish Arora, Anne Pernille Ofstad, Geir R Ulimoen, Kåre I Birkeland, Knut Endresen, Lars Gullestad, Odd Erik Johansen, Satish Arora, Anne Pernille Ofstad, Geir R Ulimoen, Kåre I Birkeland, Knut Endresen, Lars Gullestad, Odd Erik Johansen

Abstract

Aims: The prevalence of asymptomatic coronary artery disease (CAD) in type 2 diabetes (T2D) is unclear. We investigated the extent and prevalence of asymptomatic CAD in T2D patients by utilizing invasive coronary angiography (ICA) and intravascular ultrasound (IVUS), and whether CAD progression, evaluated by ICA, could be modulated with a multi-intervention to reduce cardiovascular (CV) risk.

Methods: Fifty-six T2D patients with ≥ 1 additional CV risk factor participated in a 2 year randomized controlled study comparing hospital-based multi-intervention (multi, n = 30) versus standard care (stand, n = 26), with a pre-planned follow-up at year seven. They underwent ICA at baseline and both ICA and IVUS at year seven. ICA was described by conventional CAD severity and extent scores. IVUS was described by maximal intimal thickness (MIT), percent and total atheroma volume and compared with individuals without T2D and CAD (heart transplant donors who had IVUS performed 7-11 weeks post-transplant, n = 147).

Results: Despite CV risk reduction in multi after 2 years intervention, there was no between-group difference in the progression of CAD at year seven. Overall, the prevalence of CAD defined by MIT ≥ 0.5 mm in the T2DM subjects was 84%, and as compared to the non-T2DM controls there was a significantly higher atheroma burden (mean MIT, PAV and TAV in the T2D population were 0.75 ± 0.27 mm, 33.8 ± 9.8% and 277.0 ± 137.3 mm3 as compared to 0.41 ± 0.19 mm, 17.8 ± 7.3% and 134.9 ± 100.6 mm3 in the reference population).

Conclusion: We demonstrated that a 2 year multi-intervention, despite improvement in CV risk factors, did not influence angiographic progression of CAD. Further, IVUS revealed that the prevalence of asymptomatic CAD in T2D patients is high, suggesting a need for a broader residual CV risk management using alternative approaches. Trial registration Clinical trials.gov id: NCT00133718 ( https://ichgcp.net/clinical-trials-registry/NCT00133718 ).

Keywords: Atheroma burden; Coronary artery disease; Intravascular ultrasound; Invasive coronary angiography; Multi-factorial treatment; Type 2 diabetes mellitus.

Figures

Fig. 1
Fig. 1
Coronary artery disease (CAD) severity (a) and extent (b) score according to treatment group, p indicates p-value for between-group difference in change in CAD severity and extent score from baseline to 7 years
Fig. 2
Fig. 2
Comparison of quantitative IVUS measurements in the T2D study population (n = 59) with a reference population (donor heart transplants) without known coronary artery disease or type 2 diabetes (n = 147)
Fig. 3
Fig. 3
Age-stratified prevalence of coronary heart disease (defined as MIT ≥ 0.5 mm) in the T2D study population (n = 59) with a reference population (heart transplant donors) without coronary artery disease or type 2 diabetes (n = 147). MIT maximal intima thickness, T2D type 2 diabetes

