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Cardiology Research

Original Article

Volume 9, Number 1, February 2018, pages 22-27

Early Diagnosis and Treatment of Coronary Heart Disease in Asymptomatic Subjects With Advanced Vascular Atherosclerosis of the Carotid Artery (Type III and IV b Findings Using Ultrasound) and Risk Factors

Within the scope of an occupational screening program in the Koblenz area people working in diverse sectors of the economy such as chemicals, glass, pharmaceuticals, administration, steel production, social services, paper production, printing, ceramics, IT, university, universities of applied science and retail were given the opportunity to determine their risk of heart attack. During the study the total plaque area (TPA), the maximum plaque thickness in the carotid artery and the PROCAM-Scores of 6,008 healthy subjects (who had had no previous history of a cardiovascular event) between the ages of 20 and 64 years (3,748 men and 2,260 women) were determined.

In the mean follow-up study of period of 47.3 ± 23 months, eight strokes and 31 heart attacks have occurred to date. A total of 10 bypass operations and nine stent implantations have been performed, and stenoses (30% - 100% respectively) have been revealed in seven patients who underwent a coronary angiogram. Five subjects exhibited a type III finding and 45 subjects a type IV b finding in the ultrasound examination of the baseline study.

The testing method involving the measurement of plaque burden and maximum plaque thickness was validated by means of a blinded examination of 500 patients in hospital 1 day prior to a scheduled coronary angiogram. This allowed the classification of the ultrasound findings into four types [1]. Study of the patients with a type III or a type IV b finding in the ultrasound examination revealed one, two or three-vessel disease in 83% of the cases. Totally 87% of the patients suffering from a stenosing coronary heart condition were accurately predicted (type III or type IV b finding during the carotid duplex).

Subsequently, 464 healthy subjects (84 of them women) with a type III or type IV b finding were contacted and specifically asked if they had experienced, or were experiencing symptoms such as exertional dyspnea or angina pectoris. Totally 39 subjects (32 men and 7 women aged between 43 and 61 years) complained of exertional dyspnea or of atypical angina pectoris or typical angina pectoris. In the case of all subjects there was advanced atherosclerosis of the carotid artery (type III or type IV b finding), and further cardiac assessment was recommended.

In the final analysis three patients had entirely smooth coronary arteries, seven had coronary sclerosis, eight had a 30-40%, and 21 patients had a stenosis ≥ 50%. A stent was inserted into seven of these patients and two patients underwent emergency bypass surgery following a coronary angiogram (both patients had main stem stenosis, three-vessel disease) [2].

In a pilot study 33 asymptomatic subjects with a type III or IV b finding in the ultrasound examination and with at minimum one risk factor (LDL-cholesterol ≥ 180 mg/dL, HDL-cholesterin ≤ 40 mg/dL, positive family history) were assessed using a computed tomography (CT) coronary angiogram. Additional 10 asymptomatic subjects were examined independently to undergo further cardiac examinations.

The carotid artery (common carotid artery both externally and internally using B-mode ultrasound) was examined on both sides, as far as could be made visible, for plaques on the long and short axis from the clavicle through to the temporomandibular joint in a caudal to cranial direction by means of anterior, anterolateral, lateral and posterolateral insonation. A portable ultrasound device with a 10 MHz linear transducer of the type Imagic Agile and manufactured by the company Kontron Medical was used during testing. Only carotid artery wall thickness increases with an intima media thickness (IMT) > 1mm were evaluated as plaque. Using the device’s surface area measurement program it was possible to identify all the plaques in a longitudinal section (the sum total of all plaque surface areas TPA) by tracing the perimeter of each plaque with the cursor at its maximum enlargement in the B-mode image. Furthermore, the maximum plaque thickness was measured. The findings of the ultrasound examinations were classified according to four types ranging from type I to type IV b [1].

Type I: no or only minimal atherosclerosis of the carotid artery with a TPA of up to 24 mm²; Type II a: only flat plaques ≤ 2mm IMT with plaque surface area < age- related cut-off in the carotid artery; Type II b: only flat plaques ≤ 2mm IMT with a large plaque surface area above age-related cut-off in the carotid artery; Type III: carotid plaques with an IMT ≥ 3.5 mm and a plaque surface area < age-related cut-off; Type IV (mixed type): a) with flat carotid plaques and plaques > 2 mm IMT and a plaque surface area < age-related cut-off, b) with flat carotid plaques and plaques > 2mm IMT and a large plaque surface area over age-related cut-off.

The TPA cut-off in the case of subjects < 40 years of age is 60 mm², from 40 to 49 years of age is 80 mm², from 50 to 59 years of age is 110 mm², and from 60 to 64 years of age is 130 mm². The cut-off for maximum plaque thickness is > 2 mm, or irrespective of the TPA is ≥ 3.5 mm.

