When comparing baseline characteristics between patients with SCAD and patients with NSTE-ACS (Table 1), statin use before study inclusion (>6 months) and HDL cholesterol (HDL-C) were higher in patients with SCAD versus those in patients with NSTE-ACS (both P < 0.05). Fourteen of 18 patients in the SCAD group used statins before study enrolment compared with five of 18 patients in the NSTE-ACS group, and HDL-C was 1.4 mM (1.3–1.7) in the SCAD group compared with 1.1 mM (1.0–1.3) in the NSTE-ACS group. In a sensitivity analysis, neither statin use before study enrolment nor HDL-C was significantly associated with the change in necrotic core volume or plaque burden (P > 0.2 for all tests).
Statin use before enrolment was more frequent in the SCAD group than in the NSTE-ACS group. This difference in statin use at baseline was neither significantly associated with the change in necrotic core volume (P = 0.70) nor plaque burden (P = 0.27) in our study. This is in contrast to the study of Rodes-Cabau et al. (25) where initiation of statins after ACS was associated with rapid regression of plaque burden. Accordingly, the different statin use at baseline in our study may have resulted in an underestimation of the exercise-induced difference in plaque burden reduction between patients with SCAD and patients with NSTE-ACS. No previous statin trial in patients with SCAD (23) or ACS (24) has demonstrated a reduction in necrotic core. Whether the imbalance in statin use at baseline in our study also led to an underestimation of the exercise-induced difference in necrotic core reduction between patients with SCAD and patients with NSTE-ACS cannot be concluded.
HDL-C levels were slightly higher in the SCAD group than that in the NSTE-ACS group at baseline. One study found higher incidence of attenuated grayscale intravascular ultrasound plaques in patients with very low HDL-C (14), arguing for greater plaque vulnerability in patients with low HDL-C. However, necrotic core content at baseline did not differ between patients with SCAD and patients with NSTE-ACS (Table 2), HDL-C was not associated with change in necrotic core (P = 0.81), and there was no evidence for HDL-C as an explanatory variable for necrotic core reduction in the random forest analysis. It is therefore unlikely that a small group difference in baseline HDL-C levels at baseline can explain our findings.
Our study is limited by its small sample size. Therefore, our results must be interpreted with caution and should be seen as hypothesis generating for future studies. Nevertheless, we demonstrated a strong association between clinical presentation of CAD and necrotic core reduction after aerobic exercise that could be clinically important with respect to exercise-induced effects on coronary atherosclerosis. Our data provide a basis for optimism regarding the beneficial intracoronary effects from exercise in patients with SCAD.
We thank Tove Vindsetmo, Ann Mari Myraunet, Anita Størdal, Ingerid Arbo, and Kirsti Krohn Garnæs for their assistance in patient inclusion and follow-up.
This study was funded by the following non-profit organizations: the Liaison Committee for Central Norway Regional Health Authority and the Norwegian University of Science and Technology, the Research Fund at St. Olavs University Hospital, the Norwegian Council on Cardiovascular Disease, and the Norwegian Council for Public Health.
The authors declare that there is no conflict of interest.
The results of the study do not constitute endorsement by the American College of Sports Medicine.
1. Ahmed HM, Blaha MJ, Nasir K, Rivera JJ, Blumenthal RS. Effects of physical activity on cardiovascular disease. Am J Cardiol
. 2012; 109( 2): 288–95.
2. Astengo M, Dahl A, Karlsson T, Mattsson-Hulten L, Wiklund O, Wennerblom B. Physical training after percutaneous coronary intervention in patients with stable angina: effects on working capacity, metabolism, and markers of inflammation. Eur J Cardiovasc Prev Rehabil
. 2010; 17( 3): 349–54.
3. Baruch A, van Bruggen N, Kim JB, Lehrer-Graiwer JE. Anti-inflammatory strategies for plaque stabilization after acute coronary syndromes. Curr Atheroscler Rep
. 2013; 15( 6): 327.
4. Beaglehole R, Ebrahim S, Reddy S, Voute J, Leeder S. Prevention of chronic diseases: a call to action. Lancet
. 2007; 370( 9605): 2152–7.
5. Beavers KM, Brinkley TE, Nicklas BJ. Effect of exercise training on chronic inflammation. Clin Chim Acta
. 2010; 411( 11–12): 785–93.
6. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med
. 2004; 350( 15): 1495–504.
7. Dutta P, Courties G, Wei Y, et al. Myocardial infarction accelerates atherosclerosis
. 2012; 487( 7407): 325–9.
8. Galon MZ, Wang Z, Bezerra HG, et al. Differences determined by optical coherence tomography volumetric analysis in non-culprit lesion morphology and inflammation in ST-segment elevation myocardial infarction and stable angina pectoris patients. Catheter Cardiovasc Interv
. 2015; 85( 4): E108–15.
9. Garcia-Garcia HM, Costa MA, Serruys PW. Imaging of coronary atherosclerosis
: intravascular ultrasound
. Eur Heart J
. 2010; 31( 20): 2456–69.
10. Garcia-Garcia HM, Mintz GS, Lerman A, et al. Tissue characterisation using intravascular radiofrequency data analysis: recommendations for acquisition, analysis, interpretation and reporting. EuroIntervention
. 2009; 5( 2): 177–89.