References

    1. Diabetes Atlas 8th Edition. International Diabetes Federation. . Accessed Sept 10 2018.
    1. Stratmann B, Tschoepe D. Heart in diabetes: not only a macrovascular disease. Diabetes Care. 2011;34(Suppl 2):S138–S144.
    1. Fox CS. Cardiovascular disease risk factors, type 2 diabetes mellitus, and the Framingham Heart Study. Trends Cardiovasc Med. 2010;20(3):90–95.
    1. Martin-Timon I, Sevillano-Collantes C, Segura-Galindo A, Del Canizo-Gomez FJ. Type 2 diabetes and cardiovascular disease: have all risk factors the same strength? World J Diabetes. 2014;5(4):444–470.
    1. The American Diabetes Association. The National Heart, Lung, and Blood Institute. The Juvenile Diabetes Foundation International. The National Institute of Diabetes and Digestive and Kidney Diseases. The American Heart Association Diabetes mellitus: a major risk factor for cardiovascular disease. A joint editorial statement. Circulation. 1999;100(10):1132–1133.
    1. Bravo PE, Psaty BM, Di Carli MF, Branch KR. Identification of coronary heart disease in asymptomatic individuals with diabetes mellitus: to screen or not to screen. Colombia Med. 2015;46(1):41–46.
    1. Summary of Revisions Standards of medical care in diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S4–S6.
    1. Young LH, Wackers FJ, Chyun DA, Davey JA, Barrett EJ, Taillefer R, et al. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA. 2009;301(15):1547–1555.
    1. Ryden L, Grant PJ, Anker SD, Berne C, Cosentino F, Danchin N, et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD) Eur Heart J. 2013;34(39):3035–3087.
    1. Norgaard BL, Leipsic J, Koo BK, Zarins CK, Jensen JM, Sand NP, et al. Coronary computed tomography angiography derived fractional flow reserve and plaque stress. Curr Cardiovasc Imaging Rep. 2016;9:2.
    1. Nissen SE, Yock P. Intravascular ultrasound: novel pathophysiological insights and current clinical applications. Circulation. 2001;103(4):604–616.
    1. Tuzcu EM, Kapadia SR, Sachar R, Ziada KM, Crowe TD, Feng J, et al. Intravascular ultrasound evidence of angiographically silent progression in coronary atherosclerosis predicts long-term morbidity and mortality after cardiac transplantation. J Am Coll Cardiol. 2005;45(9):1538–1542.
    1. Johansen OE, Gullestad L, Blaasaas KG, Orvik E, Birkeland KI. Effects of structured hospital-based care compared with standard care for Type 2 diabetes-The Asker and Baerum Cardiovascular Diabetes Study, a randomized trial. Diabet Med. 2007;24(9):1019–1027.
    1. American Diabetes Association Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2002;25(1):213–229.
    1. Ofstad AP, Ulimoen GR, Orvik E, Birkeland KI, Gullestad LL, Fagerland MW, et al. Long-term follow-up of a hospital-based, multi-intervention programme in type 2 diabetes mellitus: impact on cardiovascular events and death. J Int Med Res. 2017;45(5):1535–1552.
    1. Ledru F, Ducimetiere P, Battaglia S, Courbon D, Beverelli F, Guize L, et al. New diagnostic criteria for diabetes and coronary artery disease: insights from an angiographic study. J Am Coll Cardiol. 2001;37(6):1543–1550.
    1. Mintz GS, Nissen SE, Anderson WD, Bailey SR, Erbel R, Fitzgerald PJ, et al. American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2001;37(5):1478–1492.
    1. Bax JJ, Inzucchi SE, Bonow RO, Schuijf JD, Freeman MR, Barrett EJ. Cardiac imaging for risk stratification in diabetes. Diabetes Care. 2007;30(5):1295–1304.
    1. Budoff MJ, Raggi P, Beller GA, Berman DS, Druz RS, Malik S, et al. Noninvasive cardiovascular risk assessment of the asymptomatic diabetic patient: The Imaging Council of the American College of Cardiology. JACC Cardiovasc Imaging. 2016;9(2):176–192.
    1. Bulugahapitiya U, Siyambalapitiya S, Sithole J, Idris I. Is diabetes a coronary risk equivalent? Systematic review and meta-analysis. Diabet Med. 2009;26(2):142–148.
    1. Rahmani S, Nakanishi R, Budoff MJ. Imaging atherosclerosis in diabetes: current state. Curr Diab Rep. 2016;16(11):105.