According to this classification it was possible to predict coronary stenosis in patients who were examined one day prior to their undergoing a coronary angiogram with a sensitivity level of 87% [1].

Totally 40 subjects were assessed using a CT coronary angiogram (80 row MS-CT Toshiba Aquillon Prime) with native scan and bolus triggered contrast media and in three subjects directly using coronary angiograms because of pathological exercise ECG or dysrhythmia.

The study was approved by the responsible Ethics Committee and Federal Office for Radiation Protection.

The initial cardiac diagnostic testing was conducted on 40 subjects using a CT coronary angiogram and three subjects were assessed using coronary angiogram.

An ultrasound examination of the carotid artery of 40 patients revealed a type IV b finding, and in three subjects the examination revealed a type III finding.

In the final analysis five subjects had entirely smooth coronary arteries, six had coronary sclerosis, eight had a 30% stenosis, one patient had a 30-50% stenosis and 23 patients had a stenosis ≥ 50%. A stent was inserted into five of these patients and two patients underwent emergency bypass surgery following a coronary angiogram (both patients had main stem stenosis, three-vessel disease)

Table 1 gives an overview of the clinical data. Table 2 gives an overview of the baseline-data of the assessed subjects.

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Table 1. Test Results of the 43 Asymptomatic Subjects With a Type III or IV b Finding in the Ultrasound Examination

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Table 2. Baseline Characteristics of All Subjects Between the Ages of 35 to 64 Years

Atherosclerosis is an inflammatory disease of the arteries and continues to be the most common cause of death (40%) in the developed industrial nations. The disease can even begin from the age of 20 years and often remains undetected until it is in its later stages, resulting in clinical events such as acute coronary syndrome, stable angina, apoplexy and peripheral artery disease (PAD). Several studies demonstrate that even insignificant coronary stenoses are associated with an increased risk of heart attack [3-5]. An extensive multicenter research study (CONFIRM-Study) using 27,000 CT coronary angiograms revealed that statin therapy contributes towards an improvement in survival chances even in the case of stenoses < 50% [6]. The improvement in survival chances achieved by using statin therapy in the group of subjects with non-obstructive coronary heart disease (CHD) was at a hazard ratio of 0.39; 95% confidence interval (CI) (0.23 - 0.65); P < 0.001.This effect was not verifiable in the group with normal coronary arteries. It therefore appears important that atherosclerosis is both diagnosed and treated in its early stages in order to delay the final outcome of the disease as long into the future as is possible. Several studies revealed that statin therapy contributes towards an improvement in survival chances in primary prevention [7-9] and that that subjects with advanced carotid atherosclerosis have significantly increased risk for heart attack and stroke [10-25].

In total, 382 of the examined men and 82 of the examined women showed this finding. In the follow-up study it was found that 49% of the men and 33% of the women who were examined with ultrasound between 2009 and 2011 and showed a type III or type IV b finding were already diseased.

In total, 23.7% of the men and women with a type III or IV b finding are diseased (e.g. apoplex, infarction, bypass-operation, stent, coronary stenosis ≥ 30%). In the baseline examination with ultrasound 80% of the 65 diseased men and women in the follow-up showed a type III or IV b finding. Overall, 10% of the 82 subjects (39 symptomatic, 43 asymptomatic) who were examined with a cardiac CT or a coronary angiography showed smooth vessels, 74% showed a coronary stenosis of 30-100% and 53% a stenosis ≥ 50%. The correlation between atherosclerosis of the carotid artery and the coronary vessels in the case of asymptomatic subjects has been studied many times with the result that the positive predictive value (PPV) for CHD was significantly lower [26-30]. A possible reason for this result could be that the plaque burden of the carotid artery has not been quantified. For the 82 subjects the PPV for a coronary stenosis ≥ 30% is 0.74; (95% CI: 0.64 - 0.83). Interestingly, the results for the symptomatic and asymptomatic cohort are almost identical. Measuring plaque burden of carotid artery with quantification of the TPA and the maximal plaque thickness is a cost-effective, non-invasive screening tool without side effects which can be used to diagnose and to treat CHD in an early stadium. Assuming a prevalence of CHD of 5.5% for healthy men aged between 35 and 64 years and a senstitivity of the examination method of 80% for diagnosing coronary stenosis one finds the negative predictive value (NPV) to be 99% for the case of no type III or IV b finding. The actual results justify a therapy with statins for asymptomatic men and women with advanced atherosclerosis of the carotid artery. Though this kind of therapy is recommended in the current guidelines in the case of diagnosed plaques, there is no exact quantification of the total amount of plaque burden [31]. Because 96% of the men aged between 60 and 64 years show plaques in the carotid artery, a therapy with statins would certainly lead to an overtreatment.