11. Goldhammer E, Tanchilevitch A, Maor I, Beniamini Y, Rosenschein U, Sagiv M. Exercise training modulates cytokines activity in coronary heart disease patients. Int J Cardiol
. 2005; 100( 1): 93–9.
12. Hothorn T, Buhlmann P, Dudoit S, Molinaro A, van der Laan MJ. Survival ensembles. Biostatistics
. 2006; 7( 3): 355–73.
13. Kato K, Yonetsu T, Kim SJ, et al. Nonculprit plaques in patients with acute coronary syndromes have more vulnerable features compared with those with non-acute coronary syndromes: a 3-vessel optical coherence tomography study. Circ Cardiovasc Imaging
. 2012; 5( 4): 433–40.
14. Kitabata H, Loh JP, Pendyala LK, et al. Intravascular ultrasound
analysis to determine the relationship between high-density lipoprotein cholesterol and lesion characteristics in patients with coronary artery disease
. J Interv Cardiol
. 2014; 27( 3): 325–33.
15. Laughlin MH, Newcomer SC, Bender SB. Importance of hemodynamic forces as signals for exercise-induced changes in endothelial cell phenotype. J Appl Physiol (1985)
. 2008; 104( 3): 588–600.
16. Lawler PR, Filion KB, Eisenberg MJ. Efficacy of exercise-based cardiac rehabilitation post-myocardial infarction: a systematic review and meta-analysis of randomized controlled trials. Am Heart J
. 2011; 162( 4): 571–84.
17. MacNeill BD, Jang IK, Bouma BE, et al. Focal and multi-focal plaque macrophage distributions in patients with acute and stable presentations of coronary artery disease
. J Am Coll Cardiol
. 2004; 44( 5): 972–9.
18. Madssen E, Moholdt T, Videm V, Wisloff U, Hegbom K, Wiseth R. Coronary atheroma regression and plaque characteristics assessed by grayscale and radiofrequency intravascular ultrasound
after aerobic exercise
. Am J Cardiol
. 2014; 114( 10): 1504–11.
19. Mintz GS, Garcia-Garcia HM, Nicholls SJ, et al. Clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound
regression/progression studies. EuroIntervention
. 2011; 6( 9): 1123–30, 9.
20. Niebauer J, Hambrecht R, Velich T, et al. Attenuated progression of coronary artery disease
after 6 years of multifactorial risk intervention: role of physical exercise. Circulation
. 1997; 96( 8): 2534–41.
21. Nytroen K, Rustad LA, Erikstad I, et al. Effect of high-intensity interval training on progression of cardiac allograft vasculopathy. J Heart Lung Transplant
. 2013; 32( 11): 1073–80.
22. Ornish D, Scherwitz LW, Billings JH, et al. Intensive lifestyle changes for reversal of coronary heart disease. JAMA
. 1998; 280( 23): 2001–7.
23. Puri R, Libby P, Nissen SE, et al. Long-term effects of maximally intensive statin therapy on changes in coronary atheroma composition: insights from SATURN. Eur Heart J Cardiovasc Imaging
. 2014; 15( 4): 380–8.
24. Raber L, Taniwaki M, Zaugg S, et al. Effect of high-intensity statin therapy on atherosclerosis
in non-infarct-related coronary arteries (IBIS-4): a serial intravascular ultrasonography study. Eur Heart J
. 2015; 36( 8): 490–500.
25. Rodes-Cabau J, Tardif JC, Cossette M, et al. Acute effects of statin therapy on coronary atherosclerosis
following an acute coronary syndrome. Am J Cardiol
. 2009; 104( 6): 750–7.
26. Rognmo O, Hetland E, Helgerud J, Hoff J, Slordahl SA. High intensity aerobic interval exercise is superior to moderate intensity exercise for increasing aerobic capacity in patients with coronary artery disease
. Eur J Cardiovasc Prev Rehabil
. 2004; 11( 3): 216–22.
27. Schuler G, Hambrecht R, Schlierf G, et al. Regular physical exercise and low-fat diet. Effects on progression of coronary artery disease
. 1992; 86( 1): 1–11.
28. Sixt S, Beer S, Bluher M, et al. Long- but not short-term multifactorial intervention with focus on exercise training improves coronary endothelial dysfunction in diabetes mellitus type 2 and coronary artery disease
. Eur Heart J
. 2010; 31( 1): 112–9.
29. Steffen-Batey L, Nichaman MZ, Goff DC Jr, et al. Change in level of physical activity and risk of all-cause mortality or reinfarction: the Corpus Christi Heart Project. Circulation
. 2000; 102( 18): 2204–9.
30. Strobl C, Malley J, Tutz G. An introduction to recursive partitioning: rationale, application, and characteristics of classification and regression trees, bagging, and random forests. Psychol Methods
. 2009; 14( 4): 323–48.
31. Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the vulnerable plaque. J Am Coll Cardiol
. 2006; 47( 8 Suppl): C13–8.
32. Walther C, Mobius-Winkler S, Linke A, et al. Regular exercise training compared with percutaneous intervention leads to a reduction of inflammatory markers and cardiovascular events in patients with coronary artery disease
. Eur J Cardiovasc Prev Rehabil
. 2008; 15( 1): 107–12.
33. Wilensky RL. In search of the elusive vulnerable plaque: reducing the gap between coronary imaging and necropsy findings. J Am Coll Cardiol
. 2013; 61( 10): 1052–3.