    1. Bates RE, Omer M, Abdelmoneim SS, Arruda-Olson AM, Scott CG, Bailey KR, et al. Impact of stress testing for coronary artery disease screening in asymptomatic patients with diabetes mellitus: a community-based study in Olmsted County, Minnesota. Mayo Clin Proc. 2016;91(11):1535–1544.
    1. Rajagopalan N, Miller TD, Hodge DO, Frye RL, Gibbons RJ. Identifying high-risk asymptomatic diabetic patients who are candidates for screening stress single-photon emission computed tomography imaging. J Am Coll Cardiol. 2005;45(1):43–49.
    1. Beller E, Meinel FG, Schoeppe F, Kunz WG, Thierfelder KM, Hausleiter J, et al. Predictive value of coronary computed tomography angiography in asymptomatic individuals with diabetes mellitus: systematic review and meta-analysis. J Cardiovasc Comput Tomogr. 2018;12(4):320–328.
    1. Guaricci AI, Lorenzoni V, Guglielmo M, Mushtaq S, Muscogiuri G, Cademartiri F, et al. Prognostic relevance of subclinical coronary and carotid atherosclerosis in a diabetic and nondiabetic asymptomatic population. Clin Cardiol. 2018;41(6):769–777.
    1. Jeevarethinam A, Venuraju S, Dumo A, Ruano S, Rosenthal M, Nair D, et al. Usefulness of carotid plaques as predictors of obstructive coronary artery disease and cardiovascular events in asymptomatic individuals with diabetes mellitus. Am J Cardiol. 2018;121(8):910–916.
    1. Swoboda PP, Erhayiem B, Kan R, McDiarmid AK, Garg P, Musa TA, et al. Cardiovascular magnetic resonance measures of aortic stiffness in asymptomatic patients with type 2 diabetes: association with glycaemic control and clinical outcomes. Cardiovasc Diabetol. 2018;17(1):35.
    1. Raggi P, Shaw LJ, Berman DS, Callister TQ. Prognostic value of coronary artery calcium screening in subjects with and without diabetes. J Am Coll Cardiol. 2004;43(9):1663–1669.
    1. Anand DV, Lim E, Hopkins D, Corder R, Shaw LJ, Sharp P, et al. Risk stratification in uncomplicated type 2 diabetes: prospective evaluation of the combined use of coronary artery calcium imaging and selective myocardial perfusion scintigraphy. Eur Heart J. 2006;27(6):713–721.
    1. Yoshida N, Yamamoto H, Shinke T, Otake H, Kuroda M, Terashita D, et al. Impact of CD14(++)CD16(+) monocytes on plaque vulnerability in diabetic and non-diabetic patients with asymptomatic coronary artery disease: a cross-sectional study. Cardiovasc Diabetol. 2017;16(1):96.
    1. Moise A, Theroux P, Taeymans Y, Waters DD, Lesperance J, Fines P, et al. Clinical and angiographic factors associated with progression of coronary artery disease. J Am Coll Cardiol. 1984;3(3):659–667.
    1. Won KB, Han D, Lee JH, Lee SE, Sung JM, Choi SY, et al. Evaluation of the impact of glycemic status on the progression of coronary artery calcification in asymptomatic individuals. Cardiovasc Diabetol. 2018;17(1):4.
    1. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348(5):383–393.
    1. Ueki K, Sasako T, Okazaki Y, Kato M, Okahata S, Katsuyama H, et al. Effect of an intensified multifactorial intervention on cardiovascular outcomes and mortality in type 2 diabetes (J-DOIT3): an open-label, randomised controlled trial. Lancet Diabetes Endocrinol. 2017;5:951–964.
    1. Gerstein HC, Miller ME, Byington RP, Goff DC, Jr, Bigger JT, Buse JB, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545–2559.
    1. Muhlestein JB, Lappe DL, Lima JA, Rosen BD, May HT, Knight S, et al. Effect of screening for coronary artery disease using CT angiography on mortality and cardiac events in high-risk patients with diabetes: the FACTOR-64 randomized clinical trial. JAMA. 2014;312(21):2234–2243.
    1. Kataoka Y, Yasuda S, Miyamoto Y, Sase K, Kosuge M, Kimura K, et al. Effects of voglibose and nateglinide on glycemic status and coronary atherosclerosis in early-stage diabetic patients. Circ J. 2012;76(3):712–720.
    1. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–2128.
    1. Nauck MA, Meier JJ, Cavender MA, Abd El Aziz M, Drucker DJ. Cardiovascular actions and clinical outcomes with glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Circulation. 2017;136(9):849–870.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa