Top

Published in:

01-07-2014 | Original Article

Impacts of age on coronary atherosclerosis and vascular response to statin therapy

Authors: Tsuyoshi Nozue, Shingo Yamamoto, Shinichi Tohyama, Kazuki Fukui, Shigeo Umezawa, Yuko Onishi, Tomoyuki Kunishima, Akira Sato, Toshihiro Nozato, Shogo Miyake, Youichi Takeyama, Yoshihiro Morino, Takao Yamauchi, Toshiya Muramatsu, Tsutomu Hirano, Kiyoshi Hibi, Mitsuyasu Terashima, Ichiro Michishita

Published in: Heart and Vessels | Issue 4/2014

Abstract

Age is a well-established risk factor for cardiovascular disease. Recent trials using intravascular ultrasound (IVUS) have shown that lipid-lowering therapy with statins halts the progression or induces the regression of coronary artery plaques. However, impacts of age on coronary atherosclerosis and vascular response to statin therapy have not been fully evaluated. The effects of 8-month statin therapy on coronary atherosclerosis were evaluated using virtual histology-IVUS. IVUS data were analyzed from 119 patients who were divided into two groups according to age: elderly patients (≥65 years, n = 72) and non-elderly patients (<65 years, n = 47). No patients were taking statins or other lipid-lowering therapies at baseline. At baseline, external elastic membrane (EEM) volume (17.27 vs. 14.95 mm³/mm, p = 0.02) and plaque volume (9.49 vs. 8.11 mm³/mm, p = 0.03) in the elderly patients were significantly greater than in the non-elderly patients. The EEM volume (−2.4 %, p = 0.007) and plaque volume (−3.1 %, p = 0.007) after 8-month of statin therapy had significantly decreased in the non-elderly patients but not in the elderly patients. A significant positive correlation was observed between age and percentage change in plaque volume (r = 0.265, p = 0.004). A multivariate regression analysis showed that age was a significant predictor of the percentage change in plaque volume during statin therapy (β = 0.223, p = 0.02). Coronary atherosclerosis was more advanced and vascular responses to statin therapy were attenuated in the elderly patients compared to the non-elderly patients.

Lakatta EG, Levy D (2003) Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a “set up” for vascular disease. Circulation 107:139–146PubMedCrossRef

Burke AP, Farb A, Pestaner J, Malcom GT, Zieske A, Kutys R, Smialek J, Virmani R (2002) Traditional risk factors and the incidence of sudden coronary death with and without coronary thrombosis in blacks. Circulation 105:419–424PubMedCrossRef

Hong YJ, Jeong MH, Ahn Y, Sim DS, Chung JW, Cho JS, Yoon NS, Yoon HJ, Moon JY, Kim KH, Park HW, Kim JH, Cho JG, Park JC, Kang JC (2008) Age-related differences in intravascular ultrasound findings in 1,009 coronary artery disease patients. Circ J 72:1270–1275PubMedCrossRef

Ruiz-García J, Lerman A, Weisz G, Maehara A, Mintz GS, Fahy M, Xu K, Lansky AJ, Cristea E, Farah TG, Teles R, Botker HE, Templin B, Zhang Z, de Bruyne B, Serruys PW, Stone GW (2012) Age- and gender-related changes in plaque composition in patients with acute coronary syndrome: the prospect study. Euro Interv 8:929–938

Qian J, Maehara A, Mintz GS, Margolis MP, Lerman A, Rogers J, Banai S, Kazziha S, Castellanos C, Dani L, Fahy M, Stone GW, Leon MB (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 103:1210–1214PubMedCrossRef

Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, Crowe T, Howard G, Cooper CJ, Brodie B, Grines CL, DeMaria AN; REVERSAL Investigators (2004) Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA 291:1071–1080

Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, Davignon J, Erbel R, Fruchart JC, Tardif JC, Schoenhagen P, Crowe T, Cain V, Wolski K, Goormastic M, Tuzcu EM; ASTEROID Investigators (2006) Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the asteroid trial. JAMA 295:1556–1565

Nozue T, Yamamoto S, Tohyama S, Umezawa S, Kunishima T, Sato A, Miyake S, Takeyama Y, Morino Y, Yamauchi T, Muramatsu T, Hibi K, Sozu T, Michishita I (2012) Statin Treatment for coronary artery plaque composition based on intravascular ultrasound radiofrequency data analysis. Am Heart J 163:191–199PubMedCrossRef

Nozue T, Yamamoto S, Tohyama S, Umezawa S, Kunishima T, Sato A, Miyake S, Takeyama Y, Morino Y, Yamauchi T, Muramatsu T, Hibi K, Sozu T, Michishita I; Kanagawa PTCA Conference Study Group (2009) Treatment with statin on atheroma regression evaluated by intravascular ultrasound with virtual histology (TRUTH study): rationale and design. Circ J 73:352–355CrossRef

10.

García-García HM, Mintz GS, Lerman A, Vince DG, Margolis MP, van Es GA, Morel MA, Nair A, Virmani R, Burke AP, Stone GW, Serruys PW (2009) Tissue characterisation using intravascular radiofrequency data analysis: recommendations for acquisition, analysis, interpretation and reporting. Euro Interv 5:177–189

11.

Mintz GS, Nissen SE, Anderson WD, Bailey SR, Erbel R, Fitzgerald PJ, Pinto FJ, Rosenfield K, Siegel RJ, Tuzcu EM, Yock PG (2001) 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 37:1478–1492PubMedCrossRef

12.

Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ (1987) Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 316:1371–1375PubMedCrossRef

13.

Burke AP, Kolodgie FD, Farb A, Weber D, Virmani R (2002) Morphological predictors of arterial remodeling in coronary atherosclerosis. Circulation 105:297–303PubMedCrossRef

14.

Varnava AM, Mills PG, Davies MJ (2002) Relationship between coronary artery remodeling and plaque vulnerability. Circulation 105:939–943PubMedCrossRef

15.

Fujii K, Carlier SG, Mintz GS, Wijns W, Colombo A, Bose D, Erbel R, de Ribamar Costa J Jr, Kimura M, Sano K, Costa RA, Lui J, Stone GW, Moses JW, Leon MB (2005) Association of plaque characterization by intravascular ultrasound virtual histology and arterial remodeling. Am J Cardiol 96:1476–1483

16.

Nakamura M, Nishikawa H, Mukai S, Setsuda M, Nakajima K, Tamada H, Suzuki H, Ohnishi T, Kakuta Y, Nakano T, Yeung AC (2001) Impact of coronary artery remodeling on clinical presentation of coronary artery disease: an intravascular ultrasound study. J Am Coll Cardiol 37:63–69PubMedCrossRef

17.

Schoenhagen P, Ziada KM, Kapadia SR, Crowe TD, Nissen SE, Tuzcu EM (2000) Extent and direction of artery remodeling in stable versus unstable coronary syndromes: an intravascular ultrasound study. Circulation 101:598–603PubMedCrossRef

18.

Ehara S, Naruko T, Kobayashi Y, Kataoka T, Nakagawa M, Shirai N, Ishii H, Okuyama T, Oe H, Sugioka K, Hozumi T, Haze K, Yoshikawa J, Yoshiyama M, Ueda M (2007) Comparison of clinical characteristics and arterial remodeling by intravascular ultrasonic imaging in three age groups (< or = 55, 56–69 and > or = 70 years) of Japanese patients with acute myocardial infarction. Am J Cardiol 100:1713–1717PubMedCrossRef

19.

Surmely JF, Nasu K, Fujita H, Terashima M, Matsubara T, Tsuchikane E, Ehara M, Kinoshita Y, Zheng QX, Tanaka N, Katoh O, Suzuki T (2006) Coronary plaque composition of culprit/target lesions according to the clinical presentation: a virtual histology intravascular ultrasound analysis. Eur Heart J 27:2939–2944PubMedCrossRef

20.

Kawasaki M, Sano K, Okubo M, Yokoyama H, Ito Y, Murata I, Tsuchiya K, Minatoguchi S, Zhou X, Fujita H, Fujiwara H (2005) Volumetric quantitative analysis of tissue characteristics of coronary plaques after statin therapy using three-dimensional integrated backscatter intravascular ultrasound. J Am Coll Cardiol 45:1946–1953PubMedCrossRef

21.

Schartl M, Bocksch W, Koschyk DH, Voelker W, Karsch KR, Kreuzer J, Hausmann D, Beckmann S, Gross M (2001) Use of intravascular ultrasound to compare effects of different strategies of lipid-lowering therapy on plaque volume and composition in patients with coronary artery disease. Circulation 104:387–392PubMedCrossRef

22.

Crisby M, Nordin-Fredriksson G, Shah PK, Yano J, Zhu J, Nilsson J (2001) Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation 103:926–933PubMedCrossRef

23.

Kovarnik T, Mintz GS, Skalicka H, Kral A, Horak J, Skulec R, Uhrova J, Martasek P, Downe RW, Wahle A, Sonka M, Mrazek V, Aschermann M, Linhart A (2012) Virtual histology evaluation of atherosclerosis regression during atorvastatin and ezetimibe administration: heaven study. Circ J 76:176–183PubMedCrossRef

24.

Lee SW, Hau WK, Kong SL, Chan KK, Chan PH, Lam SC, Tam FC, Wong MK, Chan CW, Lam YM, Tse HF, Chan RH (2012) Virtual histology findings and effects of varying doses of atorvastatin on coronary plaque volume and composition in statin-naive patients. Circ J 76:2662–2672PubMedCrossRef

25.

Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association (2004) Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 110:227–239

26.

Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators (2004) Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 350:1495–1504

27.