The limitation of this research is that only a small number of asymptomatic subjects were examined.

Asymptomatic subjects with advanced atherosclerosis of the carotid artery (type III or type IV b finding) have a high risk of CHD and should be treated with statins.

TPA and plaque thickness measurement using ultrasound is a low-cost and simple screening method, and advisable for everyone over the age of 35 years.

Conflict of Interest

The authors confirm that they have no conflict of interest.

Abbreviations

TPA: total plaque area; FA: Family history positive; DM: Diabetes mellitus; HDL: HDL-cholesterol ≤ 40 mg/dL; LDL: LDL-cholesterol ≥ 180 mg/dL; AP: Angina pectoris; Coro: Coronary angiogram; CT: Computer tomography; HS: Left main; RF: Risk factor; Nik: Nicotine use; KHK: Coronary artery disease; PTP: Pre-test probability; GE: Vascular disease; ACS: Acute coronary syndrome

1. Adams A, Bojara W. Vorhersage einer stenosierenden KHK durch Bestimmung von Plaque-Flache und-Dicke vs. IMT an der A. carotis. Herz. 2015;40(5):817-822.
   doi pubmed
2. Adams A, Bojara W, Schunk K. Early diagnosis and treatment of coronary heart disease in symptomatic subjects with advanced vascular atherosclerosis of the carotid artery (Type III and IV b Findings Using Ultrasound). Cardiol Res. 2017;8(1):7-12.
   doi pubmed
3. Proudfit WL, Bruschke VG, Sones FM, Jr. Clinical course of patients with normal or slightly or moderately abnormal coronary arteriograms: 10-year follow-up of 521 patients. Circulation. 1980;62(4):712-717.
   doi pubmed
4. Stone GW, Maehara A, Lansky AJ, de Bruyne B, Cristea E, Mintz GS, Mehran R, et al. A prospective natural-history study of coronary atherosclerosis. N Engl J Med. 2011;364(3):226-235.
   doi pubmed
5. Maddox TM, Stanislawski MA, Grunwald GK, Bradley SM, Ho PM, Tsai TT, Patel MR, et al. Nonobstructive coronary artery disease and risk of myocardial infarction. JAMA. 2014;312(17):1754-1763.
   doi pubmed
6. Chow BJ, Small G, Yam Y, Chen L, McPherson R, Achenbach S, Al-Mallah M, et al. Prognostic and therapeutic implications of statin and aspirin therapy in individuals with nonobstructive coronary artery disease: results from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry) registry. Arterioscler Thromb Vasc Biol. 2015;35(4):981-989.
   doi pubmed
7. Cholesterol Treatment Trialists C, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-1681.
   doi
8. Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial - Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361(9364):1149-1158.
   doi
9. L’Italien G, Ford I, Norrie J, LaPuerta P, Ehreth J, Jackson J, Shepherd J. The cardiovascular event reduction tool (CERT) - a simplified cardiac risk prediction model developed from the West of Scotland Coronary Prevention Study (WOSCOPS). Am J Cardiol. 2000;85(6):720-724.
   doi
10. Johri AM, Behl P, Hetu MF, Haqqi M, Ewart P, Day AG, Parfrey B, et al. Carotid Ultrasound Maximum Plaque Height-A Sensitive Imaging Biomarker for the Assessment of Significant Coronary Artery Disease. Echocardiography. 2016;33(2):281-289.
    doi pubmed
11. Belcaro G, Nicolaides AN, Ramaswami G, Cesarone MR, De Sanctis M, Incandela L, Ferrari P, et al. Carotid and femoral ultrasound morphology screening and cardiovascular events in low risk subjects: a 10-year follow-up study (the CAFES-CAVE study(1)). Atherosclerosis. 2001;156(2):379-387.
    doi
12. Johnsen SH, Mathiesen EB, Joakimsen O, Stensland E, Wilsgaard T, Lochen ML, Njolstad I, et al. Carotid atherosclerosis is a stronger predictor of myocardial infarction in women than in men: a 6-year follow-up study of 6226 persons: the Tromso Study. Stroke. 2007;38(11):2873-2880.
    doi pubmed
13. Spence JD, Eliasziw M, DiCicco M, Hackam DG, Galil R, Lohmann T. Carotid plaque area: a tool for targeting and evaluating vascular preventive therapy. Stroke. 2002;33(12):2916-2922.
    doi pubmed
14. Brook RD, Bard RL, Patel S, Rubenfire M, Clarke NS, Kazerooni EA, Wakefield TW, et al. A negative carotid plaque area test is superior to other noninvasive atherosclerosis studies for reducing the likelihood of having underlying significant coronary artery disease. Arterioscler Thromb Vasc Biol. 2006;26(3):656-662.
    doi pubmed
15. Griffin M, Nicolaides A, Tyllis T, Georgiou N, Martin RM, Bond D, Panayiotou A, et al. Plaque area at carotid and common femoral bifurcations and prevalence of clinical cardiovascular disease. Int Angiol. 2010;29(3):216-225.
    pubmed
16. Johnsen SH, Mathiesen EB. Carotid plaque compared with intima-media thickness as a predictor of coronary and cerebrovascular disease. Curr Cardiol Rep. 2009;11(1):21-27.
    doi
17. Nambi V, Chambless L, Folsom AR, He M, Hu Y, Mosley T, Volcik K, et al. Carotid intima-media thickness and presence or absence of plaque improves prediction of coronary heart disease risk: the ARIC (Atherosclerosis Risk In Communities) study. J Am Coll Cardiol. 2010;55(15):1600-1607.
    doi pubmed
18. Romanens M, Miserez A R, Ackermann F, Riesen W, Spence J D, Darioli R. Imaging as a cardiovascular risk modifier in primary care patients using predictor models of the European and international atherosclerosis societies. Kariovaskulare Medizin. 2007;10:139-150.
19. Nambi V, Brunner G, Ballantyne CM. Ultrasound in cardiovascular risk prediction: don’t forget the plaque! J Am Heart Assoc. 2013;2(2):e000180.
    doi pubmed
20. Polak JF, Szklo M, Kronmal RA, Burke GL, Shea S, Zavodni AE, O’Leary DH. The value of carotid artery plaque and intima-media thickness for incident cardiovascular disease: the multi-ethnic study of atherosclerosis. J Am Heart Assoc. 2013;2(2):e000087.
    doi pubmed
21. Mathiesen EB, Johnsen SH, Wilsgaard T, Bonaa KH, Lochen ML, Njolstad I. Carotid plaque area and intima-media thickness in prediction of first-ever ischemic stroke: a 10-year follow-up of 6584 men and women: the Tromso Study. Stroke. 2011;42(4):972-978.
    doi pubmed
22. Inaba Y, Chen JA, Bergmann SR. Carotid plaque, compared with carotid intima-media thickness, more accurately predicts coronary artery disease events: a meta-analysis. Atherosclerosis. 2012;220(1):128-133.
    doi pubmed
23. Rundek T, Arif H, Boden-Albala B, Elkind MS, Paik MC, Sacco RL. Carotid plaque, a subclinical precursor of vascular events: the Northern Manhattan Study. Neurology. 2008;70(14):1200-1207.
    doi pubmed
24. Baber U, Mehran R, Sartori S, Schoos MM, Sillesen H, Muntendam P, Garcia MJ, et al. Prevalence, impact, and predictive value of detecting subclinical coronary and carotid atherosclerosis in asymptomatic adults: the BioImage study. J Am Coll Cardiol. 2015;65(11):1065-1074.
    doi pubmed
25. Adams A. Die Plaqueflache an der Arteria carotis: Ein besseres Tool für die Risikostratifizierung in der Primarpravention als der PROCAM-Score oder die IMT-Messung. Arbeitsmedizin Sozialmedizin Umweltmedizin. 2015;50:53-57.
26. Cohen GI, Aboufakher R, Bess R, Frank J, Othman M, Doan D, Mesiha N, et al. Relationship between carotid disease on ultrasound and coronary disease on CT angiography. JACC Cardiovasc Imaging. 2013;6(11):1160-1167.
    doi pubmed
27. Choi EK, Choi SI, Rivera JJ, Nasir K, Chang SA, Chun EJ, Kim HK, et al. Coronary computed tomography angiography as a screening tool for the detection of occult coronary artery disease in asymptomatic individuals. J Am Coll Cardiol. 2008;52(5):357-365.
    doi pubmed
28. Bonomo V, Piraino D, Bracale UM, Evola S, Di Piazza M, Vicari C, Lupo A, et al. An evaluation of coronary atherosclerosis using coronary CT in subjects with asymptomatic carotid lesions. Transl Med UniSa. 2014;(10):22-28.
29. Plank F, Friedrich G, Dichtl W, Klauser A, Jaschke W, Franz WM, Feuchtner G. The diagnostic and prognostic value of coronary CT angiography in asymptomatic high-risk patients: a cohort study. Open Heart. 2014;1(1):e000096.
    doi pubmed
30. Okahara A, Sadamatsu K, Matsuura T, Koga Y, Mine D, Yoshida K. Coronary artery disease screening with carotid ultrasound examination by a primary care physician. Cardiol Res. 2016;7(1):9-16.
    doi pubmed
31. Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney MT, 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):2315-2381.
    doi pubmed

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