Tani S, Matsumoto M, Anazawa T, Kawamata H, Furuya S, Takahashi H, Iida K, Washio T, Kumabe N, Kobori M, Nagao K, Hirayama A (2012) Development of a model for prediction of coronary atherosclerotic regression: evaluation of high-density lipoprotein cholesterol level and peripheral blood monocyte count. Heart Vessels 27:143–150PubMedCrossRef

28.

Jia X, Wei M, Fu X, Gu X, Fan W, Zhang J, Xue L (2009) Intensive cholesterol-lowering therapy improves large artery elasticity in acute myocardial infarction patients. Heart Vessels 24:340–346PubMedCrossRef

29.

Suzuki T, Nozawa T, Fujii N, Sobajima M, Ohori T, Shida T, Matsuki A, Kameyama T, Inoue H (2011) Plaque regression in one artery is not necessarily associated with parallel changes in other vascular beds. Heart Vessels 26:242–251PubMedCrossRef

30.

Nozue T, Yamamoto S, Tohyama S, Fukui K, Umezawa S, Onishi Y, Kunishima T, Sato A, Nozato T, Miyake S, Takeyama Y, Morino Y, Yamauchi T, Muramatsu T, Hibi K, Terashima M, Michishita I; TRUTH Investigators (2012) Comparison of arterial remodeling and changes in plaque composition between patients with progression versus regression of coronary atherosclerosis during statin therapy (from the TRUTH study). Am J Cardiol 109:1247–1253

31.

Bayturan O, Kapadia S, Nicholls SJ, Tuzcu EM, Shao M, Uno K, Shreevatsa A, Lavoie AJ, Wolski K, Schoenhagen P, Nissen SE (2010) Clinical predictors of plaque progression despite very low levels of low-density lipoprotein cholesterol. J Am Coll Cardiol 55:2736–2742PubMedCrossRef

32.

Nozue T, Yamamoto S, Tohyama S, Fukui K, Umezawa S, Onishi Y, Kunishima T, Sato A, Nozato T, Miyake S, Takeyama Y, Morino Y, Yamauchi T, Muramatsu T, Hibi K, Terashima M, Michishita I (2013) Effects of serum n-3 to n-6 polyunsaturated fatty acids ratios on coronary atherosclerosis in statin-treated patients with coronary artery disease. Am J Cardiol 111:6–11PubMedCrossRef

33.

Puri R, Nissen SE, Ballantyne CM, Barter PJ, Chapman MJ, Erbel R, Libby P, Raichlen JS, St John J, Wolski K, Uno K, Kataoka Y, Nicholls SJ (2013) Factors underlying regression of coronary atheroma with potent statin therapy. Eur Heart J 34:1818–1825

34.

Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R (2010) Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376:1670–1681

35.

Itakura H, Nakaya N, Kusunoki T, Shimizu N, Hirai S, Mochizuki S, Ishikawa T (2011) Long-term event monitoring study of fluvastatin in Japanese patients with hypercholesterolemia: efficacy and incidence of cardiac and other events in elderly patients (≥65 years old). J Cardiol 57:77–88PubMedCrossRef

36.

de Graaf MA, van Velzen JE, de Graaf FR, Schuijf JD, Dijkstra J, Bax JJ, Reiber JH, Schalij MJ, van der Wall EE, Jukema JW (2013) The maximum necrotic core area is most often located proximally to the site of most severe narrowing: a virtual histology intravascular ultrasound study. Heart Vessels 28:166–172PubMedCrossRef

Title: Impacts of age on coronary atherosclerosis and vascular response to statin therapy
Authors: Tsuyoshi Nozue
Shingo Yamamoto
Shinichi Tohyama
Kazuki Fukui
Shigeo Umezawa
Yuko Onishi
Tomoyuki Kunishima
Akira Sato
Toshihiro Nozato
Shogo Miyake
Youichi Takeyama
Yoshihiro Morino
Takao Yamauchi
Toshiya Muramatsu
Tsutomu Hirano
Kiyoshi Hibi
Mitsuyasu Terashima
Ichiro Michishita
Publication date: 01-07-2014
Publisher: Springer Japan
Published in: Heart and Vessels / Issue 4/2014
Print ISSN: 0910-8327
Electronic ISSN: 1615-2573
DOI: https://doi.org/10.1007/s00380-013-0387-1

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Impacts of age on coronary atherosclerosis and vascular response to statin therapy

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2014

Novel use of the ultra-short-acting intravenous β1-selective blocker landiolol for supraventricular tachyarrhythmias in patients with congestive heart failure

Congenital long QT syndrome with compound mutations in the KCNH2 gene

Long-term incidence and prognostic factors of the progression of new coronary lesions in Japanese coronary artery disease patients after percutaneous coronary intervention

Resolution of a left ventricular thrombus by the thrombolytic action of dabigatran

Unusual “ratchet syndrome”: spontaneous lead retraction after a generator exchange

The autopsy study of 553 cases of sudden cardiac death in Chinese adults

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page